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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 0.5%...

  2. Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1.

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    Robinson, Jessica L L; Macarthur, Stewart; Ross-Innes, Caryn S; Tilley, Wayne D; Neal, David E; Mills, Ian G; Carroll, Jason S

    2011-06-24

    Breast cancer is a heterogeneous disease and several distinct subtypes exist based on differential gene expression patterns. Molecular apocrine tumours were recently identified as an additional subgroup, characterised as oestrogen receptor negative and androgen receptor positive (ER- AR+), but with an expression profile resembling ER+ luminal breast cancer. One possible explanation for the apparent incongruity is that ER gene expression programmes could be recapitulated by AR. Using a cell line model of ER- AR+ molecular apocrine tumours (termed MDA-MB-453 cells), we map global AR binding events and find a binding profile that is similar to ER binding in breast cancer cells. We find that AR binding is a near-perfect subset of FoxA1 binding regions, a level of concordance never previously seen with a nuclear receptor. AR functionality is dependent on FoxA1, since silencing of FoxA1 inhibits AR binding, expression of the majority of the molecular apocrine gene signature and growth cell growth. These findings show that AR binds and regulates ER cis-regulatory elements in molecular apocrine tumours, resulting in a transcriptional programme reminiscent of ER-mediated transcription in luminal breast cancers.

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

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

    2015-09-01

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

  4. Androgen receptor- and PIAS1-regulated gene programs in molecular apocrine breast cancer cells.

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    Malinen, Marjo; Toropainen, Sari; Jääskeläinen, Tiina; Sahu, Biswajyoti; Jänne, Olli A; Palvimo, Jorma J

    2015-10-15

    We have analyzed androgen receptor (AR) chromatin binding sites (ARBs) and androgen-regulated transcriptome in estrogen receptor negative molecular apocrine breast cancer cells. These analyses revealed that 42% of ARBs and 39% androgen-regulated transcripts in MDA-MB453 cells have counterparts in VCaP prostate cancer cells. Pathway analyses showed a similar enrichment of molecular and cellular functions among AR targets in both breast and prostate cancer cells, with cellular growth and proliferation being among the most enriched functions. Silencing of the coregulator SUMO ligase PIAS1 in MDA-MB453 cells influenced AR function in a target-selective fashion. An anti-apoptotic effect of the silencing suggests involvement of the PIAS1 in the regulation of cell death and survival pathways. In sum, apocrine breast cancer and prostate cancer cells share a core AR cistrome and target gene signature linked to cancer cell growth, and PIAS1 plays a similar coregulatory role for AR in both cancer cell types.

  5. Clinical and Molecular Evidence of ABCC11 Protein Expression in Axillary Apocrine Glands of Patients with Axillary Osmidrosis

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    Toyoda, Yu; Takada, Tappei; Gomi, Tsuneaki; Nakagawa, Hiroshi; Ishikawa, Toshihisa; Suzuki, Hiroshi

    2017-01-01

    Accumulating evidence suggests that the risk of axillary osmidrosis is governed by a non-synonymous single nucleotide polymorphism (SNP) 538G>A in human ATP-binding cassette C11 (ABCC11) gene. However, little data are available for the expression of ABCC11 protein in human axillary apocrine glands that produce apocrine sweat—a source of odor from the armpits. To determine the effect of the non-synonymous SNP ABCC11 538G>A (G180R) on the ABCC11 in vivo, we generated transiently ABCC11-expressing transgenic mice with adenovirus vector, and examined the protein levels of each ABCC11 in the mice with immunoblotting using an anti-ABCC11 antibody we have generated in the present study. Furthermore, we examined the expression of ABCC11 protein in human axillary apocrine glands extracted from axillary osmidrosis patients carrying each ABCC11 genotype: 538GG, GA, and AA. Analyses of transiently ABCC11-expressing transgenic mice showed that ABCC11 538G>A diminishes the ABCC11 protein levels in vivo. Consistently, ABCC11 protein was detected in the human axillary apocrine glands of the 538GG homozygote or 538GA heterozygote, not in the 538AA homozygote. These findings would contribute to a better understanding of the molecular basis of axillary osmidrosis. PMID:28212277

  6. Tubular apocrine adenoma.

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    Toribio, J; Zulaica, A; Peteiro, C

    1987-04-01

    We report a case of tubular apocrine adenoma located on the scalp, with characteristics of syringocystadenoma papilliferum in the superior part of the lesion. An interesting feature of the growth is its connective tissue involvement.

  7. 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.

  8. Apocrine adenocarcinoma of the vulva

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    Babita Kajal

    2013-09-01

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

  9. Molecular subtypes and imaging phenotypes of breast cancer

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    Cho, Nariya [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-08-15

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  10. Molecular subtypes and clinicopathological features of breastcancer

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    Irianiwati Irianiwati

    2013-04-01

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

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

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

    2014-01-01

    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 f...

  12. Molecular subtyping of Treponema pallidum subsp. pallidum in Lisbon, Portugal.

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

    2009-08-01

    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.

  13. Molecular subtypes of glioblastoma are relevant to lower grade glioma.

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    Xiaowei Guan

    Full Text Available Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas.Gene expression array, single nucleotide polymorphism (SNP array and clinical data were obtained for 228 GBMs and 176 grade II/II gliomas (GII/III from the publically available Rembrandt dataset. Two additional datasets with IDH1 mutation status were utilized as validation datasets (one publicly available dataset and one newly generated dataset from MD Anderson. Unsupervised clustering was performed and compared to gene expression subtypes assigned using the Verhaak et al 840-gene classifier. The glioma-CpG Island Methylator Phenotype (G-CIMP was assigned using prediction models by Fine et al.Unsupervised clustering by gene expression aligned with the Verhaak 840-gene subtype group assignments. GII/IIIs were preferentially assigned to the proneural subtype with IDH1 mutation and G-CIMP. GBMs were evenly distributed among the four subtypes. Proneural, IDH1 mutant, G-CIMP GII/III s had significantly better survival than other molecular subtypes. Only 6% of GBMs were proneural and had either IDH1 mutation or G-CIMP but these tumors had significantly better survival than other GBMs. Copy number changes in chromosomes 1p and 19q were associated with GII/IIIs, while these changes in CDKN2A, PTEN and EGFR were more commonly associated with GBMs.GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression.

  14. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes

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    de Anda-Jáuregui, Guillermo; Velázquez-Caldelas, Tadeo E.; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2016-01-01

    Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples) is also inferred and analyzed. Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e., CNR2) or to a particular subtype (such as LCK). Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance. With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer. PMID:27920729

  15. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes

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    Guillermo de Anda-Jáuregui

    2016-11-01

    Full Text Available Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes.In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples is also inferred and analyzed.Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e. CNR2 or to a particular subtype (such as LCK. Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance.With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer.

  16. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes.

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    de Anda-Jáuregui, Guillermo; Velázquez-Caldelas, Tadeo E; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2016-01-01

    Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples) is also inferred and analyzed. Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e., CNR2) or to a particular subtype (such as LCK). Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance. With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer.

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

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

    2015-11-01

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

  18. Molecular Subtypes of Uterine Leiomyosarcoma and Correlation with Clinical Outcome

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    Joyce N. Barlin

    2015-02-01

    Full Text Available The molecular etiology of uterine leiomyosarcoma (ULMS is poorly understood, which accounts for the wide disparity in outcomes among women with this disease. We examined and compared the molecular profiles of ULMS and normal myometrium (NL to identify clinically relevant molecular subtypes. Discovery cases included 29 NL and 23 ULMS specimens. RNA was hybridized to Affymetrix U133A 2.0 transcription microarrays. Differentially expressed genes and pathways were identified using standard methods. Fourteen NL and 44 ULMS independent archival samples were used for external validation. Molecular subgroups were correlated with clinical outcome. Pathway analyses of differentially expressed genes between ULMS and NL samples identified overrepresentation of cell cycle regulation, DNA repair, and genomic integrity. External validation confirmed differential expression in 31 genes (P < 4.4 × 10−4, Bonferroni corrected, with 84% of the overexpressed genes, including CDC7, CDC20, GTSE1, CCNA2, CCNB1, and CCNB2, participating in cell cycle regulation. Unsupervised clustering of ULMS identified two clades that were reproducibly associated with progression-free (median, 4.0 vs 26.0 months; P = .02; HR, 0.33 and overall (median, 18.2 vs 77.2 months; P = .04; HR, 0.33 survival. Cell cycle genes play a key role in ULMS sarcomagenesis, providing opportunities for therapeutic targeting. Reproducible molecular subtypes associated with clinical outcome may permit individualized adjuvant treatment after clinical trial validation.

  19. Breast cancer molecular subtypes: from TNBC to QNBC

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

    2016-01-01

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

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

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    Jansen Mona D

    2010-08-01

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

  1. 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.

  2. Advances in Molecular Serotyping and Subtyping of Escherichia coli

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    Pina M. Fratamico

    2016-05-01

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

  3. Discovery of new molecular subtypes in oesophageal adenocarcinoma.

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

    2011-01-01

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

  4. Discovery of new molecular subtypes in oesophageal adenocarcinoma.

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    Daniela Berg

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

  5. Molecular subtypes of PMI/RaRa in patients with acute promyelocytic leukemia

    OpenAIRE

    2014-01-01

    The objective was to describe the frequency of molecular subtypes of PML/RARα in patients with acute promyelocytic leukemia (APL) and their distribution according to risk of recurrence and cytomorphology. A case series was carried out, including fifty patients registered at the National Institute of Neoplastic Diseases (INEN) during 2010-2012, with molecular diagnosis of APL PML/RARα and bcr1, bcr2 and bcr3 subtypes by reverse-transcription polymerase chain reaction (RT-PCR). Bcr1 subtype...

  6. 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

  7. 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....

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

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    Park Hyung Seok

    2012-01-01

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

  9. Different response to neoadjuvant chemotherapy for different molecular subtypes in patients with locally advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Huafeng Kang; Zhijun Dai; Xiaobin Ma; Xing Bao; Shuai Lin; Hongbing Ma; Xiaoxu Liu; Xijing Wang

    2013-01-01

    Objective: The aim of this study was to evaluate the impact of different molecular subtypes defined by immunohistochemistry (IHC) staining on the response rate for patients with locally advanced breast cancer received neoadjuvant chemotherapy. Methods: One hundred and seven breast cancer patients admitted from 2007 to 2011 who received 4 cycles of docetaxel/epirubicin-combined (TE) neoadjuvant chemotherapy were retrospectively reviewed, the patients were classified into 4 subtypes: luminal A, luminal B, HER-2 and triple negative breast cancer (TNBC) according to different combination patterns of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor-2 (HER-2) expression defined by IHC method. The correlation between response rate and the molecular subtypes were analyzed. Results: The pathological complete response (PCR), clinical complete response (CCR), clinical partial response (CPR), and clinical stable disease (CSD) rate of whole group was 15.89% (17/107), 22.43% (24/107), 63.55% (68/107), 14.02% (15/107), respectively, and the overall response rate (ORR) was 85.98% (92/107). The PCR rate and ORR of luminal A, luminal B, HER-2 and TNBC subtypes was 4.76% and 73.81%; 16.67% and 83.33%;17.65% and 100.00%; 30.00% and 96.67%, respectively. The PCR and ORR rate of HER-2/TNBC subtypes was higher than that of luminal A/B subtypes (P = 0.019, P = 0.002, respectively). Conclusion: Different molecular subtypes display different response rate for patients with locally advanced breast cancer received neoadjuvant TE chemotherapy, HER-2/TNBC subtypes have a higher PCR and ORR rate than that of luminal A/B subtypes.

  10. 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

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

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

    2013-01-01

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

  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. Metastatic apocrine sweat gland adenocarcinoma in a terrier dog

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

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    Ujjwal Neogi

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

  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. Stroma-associated master regulators of molecular subtypes predict patient prognosis in ovarian cancer

    Science.gov (United States)

    Zhang, Shengzhe; Jing, Ying; Zhang, Meiying; Zhang, Zhenfeng; Ma, Pengfei; Peng, Huixin; Shi, Kaixuan; Gao, Wei-Qiang; Zhuang, Guanglei

    2015-01-01

    High-grade serous ovarian carcinoma (HGS-OvCa) has the lowest survival rate among all gynecologic cancers and is hallmarked by a high degree of heterogeneity. The Cancer Genome Atlas network has described a gene expression-based molecular classification of HGS-OvCa into Differentiated, Mesenchymal, Immunoreactive and Proliferative subtypes. However, the biological underpinnings and regulatory mechanisms underlying the distinct molecular subtypes are largely unknown. Here we showed that tumor-infiltrating stromal cells significantly contributed to the assignments of Mesenchymal and Immunoreactive clusters. Using reverse engineering and an unbiased interrogation of subtype regulatory networks, we identified the transcriptional modules containing master regulators that drive gene expression of Mesenchymal and Immunoreactive HGS-OvCa. Mesenchymal master regulators were associated with poor prognosis, while Immunoreactive master regulators positively correlated with overall survival. Meta-analysis of 749 HGS-OvCa expression profiles confirmed that master regulators as a prognostic signature were able to predict patient outcome. Our data unraveled master regulatory programs of HGS-OvCa subtypes with prognostic and potentially therapeutic relevance, and suggested that the unique transcriptional and clinical characteristics of ovarian Mesenchymal and Immunoreactive subtypes could be, at least partially, ascribed to tumor microenvironment. PMID:26530441

  18. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-15

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

  20. Raf kinase inhibitory protein role in the molecular subtyping of breast cancer.

    Science.gov (United States)

    Al-Mulla, Fahd; Marafie, Makia; Zea Tan, Tuan; Paul Thiery, Jean

    2014-03-01

    In this study, we examined the association between the RKIP expression and the molecular subtypes of breast cancer. Microarray gene expression data of 2,333 human breast cancer from 26 different cohorts performed on Affymetrix U133A or U133Plus2 platforms were downloaded from Array Express and Gene Expression Omnibus and the molecular subtype of breast cancer for the samples was determined by single sample Gene Set Enrichment Analysis. Differences in recurrence-free survival (RFS) were tested using the Log-rank test in univariate analysis and displayed using Kaplan-Meier curves. Cox proportional-hazards model was used to calculate the hazard ratio using univariate and multivariate analysis. Loss or reduced RKIP expression was associated with reduced RFS in breast cancer using univariate and multivariate analyses, which was independent of lymph node (LN) metastasis status. Basal-like, Claudin-low, and Her-2-enriched tumors had significantly lower RKIP levels compared to other subclasses (P < 0.0001). Conversely, the Luminal subclass exhibited the highest expression levels of RKIP (P < 0.0001 for Luminal A and P = 0.0005 for Luminal B subtype), while in normal-like breast cancer subtype, RKIP expression was not informative. RKIP expression was prognostic in ER+ and ER- subgroups. RKIP expression had no significant prognostic power within Basal-like, Claudine-low, Luminal B, or Her-2-enriched breast cancer subtypes. However, its expression pinpointed excellent from intermediate-poor Luminal A survivors, in both ER+ (P = 0.035) and ER- (P = 0.012) subgroups, especially in LN negative breast cancers. In conclusion, RKIP expression adds significant value to the molecular subclassification of breast cancer especially for the Luminal A subtype.

  1. 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.

  2. Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling.

    Science.gov (United States)

    Verhaak, Roel G W; Wouters, Bas J; Erpelinck, Claudia A J; Abbas, Saman; Beverloo, H Berna; Lugthart, Sanne; Löwenberg, Bob; Delwel, Ruud; Valk, Peter J M

    2009-01-01

    We examined the gene expression profiles of two independent cohorts of patients with acute myeloid leukemia [n=247 and n=214 (younger than or equal to 60 years)] to study the applicability of gene expression profiling as a single assay in prediction of acute myeloid leukemia-specific molecular subtypes. The favorable cytogenetic acute myeloid leukemia subtypes, i.e., acute myeloid leukemia with t(8;21), t(15;17) or inv(16), were predicted with maximum accuracy (positive and negative predictive value: 100%). Mutations in NPM1 and CEBPA were predicted less accurately (positive predictive value: 66% and 100%, and negative predictive value: 99% and 97% respectively). Various other characteristic molecular acute myeloid leukemia subtypes, i.e., mutant FLT3 and RAS, abnormalities involving 11q23, -5/5q-, -7/7q-, abnormalities involving 3q (abn3q) and t(9;22), could not be correctly predicted using gene expression profiling. In conclusion, gene expression profiling allows accurate prediction of certain acute myeloid leukemia subtypes, e.g. those characterized by expression of chimeric transcription factors. However, detection of mutations affecting signaling molecules and numerical abnormalities still requires alternative molecular methods.

  3. A Rare Case of Invasive Apocrine Carcinoma of the Breast with Unusual Radiologic Findings

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    Min Kim

    2016-05-01

    Full Text Available Invasive apocrine carcinoma (IAC of the breast is a rare subtype of breast malignancy. Its incidence is not well known, but it is approximately less than 1% to 4%. For these reasons, there are few reports and little information on the radiologic appearance of IAC. Furthermore, most of the case reports show malignant features which are similar to invasive ductal carcinoma (IDC. We present a rare case of IAC without typical malignant feature on mammography, and ultrasonography (USG. Imaging findings on computed tomography (CT, magnetic resonance imaging (MRI, and 18F-fluorodeoxyglucose (FDG positron emission tomography (PET/CT are also presented. The nodule in our case showed a relatively benign feature on USG and it is the first case of IAC with unusual findings. Therefore, this report may encourage radiologists to consider the malignant potential and perform pathologic correlation even if a newly developed nodule does not present with a typical malignant feature on USG.

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

    OpenAIRE

    Sarli Giuseppe; Castellani Gastone; Benazzi Cinzia; Sassi Francesco

    2010-01-01

    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 a...

  5. Effect of HIV-1 Subtype C integrase mutations implied using molecular modeling and docking data

    Science.gov (United States)

    Sachithanandham, Jaiprasath; Konda Reddy, Karnati; Solomon, King; David, Shoba; Kumar Singh, Sanjeev; Vadhini Ramalingam, Veena; Alexander Pulimood, Susanne; Cherian Abraham, Ooriyapadickal; Rupali, Pricilla; Sridharan, Gopalan; Kannangai, Rajesh

    2016-01-01

    The degree of sequence variation in HIV-1 integrase genes among infected patients and their impact on clinical response to Anti retroviral therapy (ART) is of interest. Therefore, we collected plasma samples from 161 HIV-1 infected individuals for subsequent integrase gene amplification (1087 bp). Thus, 102 complete integrase gene sequences identified as HIV-1 subtype-C was assembled. This sequence data was further used for sequence analysis and multiple sequence alignment (MSA) to assess position specific frequency of mutations within pol gene among infected individuals. We also used biophysical geometric optimization technique based molecular modeling and docking (Schrodinger suite) methods to infer differential function caused by position specific sequence mutations towards improved inhibitor selection. We thus identified accessory mutations (usually reduce susceptibility) leading to the resistance of some known integrase inhibitors in 14% of sequences in this data set. The Stanford HIV-1 drug resistance database provided complementary information on integrase resistance mutations to deduce molecular basis for such observation. Modeling and docking analysis show reduced binding by mutants for known compounds. The predicted binding values further reduced for models with combination of mutations among subtype C clinical strains. Thus, the molecular basis implied for the consequence of mutations in different variants of integrase genes of HIV-1 subtype C clinical strains from South India is reported. This data finds utility in the design, modification and development of a representative yet an improved inhibitor for HIV-1 integrase.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yongming Sang

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

  8. Radiomic analysis reveals DCE-MRI features for prediction of molecular subtypes of breast cancer

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

    2017-01-01

    The purpose of this study was to investigate the role of features derived from breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and to incorporated clinical information to predict the molecular subtypes of breast cancer. In particular, 60 breast cancers with the following four molecular subtypes were analyzed: luminal A, luminal B, human epidermal growth factor receptor-2 (HER2)-over-expressing and basal-like. The breast region was segmented and the suspicious tumor was depicted on sequentially scanned MR images from each case. In total, 90 features were obtained, including 88 imaging features related to morphology and texture as well as dynamic features from tumor and background parenchymal enhancement (BPE) and 2 clinical information-based parameters, namely, age and menopausal status. An evolutionary algorithm was used to select an optimal subset of features for classification. Using these features, we trained a multi-class logistic regression classifier that calculated the area under the receiver operating characteristic curve (AUC). The results of a prediction model using 24 selected features showed high overall classification performance, with an AUC value of 0.869. The predictive model discriminated among the luminal A, luminal B, HER2 and basal-like subtypes, with AUC values of 0.867, 0.786, 0.888 and 0.923, respectively. An additional independent dataset with 36 patients was utilized to validate the results. A similar classification analysis of the validation dataset showed an AUC of 0.872 using 15 image features, 10 of which were identical to those from the first cohort. We identified clinical information and 3D imaging features from DCE-MRI as candidate biomarkers for discriminating among four molecular subtypes of breast cancer. PMID:28166261

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

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    Alexandre Andrade dos Anjos Jácome

    2016-04-01

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

  10. Expression of Neuroendocrine Markers in Different Molecular Subtypes of Breast Carcinoma

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    David L. Wachter

    2014-01-01

    Full Text Available Background. Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic luminal A subtype. Methods. We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin. Results. We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A. In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior. Conclusions. We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies.

  11. Expression of Neuroendocrine Markers in Different Molecular Subtypes of Breast Carcinoma

    Science.gov (United States)

    Wachter, David L.; Hartmann, Arndt; Beckmann, Matthias W.; Fasching, Peter A.; Hein, Alexander; Bayer, Christian M.; Agaimy, Abbas

    2014-01-01

    Background. Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic) luminal A subtype. Methods. We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin). Results. We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A). In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior. Conclusions. We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies. PMID:24701575

  12. 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.

  13. 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

  14. Investigating the link between molecular subtypes of glioblastoma, epithelial-mesenchymal transition, and CD133 cell surface protein.

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    Hadi Zarkoob

    Full Text Available In this manuscript, we use genetic data to provide a three-faceted analysis on the links between molecular subclasses of glioblastoma, epithelial-to-mesenchymal transition (EMT and CD133 cell surface protein. The contribution of this paper is three-fold: First, we use a newly identified signature for epithelial-to-mesenchymal transition in human mammary epithelial cells, and demonstrate that genes in this signature have significant overlap with genes differentially expressed in all known GBM subtypes. However, the overlap between genes up regulated in the mesenchymal subtype of GBM and in the EMT signature was more significant than other GBM subtypes. Second, we provide evidence that there is a negative correlation between the genetic signature of EMT and that of CD133 cell surface protein, a putative marker for neural stem cells. Third, we study the correlation between GBM molecular subtypes and the genetic signature of CD133 cell surface protein. We demonstrate that the mesenchymal and neural subtypes of GBM have the strongest correlations with the CD133 genetic signature. While the mesenchymal subtype of GBM displays similarity with the signatures of both EMT and CD133, it also exhibits some differences with each of these signatures that are partly due to the fact that the signatures of EMT and CD133 are inversely related to each other. Taken together these data shed light on the role of the mesenchymal transition and neural stem cells, and their mutual interaction, in molecular subtypes of glioblastoma multiforme.

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

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    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.

  16. Molecular subtyping of Clostridium botulinum by pulsed-field gel electrophoresis.

    Science.gov (United States)

    Lúquez, Carolina; Joseph, Lavin A; Maslanka, Susan E

    2015-01-01

    Pulsed-field gel electrophoresis (PFGE) has been extensively used to estimate the genetic diversity of Clostridium botulinum. In addition, PFGE is the standard method for investigating foodborne outbreaks associated with various enteric pathogens, including C. botulinum. PFGE can be used to exclude a suspected but not confirmed food source when the patterns of the food and clinical isolates are different. Indistinguishable PFGE patterns may also be useful for linking isolates between patients or to a food source, but results must be interpreted within an epidemiological context to ensure isolates are truly related. Here, we describe a standardized laboratory protocol for molecular subtyping of C. botulinum by PFGE.

  17. 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.

  18. Calretinin expression as a reliable prognostic marker in different molecular subtypes of breast carcinoma

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    Mayada Saad Farrag

    2017-01-01

    Full Text Available Background: Calretinin (CR, a known mesothelial marker, is expressed in both epithelial and mesenchymal malignancies including breast cancer. Aims: We aimed to measure the frequency of CR expression in correlation with other clinicopathological parameters of different molecular subtypes of invasive breast carcinoma and to study its prognostic implications in this common cancer.Study Design: Tissue microarrays were constructed from 225 tissue samples of breast carcinoma cases. Subjects and Methods: Immunostaining for CR in addition to estrogen receptors, progesterone receptors, human epidermal growth factor receptor 2 (HER2, epidermal growth factor receptor, CK5/6, and Ki-67 for molecular subtyping. Statistical Analysis Used: Chi-square and Fisher's exact tests were done using SPSS 18.0 software (IBM Inc.. Survival data were analyzed using Kaplan–Meier test, Log-rank test, and Cox proportional hazard models. Results: Cases of invasive breast carcinomas with different grades were classified into 84 luminal A, 45 luminal B, 27 HER2 positive, 40 basal-like, and 29 unclassified. High CR expression was associated with tumors of high grade (P < 0.0001, high locoregional recurrence (P = 0.005, hormonal receptors negative, and high Ki-67 indices. They frequently display a basal-like phenotype (70%, P < 0.0001, HER2 (59.3%, and luminal B (33.3% tumors compared to luminal A (9.5% and unclassified subtypes (17.2%. Moreover, it is associated with poor overall patient survival (P = 0.034, but it does not affect disease-free survival. Conclusions: Calretinin could be a reliable predictor marker of adverse prognosis in breast cancer.

  19. Precision Subtypes of T Cell-Mediated Rejection Identified by Molecular Profiles

    Science.gov (United States)

    Kadota, Paul Ostrom; Hajjiri, Zahraa; Finn, Patricia W.; Perkins, David L.

    2015-01-01

    Among kidney transplant recipients, the treatment of choice for acute T cell-mediated rejection (TCMR) with pulse steroids or antibody protocols has variable outcomes. Some rejection episodes are resistant to an initial steroid pulse, but respond to subsequent antibody protocols. The biological mechanisms causing the different therapeutic responses are not currently understood. Histological examination of the renal allograft is considered the gold standard in the diagnosis of acute rejection. The Banff Classification System was established to standardize the histopathological diagnosis and to direct therapy. Although widely used, it shows variability among pathologists and lacks criteria to guide precision individualized therapy. The analysis of the transcriptome in allograft biopsies, which we analyzed in this study, provides a strategy to develop molecular diagnoses that would have increased diagnostic precision and assist the development of individualized treatment. Our hypothesis is that the histological classification of TCMR contains multiple subtypes of rejection. Using R language algorithms to determine statistical significance, multidimensional scaling, and hierarchical, we analyzed differential gene expression based on microarray data from biopsies classified as TCMR. Next, we identified KEGG functions, protein–protein interaction networks, gene regulatory networks, and predicted therapeutic targets using the integrated database ConsesnsusPathDB (CPDB). Based on our analysis, two distinct clusters of biopsies termed TCMR01 and TCMR02 were identified. Despite having the same Banff classification, we identified 1933 differentially expressed genes between the two clusters. These genes were further divided into three major groups: a core group contained within both the TCMR01 and TCMR02 subtypes, as well as genes unique to TCMR01 or TCMR02. The subtypes of TCMR utilized different biological pathways, different regulatory networks and were predicted to

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

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

    2012-09-15

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

  1. Molecular subtypes of breast cancer and amplification of topoisomerase II alpha : predictive role in dose intensive adjuvant chemotherapy

    NARCIS (Netherlands)

    Hannemann, J.; Kristel, P.; van Tinteren, H.; Bontenbal, M.; van Hoesel, Q. G. C. M.; Smit, W. M.; Nooij, M. A.; Voest, E. E.; van der Wall, E.; Hupperets, P.; de Vries, E. G. E.; Rodenhuis, S.; van de Vijver, M. J.

    2006-01-01

    Benefit from chemotherapy treatment in breast cancer patients is determined by the molecular make-up of the tumour. In a retrospective analysis, we determined the molecular subtypes of breast cancer originally defined by expression microarrays by immunohistochemistry in tumours of patients who took

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

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    Perez Villamil Beatriz

    2012-06-01

    Full Text Available Abstract Background 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. Methods 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. Results Hierarchical clustering identified four robust tumor subtypes with biologically and clinically distinct behavior. Stromal components (p 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. Conclusions We have identified novel molecular subtypes in colon cancer with distinct biological and clinical behavior that are established from the initiation of the tumor. Tumor microenvironment is important for the classification and for the malignant power of the tumor. Differential gene sets and biological pathways characterize each tumor subtype reflecting underlying mechanisms of carcinogenesis that may be used for the selection of targeted therapeutic procedures. This classification may contribute to an improvement in the management of the patients with CRC and to a

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

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    Yaxelis Mendoza

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

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

    Science.gov (United States)

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

    2014-01-01

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

  5. 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.

  6. Why do we have apocrine and sebaceous glands?

    OpenAIRE

    Williams, Edward S

    2001-01-01

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

  7. Apocrine carcinoma arising in a complex fibroadenoma: a case report.

    Science.gov (United States)

    Mele, Marco; Vahl, Pernille; Funder, Jonas Amstrup; Sorensen, Anne Schmidt; Jensen, Vibeke

    2014-01-01

    A carcinoma arising in a fibroadenoma is a rare event, which often entails a diagnostic challenge. The most common type is the lobular carcinoma and secondary a ductal carcinoma. We present an extremely rare case of malignant development of an invasive apocrine carcinoma in a complex fibroadenoma and underline the importance for clinicians to recognize the possibility of benign and malignant co-existence especially in older women.

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

    Science.gov (United States)

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

    2016-10-01

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

  9. Glycoprotein C gene based molecular subtyping of a bovine herpesvirus -1 isolate from uttar pradesh, India.

    Science.gov (United States)

    Ravishankar, Chintu; Nandi, S; Chander, V; Mohapatra, T K

    2012-12-01

    Bovine herpesvirus -1 (BHV-1) is the etiological agent of many clinical syndromes in cattle which causes huge economic losses to the animal husbandry sector annually. Since the first report of its presence in India in 1976, the disease is considered to be endemic in the country. In the present study, a case of keratoconjunctivitis in a cow was investigated to find out the underlying cause of the condition. The clinical material (ocular swab) was tested by BHV-1 glycoprotein D gene specific PCR using in house designed primers and found to be positive by the presence of a 212 bp DNA product in agarose gel electrophoresis. The virus was isolated in MDBK cell line in the third passage and the serum from the animal, was positive for antibodies against BHV-1 by ELISA. A 575 bp segment of the glycoprotein C gene of the isolate was amplified by PCR, cloned and sequenced. On phylogenetic analysis, it was seen that the sequence matched with published BHV-1.1 sequences from USA and Uruguay whereas it was divergent from Brazilian BHV-1.1 isolates. This study highlights the isolation, rapid and sensitive detection of BHV-1 virus from clinical cases and its subtyping by nucleotide sequencing and subsequent phylogenetic analysis which gives invaluable information about the molecular epidemiology of BHV-1 subtypes prevalent in the country.

  10. Molecular Subtyping of Primary Prostate Cancer Reveals Specific and Shared Target Genes of Different ETS Rearrangements

    Directory of Open Access Journals (Sweden)

    Paula Paulo

    2012-07-01

    Full Text Available This work aimed to evaluate whether ETS transcription factors frequently involved in rearrangements in prostate carcinomas (PCa, namely ERG and ETV1, regulate specific or shared target genes. We performed differential expression analysis on nine normal prostate tissues and 50 PCa enriched for different ETS rearrangements using exon-level expression microarrays, followed by in vitro validation using cell line models. We found specific deregulation of 57 genes in ERG-positive PCa and 15 genes in ETV1-positive PCa, whereas deregulation of 27 genes was shared in both tumor subtypes. We further showed that the expression of seven tumor-associated ERG target genes (PLA1A, CACNA1D, ATP8A2, HLA-DMB, PDE3B, TDRD1, and TMBIM1 and two tumor-associated ETV1 target genes (FKBP10 and GLYATL2 was significantly affected by specific ETS silencing in VCaP and LNCaP cell line models, respectively, whereas the expression of three candidate ERG and ETV1 shared targets (GRPR, KCNH8, and TMEM45B was significantly affected by silencing of either ETS. Interestingly, we demonstrate that the expression of TDRD1, the topmost overexpressed gene of our list of ERG-specific candidate targets, is inversely correlated with the methylation levels of a CpG island found at -66 bp of the transcription start site in PCa and that TDRD1 expression is regulated by direct binding of ERG to the CpG island in VCaP cells. We conclude that ETS transcription factors regulate specific and shared target genes and that TDRD1, FKBP10, and GRPR are promising therapeutic targets and can serve as diagnostic markers for molecular subtypes of PCa harboring specific fusion gene rearrangements.

  11. Crosstalk events in the estrogen signaling pathway may affect tamoxifen efficacy in breast cancer molecular subtypes.

    Science.gov (United States)

    de Anda-Jáuregui, Guillermo; Mejía-Pedroza, Raúl A; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2015-12-01

    Steroid hormones are involved on cell growth, development and differentiation. Such effects are often mediated by steroid receptors. One paradigmatic example of this coupling is the estrogen signaling pathway. Its dysregulation is involved in most tumors of the mammary gland. It is thus an important pharmacological target in breast cancer. This pathway, however, crosstalks with several other molecular pathways, a fact that may have consequences for the effectiveness of hormone modulating drug therapies, such as tamoxifen. For this work, we performed a systematic analysis of the major routes involved in crosstalk phenomena with the estrogen pathway - based on gene expression experiments (819 samples) and pathway analysis (493 samples) - for biopsy-captured tissue and contrasted in two independent datasets with in vivo and in vitro pharmacological stimulation. Our results confirm the presence of a number of crosstalk events across the estrogen signaling pathway with others that are dysregulated in different molecular subtypes of breast cancer. These may be involved in proliferation, invasiveness and apoptosis-evasion in patients. The results presented may open the way to new designs of adjuvant and neoadjuvant therapies for breast cancer treatment.

  12. Molecular subtyping of Treponema pallidum during a local syphilis epidemic in men who have sex with men in Melbourne, Australia.

    Science.gov (United States)

    Azzato, Francesca; Ryan, Norbert; Fyfe, Janet; Leslie, David E

    2012-06-01

    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.

  13. 16S rRNA partial gene sequencing for the differentiation and molecular subtyping of Listeria species.

    Science.gov (United States)

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

    2013-12-01

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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Human T-cell lymphotropic virus type 1 subtype C molecular variants among indigenous australians: new insights into the molecular epidemiology of HTLV-1 in Australo-Melanesia.

    Directory of Open Access Journals (Sweden)

    Olivier Cassar

    Full Text Available BACKGROUND: HTLV-1 infection is endemic among people of Melanesian descent in Papua New Guinea, the Solomon Islands and Vanuatu. Molecular studies reveal that these Melanesian strains belong to the highly divergent HTLV-1c subtype. In Australia, HTLV-1 is also endemic among the Indigenous people of central Australia; however, the molecular epidemiology of HTLV-1 infection in this population remains poorly documented. FINDINGS: Studying a series of 23 HTLV-1 strains from Indigenous residents of central Australia, we analyzed coding (gag, pol, env, tax and non-coding (LTR genomic proviral regions. Four complete HTLV-1 proviral sequences were also characterized. Phylogenetic analyses implemented with both Neighbor-Joining and Maximum Likelihood methods revealed that all proviral strains belong to the HTLV-1c subtype with a high genetic diversity, which varied with the geographic origin of the infected individuals. Two distinct Australians clades were found, the first including strains derived from most patients whose origins are in the North, and the second comprising a majority of those from the South of central Australia. Time divergence estimation suggests that the speciation of these two Australian clades probably occurred 9,120 years ago (38,000-4,500. CONCLUSIONS: The HTLV-1c subtype is endemic to central Australia where the Indigenous population is infected with diverse subtype c variants. At least two Australian clades exist, which cluster according to the geographic origin of the human hosts. These molecular variants are probably of very ancient origin. Further studies could provide new insights into the evolution and modes of dissemination of these retrovirus variants and the associated ancient migration events through which early human settlement of Australia and Melanesia was achieved.

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

    Directory of Open Access Journals (Sweden)

    Yung Hou Wong

    2013-09-01

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

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

    Science.gov (United States)

    Saga, K; Takahashi, M

    1992-02-01

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

  1. Radiogenomics of glioblastoma: a pilot multi-institutional study to investigate a relationship between tumor shape features and tumor molecular subtype

    Science.gov (United States)

    Czarnek, Nicholas M.; Clark, Kal; Peters, Katherine B.; Collins, Leslie M.; Mazurowski, Maciej A.

    2016-03-01

    Genomic subtype has been shown to be an important predictor of therapy response for patients with glioblastomas. Unfortunately, obtaining the genomic subtype is an expensive process that is not typically included in the standard of care. It is therefore of interest to investigate potential surrogates of molecular subtypes that use standard diagnostic data such as magnetic resonance (MR) imaging. In this study, we analyze the relationship between tumor genomic subtypes, proposed by Verhaak et al, 2010, and novel features that capture the shape of abnormalities as seen in fluid attenuated inversion recovery (FLAIR) MR images. In our study, we used data from 54 patients with glioblastomas from four institutions provided by The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA). We explore five shape features calculated by computer algorithms implemented in our laboratory that assess shape both in individual slices and in rendered three-dimensional tumor volumes. The association between each feature and molecular subtype was assessed using area under the receiver operating characteristic curve analysis. We show that the two dimensional measures of edge complexity are significant discriminators between mesenchymal and classical tumors. These preliminary findings show promise for an imaging-based surrogate of molecular subtype and contribute to the understanding of the relationship between tumor biology and its radiology phenotype.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Molecular cloning and expression of rat prostaglandin E receptor EP2 subtype.

    Science.gov (United States)

    Sando, T; Usui, T; Tanaka, I; Mori, K; Sasaki, Y; Fukuda, Y; Namba, T; Sugimoto, Y; Ichikawa, A; Narumiya, S

    1994-05-16

    A cDNA clone encoding the rat prostaglandin (PG) E receptor EP2 subtype was cloned from a rat lung cDNA library. It encodes 488 amino acid residues with putative seven-transmembrane domains. Specific binding of [3H]PGE2 was found in COS-7 cells transfected with the cDNA and was displaced with unlabeled prostaglandins in the order of PGE2 = PGE1 > iloprost > or = PGF2 alpha > or = PGD2. The binding was also inhibited by misoprostol, an EP2 and EP3 agonist, but not by sulprostone, an EP1 and EP3 agonist. Northern blot analysis demonstrated that the EP2 mRNA is widely expressed in various tissues, the significant expression being observed in the thymus, lung, spleen, heart stomach, and pancreas.

  5. Molecular determinants of subtype-selective efficacies of cytisine and the novel compound NS3861 at heteromeric nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Harpsøe, Kasper; Hald, Helle; Timmermann, Daniel B;

    2013-01-01

    Deciphering which specific agonist-receptor interactions affect efficacy levels is of high importance, because this will ultimately aid in designing selective drugs. The novel compound NS3861 and cytisine are agonists of nicotinic acetylcholine receptors (nAChRs) and both bind with high affinity...... electrophysiological measurements of efficacy levels at heteromeric combinations of a3- and a4-, with ß2- and ß4-subunits, and various chimeric constructs thereof. Compared with cytisine, which selectively activates receptors containing ß4- but not ß2-subunits, NS3861 displays the opposite ß-subunit preference...... and a complete lack of activation at a4-containing receptors. The maximal efficacy of NS3861 appeared solely dependent on the nature of the ligand-binding domain, whereas efficacy of cytisine was additionally affected by the nature of the ß-subunit transmembrane domain. Molecular docking to nAChR subtype...

  6. Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes.

    Science.gov (United States)

    Prat, Aleix; Karginova, Olga; Parker, Joel S; Fan, Cheng; He, Xiaping; Bixby, Lisa; Harrell, J Chuck; Roman, Erick; Adamo, Barbara; Troester, Melissa; Perou, Charles M

    2013-11-01

    Five molecular subtypes (luminal A, luminal B, HER2-enriched, basal-like, and claudin-low) with clinical implications exist in breast cancer. Here, we evaluated the molecular and phenotypic relationships of (1) a large in vitro panel of human breast cancer cell lines (BCCLs), human mammary fibroblasts (HMFs), and human mammary epithelial cells (HMECs); (2) in vivo breast tumors; (3) normal breast cell subpopulations; (4) human embryonic stem cells (hESCs); and (5) bone marrow-derived mesenchymal stem cells (hMSC). First, by integrating genomic data of 337 breast tumor samples with 93 cell lines we were able to identify all the intrinsic tumor subtypes in the cell lines, except for luminal A. Secondly, we observed that the cell lines recapitulate the differentiation hierarchy detected in the normal mammary gland, with claudin-low BCCLs and HMFs cells showing a stromal phenotype, HMECs showing a mammary stem cell/bipotent progenitor phenotype, basal-like cells showing a luminal progenitor phenotype, and luminal B cell lines showing a mature luminal phenotype. Thirdly, we identified basal-like and highly migratory claudin-low subpopulations of cells within a subset of triple-negative BCCLs (SUM149PT, HCC1143, and HCC38). Interestingly, both subpopulations within SUM149PT were enriched for tumor-initiating cells, but the basal-like subpopulation grew tumors faster than the claudin-low subpopulation. Finally, claudin-low BCCLs resembled the phenotype of hMSCs, whereas hESCs cells showed an epithelial phenotype without basal or luminal differentiation. The results presented here help to improve our understanding of the wide range of breast cancer cell line models through the appropriate pairing of cell lines with relevant in vivo tumor and normal cell counterparts.

  7. 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.

  8. Molecular cloning and characterization of the canine prostaglandin E receptor EP2 subtype.

    Science.gov (United States)

    Hibbs, T A; Lu, B; Smock, S L; Vestergaard, P; Pan, L C; Owen, T A

    1999-05-01

    Prostaglandin E2 (PGE2) binds to four G-protein coupled cell surface receptors (EP1-EP4) and has been implicated as a local mediator of bone anabolism via a cyclic AMP mediated pathway following activation of the EP2 and/or EP4 receptor subtype. A canine kidney cDNA library was screened using a human EP2 probe, and a clone with an open reading frame of 1083 bp, potentially encoding a protein of 361 amino acids, was characterized. This open reading frame has 89% identity to the human EP2 cDNA at the nucleotide level and 87% identity at the predicted protein level. Scatchard analysis of a CHO cell line stably transfected with canine EP2 yielded a dissociation constant of 22 nM for PGE2. Competition binding studies, using 3H-PGE2 as ligand, demonstrated specific displacement by PGE2, Prostaglandin E1, Prostaglandin A3, and butaprost (an EP2 selective ligand), but not by ligands with selectivity for the related DP, FP, IP, or TP receptors. Specific ligand binding also resulted in increased levels of cAMP in EP2 transfected cells with no evidence of short-term, ligand-induced desensitization. Northern blot analysis revealed two transcripts of 3300 and 2400 bp in canine lung, and reverse-transcription polymerase chain reaction showed expression in all tissues examined. Southern blot analysis suggests the presence of a single-copy gene for EP2 in the dog.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Molecular analysis of the interaction of the four histamine receptor subtypes with antidepressant and antipsychotic drugs

    OpenAIRE

    Appl, Heidrun

    2010-01-01

    Antidepressant and antipsychotic drugs are known to affect multiple molecular targets. Beside their determinant effects on the neurotransmission of serotonin, norepinephrine and dopamine via several transporters and receptors, they may also modulate muscarinic acetylcholine receptors and the histamine H1 receptor (H1R). Consequently, these drugs do not only yield unique profiles of desired effects but also several unwanted side effects that may impact therapy. In addition to the H1R, the hist...

  11. 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.

  12. 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.

  13. Molecular determinants of subtype-selective efficacies of cytisine and the novel compound NS3861 at heteromeric nicotinic acetylcholine receptors.

    Science.gov (United States)

    Harpsøe, Kasper; Hald, Helle; Timmermann, Daniel B; Jensen, Marianne L; Dyhring, Tino; Nielsen, Elsebet Ø; Peters, Dan; Balle, Thomas; Gajhede, Michael; Kastrup, Jette S; Ahring, Philip K

    2013-01-25

    Deciphering which specific agonist-receptor interactions affect efficacy levels is of high importance, because this will ultimately aid in designing selective drugs. The novel compound NS3861 and cytisine are agonists of nicotinic acetylcholine receptors (nAChRs) and both bind with high affinity to heteromeric α3β4 and α4β2 nAChRs. However, initial data revealed that the activation patterns of the two compounds show very distinct maximal efficacy readouts at various heteromeric nAChRs. To investigate the molecular determinants behind these observations, we performed in-depth patch clamp electrophysiological measurements of efficacy levels at heteromeric combinations of α3- and α4-, with β2- and β4-subunits, and various chimeric constructs thereof. Compared with cytisine, which selectively activates receptors containing β4- but not β2-subunits, NS3861 displays the opposite β-subunit preference and a complete lack of activation at α4-containing receptors. The maximal efficacy of NS3861 appeared solely dependent on the nature of the ligand-binding domain, whereas efficacy of cytisine was additionally affected by the nature of the β-subunit transmembrane domain. Molecular docking to nAChR subtype homology models suggests agonist specific interactions to two different residues on the complementary subunits as responsible for the β-subunit preference of both compounds. Furthermore, a principal subunit serine to threonine substitution may explain the lack of NS3861 activation at α4-containing receptors. In conclusion, our results are consistent with a hypothesis where agonist interactions with the principal subunit (α) primarily determine binding affinity, whereas interactions with key amino acids at the complementary subunit (β) affect agonist efficacy.

  14. Molecular Determinants of Subtype-selective Efficacies of Cytisine and the Novel Compound NS3861 at Heteromeric Nicotinic Acetylcholine Receptors*

    Science.gov (United States)

    Harpsøe, Kasper; Hald, Helle; Timmermann, Daniel B.; Jensen, Marianne L.; Dyhring, Tino; Nielsen, Elsebet Ø.; Peters, Dan; Balle, Thomas; Gajhede, Michael; Kastrup, Jette S.; Ahring, Philip K.

    2013-01-01

    Deciphering which specific agonist-receptor interactions affect efficacy levels is of high importance, because this will ultimately aid in designing selective drugs. The novel compound NS3861 and cytisine are agonists of nicotinic acetylcholine receptors (nAChRs) and both bind with high affinity to heteromeric α3β4 and α4β2 nAChRs. However, initial data revealed that the activation patterns of the two compounds show very distinct maximal efficacy readouts at various heteromeric nAChRs. To investigate the molecular determinants behind these observations, we performed in-depth patch clamp electrophysiological measurements of efficacy levels at heteromeric combinations of α3- and α4-, with β2- and β4-subunits, and various chimeric constructs thereof. Compared with cytisine, which selectively activates receptors containing β4- but not β2-subunits, NS3861 displays the opposite β-subunit preference and a complete lack of activation at α4-containing receptors. The maximal efficacy of NS3861 appeared solely dependent on the nature of the ligand-binding domain, whereas efficacy of cytisine was additionally affected by the nature of the β-subunit transmembrane domain. Molecular docking to nAChR subtype homology models suggests agonist specific interactions to two different residues on the complementary subunits as responsible for the β-subunit preference of both compounds. Furthermore, a principal subunit serine to threonine substitution may explain the lack of NS3861 activation at α4-containing receptors. In conclusion, our results are consistent with a hypothesis where agonist interactions with the principal subunit (α) primarily determine binding affinity, whereas interactions with key amino acids at the complementary subunit (β) affect agonist efficacy. PMID:23229547

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

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    Alessandra Cenci

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

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Alice Fraveto

    Full Text Available 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

  18. Epidemiological and histopathological analysis of 40 apocrine sweat gland carcinomas in dogs: a retrospective study

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    Kycko Anna

    2016-09-01

    Full Text Available Introduction: Apocrine sweat gland carcinomas (ASGCs are malignant neoplasms of dogs and other animals, rarely reported worldwide. The aim of this study was to summarise the occurrence of this cancer in a population of dogs in Poland between 2009 and 2014 with regards to histological features and body location of the tumours, as well as age, sex and breed of the cancer-affected dogs.

  19. 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.

  20. The effect of molecular subtype and body mass index on neo-adjuvant chemotherapy in breast cancer patients.

    Science.gov (United States)

    Iwase, Toshiaki; Nakamura, Rikiya; Yamamoto, Naohito; Yoshi, Atushi; Itami, Makiko; Miyazaki, Masaru

    2014-06-01

    The aim of the present study was to analyze the effect of subtype and body mass index (BMI) on neo-adjuvant chemotherapy (NAC) and postoperative prognosis. Two-hundred and forty nine patients who underwent surgery after NAC were included. A multivariate analysis and survival analysis were used to clarify the relationship between BMI, subtype, and NAC. In the logistic regression model, the pCR rate had a significant relationship with the subtype and tumor stage. In the non-pCR group, more overweight patients had significantly a worse disease-free survival (DFS) compared to normal range patients (Log lank test, p < 0.05). In the Cox proportional hazards model, subtype and tumor stage were significantly associated with decreased DFS. In conclusion, patients with the ER (+), HER (-) type and a high BMI had a high risk for recurrence when they achieved non-pCR after NAC.

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

    Science.gov (United States)

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

    2016-03-01

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

  2. 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.

  3. Distributed Subtyping

    OpenAIRE

    Baehni, Sébastien; Barreto, Joao; Guerraoui, Rachid

    2006-01-01

    One of the most frequent operations in object-oriented programs is the "instanceof" test, also called the "subtyping" test or the "type inclusion" test. This test determines if a given object is an instance of some type. Surprisingly, despite a lot of research on distributed object-oriented languages and systems, almost no work has been devoted to the implementation of this test in a distributed environment. This paper presents the first algorithm to implement the "subtyping" test on an obje...

  4. 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

  5. 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

  6. Apocrine Fibroadenoma on the Face: Case Report and Review of the Literature.

    Science.gov (United States)

    Khalsa, Amrit; Conway, Andrea; Ali, Liaqat; Heaney, Steven; Helm, Klaus

    2016-03-01

    Apocrine fibroadenoma (AFA) is a common benign entity found in the breast but is rarely seen at other sites. Several studies have documented cases in the anogenital region, but to date, there have been only 4 cases (excluding the current case) of an AFA located in the skin on other parts of the body. The authors present a case of a 66-year-old woman with a 6-year history of a slow growing red nodule on her face. The histopathologic diagnosis was consistent with an AFA. An extensive review of the literature to elucidate a possible pathogenesis of these lesions and relationship to the anogenital counterparts is presented.

  7. Antimicrobial resistance, virulence profiles and molecular subtypes of Salmonella enterica serovars Typhi and Paratyphi A blood isolates from Kolkata, India during 2009-2013.

    Science.gov (United States)

    Dutta, Shanta; Das, Surojit; Mitra, Utpala; Jain, Priyanka; Roy, Indranil; Ganguly, Shelley S; Ray, Ujjwayini; Dutta, Phalguni; Paul, Dilip Kumar

    2014-01-01

    Enteric fever, caused by Salmonella enterica, remains an unresolved public health problem in India and antimicrobial therapy is the main mode of treatment. The objective of this study was to characterize the Salmonella enterica isolates from Kolkata with respect to their antimicrobial resistance (AMR), virulence profiles and molecular subtypes. Salmonella enterica blood isolates were collected from clinically suspected enteric fever patients attending various hospitals in Kolkata, India from January 2009 to June 2013 and were tested for AMR profiles by standard protocols; for resistance gene transfer by conjugation; for resistance and virulence genes profiles by PCR; and for molecular subtypes by Pulsed Field Gel Electrophoresis (PFGE). A total of 77 Salmonella enterica serovar Typhi (S. Typhi) and 25 Salmonella enterica serovar Paratyphi A (S. Paratyphi A) from Kolkata were included in this study. Although multidrug resistance (resistance to chloramphenicol, ampicillin, co-trimoxazole) was decreasing in S. Typhi (18.2%) and absent in S. Paratyphi A, increased resistance to fluoroquinolone, the current drug of choice, caused growing concern for typhoid treatment. A single, non-conjugative non-IncHI1 plasmid of 180 kb was found in 71.4% multidrug resistant (MDR) S. Typhi; the remaining 28.6% isolates were without plasmid. Various AMR markers (blaTEM-1, catA, sul1, sul2, dfrA15, strA-strB) and class 1 integron with dfrA7 gene were detected in MDR S. Typhi by PCR and sequencing. Most of the study isolates were likely to be virulent due to the presence of virulence markers. Major diversity was not noticed among S. Typhi and S. Paratyphi A from Kolkata by PFGE. The observed association between AMR profiles and S. Typhi pulsotypes might be useful in controlling the spread of the organism by appropriate intervention. The study reiterated the importance of continuous monitoring of AMR and molecular subtypes of Salmonella isolates from endemic regions for better

  8. 肺癌分子分型与靶向治疗研究进展%Advances of Molecular Subtype and Targeted Therapy of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    邵岚; 宋正波; 张沂平; 苏丹

    2012-01-01

    随着肺癌发生、发展和预后相关分子机制研究的不断深入,肺癌靶向治疗取得了较大的进展,每一种分子分型的发现都会带来相应靶向药物的研究2004年表皮生长因子受体(epidermal growth factor receptor,EGFR)基因在非小细胞肺癌中的发现,为我们带来了EGFR突变高度敏感有效的酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI) 2007年棘皮类微管相关样蛋白-4-间变型淋巴瘤激酶(EML4-ALK)融合基因的出现为肺癌的分子发展带来了新的有效靶点.目前多个肺癌分子靶点及其靶向药物正在研究中.本文旨在回顾并总结肺癌分子分型及其靶向治疗的研究进展.%The discovery of multiple molecular mechanisms underlying the development, progression, and prognosis of lung cancer, has created new opportunities for targeted therapy, fiach subtype is associated with molecular tests that define the subtype and drugs that may have potential therapeutic effect on lung cancer. In 2004, mutations in the epidermal growth factor receptor (epidermal growth factor receptor, EGFR) gene were discovered in non-small cell lung cancers (NSCLC), especially in adenocarcinomas. And they are strongly associated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Moreover, in 2007 the existence of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene was discovered in NSCLC, and the same as EGFR-TKIs, ALK inhibitors are being found to be highly effective in lung cancers. At present, multiple molecular subtype of lung cancer and relevant targeted drugs are undering study. Here, we review the remarkable progress in molecular subtype of lung cancer and the related targeted therapy.

  9. Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter-rater study among surveillance centres in Europe and USA

    Science.gov (United States)

    de Boni, Laura; Saverioni, Daniela; Cohen, Mark L.; Ferrer, Isidro; Gambetti, Pierluigi; Gelpi, Ellen; Giaccone, Giorgio; Hauw, Jean-Jacques; Höftberger, Romana; Ironside, James W.; Jansen, Casper; Kovacs, Gabor G.; Rozemuller, Annemieke; Seilhean, Danielle; Tagliavini, Fabrizio; Giese, Armin

    2013-01-01

    The current classification of human sporadic prion diseases recognizes six major phenotypic subtypes with distinctive clinicopathological features, which largely correlate at the molecular level with the genotype at the polymorphic codon 129 (methionine, M, or valine, V) in the prion protein gene and with the size of the protease-resistant core of the abnormal prion protein, PrPSc (i.e. type 1 migrating at 21 kDa and type 2 at 19 kDa). We previously demonstrated that PrPSc typing by Western blotting is a reliable means of strain typing and disease classification. Limitations of this approach, however, particularly in the interlaboratory setting, are the association of PrPSc types 1 or 2 with more than one clinicopathological phenotype, which precludes definitive case classification if not supported by further analysis, and the difficulty of fully recognizing cases with mixed phenotypic features. In this study, we tested the inter-rater reliability of disease classification based only on histopathological criteria. Slides from 21 cases covering the whole phenotypic spectrum of human sporadic prion diseases, and also including two cases of variant Creutzfeldt–Jakob disease (CJD), were distributed blindly to 13 assessors for classification according to given instructions. The results showed good-to-excellent agreement between assessors in the classification of cases. In particular, there was full agreement (100 %) for the two most common sporadic CJD subtypes and variant CJD, and very high concordance in general for all pure phenotypes and the most common subtype with mixed phenotypic features. The present data fully support the basis for the current classification of sporadic human prion diseases and indicate that, besides molecular PrPSc typing, histopathological analysis permits reliable disease classification with high interlaboratory accuracy. PMID:22744790

  10. A coupling of homology modeling with multiple molecular dynamics simulation for identifying representative conformation of GPCR structures: a case study on human bombesin receptor subtype-3.

    Science.gov (United States)

    Nowroozi, Amin; Shahlaei, Mohsen

    2017-02-01

    In this study, a computational pipeline was therefore devised to overcome homology modeling (HM) bottlenecks. The coupling of HM with molecular dynamics (MD) simulation is useful in that it tackles the sampling deficiency of dynamics simulations by providing good-quality initial guesses for the native structure. Indeed, HM also relaxes the severe requirement of force fields to explore the huge conformational space of protein structures. In this study, the interaction between the human bombesin receptor subtype-3 and MK-5046 was investigated integrating HM, molecular docking, and MD simulations. To improve conformational sampling in typical MD simulations of GPCRs, as in other biomolecules, multiple trajectories with different initial conditions can be employed rather than a single long trajectory. Multiple MD simulations of human bombesin receptor subtype-3 with different initial atomic velocities are applied to sample conformations in the vicinity of the structure generated by HM. The backbone atom conformational space distribution of replicates is analyzed employing principal components analysis. As a result, the averages of structural and dynamic properties over the twenty-one trajectories differ significantly from those obtained from individual trajectories.

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

    Directory of Open Access Journals (Sweden)

    Sebastian Grossmann

    2015-06-01

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

  12. The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer

    Science.gov (United States)

    McGuire, Kandace; Alco, Gul; Nur Pilanci, Kezban; Koksal, Ulkuhan I; Elbüken, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Sarsenov, Dauren; Öztürk, Alper; İğdem, Şefik; Okkan, Sait; Eralp, Yeşim; Dincer, Maktav; Ozmen, Vahit

    2016-01-01

    Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival. PMID:27433412

  13. Construction of a Pan-Genome Allele Database of Salmonella enterica Serovar Enteritidis for Molecular Subtyping and Disease Cluster Identification

    Directory of Open Access Journals (Sweden)

    Yen-Yi Liu

    2016-12-01

    Full Text Available We built a pan-genome allele database with 395 genomes of Salmonella enterica serovar Enteritidis and developed computer tools for analysis of whole genome sequencing (WGS data of bacterial isolates for disease cluster identification. A web server (http://wgmlst.imst.nsysu.edu.tw was set up with the database and the tools, allowing users to upload WGS data to generate whole genome multilocus sequence typing (wgMLST profiles and to perform cluster analysis of wgMLST profiles. The usefulness of the database in disease cluster identification was demonstrated by analyzing a panel of genomes from 55 epidemiologically well-defined S. Enteritidis isolates provided by the Minnesota Department of Health. The wgMLST-based cluster analysis revealed distinct clades that were concordant with the epidemiologically defined outbreaks. Thus, using a common pan-genome allele database, wgMLST can be a promising WGS-based subtyping approach for disease surveillance and outbreak investigation across laboratories.

  14. Molecular subtyping of diffuse large B-cell lymphoma: update on biology, diagnosis and emerging platforms for practising pathologists.

    Science.gov (United States)

    Gifford, Grace K; Gill, Anthony J; Stevenson, William S

    2016-01-01

    Molecular classification of diffuse large B-cell lymphoma (DLBCL) is critical. Numerous methodologies have demonstrated that DLBCL is biologically heterogeneous despite morphological similarities. This underlies the disparate outcomes of treatment response or failure in this common non-Hodgkin lymphoma. This review will summarise historical approaches to lymphoma classifications, current diagnosis of DLBCL, molecular techniques that have primarily been used in the research setting to distinguish and subclassify DLBCL, evaluate contemporary diagnostic methodologies that seek to translate lymphoma biology into clinical practice, and introduce novel diagnostic platforms that may overcome current issues. The review concludes with an overview of key molecular lesions currently identified in DLBCL, all of which are potential targets for drug treatments that may improve survival and cure.

  15. Etiologic subtypes of attention-deficit/hyperactivity disorder : Brain imaging, molecular genetic and environmental factors and the dopamine hypothesis

    NARCIS (Netherlands)

    Swanson, James M.; Kinsbourne, Marcel; Nigg, Joel; Lanphear, Bruce; Stefanatos, Gerry A.; Volkow, Nora; Taylor, Eric; Casey, B. J.; Castellanos, F. Xavier; Wadhwa, Pathik D.

    2007-01-01

    Multiple theories of Attention-Deficit/Hyperactivity Disorder (ADHD) have been proposed, but one that has stood the test of time is the dopamine deficit theory. We review the narrow literature from recent brain imaging and molecular genetic studies that has improved our understanding of the role of

  16. Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

    Science.gov (United States)

    San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

    2014-12-01

    Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: In more than 70% of families with a strong history of breast and ovarian cancers, pathogenic mutation in BRCA1 or BRCA2 cannot be identified, even though hereditary factors are expected to be involved. It has been proposed that tumors with similar molecular phenotypes also share similar...... underlying pathophysiological mechanisms. In the current study, the aim was to investigate if global RNA profiling can be used to identify functional subgroups within breast tumors from families tested negative for BRCA1/2 germline mutations and how these subgroupings relate to different breast cancer...... patients within the same family. METHODS: In the current study we analyzed a collection of 70 frozen breast tumor biopsies from a total of 58 families by global RNA profiling and promoter methylation analysis. RESULTS: We show that distinct functional subgroupings, similar to the intrinsic molecular breast...

  18. [Detection of an NA gene molecular marker in H7N9 subtype avian influenza viruses by pyrosequencing].

    Science.gov (United States)

    Zhao, Yong-Gang; Liu, Hua-Lei; Wang, Jing-Jing; Zheng, Dong-Xia; Zhao, Yun-Ling; Ge, Sheng-Qiang; Wang, Zhi-Liang

    2014-07-01

    This study aimed to establish a method for the detection and identification of H7N9 avian influenza viruses based on the NA gene by pyrosequencing. According to the published NA gene sequences of the avian influenza A (H7N9) virus, a 15-nt deletion was found in the NA gene of H7N9 avian influenza viruses. The 15-nt deletion of the NA gene was targeted as the molecular marker for the rapid detection and identification of H7N9 avian influenza viruses by pyrosequencing. Three H7N9 avian influenza virus isolates underwent pyrosequencing using the same assay, and were proven to have the same 15-nt deletion. Pyrosequencing technology based on the NA gene molecular marker can be used to identify H7N9 avian influenza viruses.

  19. Pleomorphic adenoma of the eyelid with apocrine gland origin; an atypical location

    Directory of Open Access Journals (Sweden)

    Renata T Rothwell

    2016-01-01

    Full Text Available Purpose: To describe the clinical presentation and treatment of a patient with a cutaneous pleomorphic adenoma of the eyelid. Case Report: A 73-year-old male patient presented with a nodular mass on the lateral third of his right upper eyelid, which had slowly enlarged over 10 years. Radiologic features were of an extra-conical mass, with no invasion of adjacent structures. An excisional biopsy of the lesion was performed. The histopathological examination revealed a biphasic tumor, composed of tubules with a double layer of epithelial cells arranged in a chondromyxoid stroma. The inner epithelial cells were positive for pancytokeratins AE1/AE3 and carcinoembryonic antigen. The outer epithelial cells and stromal component expressed vimentin and S100 protein. These pathologic findings were consistent with a palpebral pleomorphic adenoma, with an apocrine gland origin. Conclusion: Pleomorphic adenomas of the skin are rare tumors, and even less frequent as tumors of the ocular adnexa. These lesions should be considered in the differential diagnosis of palpebral nodular masses, and complete excision should be attempted due to the possibility of malignant transformation.

  20. Profile of molecular subtypes of breast cancer with special reference to triple negative: A study from Northeast India

    Directory of Open Access Journals (Sweden)

    Gayatri Gogoi

    2016-01-01

    Full Text Available Background: Different molecular classes of breast cancer (BRCA correlate with prognosis and response to therapy. Triple-negative breast cancer (TNBC is a newer concept and very limited studies were carried out in India. The aim of this study was to profile the molecular types with a particular emphasis on TNBCs. Materials and Methods: Prospectively evaluated descriptive study for 2 years from June 2014 to March 2016, was carried out in the Department of Pathology and Surgery in a tertiary care institute. Cases included were of invasive breast carcinoma in females, confirmed by histopathology. Ethical clearance was received. Data were analyzed using Statistical SAS software. Results: A total of 123 cases of invasive BRCA were studied and mean age was 44.64 years. The peak age group was 36–45 years (43.9%. Tumor sizes ≥2 cm was 30%, between 2 and 5 cm was 50.40%, over 5 cm was 19.51%. Invasive duct carcinoma was 82.11% and invasive lobular carcinoma 8.13%. Only 21% of subjects presented as early breast carcinoma. Cases of 1–3 nodes were 22.8%, 4–5 nodes 21.1%, more than five nodes were 34%. Histologic Grade 3 was 50.4%, Grade 2 was 41%, and Grade 1 was only 8.1. The American Joint Committee on Cancer, Stage 1 (17.9% in Stage 2 (29.3% Stage 3 was 46.3%, Stage 4 was 6.5%. Estrogen receptor was in 40.62%, progesterone receptor 35.77%, Her2/Neu 18.69% luminal A (19.51%, luminal B (21.13%, Her2/Neu type (17.88%, and triple negatives (38.21. Conclusion: The present study showed significantly higher TNBC with poor prognostic factors in younger women in a background of peculiar ethic spectrum in this geographical region.

  1. Liposomal Nanoparticles Carrying anti-IL6R Antibody to the Tumour Microenvironment Inhibit Metastasis in Two Molecular Subtypes of Breast Cancer Mouse Models

    Science.gov (United States)

    Guo, Chunlei; Chen, Yanan; Gao, Wenjuan; Chang, Antao; Ye, Yujie; Shen, Wenzhi; Luo, Yunping; Yang, Shengyong; Sun, Peiqing; Xiang, Rong; Li, Na

    2017-01-01

    Tumour microenvironment (TME) contributes significantly towards potentiating the stemness and metastasis properties of cancer cells. IL6-Stat3 is one of the important cell signaling pathways in mediating the communication between tumour and immune cells. Here, we have systematically developed a novel anti-CD44 antibody-mediated liposomal nanoparticle delivery system loaded with anti-IL6R antibody, which could specifically target the TME of CD44+ breast cancer cells in different mouse models for triple negative and luminal breast cancer. This nanoparticle had an enhanced and specific tumour targeting efficacy with dramatic anti-tumour metastasis effects in syngeneic BALB/c mice bearing 4T1 cells as was in the syngeneic MMTV-PyMT mice. It inhibited IL6R-Stat3 signaling and moderated the TME, characterized by the reduced expression of genes encoding Stat3, Sox2, VEGFA, MMP-9 and CD206 in the breast tissues. Furthermore, this nanoparticle reduced the subgroups of Sox2+ and CD206+ cells in the lung metastatic foci, demonstrating its inhibitory effect on the lung metastatic niche for breast cancer stem cells. Taken together, the CD44 targeted liposomal nanoparticles encapsulating anti-IL6R antibody achieved a significant effect to inhibit the metastasis of breast cancer in different molecular subtypes of breast cancer mouse models. Our results shed light on the application of nanoparticle mediated cancer immune-therapy through targeting TME. PMID:28255366

  2. Molecular typing of the recently expanding subtype B HIV-1 epidemic in Romania: evidence for local spread among MSMs in Bucharest area.

    Science.gov (United States)

    Paraschiv, Simona; Otelea, Dan; Batan, Ionelia; Baicus, Cristian; Magiorkinis, Gkikas; Paraskevis, Dimitrios

    2012-07-01

    HIV-1 subtype B is predominant in Europe except in some countries from Eastern Europe which are characterized by a high prevalence of non-B subtypes and circulating recombinant forms (CRFs). Romania is a particular case: the HIV-1 epidemic started with subtype F1 which is still the most prevalent. Previous studies have shown an increasing prevalence of subtype B which is the second most frequent one among the newly diagnosed individuals, followed by subtype C and several CRFs as well as unique recombinant forms (URFs). Our objective was to analyze in detail the characteristics (way of dispersal, association with transmission risk groups) of the subtype B infections in Romania by means of phylogenetic analysis. Among all the individuals sampled during 2003-2010, 71 out of 1127 patients (6.3%) have been identified to be infected with subtype B strains. The most frequent route of infection identified in HIV-1 subtype B patients in Romania was MSM transmission (39.6%), followed by the heterosexual route (35.2%). Many of the patients acquired the infection abroad, mainly in Western European countries. Phylogenetic analysis indicated the existence of a local transmission network (monophyletic clade) including 14 patients, mainly MSM living in the Bucharest area. We estimate the origin of the local transmission network that dates at the beginning of the 90s; the introduction of the F1 and C subtypes occurred earlier. The rest of the sequences were intermixed with reference strains sampled across Europe suggesting that single infection were not followed by subsequent dispersal within the local population. Although HIV-1 subtype B epidemic in Romania is recent, there is evidence for local spread among the MSMs, in addition to multiple introductions.

  3. Molecular typing of the recently expanding subtype B HIV-1 epidemic in Romania: Evidence for local spread among MSMs in Bucharest area☆☆☆

    Science.gov (United States)

    Paraschiv, Simona; Otelea, Dan; Batan, Ionelia; Baicus, Cristian; Magiorkinis, Gkikas; Paraskevis, Dimitrios

    2012-01-01

    HIV-1 subtype B is predominant in Europe except in some countries from Eastern Europe which are characterized by a high prevalence of non-B subtypes and circulating recombinant forms (CRFs). Romania is a particular case: the HIV-1 epidemic started with subtype F1 which is still the most prevalent. Previous studies have shown an increasing prevalence of subtype B which is the second most frequent one among the newly diagnosed individuals, followed by subtype C and several CRFs as well as unique recombinant forms (URFs). Our objective was to analyze in detail the characteristics (way of dispersal, association with transmission risk groups) of the subtype B infections in Romania by means of phylogenetic analysis. Among all the individuals sampled during 2003–2010, 71 out of 1127 patients (6.3%) have been identified to be infected with subtype B strains. The most frequent route of infection identified in HIV-1 subtype B patients in Romania was MSM transmission (39.6%), followed by the heterosexual route (35.2%). Many of the patients acquired the infection abroad, mainly in Western European countries. Phylogenetic analysis indicated the existence of a local transmission network (monophyletic clade) including 14 patients, mainly MSM living in the Bucharest area. We estimate the origin of the local transmission network that dates at the beginning of the 90s; the introduction of the F1 and C subtypes occurred earlier. The rest of the sequences were intermixed with reference strains sampled across Europe suggesting that single infection were not followed by subsequent dispersal within the local population. Although HIV-1 subtype B epidemic in Romania is recent, there is evidence for local spread among the MSMs, in addition to multiple introductions. PMID:22430050

  4. Subtipos moleculares de PML/RARα en pacientes con leucemia promielocítica aguda Molecular subtypes of PML/RARα in patients with acute promyelocytic leukemia

    OpenAIRE

    2013-01-01

    El objetivo fue describir la frecuencia de los subtipos moleculares de PML/RARα en pacientes con leucemia promielocítica aguda (LPA) y su distribución según grupo de riesgo de recaída y citomorfología. Se realizó una serie de casos que incluyó a cincuenta pacientes registrados en el Instituto Nacional de Enfermedades Neoplásicas (INEN), durante el periodo 2010-2012, con diagnóstico molecular de LPA PML/RARα y subtipos bcr1, bcr2 y bcr3 por reacción en cadena de la polimerasa con tra...

  5. Expression of MDR1 gene in cancer stem cells in breast cancer tissues of different molecular subtypes%不同分子分型乳腺癌干细胞MDR1表达的研究

    Institute of Scientific and Technical Information of China (English)

    杨国华; 薛芳沁; 陈晓耕

    2012-01-01

    目的 探讨乳腺癌干细胞MDR1表达与乳腺癌不同分子分型的关系.方法 根据ER、PR、Her-2及CK5/14的水平划分为5个分子亚型,分为5组,通过PCR法分析不同分子分型乳腺癌组织中癌干细胞MDR1表达,分析乳癌干细胞中MDR1表达量与乳腺癌不同分子分型的关系.结果 LuminalA型组癌干细胞MDR1量(0.26±0.04)和Luminal B型组(0.31±0.03)最少,两组MDR1量无显著性差异(P>0.05);HER-2+型组乳腺癌干细胞MDR1量(0.56±0.05)明显多于A组和B组,具有显著性差异(P<0.05);Basal-like型癌干细胞的MDR1量(0.98±0.01)和Normal-like型的MDR1量(0.90±0.15)最多,两组无显著性差异(P>0.05),但明显多于LuminalA型/B组、HER-2(+)型组,具有显著性差异(P<0.05).结论 乳腺癌干细胞MDR1表达与其分子分型有关.%Objective To investigate the association between MDR1 gene expression in breast cancer stem cells and the molecular subtypes of breast cancer tissue. Methods According to ER, PR, Her-2 and CK5/14 expression profiles, 153 breast cancer specimens were divided into 5 molecular molecular subtypes, in which the expression of MDR1 was detected to analyze the relationship between MDR1 gene expression and the subtypes of breast cancer stem cells. Results The expression of MDR1 in Luminal A subtype breast cancer was 0.26±0.04, which showed no significant difference from that of Luminal B subtype (0.31±0.03, P>0.05). Compared with these two subtypes, HER-2 (+) subtype breast cancer tissues showed a significantly higher MDR1 expression(0.56±0.05, P0.05), but both significantly higher than that in Luminal A and B subtypes and HER-2 (+) subtype (P<0.05). Conclusion The expression of MDR1 gene in cancer stem cells is related with the molecular subtypes of breast cancer tissue .

  6. Prognosis value of molecular sub-types in breast cancers free of ganglionary invasion after mastectomy and impact of radiotherapy; Valeur pronostique des sous-types moleculaires dans les cancers du sein indemnes d'envahissement ganglionnaire apres mastectomie et impact de la radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Selz, J.; Stevens, D.; Jouanneau, L.; Labib, A.; Le Scodan, R. [Hopital Rene-Huguenin, Saint-Cloud (France)

    2011-10-15

    The authors report the assessment of the prognosis value in terms of local control of molecular subtypes in patients suffering from breast cancer without ganglionary invasion, and of their predictive value for adjuvant irradiation. Medical files of nearly 700 patients have been analyzed. Some had an irradiation after mastectomy, some hadn't. The distribution of molecular sub-types is indicated, and the relationship with relapse is examined. The different molecular sub-types do not allow sub-groups with high risk of relapse to be defined. Breast cancers of stage pN0 after mastectomy seem to have a very good prognosis. Short communication

  7. Advances in molecular epidemiology of Treponema pallidum and its neurotropic subtypes%梅毒螺旋体分子流行病学及亲神经亚型菌株研究进展

    Institute of Scientific and Technical Information of China (English)

    吴开奇; 楼永良; 周平玉

    2015-01-01

    1998年建立基于梅毒螺旋体tpr和arp基因分子分型系统,世界各国均有梅毒螺旋体亚型菌株流行特征的报道并结合tp0548或rpsA基因以加强分型,发现了各地的优势亚型菌株及亚型菌株存在多样性,其中14d和14f是出现频率较高的亚型.另外,某些特定亚型与临床表现之间存在相关性.有研究发现,某些特定亚型菌株可能有亲神经现象,其中14a、14d/f、19d/c与神经梅毒相关.确定特定亚型菌株与神经梅毒的相关性对临床诊治和判断梅毒患者预后意义重大.%Since the development of molecular typing system for Treponema pallidum based on acidic repeat protein (arp) gene and Treponema pallidum repeat (tpr) gene in 1998,there have been reports on the epidemiological characteristics of Treponema pallidum subtypes from various countries in the world.The tp0548 and rpsA genes also have been used for enhancing the molecular typing of Treponema pallidum.Predominant subtypes of Treponema pallidum have been reported in various regions,and there is a high variety in the subtypes of Treponema pallidum,with 14d and 14f as the most frequent subtypes.Further more,some specific subtypes of Treponema pallidum are associated with clinical manifestations of syphilis.Studies have found that some neurotropic subtypes of Treponema pallidum,for example,14a,14d/f and 19d/c types are related to neurosyphilis.Determining specific Treponema pallidum subtypes associated with neurosyphilis is of great significance for the clinical diagnosis,treatment and prediction of prognosis of syphilis.

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

    Science.gov (United States)

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

    2011-08-01

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

  9. Antimicrobial resistance and molecular subtypes of Salmonella enterica serovar Typhi isolates from Kolkata, India over a 15 years period 1998-2012.

    Science.gov (United States)

    Das, Surojit; Samajpati, Sriparna; Ray, Ujjwayini; Roy, Indranil; Dutta, Shanta

    2017-01-01

    Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), remains an unresolved public health problem in India. Emergence of antimicrobial resistant strains poses a great concern for typhoid treatment and influences reshaping of current S. Typhi population. We included representative S. Typhi strains (n=164) from retrospective studies, both community and hospital based, conducted at National Institute of Cholera and Enteric Diseases, Kolkata during 15 years period (1998-2012) to analyze their antimicrobial resistance (AMR) profiles, mechanism of AMR and molecular subtypes of the strains. More than 60% of the S. Typhi isolates were obtained from community based studies. During the study period, steady decline (46.4%-15.6%) in isolation of multidrug-resistant (MDR, resistant to ampicillin, chloramphenicol and co-trimoxazole) S. Typhi was noticed with parallel increase of nalidixic acid-resistant (NAL(R)) strains (60.7%-93.8%) and ciprofloxacin resistant (CIP(R)) strains (0%-25%). Of 53 MDR strains, 46 (86.8%) were NAL(R) showing decreased ciprofloxacin susceptible (DCS) (MIC for ciprofloxacin 0.12-0.5μg/ml) phenotype. Conjugative IncHI1 (230kb) and non-conjugative non-IncHI1 (180kb) plasmids were found in 23 (43.4%) and 14 (26.4%) MDR strains respectively, plasmid was absent in 16 (30.2%) MDR strains. MDR strains with or without plasmid shared the same set of resistance genes (blaTEM-1, catA1, sul1, sul2, strA and strB) and class 1 integron possessing dfrA7 gene cassette. Two S. Typhi strains harbored 50kb transferrable plasmids carrying dfrA15 and aadA1 gene cassettes in class 1 integron. The majority of the strains (135/164, 82.3%) belonged to H58 haplotype. Among the MDR isolates, fluoroquinolone resistant or combined resistant isolates (n=147), 127 (86.4%) were H58 and 20 (13.6%) belonged to non-H58. NAL(R)S. Typhi strains with decreased susceptibility or resistance to ciprofloxacin had point mutation(s) in quinolone resistance-determining region of

  10. Clinico-pathologic characteristics of different molecular subtypes of 146 young breast cancer cases%146例不同分子亚型年轻乳腺癌的临床病理特征分析

    Institute of Scientific and Technical Information of China (English)

    段海明; 陈晶; 王娜; 王闽全; 欧江华

    2015-01-01

    Objective To study the clinico-pathologic characteristics of different molecular subtypes of young breast cancer patients. Methods The clinical data of 146 breast cancer patients (≤40 years old)treated in Department of Breast Surgery,The Cancer Hospi-tal Affiliated to Xinjiang Medical University and Department of Oncology,Second Affiliated Hospital of Xinjiang Medical University, from January 2012 to April 2014 were retrospectively analyzed.These 146 patients,all diagnosed as invasive cancer,were categorized in-to four molecular subtypes:Luminal A,Luminal B,HER2 over-expression and Basal-like,based on the expression of ER,PR,HER2 and Ki-67.Then the differences in clinical pathological characteristics among different molecular subtypes were analyzed.Results There were 24 patients in Luminal A subtype,77 in Luminal B subtype,17 in HER2 over-expression subtype,and 28 in Basal-like subtype. There were statistically significant differences among different molecular subtypes regarding the tumor size and histological grade,howev-er ,there were no statistically differences regarding the pathological type,lymph node metastasis and clinical stage.Conclusions A-mong different molecular subtypes of young breast cancer there are statistically significant differences in some clinical pathological char-acteristics,which indicate that different molecular subtypes may have different characteristics in treatment and prognosis.Therefore,it will provide a theoretical basis for individual treatment in breast cancer.%目的探讨不同分子亚型年轻乳腺癌的临床及病理特点。方法回顾性分析新疆医科大学附属肿瘤医院乳腺外科及新疆医科大学第二附属医院肿瘤外科2012年1月—2014年4月收治的146例均经术后病理证实的浸润性乳腺癌患者的临床资料(年龄均≤40岁),按照患者乳腺癌组织 ER(雌激素受体),PR(孕激素受体),HER-2(人表皮生长因子受体2),Ki-67(肿瘤细胞增殖相

  11. 乳腺导管内癌分子分型及其与病理因素的相关性分析%Study on correlation between molecular subtyping and pathological factors in mammary ductal carcinoma in situ

    Institute of Scientific and Technical Information of China (English)

    童彩玲; 陆慧敏; 黄梅; 谢丹; 李军; 吴代陆

    2015-01-01

    Objective To explore the molecular subtyping of mammary ductal carcinoma in situ( DCIS)and to study the relationship be-tween molecular subtyping and pathological factors. Methods The pathological data of 57 DCIS patients were retrospectively analyzed,ER,PR, HER-2 and Ki-67 were detected by immunohistochemical method,the histological differentiation was detected by HE staining. Results A-mong 57 patients with mammary intraductal carcinoma,26 cases(45. 6%)belonged to Luminal A type,17 cases(29. 8%)belonged to Luminal B,over-expression of HER-2 had been seen in 11 cases(19. 3%);and triple negative type in 3 cases(5. 3%). Luminal A type was the highest percentage in DCIS group,and the difference between invasive ductal carcinoma and Luminal A was statistically significant( P ﹤0. 01). The difference in percentage of at least three negative types,and invasive ductal carcinoma in triple-negative type phase was statistically signifi-cant( P ﹤0. 05);further study found that a high-level model in the Luminal A lower proportion of DCIS,with Luminal B type,Her-2 overex-pression and triple negative type,the difference was statistically significant( P ﹤0. 01). Luminal B type,HER-2 overexpression and triple-negative Ki-67 index were significantly higher than Luminal A type( P ﹤0. 01),and there was no significant difference in Ki-67 index among Luminal B type,HER-2 overexpression type and triple-negative breast cancer( P ﹥0. 05). Conclusion The subtype in most patients with DCIS is Luminal subtype,especially Luminal A subtype. The most of Luminal subtypes,particularly Luminal A subtype,were not only with low grade DICS but also with lower index of Ki-67,the result showed that Luminal A subtype has positive correlation with rates of recurrence and free survival of the disease. In contrast,all of HER-2 overexpression subtype and normal subtype are high grade and high index of Ki-67,and the result indicatedthat the risk of progression to IDC is more possible than that of

  12. 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.

  13. 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 distributions of these subtypes and their potential physiological roles are discussed. By use of molecular genetic manipulation of cloned muscarinic receptor cDNAs, the regions of muscarinic receptors that specify G-protein coupling and ligand binding have been defined in several recent studies. Overall...

  14. A case of apocrine hidrocystoma of the scrotum%阴囊大汗腺汗囊瘤

    Institute of Scientific and Technical Information of China (English)

    秦晓明; 徐磊; 吴丽; 孔雷

    2012-01-01

    A 73-year-old man developed a skin-colored granule-sized papule on the scrotum 10 years prior to the presentation,which had increased in size and number without obvious symptoms.Histopathological examination showed multiple enlarged intradermal cysts.The cyst wall consisted of one or two layers of flat or columnar cells.Decapitation secretion was seen in the inner layer cells,and the out layer of cysts was formed by flat or cubic myoepithelial cells.A diagnosis of apocrine hidrocystoma of the scrotum is made.%患者男,73岁.阴囊处出现一米粒大肤色丘疹,渐增大10年,无明显自觉症状.组织病理检查:真皮内可见多个扩大的囊腔,囊壁由单层和双层扁平或柱状细胞组成,内层细胞可见断头分泌,外层为扁平或立方形肌上皮细胞.诊断为阴囊大汗腺囊瘤.

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

    Institute of Scientific and Technical Information of China (English)

    兰全学; 扈庆华; 石晓路; 王冰; 林一曼; 程锦泉; 张顺祥

    2008-01-01

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

  16. Salmonella source attribution based on microbial subtyping

    DEFF Research Database (Denmark)

    Barco, Lisa; Barrucci, Federica; Olsen, John Elmerdahl

    2013-01-01

    Source attribution of cases of food-borne disease represents a valuable tool for identifying and prioritizing effective food-safety interventions. Microbial subtyping is one of the most common methods to infer potential sources of human food-borne infections. So far, Salmonella microbial subtyping...... source attribution models have been implemented by using serotyping and phage-typing data. Molecular-based methods may prove to be similarly valuable in the future, as already demonstrated for other food-borne pathogens like Campylobacter. This review assesses the state of the art concerning Salmonella...... in the context of their potential applicability for Salmonella source attribution studies....

  17. 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

  18. Identification of Blastocystis subtype 1 variants in the Home for Girls, Bangkok, Thailand.

    Science.gov (United States)

    Thathaisong, Umaporn; Siripattanapipong, Suradej; Mungthin, Mathirut; Pipatsatitpong, Duangnate; Tan-ariya, Peerapan; Naaglor, Tawee; Leelayoova, Saovanee

    2013-02-01

    A cross-sectional study of Blastocystis infection was conducted to evaluate the prevalence, risk factors, and subtypes of Blastocystis at the Home for Girls, Bangkok, Thailand in November 2008. Of 370 stool samples, 118 (31.9%) were infected with Blastocystis. Genotypic characterization of Blastocystis was performed by polymerase chain reaction and sequence analysis of the partial small subunit ribosomal RNA (SSU rRNA) gene. Subtype 1 was the most predominant (94.8%), followed by subtype 6 (3.5%) and subtype 2 (1.7%). Sequence analyses revealed nucleotide polymorphisms for Blastocystis subtype 1, which were described as subtype 1/variant 1, subtype 1/variant 2. Blastocystis subtype 1/variant 1 was the most predominant infection occurring in almost every house. The results showed that subtype analysis of Blastocystis was useful for molecular epidemiological study.

  19. 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…

  20. Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA.

    Science.gov (United States)

    Henderson, Douglas W; Reid, Glen; Kao, Steven C; van Zandwijk, Nico; Klebe, Sonja

    2013-10-01

    Pleural malignant mesothelioma (MM) includes several unusual and even rare but distinctive histological subtypes, in addition to the usual subdivision into epithelioid, biphasic and sarcomatoid MM. Criteria for discrimination between fibrous pleuritis versus desmoplastic mesothelioma include evidence of neoplastic invasion for diagnosis of desmoplastic MM, but this histological assessment is complicated by the recently-described 'fake fat phenomenon' in cases of fibrous pleuritis. The distinction between biphasic and monophasic synovial sarcoma of the pleura versus biphasic and sarcomatoid MM can be problematical and is most cogently based upon molecular detection of the t(X;18) translocation, whereas a clear diagnosis of MM for a pleural tumour histologically resembling synovial sarcoma is favoured by a negative result for this translocation and, probably, microRNA evidence supportive of a diagnosis of MM. Aquaporin-1 (AQP1) is a molecule involved in the growth of MM cells, and yet is a factor reported to correlate with improved survival rates for MM with an epithelioid component, in comparison to AQP1-poor MM, as assessed from AQP1 expression by epithelioid MM cells only (apart from co-expression by stromal endothelial cells in addition to the tumour cells). Recent reports have also focused upon germline mutations in the BRCA1-associated protein 1 (BAP1), not only in cases of familial mesothelioma, but also BAP1 deletion in sporadic MM. Prognostic factors for MM include not only the histological subtypes, but other independent variables that include (among others), AQP1 expression by mesothelioma cells, the clinical status of the patient, the serum neutrophil:lymphocyte ratio and blood thrombocytosis.

  1. 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.

  2. 一个Bw亚型家系的血型分子机制及临床输血分析%Molecular basis and clinical transfusion of a family with Bw subtype of ABO blood group system

    Institute of Scientific and Technical Information of China (English)

    邓刚; 黄丹丹; 郭雯玉; 许德义; 杜勇; 马幼丽; 张哲

    2013-01-01

    Objective To study a family with Bw subtype of ABO blood group system,and to review safety issues in relation with clinical transfusion.Methods The molecular basis for the blood type was studied with serological assay,polymerase chain reaction-sequence specific primer (PCR-SSP) and DNA sequencing,TA clone and haplotype analysis in one blood donor whose ABO blood group were difficultly typed and her family.The bioinformatics analysis was carried out by biological analysis software to investigate the change of structure and function of enzymes influenced by the change amino acid.A retrospective survey was carried out to investigate what is the actual position that the donor blood was used in the clinical transfusion.Results Three members from the family were found to have a Bw subtype.A substitution of nucleotide C by T at position 721 in exon 7 was discovered,which resulted in replacement of amino acid Arg to Trp.Review of clinical record suggested that there has been no significant abnormality association with past three blood transfusions.Conclusion A 721C>T mutation of the ABO gene probably underlies the Bw subtype.Further research is needed for understanding the clinical significance of this subtype in the blood transfusion.%目的 对1个Bw亚型血型家系的分子机制进行研究,并探讨该亚型的临床输血情况.方法 对1名ABO血型正反定型不符的无偿献血者及其家人的血型进行血清学鉴定,并应用聚合酶链反应-序列特异性引物法、ABO基因直接测序、TA克隆单倍型分析及相关软件对该突变引起的酶结构及功能变化进行分析等方法,同时对该献血者以往3次所献的血样的临床输血情况进行回顾.结果 在该家系中发现了3例较为罕见的Bw亚型.该亚型是由于ABO基因第7外显子存在721C/T杂合,导致R241W氨基酸改变所致.临床回顾提示3次输血均未发现明显异常.结论 ABO基因721C>T突变是导致Bw亚型的分子遗传基础之一,

  3. Frequent copy number gains at 1q21 and 1q32 are associated with overexpression of the ETS transcription factors ETV3 and ELF3 in breast cancer irrespective of molecular subtypes.

    Science.gov (United States)

    Mesquita, Bárbara; Lopes, Paula; Rodrigues, Ana; Pereira, Deolinda; Afonso, Mariana; Leal, Conceição; Henrique, Rui; Lind, Guro E; Jerónimo, Carmen; Lothe, Ragnhild A; Teixeira, Manuel R

    2013-02-01

    Several ETS transcription factors are involved in the pathogenesis of human cancers by different mechanisms. As gene copy number gain/amplification is an alternative mechanism of oncogenic activation and 1q gain is the most common copy number change in breast carcinoma, we investigated how that genomic change impacts in the expression of the three 1q ETS family members ETV3, ELK4, and ELF3. We have first evaluated 141 breast carcinomas for genome-wide copy number changes by chromosomal CGH and showed that 1q21 and 1q32 were the two chromosome bands with most frequent genomic copy number gains. Second, we confirmed by FISH with locus-specific BAC clones that cases showing 1q gain/amplification by CGH showed copy number increase of the ETS genes ETV3 (located in 1q21~23), ELF3, and ELK4 (both in 1q32). Third, gene expression levels of the three 1q ETS genes, as well as their potential targets MYC and CRISP3, were evaluated by quantitative real-time PCR. We here show for the first time that the most common genomic copy number gains in breast cancer, 1q21 and 1q32, are associated with overexpression of the ETS transcription factors ETV3 and ELF3 (but not ELK4) at these loci irrespective of molecular subtypes. Among the three 1q ETS genes, ELF3 has a relevant role in breast carcinogenesis and is also the most likely target of the 1q copy number increase. The basal-like molecular subtype presented the worst prognosis regarding disease-specific survival, but no additional prognostic value was found for 1q copy number status or ELF3 expression. In addition, we show that there is a correlation between the expression of the oncogene MYC, irrespectively of copy number gain at its loci in 8q24, and the expression of both the transcriptional repressor ETV3 and the androgen respondent ELK4.

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

    Institute of Scientific and Technical Information of China (English)

    贺连华; 吴平芳; 陈妙玲; 王冰; 林爱红; 吕东月

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Gene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center B-cell like and activated B-cell like. This classification has prognostic significance, but GEP...... on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver...

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

    Directory of Open Access Journals (Sweden)

    Pan Wang

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

  7. 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.

  8. Targeted Next-Generation Sequencing in Molecular Subtyping of Lower-Grade Diffuse Gliomas: Application of the World Health Organization's 2016 Revised Criteria for Central Nervous System Tumors.

    Science.gov (United States)

    Carter, Jamal H; McNulty, Samantha N; Cimino, Patrick J; Cottrell, Catherine E; Heusel, Jonathan W; Vigh-Conrad, Katinka A; Duncavage, Eric J

    2017-03-01

    The 2007 World Health Organization Classification of Tumours of the Central Nervous System classifies lower-grade gliomas [LGGs (grades II to III diffuse gliomas)] morphologically as astrocytomas or oligodendrogliomas, and tumors with unclear ambiguous morphology as oligoastrocytomas. The World Health Organization's newly released (2016) classification incorporates molecular data. A single, targeted next-generation sequencing (NGS) panel was used for detecting single-nucleotide variation and copy number variation in 50 LGG cases originally classified using the 2007 criteria, including 36 oligoastrocytomas, 11 oligodendrogliomas, 2 astrocytomas, and 1 LGG not otherwise specified. NGS results were compared with those from IHC analysis and fluorescence in situ hybridization to assess concordance and to categorize the tumors according to the 2016 criteria. NGS results were concordant with those from IHC analysis in all cases. In 3 cases, NGS was superior to fluorescence in situ hybridization in distinguishing segmental chromosomal losses from whole-arm deletions. The NGS approach was effective in reclassifying 36 oligoastrocytomas as 30 astrocytomas (20 IDH1/2 mutant and 10 IDH1/2 wild type) and 6 oligodendrogliomas, and 1 oligodendroglioma as an astrocytoma (IDH1/2 mutant). Here we show that a single, targeted NGS assay can serve as the sole testing modality for categorizing LGG according to the World Health Organization's 2016 diagnostic scheme. This modality affords greater accuracy and efficiency while reducing specimen tissue requirements compared with multimodal approaches.

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

    Institute of Scientific and Technical Information of China (English)

    顾玲; 周璐; 董晨; 崔志刚; 谈忠鸣; 张艺飓

    2013-01-01

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

  10. HIV-1 subtypes in Yugoslavia.

    Science.gov (United States)

    Stanojevic, Maja; Papa, Anna; Papadimitriou, Evagelia; Zerjav, Sonja; Jevtovic, Djordje; Salemovic, Dubravka; Jovanovic, Tanja; Antoniadis, Antonis

    2002-05-01

    To gain insight concerning the genetic diversity of HIV-1 viruses associated with the HIV-1 epidemic in Yugoslavia, 45 specimens from HIV-1-infected individuals were classified into subtypes by sequence-based phylogenetic analysis of the polymerase (pol) region of the viral genome. Forty-one of 45 specimens (91.2%) were identified as pol subtype B, 2 of 45 as subtype C (4.4%), 1 of 45 as CRF01_AE (2.2%), and 1 as CRF02_AG recombinant (2.2%). Nucleotide divergence among subtype B sequences was 4.8%. Results of this study show that among HIV-1-infected patients in Yugoslavia subtype B predominates (91.5%), whereas non-B subtypes are present at a low percentage, mostly related to travel abroad.

  11. 不同分子亚型乳腺癌首发肝转移患者的临床特征和预后%Clinical features and prognosis of patients with first-episode liver metastasis of different molecular subtypes of breast cancer

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Objective To investigate the clinical features and prognosis of patients with first-episode liver metastasis of different molecular subtypes of breast cancer and risk factors for liver metastasis of breast cancer.Methods A retrospective analysis was performed for 122 breast cancer patients with first-episode liver metastasis from January 2009 to January 2014.According to the cell surface receptors of breast cancer,these patients were divided into the four molecular subtypes of Luminal A,Luminal B,human epidermal growth factor receptor 2 (HER2) overexpression,and triple-negative breast cancer (TNBC).The association of patients' age at initial diagnosis,body mass index (BMI),menstruation status,clinical TNM (cTNM) stage,levels of lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) at recurrence,liver metastasis,and treatment condition with the patients' prognosis were analyzed.The chi-square test and Fisher's exact test were used for categorical data,the Kaplan-Meier method was used for survival analysis,the log-rank test was used for univariate analysis of influencing factors,and the Cox regression model was used for multivariate analysis.Results Among the 122 patients,12 had Luminal A subtype,61 had Luminal B subtype,30 had HER2 overexpression subtype,and 19 had TNBC subtype.In the patients with Luminal A,Luminal B,HER2 overexpression,and TNBC subtypes,the median disease-free survival (DFS) was 32,23,16,and 10 months,respectively (P =0.001),the median overall survival (OS) was 54,35,26,and 13 months,respectively (P =0.003),and the median OS after liver metastasis was 30,16,10,and 9 months,respectively (P =0.019).In HER2-positive patients,the application of trastuzumab in the past significantly prolonged the patients' DFS by 11 months and OS by 18 months (P < 0.05).The results of the multivariate analysis showed that cTNM stage,molecular subtype,and targeted therapy were independent influencing factors for DFS of breast cancer patients with liver metastasis

  12. Molecular Signatures of Chronic Pain Subtypes

    Science.gov (United States)

    2013-01-01

    problematic; patients experience not only nociceptive pain but also acute neuralgia and occasion- ally the immediate onset of phantom limb pain .8...post-thoracotomy pain have been initiated preoperatively.69 This preemptive effect is designed to reduce nociceptive traffic to the spinal cord and... nociceptive and inflammatory pain and has been linked to temporomandibular joint pain syndromes [50]. Even studies of COMT, however, have demonstrated

  13. Molecular Signatures of Chronic Pain Subtypes

    Science.gov (United States)

    2014-01-01

    Valagussa F. Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction : Results of GISSI- Prevenzione trial. Lipids 2001; 36:S119–26...a diagnosis of post injury amputation of all or part of one limb. Amputation injury must also have occurred between 3 and 18 months prior to

  14. Molecular subtyping of Campylobacter jejuni subsp. jejuni strains isolated from different animal species in the state of São Paulo, Brazil Subtipagem molecular de estirpes de Campylobacter jejuni subsp. jejuni isoladas de diferentes espécies animais do Estado de São Paulo, Brasil

    Directory of Open Access Journals (Sweden)

    Eliana Scarcelli

    2005-12-01

    Full Text Available The objective of the present trial was to characterize genetically strains of Campylobacter jejuni subsp. jejuni isolated from humans and several animal sources (bovines, swine, dogs, primates, wild boars and poultry. A total of 828 different animal samples (feces, carcass, aborted fetus and hysterectomized uterus were analysed by means of routine bacteriological methods, and 36 C. jejuni strains were isolated. Thirty strains of human fecal origin were obtained in clinical analysis laboratories in the city of São Paulo. The 66 C. jejuni strains isolated were submitted to genetic characterization. Primers based on fla A gene were used in a polymerase chain reaction (PCR and amplified a fragment of the 702 bp. PCR products were evaluated by means of sequencing and genealogic analysis. Genetic variability analysis of 66 strains showed 44 different subtypes of C. jejuni. One subtype was identical to a C. jejuni strain of human origin with the sequence in the GenBank (GENBANK accession number AF050186. Subtyping analysis of C. jejuni strains based on sequencing of the fla A gene variable region and analysis of sequence alignment by the Maximum Parsimony method showed to be highly discriminatory, providing the best conditions to differentiate strains involved in outbreaks from those sporadically isolated. This is the first study of molecular subtyping analysis of human and animal C. jejuni strains using sequencing technique and genealogic analysis in the state of São Paulo, Brazil.O objetivo do presente trabalho foi caracterizar geneticamente estirpes de Campylobacter jejuni subsp. jejuni isoladas de humanos e de diferentes origens animais (bovinas, suínas, cães, primatas, javalis, suínos e aves de corte. Um total de 828 amostras (fezes, carcaças, fetos abortados e útero histerectomizado foram analisadas por métodos de rotina bacteriológica e 36 estirpes de C. jejuni foram isoladas. Trinta estirpes de origem fecal humana foram obtidas de

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

    DEFF Research Database (Denmark)

    Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C

    2016-01-01

    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. Recen...

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

    Institute of Scientific and Technical Information of China (English)

    张晓嫒; 王迪; 陈倩

    2015-01-01

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

  17. 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.

  18. 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.

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

    Institute of Scientific and Technical Information of China (English)

    赖植发; 张勇; 曾华书; 侯红斌; 李波; 刘哲民

    2013-01-01

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

  20. Dyscalculia and Attention Deficit Subtypes

    OpenAIRE

    1999-01-01

    The association of specific academic deficits with attention deficit disorder (ADD) subtypes was determined in 20 students (ages 8-12) with ADD with hyperactivity (ADD/H) compared to 20 with ADD without hyperactivity (ADD/noH), at the Department of Educational Psychology, University of Texas at Austin, TX.

  1. Electrophysiological Correlates of Dyslexic Subtypes.

    Science.gov (United States)

    Flynn, Jane M.; And Others

    1992-01-01

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

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

    Science.gov (United States)

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

    2013-03-01

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

  3. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-01-01

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

  5. 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

    目的 分析不同分子分型乳腺癌患者的长期预后,并初步探讨不同治疗方式对其预后的影响.方法 采用以人群为基础的前瞻性队列研究方法.研究对象为上海市肿瘤登记处登记的2002年3月至2006年4月上海市9个区新诊断的、具有上海市户籍的女性乳腺癌患者.共3 586例患者纳入研究,根据雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2)表达情况分为Luminal A型、Luminal B型、HER2过表达型和三阴性4种.诊断后平均6个月完成基线调查,并在诊断后18、36、60和120个月进行随访调查.通过入户调查、病史摘录和全死因库链接等途径采集信息.采用Kaplan-Meier法分析和比较不同分子分型乳腺癌患者生存率,并运用多因素Cox回归模型探讨不同治疗方式对不同分子分型预后的影响.结果 在3 586例患者中,54.5%为Luminal A型,16.6%为Luminal B型,13.9%为HER2过表达型,14.9%为三阴性.随访时间0.6~12.8年,中位随访时间10.3年.Luminal A型、Luminal B型、HER2过表达型、三阴性乳腺癌患者的10年总体生存率分别为82.7%(95% CI:80.9%~84.4%)、77.7% (95% CI:74.1%~80.8%)、76.3%(95% CI:72.3% ~ 79.8%)、74.8% (95% CI:70.9% ~78.3%),10年无病生存率分别为79.0%(95% CI:76.7%~81.0%)、76.0% (95% CI:71.9% ~79.5%)、73.6% (95% CI:68.9%~77.7%)、74.5%(95% CI:69.4% ~78.9%).不同分子分型乳腺癌总体生存率和无病生存率间差异均有统计学意义(Log-rank检验,P<0.01).多因素Cox回归分析结果显示,内分泌治疗可降低Luminal A型乳腺癌长期死亡风险和复发/乳腺癌死亡风险,辅助化疗能改善三阴性乳腺癌长期预后.结论 乳腺癌分子分型对判断患者的预后具有重要临床意义,可为制定乳腺癌个体化治疗提供重要依据.%Objectives To analyze the survival of breast cancer molecular subtypes and to

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

    Institute of Scientific and Technical Information of China (English)

    邢卫斌; 刘文芳; 赵子申; 彭军; 李兴文; 马玉枝; 王娜

    2014-01-01

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

  7. Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics.

    Science.gov (United States)

    Tsuji, Motonori; Shudo, Koichi; Kagechika, Hiroyuki

    2017-03-01

    Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands.

  8. 乳腺癌分子亚型与新辅助化疗疗效及预后的相关性分析%Predictive values of pathologic complete response for patient outcome in different molecular subtypes of breast cancer

    Institute of Scientific and Technical Information of China (English)

    刘伟; 李健斌; 王涛; 边莉; 张少华; 张会强; 周金妹; 宋三泰; 江泽飞

    2016-01-01

    目的 探讨不同分子亚型乳腺癌患者新辅助化疗后病理学缓解与远期获益的相关性.方法 收集2005年6月至2014年10月期间就诊于军事医学科学院附属医院乳腺肿瘤内科的416例接受蒽环联合紫杉类药物新辅助化疗的乳腺癌患者,总结患者临床病理学特征,对其生存结局进行随访,分析病理学缓解与患者远期预后的相关性,并对影响患者远期生存的相关因素进行分析.结果 共有416例患者纳入分析,所有患者病理完全缓解率为23.1% (96/416),其中激素受体阳性(HR+)/人表皮生长因子受体2阴性(HER2-)组6.9% (14/204),激素受体阴性(HR-)/人表皮生长因子受体2阳性(HER2+)组41.5% (27/65),HR +/HER2+组30.9%(17/55),HR-/HER2-组41.1% (37/91);对不同分子亚型中病理完全缓解与患者远期生存的相关性进行分析,总体上达到病理完全缓解的患者5年无病生存率高于未达到病理完全缓解者,在HER2阳性以及三阴型亚组患者中达到病理完全缓解的患者5年无病生存率高于未达到病理完全缓解者;在HR +/HER2-亚组病理完全缓解的患者5年无病生存率高于未达到pCR者,但差异无统计学意义.对影响患者无病生存期的相关因素分析结果显示,雌激素受体状态、是否达到病理完全缓解、肿瘤大小是患者预后的独立影响因素.结论 病理完全缓解仍是乳腺癌患者远期生存的预测因子;HER2阳性及三阴型乳腺癌患者达到病理完全缓解预示更好的生存结局,而在Luminal型则两者关联不大,病理完全缓解在未经筛选的乳腺癌患者中不作为新辅助治疗后患者远期生存的替代终点.%Objective To analyze the predict values of pathologic complete response (pCR) rates for patient outcome according to breast cancer (BC) molecular subtypes.Methods Four hundred and sixteen patients with confirmed BC who received neoadjuvant chemotherapy (NCT) in The Affiliated Hospital of

  9. Expression of HIF-1α and Markers of Angiogenesis Are Not Significantly Different in Triple Negative Breast Cancer Compared to Other Breast Cancer Molecular Subtypes: Implications for Future Therapy.

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    Lamis Yehia

    Full Text Available Triple negative breast cancer lacks estrogen, progesterone and epidermal growth factor receptors rendering it refractory to available targetedtherapies. TNBC is associated with central fibrosis and necrosis, both indicators of tumor hypoxia. Hypoxia inducible factor 1α is up-regulated under hypoxia and its expression is associated with induction of angiogenesis resulting in proliferation, aggressive tumor phenotype and metastasis. In this study we evaluate the potential use of HIF-1α as aTNBC-specific marker.62 TNBC, 64 HER2+, and 64 hormone-receptors positive breast cancer cases were evaluated for central fibrosis and necrosis, HIF-1α, HIF-1β, VEGFR3, CD31 expression and microvessel density. RNA extraction from paraffin-embedded samples, followed by quantitative real-time polymerase chain reaction (qRT-PCR evaluation of HIF-1α and VEGF transcripts was performed on 54 cases (18 from each subtype.HIF-1α protein was expressed in 35.5% TNBC, 45.3% HER2+and 25.0% ER+/PR+ (p = 0.055; χ2 test. PCRanalysis of subgroup of breast cancers, 84.2% expressed HIF-1α protein and its transcripts, while only 66.7% expressed VEGF transcripts simultaneously with the HIF-1α protein and its transcripts. Central fibrosis and necrosis was highest in TNBC (p = 0.015; χ2 test, while MVD was comparable among all groups (p = 0.928; χ2 test. VEGFR3 was highest in TNBC expressing HIF-1α. HIF-1β protein was expressed in 32.0% of HIF-1α(+, and in (44.3% of HIF-1α(- breast cancer cases (p = 0.033; χ2 test. Moreover, HIF-1α expression in cases with central fibrosis and necrosis was highest in the HER2+ followed by the TNBC (p = 0.156; χ2 test.A proportion of TNBC express HIF-1α but not in a significantly different manner from other breast cancer subtypes. The potential of anti-HIF-1α targeted therapy is therefore not a candidate for exclusive use in TNBC, but should be considered in all breast cancers, especially in the setting of clinically aggressive or

  10. Genetic contributions to subtypes of aggression

    OpenAIRE

    2005-01-01

    Boys and girls may display different styles of aggression. The aim of this study was to identify subtypes of aggression within the Child Behavior Checklist (CBCL) aggression scale, and determine their characteristics for both sexes. Maternal CBCL ratings of 7449 7-year-old twin pairs were analyzed using principal components analyses to identify subtypes of aggression, and structural equation modeling to carry out genetic analyses. Two aggression subtypes were identified: relational and direct...

  11. 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.

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

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    Chengli Shen

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

  13. Discovery and validation of breast cancer subtypes

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    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.

  14. 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.

  15. SUBTYPES OF JUVENILE SYSTEMIC SCLERODERMA

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    M N Slarovoitova

    2001-01-01

    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.

  16. Transsexual subtypes : Clinical and theoretical significance

    NARCIS (Netherlands)

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

    2005-01-01

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

  17. ADHD-hyperactive/impulsive subtype in adults

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    Stephen V. Faraone

    2010-01-01

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

  18. Caracterização molecular do HTLV-1/2 em doadores de sangue em Belém, Estado do Pará: primeira descrição do subtipo HTLV-2b na região Amazônica Molecular characterization of HTLV-1/2 among blood donors in Belém, State of Pará: first description of HTLV-2b subtype in the Amazon region

    Directory of Open Access Journals (Sweden)

    Ethienne Lobato dos Santos

    2009-06-01

    Full Text Available Este trabalho objetivou a caracterização molecular do vírus linfotrópico de células T humanas infectando doadores de sangue atendidos na Fundação Centro de Hemoterapia e Hematologia do Pará. Amostras de DNA de 79 indivíduos soropositivos para o vírus linfotrópico de células T humanas foram analisadas por meio da reação em cadeia da polimerase para as regiões genômicas pX, env e 5'LTR, de polimorfismos de comprimento de fragmentos de restrição e do seqüenciamento da região 5LTR, com posterior análise filogenética, definindo o tipo e o subtipo do HTLV circulante na população estudada. Observou-se uma maior prevalência de HTLV-1 (71% em relação ao HTLV-2 (29%. As amostras de HTLV-1 sequenciadas foram classificadas como pertencentes ao subtipo Cosmopolita, subgrupo Transcontinental, sendo as de HTLV-2 identificadas como HTLV-2c. A análise de polimorfismos de comprimento de fragmentos de restrição da região env e do sequenciamento da região 5'LTR, identificou, pela primeira vez na Amazônia Brasileira, uma amostra de HTLV-2b, enfatizando a necessidade de estudos moleculares contínuos na região para melhor entendimento da epidemiologia de transmissão do HTLV na população e permitir a vigilância epidemiológica da emergência de novos tipos e subtipos.This study aimed to perform molecular characterization on the human T-cell lymphotropic virus (HTLV infecting blood donors attended at the Hematology and Hemotherapy Center-Foundation of Pará. DNA samples from 79 HTLV-seropositive individuals were analyzed by means of the polymerase chain reaction on the pX, env and 5'LTR genomic regions; restriction fragment length polymorphism analysis; and sequencing of the 5'LTR region with subsequent phylogenetic analysis. From this, the HTLV types and subtypes circulating in the study population were defined. There was higher prevalence of HTLV-1 (71% than of HTLV-2 (29%. HTLV-1 samples were classified as belonging to the

  19. Classifying anatomical subtypes of subjective memory impairment.

    Science.gov (United States)

    Jung, Na-Yeon; Seo, Sang Won; Yoo, Heejin; Yang, Jin-Ju; Park, Seongbeom; Kim, Yeo Jin; Lee, Juyoun; Lee, Jin San; Jang, Young Kyoung; Lee, Jong Min; Kim, Sung Tae; Kim, Seonwoo; Kim, Eun-Joo; Na, Duk L; Kim, Hee Jin

    2016-12-01

    We aimed to categorize subjective memory impairment (SMI) individuals based on their patterns of cortical thickness and to propose simple models that can classify each subtype. We recruited 613 SMI individuals and 613 age- and gender-matched normal controls. Using hierarchical agglomerative cluster analysis, SMI individuals were divided into 3 subtypes: temporal atrophy (12.9%), minimal atrophy (52.4%), and diffuse atrophy (34.6%). Individuals in the temporal atrophy (Alzheimer's disease-like atrophy) subtype were older, had more vascular risk factors, and scored the lowest on neuropsychological tests. Combination of these factors classified the temporal atrophy subtype with 73.2% accuracy. On the other hand, individuals with the minimal atrophy (non-neurodegenerative) subtype were younger, were more likely to be female, and had depression. Combination of these factors discriminated the minimal atrophy subtype with 76.0% accuracy. We suggest that SMI can be largely categorized into 3 anatomical subtypes that have distinct clinical features. Our models may help physicians decide next steps when encountering SMI patients and may also be used in clinical trials.

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

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    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

  1. 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.

  2. [Differential personality features in adult ADHD subtypes].

    Science.gov (United States)

    Martínez Ortega, Yolanda; Bosch Munsó, Rosa; Gomà-i-Freixanet, Montserrat; Valero Ventura, Sergi; Ramos-Quiroga, Josep Antoni; Nogueira, Mariana; Casas Brugué, Miguel

    2010-05-01

    Attention Deficit/Hyperactivity Disorder (ADHD) and personality traits are relatively stable from childhood and across life span. The purpose of this study was to identify differential and discriminative personality traits between clinical subtypes of ADHD in adults. The Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) and the Millon Multiaxial Clinical Inventory-II (MCMI-II) were administered to a sample of 146 adults with ADHD. Activity and Aggression-Hostility dimensions from the ZKPQ allowed us to properly classify 75.8% of the inattentive and combined subtypes. Data indicates that ADHD is not a homogeneous entity, but rather, there are significant differences in personality characteristics among clinical subtypes. The results have theoretical implications about the connection between ADHD and personality, and clinical implications regarding diagnosis and treatment designs better tailored to the characteristics of each subtype.

  3. 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.

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

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    Stéphane Chevaliez

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

  5. 不同亚型乳腺癌中p16基因启动子甲基化%Study of p16 promoter methylation in different molecular subtypes of breast cancers

    Institute of Scientific and Technical Information of China (English)

    聂艳红; 刘慧; 周卫宁; 吴永平

    2012-01-01

    目的 检测4种不同分子亚型乳腺癌(腺腔A型、腺腔B型、基底样型和HER-2过表达型)中的p16蛋白表达和启动子甲基化状态及其与临床病理参数的关系,探讨p16甲基化在乳腺癌发生、发展中的意义.方法 分别采用免疫组化PV法和甲基化特异性PCR(MSP)法检测73例乳腺癌组织中p16蛋白表达和启动子甲基化水平,并分析其与临床病理参数的关系.结果 (1)腺腔A型、腺腔B型、HER-2过表达型及基底样型乳腺癌中p16蛋白阳性率分别为55%、35%、30%和15.4%,甲基化率分别为10%、25%、10%和46.2%.基底样型乳腺癌中的p16蛋白阳性率最低,与腺腔A型差异有显著性(P<0.05),而甲基化率最高,与腺腔A型和HER-2过表达型差异均有显著(P<0.05).(2)p16启动子甲基化、无甲基化的乳腺癌组中p16蛋白阳性率分别为13.3%和41.4%,差异有统计学意义(P<0.05).(3)淋巴结转移组p16基因的甲基化率为29.3%,明显高于无淋巴结转移组(9.4%)(P<0.05).(4)p16甲基化率随着组织学分级增高而增高,组织学Ⅰ级乳腺癌p16甲基化率明显低于组织学Ⅱ、Ⅲ级乳腺癌(P<0.05).结论 p16基因启动子甲基化可能是基底样型乳腺癌分子特征之一,并与乳腺癌进展相关.%Purpose To detect the pl6 gene protein expression and promoter methylation in 4 subtypes of breast cancer: luminal A, luminal B, basal-like and HER-2 overexpressing phenotype, and evaluate the relationship between pl6 methylation and clinicopatholog-ical parameters, which aim to explore the significance of pI6 methylation in breast cancer. Methods pI6 gene expression and promoter methylation were examined in 73 breast cancers using immunohistochemistry and methylation specific PCR ( MSP ) methods. The results were correlated with clinicopathological parameters. Results The frequency of pI6 protein expression in luminal A, luminal B, HER-2 overexpression and basal-like phenotype was 55% , 35% , 30% and 15. 4

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

    Directory of Open Access Journals (Sweden)

    Yansen Su

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

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

    Directory of Open Access Journals (Sweden)

    Seredick Steve D

    2012-11-01

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

  8. Human breast cancer associated fibroblasts exhibit subtype specific gene expression profiles

    Directory of Open Access Journals (Sweden)

    Tchou Julia

    2012-09-01

    Full Text Available Abstract Background Breast cancer is a heterogeneous disease for which prognosis and treatment strategies are largely governed by the receptor status (estrogen, progesterone and Her2 of the tumor cells. Gene expression profiling of whole breast tumors further stratifies breast cancer into several molecular subtypes which also co-segregate with the receptor status of the tumor cells. We postulated that cancer associated fibroblasts (CAFs within the tumor stroma may exhibit subtype specific gene expression profiles and thus contribute to the biology of the disease in a subtype specific manner. Several studies have reported gene expression profile differences between CAFs and normal breast fibroblasts but in none of these studies were the results stratified based on tumor subtypes. Methods To address whether gene expression in breast cancer associated fibroblasts varies between breast cancer subtypes, we compared the gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main subtypes; seven ER+, seven triple negative (TNBC and six Her2+. Results We observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER + cancers, particularly in pathways associated with cytoskeleton and integrin signaling. In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs likely contribute to the enhanced migration of breast cancer cells in transwell assays and may contribute to the unfavorable prognosis of Her2+ breast cancer. Conclusions These data demonstrate that in addition to the distinct molecular profiles that characterize the neoplastic cells, CAF gene expression is also differentially regulated in distinct subtypes of breast cancer.

  9. 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

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

    Science.gov (United States)

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

    2008-03-15

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    1999-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Corine M Beaufort

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

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

    Institute of Scientific and Technical Information of China (English)

    王擎; 柳大烈; 王晋煌; 陈兵; 陈伯华

    2011-01-01

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

  15. Genetic and molecular changes in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Robert L Hollis; Charlie Gourley

    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.

  16. Study of molecular subtypes of biotype 1A Yersinia enterocolitica in Shandong province from 2008 to 2009%2008-2009年山东省生物1A型小肠结肠炎耶尔森菌分子亚型的研究

    Institute of Scientific and Technical Information of China (English)

    孙文魁; 胡彬; 毕振旺; 寇增强; 侯配斌; 王鑫; 毕振强

    2012-01-01

    Objective To investigate the molecular subtypes of 73 strains of Yersinia enterocolitica biotype 1A isolated in Shandong province by PFGE,and thereby to analyze the relationship between PFGE typing and biological characteristics.Methods Seventy-three strains of Yersinia enterocolitica biotype 1A were isolated from animal feces and meat pnoducts in Gaomi city and Wulian county in Shandong province from 2008 to 2009.Motility test,serum agglutination and virulent genes detection by PCR were used to learn the biological characteristics of the isolated strains.The molecular subtypes were determined by PFGE,whose relationships with motility,serotypes and virulent genotypes were also analyzed.Results Out of the 73strains of Yersinia enterocolitica,5 showed medium-active motility while the other 68 showed well-active motility.The dominated serotypes were O∶ 5 (17/73) and O∶ 8 (14/73),followed by O∶ 9 (5/73) and O∶ 7,8(1/73),and there was no O∶ 3 serotype found.Meanwhile,36 strains couldn't be serotyped.All the strains were negative with the gene ail,ystA,yadA and virF,yet the positive rate of ystB gene was 72.6%(53/73).The 73 strains of Yersinia enterocolitica isolated could be subtyped into 54 PFGE patterns (K6GN11SD0001-K6GN11SD0054),most of which only had 1 or 2 isolated strains,and no pattern was dominant.The strains in the same or similar cluster were from different hosts; each serotype and toxic genotype scattered in the clustering trees,without specific correlation with PFGE subtypes.4 out of 5 strains,which showed medium-active motility,belonged to one branch,with the similarity coefficient at 80.9%-100.0% ; while all the toxic genotype belonged to type B.Conclusion Biotype 1A Yersinia enterocolitica has many clones,whose PFGE types had relations with motility but no relations with virulent genotype and host.%目的 对山东省73株生物1A型小肠结肠炎耶尔森菌分离株进行PFGE分型,分析菌株相关性及PFGE分型与菌株

  17. Precise subtyping for synchronous multiparty sessions

    Directory of Open Access Journals (Sweden)

    Mariangiola Dezani-Ciancaglini

    2016-02-01

    Full Text Available 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 bigger type is expected. The latter preciseness is based on the denotation of a type which is a mathematical object that describes the meaning of the type in accordance with the denotations of other expressions from the language. The result of this paper is the operational and denotational preciseness of the subtyping for a synchronous multiparty session calculus. The novelty of this paper is the introduction of characteristic global types to prove the operational completeness.

  18. 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.

  19. Integrated Classification of Prostate Cancer Reveals a Novel Luminal Subtype with Poor Outcome.

    Science.gov (United States)

    You, Sungyong; Knudsen, Beatrice S; Erho, Nicholas; Alshalalfa, Mohammed; Takhar, Mandeep; Al-Deen Ashab, Hussam; Davicioni, Elai; Karnes, R Jeffrey; Klein, Eric A; Den, Robert B; Ross, Ashley E; Schaeffer, Edward M; Garraway, Isla P; Kim, Jayoung; Freeman, Michael R

    2016-09-01

    Prostate cancer is a biologically heterogeneous disease with variable molecular alterations underlying cancer initiation and progression. Despite recent advances in understanding prostate cancer heterogeneity, better methods for classification of prostate cancer are still needed to improve prognostic accuracy and therapeutic outcomes. In this study, we computationally assembled a large virtual cohort (n = 1,321) of human prostate cancer transcriptome profiles from 38 distinct cohorts and, using pathway activation signatures of known relevance to prostate cancer, developed a novel classification system consisting of three distinct subtypes (named PCS1-3). We validated this subtyping scheme in 10 independent patient cohorts and 19 laboratory models of prostate cancer, including cell lines and genetically engineered mouse models. Analysis of subtype-specific gene expression patterns in independent datasets derived from luminal and basal cell models provides evidence that PCS1 and PCS2 tumors reflect luminal subtypes, while PCS3 represents a basal subtype. We show that PCS1 tumors progress more rapidly to metastatic disease in comparison with PCS2 or PCS3, including PSC1 tumors of low Gleason grade. To apply this finding clinically, we developed a 37-gene panel that accurately assigns individual tumors to one of the three PCS subtypes. This panel was also applied to circulating tumor cells (CTC) and provided evidence that PCS1 CTCs may reflect enzalutamide resistance. In summary, PCS subtyping may improve accuracy in predicting the likelihood of clinical progression and permit treatment stratification at early and late disease stages. Cancer Res; 76(17); 4948-58. ©2016 AACR.

  20. 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.

  1. Hormonal Modulation of Breast Cancer Gene Expression: Implications for Intrinsic Subtyping in Premenopausal Women

    Science.gov (United States)

    Bernhardt, Sarah M.; Dasari, Pallave; Walsh, David; Townsend, Amanda R.; Price, Timothy J.; Ingman, Wendy V.

    2016-01-01

    Clinics are increasingly adopting gene-expression profiling to diagnose breast cancer subtype, providing an intrinsic, molecular portrait of the tumor. For example, the PAM50-based Prosigna test quantifies expression of 50 key genes to classify breast cancer subtype, and this method of classification has been demonstrated to be superior over traditional immunohistochemical methods that detect proteins, to predict risk of disease recurrence. However, these tests were largely developed and validated using breast cancer samples from postmenopausal women. Thus, the accuracy of such tests has not been explored in the context of the hormonal fluctuations in estrogen and progesterone that occur during the menstrual cycle in premenopausal women. Concordance between traditional methods of subtyping and the new tests in premenopausal women is likely to depend on the stage of the menstrual cycle at which the tissue sample is taken and the relative effect of hormones on expression of genes versus proteins. The lack of knowledge around the effect of fluctuating estrogen and progesterone on gene expression in breast cancer patients raises serious concerns for intrinsic subtyping in premenopausal women, which comprise about 25% of breast cancer diagnoses. Further research on the impact of the menstrual cycle on intrinsic breast cancer profiling is required if premenopausal women are to benefit from the new technology of intrinsic subtyping. PMID:27896218

  2. Obesity and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

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

    2013-01-01

    Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improv...

  3. 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…

  4. Subtyping Male Perpetrators of Intimate Partner Violence

    Science.gov (United States)

    Fowler, Katherine A.; Westen, Drew

    2011-01-01

    Domestic violence is a serious problem with far-reaching consequences. This study applies a new methodology to derive subtypes of male perpetrators of intimate partner violence. As part of a larger National Institute of Mental Health (NIMH)-funded study, a national sample of randomly selected psychologists and psychiatrists describe 188 adult male…

  5. Proteomic maps of breast cancer subtypes

    DEFF Research Database (Denmark)

    Tyanova, Stefka; Albrechtsen, Reidar; Kronqvist, Pauliina

    2016-01-01

    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...

  6. HIV-1 subtype B molecular evolution across antiretroviral regimens

    OpenAIRE

    Domínguez Rodríguez, Sara; Holguín, África; Pagán, Israel

    2017-01-01

    La velocidad de evolución del VIH-1 está directamente relacionada con la velocidad de progresión de la enfermedad y la viabilidad del TAR. En este trabajo se pretende conocer la evolución del virus en los diferentes regímenes de primera línea más comunes. Para este estudio se escogieron 46 pacientes con secuencia RT disponible tratados primariamente con uno de los dos regímenes (Grupo 1: 2ITIAN+1IP vs. Grupo 2: 2ITIAN+1ITINAN). Se construyeron árboles filogenéticos mediante aproximaciones...

  7. Molecular signatures define alopecia areata subtypes and transcriptional biomarkers

    Directory of Open Access Journals (Sweden)

    Ali Jabbari

    2016-05-01

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

  8. The discovery and development of P2 receptor subtypes.

    Science.gov (United States)

    Kennedy, C

    2000-07-01

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

  9. Programming and reprogramming neuronal subtypes in the central nervous system.

    Science.gov (United States)

    Rouaux, Caroline; Bhai, Salman; Arlotta, Paola

    2012-07-01

    Recent discoveries in nuclear reprogramming have challenged the dogma that the identity of terminally differentiated cells cannot be changed. The identification of molecular mechanisms that reprogram differentiated cells to a new identity carries profound implications for regenerative medicine across organ systems. The central nervous system (CNS) has historically been considered to be largely immutable. However, recent studies indicate that even the adult CNS is imparted with the potential to change under the appropriate stimuli. Here, we review current knowledge regarding the capability of distinct cells within the CNS to reprogram their identity and consider the role of developmental signals in directing these cell fate decisions. Finally, we discuss the progress and current challenges of using developmental signals to precisely direct the generation of individual neuronal subtypes in the postnatal CNS and in the dish.

  10. [ Spectrum of oncogene mutations is different in melanoma subtypes].

    Science.gov (United States)

    Mazurenko, N N; Tsyganova, I V; Lushnikova, A A; Ponkratova, D A; Anurova, O A; Cheremushkin, E A; Mikhailova, I N; Demidov, L V

    2015-01-01

    Melanoma is the most lethal malignancy of skin, which is comprised of clinically relevant molecular subsets defined by specific "driver" mutations in BRAF, NRAS, and KIT genes. Recently, the better results in melanoma treatment were obtained with the mutation-specific inhibitors that have been developed for clinical use and target only patients with particular tumor genotypes. The aim of the study was to characterize the spectrum of "driver" mutations in melanoma subtypes from 137 patients with skin melanoma and 14 patients with mucosal melanoma. In total 151 melanoma cases, the frequency of BRAF, NRAS, KIT, PDGFRA, and KRAS mutations was 55.0, 10.6, 4.0, 0.7, and 0.7%, respectively. BRAF mutations were found in 69% of cutaneous melanoma without UV exposure and in 43% of cutaneous melanoma with chronic UV exposure (p=0.045), rarely in acral and mucosal melanomas. Most of melanomas containing BRAF mutations, V600E (92%) and V600K (6.0%) were potentially sensitive to inhibitors vemurafenib and dabrafenib. NRAS mutations were more common in cutaneous melanoma with chronic UV exposure (26.0%), in acral and mucosal melanomas; the dominant mutations being Q61R/K/L (87.5%). KIT mutations were found in cutaneous melanoma with chronic UV exposure (8.7%) and mucosal one (28.6%), but not in acral melanoma. Most of KIT mutations were identified in exon 11; these tumors being sensitive to tyrosine kinase inhibitors. This is the first monitoring of BRAF, NRAS, KIT, PDGFRA, and KRAS hotspot mutations in different subtypes of melanoma for Russian population. On the base of data obtained, one can suppose that at the molecular level melanomas are heterogeneous tumors that should be tested for "driver" mutations in the each case for evaluation of the potential sensitivity to target therapy. The obtained results were used for treatment of melanoma patients.

  11. Mir-21–Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact

    Science.gov (United States)

    Sathyan, Pratheesh; Zinn, Pascal O.; Marisetty, Anantha L.; Liu, Bin; Kamal, Mohamed Mostafa; Singh, Sanjay K.; Bady, Pierre; Lu, Li; Wani, Khalida M.; Veo, Bethany L.; Gumin, Joy; Kassem, Dina Hamada; Robinson, Frederick; Weng, Connie; Baladandayuthapani, Veerabhadran; Suki, Dima; Colman, Howard; Bhat, Krishna P.; Sulman, Erik P.; Aldape, Ken; Colen, Rivka R.; Verhaak, Roel G.W.; Lu, Zhimin; Fuller, Gregory N.; Huang, Suyun; Lang, Frederick F.; Sawaya, Raymond; Hegi, Monika

    2015-01-01

    Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21–Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21–Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21–Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not

  12. Clinical Value of Molecular Subtypes for Breast Cancer Predicting Therapeutic Effect and Prognosis of Dose Dense Docetaxel Neoadjuvant Chemotherapy%乳腺癌分子分型在多西他赛密集新辅助化疗疗效及预后中的预测价值

    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

    2013-01-01

    目的 探讨不同乳腺癌分子亚型与多西他赛密集新辅助化疗疗效及预后的相关性.方法 收集2007年3月 2009年12月可手术乳腺癌患者76例,接受四周期多西他赛密集新辅助化疗,新辅助化疗前用免疫组织化学(IHC)及荧光原位杂交(FISH)法检测肿瘤病灶中ER、PR、Her-2及Ki67的表达,根据表达水平将乳腺癌分为四个分子亚型.主要研究终点包括各亚型临床有效率(RR)、3年无病生存率(DFS)和总生存率(OS).次要研究终点是化疗不良反应、病理完全缓解率(pCR).结果 76例患者中,最常见Ⅲ~Ⅳ度粒细胞缺乏(28.9%)、肝功能损害(10.5%)、皮肤毒性(9.2%)以及肌肉和关节疼痛(6.6%)等化疗不良反应.pCR为5例;Luminal A亚型、Luminal B亚型、Her-2+亚型及三阴亚型的RR分别为86.1%、82.4%、100%、100%(P=0.256),3年DFS、OS分别为94%和97%、88%和94%、70%和70%及69%和69%.对比Luminal A亚型与Her-2+亚型、Luminal A亚型与三阴亚型的3年DFS、OS,差异均有统计学意义(P<0.05).结论 75 mg/m2多西他赛密集新辅助化疗是安全的,Luminal A亚型比Her-2+亚型、三阴亚型预后更好.%Objective To investigate the correlation between different molecular subtypes for breast cancer (BO and the therapeutic effect and prognosis of dose dense docetaxel neoadjuvant chemotherapy. Methods A total of 76 patients with operable, histologically confirmed BC received 4 cycles of dose dense docetaxel neoadjuvan chemotherapy between March 2007 and December 2009. The expression of estrogen receptor (ER) progesterone receptor (PR) , Her-2 and Ki67 were detected by immunohistochemical method and fluorescence in-situ hybridization before neoadjuvan chemotherapy. The patients were classified into 4 subtypes. The primary end points were clinical response rate(RR) ,3-year disease-free survival rates(DFS) and overall survival rate(OS) for every subtypes. Secondary end points were adverse

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Epidemiology of subtypes of hypothyroidism in Denmark

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  15. THE SUBTYPES OF PANCREATIC DUCTAL ADENOCARCINOMAS

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    Apeksha Kakkar

    2016-12-01

    Full Text Available Being the 4th leading cause of cancer deaths in the U.S. and with a global increase in incidence, above 80% of pancreatic cancers are locally advanced or metastatic at the time of diagnosis. As surgical resection is the only hope for a cure, the answer is probably in early screening, proper classification and right therapy. The advancing research will likely lead to a better understanding of Pancreatic Ductal Adenocarcinoma (PDAC as well as enhance the techniques for screening, diagnosis, accurate subtyping and enable the use of targeted therapy. Thus, instead of clubbing together various subtypes of PDAC for trials, improving the subcategorization will ensure statistical significance for the academicians, and the clinicians would avoid administration of placebo drug to a vast number of patients.

  16. Proteomic maps of breast cancer subtypes

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  17. Subtyping Obsessive-Compulsive Disorder: Neuropsychological Correlates

    Directory of Open Access Journals (Sweden)

    Catherine L. Harris

    2003-01-01

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

  18. 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.

  19. Global DNA methylation of ischemic stroke subtypes.

    Directory of Open Access Journals (Sweden)

    Carolina Soriano-Tárraga

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

  20. 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...

  1. Untypeable hepatitis C virus subtypes in Pakistan: A neglected section.

    Science.gov (United States)

    Khan, Abdul Waheed; Nasim, Zeeshan; Zahir, Fazli; Ali, Shahid; Ali, Abid; Iqbal, Aqib; Munir, Iqbal

    2016-12-01

    Diagnostically untypeable subtypes contribute a considerable percent of hepatitis C virus (HCV) subtypes in Pakistan. In the present study, chronically infected HCV patients with known viremia were subjected to HCV genotyping. Among the total retrieved samples, 92.7% (64/69) were found typeable while 7.24% (5/69) were diagnostically untypeable. In conclusion, the presence of large number of untypeable HCV subtypes emphasizes the need of an updated type-specific genotyping assay and consideration of primers for proportionally rare subtypes to minimize the number of untypeable HCV subtypes.

  2. 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.

  3. 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

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

    Science.gov (United States)

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

    2005-04-01

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

  5. Epidemic condition and molecular subtyping of ciprofloxacin and cefotaxime co-resistant Salmonella Indiana isolated from retail chicken carcasses in six provinces, China%中国六省份零售整鸡中环丙沙星与头孢噻肟双耐药印第安纳沙门菌流行状况及分子分型研究

    Institute of Scientific and Technical Information of China (English)

    胡豫杰; 黄金林; 于红霞; 李凤琴; 赫英英; 王晔茹; 崔生辉; 陈秋霞; 刘桂华; 陈倩; 周刚; 杨保伟

    2015-01-01

    目的:对中国6个省份零售整鸡中对环丙沙星与头孢噻肟双耐药的沙门菌流行状况及分子分型进行研究。方法对我国6个省份市售整鸡样品中分离的2629株沙门菌进行耐药性实验,筛选出对环丙沙星和头孢噻肟双重耐药的菌株,进行血清分型、超广谱β-内酰胺酶(ESBLs)表型确证和PFGE遗传特性研究。结果对环丙沙星与头孢噻肟双耐药的沙门菌共计227株(8.52%,227/2629),北京、吉林、广东、江苏、陕西、内蒙的检出率分别为11.67%(99/874)、8.20%(60/726)、1.39%(7/502)、15.61%(42/260)、8.56%(16/186)、0(0/81);224株为印第安纳沙门菌,其中213株(95.10%)为ESBLs阳性。所有双耐印第安纳沙门菌均耐5种以上的抗生素,17.86%的菌株(40/224)对除碳青霉烯类外的10种抗生素均耐药;50.89%的菌株(114/224)对9种抗生素耐药,25.45%的菌株(57/224)对8种抗生素耐药。224株双耐印第安纳沙门菌划分为32个基因簇和150种PFGE带型,双耐印第安纳沙门菌带型既具有地域差异,相同或不同的省份及采样时间均发现相同带型菌株。结论中国零售整鸡中环丙沙星与头孢噻肟双耐药沙门菌污染严重,是双耐药沙门菌的重要储存库,分子分型结果提示沙门菌存在交叉污染或共同污染来源。%Objective To elucidate the epidemic condition and molecular subtyping of ciprofloxacin and cefotaxime co-resistant Salmonella Indiana(S. Indiana)isolated from retail chicken carcasses in six provinces of China. Methods A total of 2 647 Salmonella strains isolated from retail chicken carcasses collected from six provinces of China were subjected to antimicrobial susceptibility testing. All Salmonella isolates co-resistant to ciprofloxacin and cefotaxime were further characterized by serotyping, extended-spectrum beta-lactamases (ESBLs) producing strains screening and pulsed field

  6. 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.

  7. 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

  8. Understanding the Underlying Mechanism of HA-Subtyping in the Level of Physic-Chemical Characteristics of Protein

    Science.gov (United States)

    Ebrahimi, Mansour; Aghagolzadeh, Parisa; Shamabadi, Narges; Tahmasebi, Ahmad; Alsharifi, Mohammed; Adelson, David L.

    2014-01-01

    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 understanding and

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

    Science.gov (United States)

    Ebrahimi, Mansour; Aghagolzadeh, Parisa; Shamabadi, Narges; Tahmasebi, Ahmad; Alsharifi, Mohammed; Adelson, David L; Hemmatzadeh, Farhid; Ebrahimie, Esmaeil

    2014-01-01

    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 understanding and

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

    Institute of Scientific and Technical Information of China (English)

    孙卫海; 张宝成; 郭莉; 李燕; 吴小会; 陈潮

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tong Wu

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

  12. 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.

  13. 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

  14. Pharmacologic specificity of alpha-2 adrenergic receptor subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Petrash, A.; Bylund, D.

    1986-03-01

    The authors have defined alpha-2 adrenergic receptor subtypes in human and rat tissues using prazosin as a subtype selective drug. Prazosin has a lower affinity (250 nM) at alpha-2A receptor and a higher affinity (5 nM) at alpha-2B receptors. In order to determine if other adrenergic drugs are selective for one or the other subtypes, the authors performed (/sup 3/H)yohimbine inhibition experiments with various adrenergic drugs in tissues containing alpha-2A, alpha-2B or both subtypes. Oxymetazoline, WB4101 and yohimbine were found to be 80-, 20- and 10-fold more potent at alpha-2A receptors than at alpha-2B receptors. Phentolamine, adazoxan, (+)- and (-)-mianserin, clonidine, (+)-butaclamol, (-)- and (+)-norepinephrine, epinephrine, dopamine and thioridazine were found to have equal affinities for the two subtypes. These results further validate the subdivision of alpha-2 adrenergic receptors into alpha-2A and alpha-2B subtypes.

  15. Can Diabetes Change the Intrinsic Subtype Specificity of Breast Cancer

    Science.gov (United States)

    2009-09-01

    TITLE: Can Diabetes Change the Intrinsic Subtype Specificity of Breast Cancer? PRINCIPAL INVESTIGATOR: Harikrishna Nakshatri, B.V.Sc., PhD. Kasi...Can Diabetes Change the Intrinsic Subtype Specificity of 5a. CONTRACT NUMBER Breast Cancer? 5b. GRANT NUMBER W81XWH-07-1...positive breast cancer. 15. SUBJECT TERMS Diabetes , Intrinsic subtypes, Breast Cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT

  16. CHARACTERIZATION OF MUSCARINIC CHOLINERGIC RECEPTOR SUBTYPES IN RAT PROSTATE

    OpenAIRE

    Pontari, M.A.; LUTHIN, G. R.; Braverman, A. S.; Ruggieri, M. R.

    1998-01-01

    The purpose of this study was to characterize the muscarinic receptor subtypes in the individual lobes of the rat prostate. Immunoprecipitation was performed on homogenates of these 3 lobes using antibodies to the m1-m4 muscarinic receptor subtypes. Reverse transcriptase polymerase chain reaction assays (RT-PCR) were also performed using primers specific for each of the five muscarinic receptor subtypes (m1-m5). The susceptibility of the receptors to degradation by endogenous prostate proteas...

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

    Science.gov (United States)

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

    2003-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  19. 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....

  20. Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.

    Science.gov (United States)

    Fishbein, Lauren; Leshchiner, Ignaty; Walter, Vonn; Danilova, Ludmila; Robertson, A Gordon; Johnson, Amy R; Lichtenberg, Tara M; Murray, Bradley A; Ghayee, Hans K; Else, Tobias; Ling, Shiyun; Jefferys, Stuart R; de Cubas, Aguirre A; Wenz, Brandon; Korpershoek, Esther; Amelio, Antonio L; Makowski, Liza; Rathmell, W Kimryn; Gimenez-Roqueplo, Anne-Paule; Giordano, Thomas J; Asa, Sylvia L; Tischler, Arthur S; Pacak, Karel; Nathanson, Katherine L; Wilkerson, Matthew D

    2017-02-13

    We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.

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

    Science.gov (United States)

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

    2013-05-01

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

  2. Comprehensive molecular portraits of human breast tumours.

    Science.gov (United States)

    2012-10-01

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

  3. Characterization of a novel subtype of hippocampal interneurons that express corticotropin-releasing hormone.

    Science.gov (United States)

    Hooper, Andrew; Maguire, Jamie

    2016-01-01

    A subset of corticotropin-releasing hormone (CRH) neurons was previously identified in the hippocampus with unknown function. Here we demonstrate that hippocampal CRH neurons represent a novel subtype of interneurons in the hippocampus, exhibiting unique morphology, electrophysiological properties, molecular markers, and connectivity. This subset of hippocampal CRH neurons in the mouse reside in the CA1 pyramidal cell layer and tract tracing studies using AAV-Flex-ChR2-tdTomato reveal dense back-projections of these neurons onto principal neurons in the CA3 region of the hippocampus. These hippocampal CRH neurons express both GABA and GAD67 and using in vitro optogenetic techniques, we demonstrate that these neurons make functional connections and release GABA onto CA3 principal neurons. The location, morphology, and importantly the functional connectivity of these neurons demonstrate that hippocampal CRH neurons represent a unique subtype of hippocampal interneurons. The connectivity of these neurons has significant implications for hippocampal function.

  4. Transcriptional coexpression network reveals the involvement of varying stem cell features with different dysregulations in different gastric cancer subtypes.

    Science.gov (United States)

    Kalamohan, Kalaivani; Periasamy, Jayaprakash; Bhaskar Rao, Divya; Barnabas, Georgina D; Ponnaiyan, Srigayatri; Ganesan, Kumaresan

    2014-10-01

    Despite the advancements in the cancer therapeutics, gastric cancer ranks as the second most common cancers with high global mortality rate. Integrative functional genomic investigation is a powerful approach to understand the major dysregulations and to identify the potential targets toward the development of targeted therapeutics for various cancers. Intestinal and diffuse type gastric tumors remain the major subtypes and the molecular determinants and drivers of these distinct subtypes remain unidentified. In this investigation, by exploring the network of gene coexpression association in gastric tumors, mRNA expressions of 20,318 genes across 200 gastric tumors were categorized into 21 modules. The genes and the hub genes of the modules show gastric cancer subtype specific expression. The expression patterns of the modules were correlated with intestinal and diffuse subtypes as well as with the differentiation status of gastric tumors. Among these, G1 module has been identified as a major driving force of diffuse type gastric tumors with the features of (i) enriched mesenchymal, mesenchymal stem cell like, and mesenchymal derived multiple lineages, (ii) elevated OCT1 mediated transcription, (iii) involvement of Notch activation, and (iv) reduced polycomb mediated epigenetic repression. G13 module has been identified as key factor in intestinal type gastric tumors and found to have the characteristic features of (i) involvement of embryonic stem cell like properties, (ii) Wnt, MYC and E2F mediated transcription programs, and (iii) involvement of polycomb mediated repression. Thus the differential transcription programs, differential epigenetic regulation and varying stem cell features involved in two major subtypes of gastric cancer were delineated by exploring the gene coexpression network. The identified subtype specific dysregulations could be optimally employed in developing subtype specific therapeutic targeting strategies for gastric cancer.

  5. Genetic analysis of HIV-1 subtypes in Nairobi, Kenya.

    Directory of Open Access Journals (Sweden)

    Suhail Khoja

    Full Text Available BACKGROUND: Genetic analysis of a viral infection helps in following its spread in a given population, in tracking the routes of infection and, where applicable, in vaccine design. Additionally, sequence analysis of the viral genome provides information about patterns of genetic divergence that may have occurred during viral evolution. OBJECTIVE: In this study we have analyzed the subtypes of Human Immunodeficiency Virus -1 (HIV-1 circulating in a diverse sample population of Nairobi, Kenya. METHODOLOGY: 69 blood samples were collected from a diverse subject population attending the Aga Khan University Hospital in Nairobi, Kenya. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs, and used in a Polymerase Chain Reaction (PCR to amplify the HIV gag gene. The PCR amplimers were partially sequenced, and alignment and phylogenetic analysis of these sequences was performed using the Los Alamos HIV Database. RESULTS: Blood samples from 69 HIV-1 infected subjects from varying ethnic backgrounds were analyzed. Sequence alignment and phylogenetic analysis showed 39 isolates to be subtype A, 13 subtype D, 7 subtype C, 3 subtype AD and CRF01_AE, 2 subtype G and 1 subtype AC and 1 AG. Deeper phylogenetic analysis revealed HIV subtype A sequences to be highly divergent as compared to subtypes D and C. CONCLUSION: Our analysis indicates that HIV-1 subtypes in the Nairobi province of Kenya are dominated by a genetically diverse clade A. Additionally, the prevalence of highly divergent, complex subtypes, intersubtypes, and the recombinant forms indicates viral mixing in Kenyan population, possibly as a result of dual infections.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

  8. 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 (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

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

    Science.gov (United States)

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

    2009-01-01

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

  10. 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...

  11. The validity and utility of subtyping bulimia nervosa

    NARCIS (Netherlands)

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

    2009-01-01

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

  12. 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.…

  13. Genetic overlap between diagnostic subtypes of ischemic stroke

    NARCIS (Netherlands)

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

    2015-01-01

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

  14. Preoperative subtyping of meningiomas by perfusion MR imaging

    NARCIS (Netherlands)

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

    2008-01-01

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

  15. 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....

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  17. Subtypes of irritable bowel syndrome in children and adolescents

    Science.gov (United States)

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

  18. 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...... infections from primates by their handlers had occurred in these cases. Data from published studies of non-human primates, other mammals and birds were collected and interpreted to generate a comprehensive overview on the ST distribution in such animals. On the basis of information on 438 samples......, it was found that Blostocystis from primates belong mainly to ST1, ST2, ST3, ST5 and ST8, ungulates and dogs mainly ST1, ST2, ST3, ST5 and ST10, rodents ST4 and birds mainly ST6 and ST7. The data indicate moderate host specificity, most clearly exemplified by the fact that STs isolated from avian and non...

  19. 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

  20. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  2. Master regulators, regulatory networks, and pathways of glioblastoma subtypes.

    Science.gov (United States)

    Bozdag, Serdar; Li, Aiguo; Baysan, Mehmet; 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 Analysis and Ingenuity Pathway Analysis on GBM expression dataset from The Cancer Genome Atlas Project to compute GBM- and GBM subtype-specific pathways. Our analysis was able to recover some of the known master regulators and pathways in GBM as well as some putative novel regulators and pathways, which will aide in our understanding of the unique biology of GBM subtypes.

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

    Directory of Open Access Journals (Sweden)

    Yoo Chong

    2011-10-01

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

  4. Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes.

    Science.gov (United States)

    Furukawa, T; Yamakawa, T; Midera, T; Sagawa, T; Mori, Y; Nukada, T

    1999-11-01

    Some dihydropyridines (DHPs), such as amlodipine and cilnidipine, have been shown to block not only L-type but also N-type Ca(2+) channels; therefore, DHPs are no longer considered as L-type-specific Ca(2+) channel blockers. However, selectivity of DHPs for Ca(2+) channel subtypes including N-, P/Q-, and R-types are poorly understood. To address this issue at the molecular level, blocking effects of 10 DHPs (nifedipine, nilvadipine, barnidipine, nimodipine, nitrendipine, amlodipine, nicardipine, benidipine, felodipine, and cilnidipine) on four subtypes of Ca(2+) channels (L-, N-, P/Q-, and R-types) were investigated in the Xenopus oocyte expression system with the use of the two-microelectrode voltage-clamp technique. L-type Ca(2+) channels expressed as alpha(1C)alpha(2)beta(1a) combination were profoundly blocked by all DHPs examined, whereas blocking actions of these DHPs on R-type (alpha(1E)alpha(2)beta(1a)) channels were equally weak. In contrast, 5 of the 10 DHPs (amlodipine, benidipine, cilnidipine, nicardipine, and barnidipine) significantly blocked N-type (alpha(1B)alpha(2)beta(1a)) and P/Q-type (alpha(1A)alpha(2)beta(1a)) Ca(2+) channels. These selectivities of DHPs in blocking Ca(2+) channel subtypes would provide useful pharmacological and clinical information on the mode of action of the drugs including side effects and adverse effects.

  5. 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.

  6. Reproducibility of histological subtyping of malignant pleural mesothelioma.

    Science.gov (United States)

    Brčić, Luka; Jakopović, Marko; Brčić, Iva; Klarić, Vlasta; Milošević, Milan; Sepac, Ana; Samaržija, Miroslav; Seiwerth, Sven

    2014-12-01

    Malignant pleural mesothelioma (MPM) has a very poor prognosis. Although clinical stage is currently the only reliable prognostic factor, histologic subtyping reportedly also affects prognosis. Some studies propose reclassification of pleomorphic epithelioid as biphasic or sarcomatoid MPM. This study assessed prognostic significance and interobserver agreement in MPM subtyping of small biopsy specimens. We analyzed biopsy specimens, and clinical and survival data from records of 108 patients who were diagnosed between 2000 and 2010 at the Institute of Pathology University of Zagreb School of Medicine, of whom 98 had epithelioid MPM, six biphasic MPM, and four sarcomatoid MPM. Among epithelioid subtypes, 44 (44.9 %) were solid, 19 (19.4 %) tubulopapillary, 18 (18.4 %) acinar, six (6.1 %) adenomatoid, five (5.1 %) pleomorphic, four (4.1 %) trabecular, and two (2.0 %) micropapillary subtype. Interobserver reliability for histological diagnosis was found to be κ = 0.72 (P sarcomatoid mesothelioma (4.0 [IQR 1.3-6.8] months; P = 0.270). We found strong reproducibility of MPM subtyping with good interobserver agreement. Furthermore, our results indicate that pleomorphic subtype to be a predictor of poor prognosis and support classifying it with sarcomatoid or biphasic MPM, as patients with the pleomorphic, biphasic, or sarcomatoid subtype show similarly poor overall survival.

  7. 汗腺剥脱时保护浅层毛囊对腋臭术后皮片坏死的影响%Effect of removing apocrine glands with protecting superficial hair follicle on skin graft anabrosis after osmidrosis surgery

    Institute of Scientific and Technical Information of China (English)

    赵李平; 袁芳; 杜晓扬; 谢远亮; 张倩倩; 张秋生

    2012-01-01

    To investigate the effect of removing apocrine glands while protecting superficial hair follicle in the precaution of skin graft anabrosis after osmidrosis surgery. Methods One or two 2 ~ 3 cm skin incisions were made along skin fold in the central region of axillary space according to the range of axillary hair, subdermal sectioning was performed in the axillary hair area and 1 cm outside, after removing apocrine glands while protecting superficial hair follicle, the subdermal vascular plexus was remained, the incision was closed with interrupted suture , drainage piece was placed, appropriate pressure dressing with elastic bandage was given to each axilla. Results Of the 51 cases,all the incisions in 102 sides healed primarily, no anabrosis in skin graft happened and no obvious scars were observed for six months to one year followed up. Conclusion Removing apocrine glands while protecting superficial hair follicle is effective in reducing anabrosis in skin graft.%目的 探讨汗腺剥脱的同时注意保护浅层毛囊对预防腋臭术后皮片坏死的效果.方法 根据腋毛区范围大小,在腋窝中部顺皮肤皱襞分别设计1~2条长2~3 cm的切口,皮下分离腋毛区及区外1 cm区域,去除汗腺,尽量保护浅层毛囊,保留真皮下血管网,切口间断缝合,皮片引流,弹性绷带适当加压包扎.结果 本组共51 例102 侧,术后切口均一期愈合,未发现切缘糜烂及皮片坏死,随访0.5~1年,瘢痕不明显.结论 汗腺剥脱的同时注意保护浅层毛囊可有效预防腋臭术后皮片坏死,提高手术效果.

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

    Directory of Open Access Journals (Sweden)

    Jorge Mauricio Cuartas Arias

    2016-09-01

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

  9. 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.

  10. 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.

  11. A differentiation-based phylogeny of cancer subtypes.

    Directory of Open Access Journals (Sweden)

    Markus Riester

    2010-05-01

    Full Text Available Histopathological classification of human tumors relies in part on the degree of differentiation of the tumor sample. To date, there is no objective systematic method to categorize tumor subtypes by maturation. In this paper, we introduce a novel computational algorithm to rank tumor subtypes according to the dissimilarity of their gene expression from that of stem cells and fully differentiated tissue, and thereby construct a phylogenetic tree of cancer. We validate our methodology with expression data of leukemia, breast cancer and liposarcoma subtypes and then apply it to a broader group of sarcomas. This ranking of tumor subtypes resulting from the application of our methodology allows the identification of genes correlated with differentiation and may help to identify novel therapeutic targets. Our algorithm represents the first phylogeny-based tool to analyze the differentiation status of human tumors.

  12. 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

  13. QuantiGene Plex Represents a Promising Diagnostic Tool for Cell-of-Origin Subtyping of Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Hall, John S; Usher, Suzanne; Byers, Richard J; Higgins, Rebekah C; Memon, Danish; Radford, John A; Linton, Kim M

    2015-07-01

    Emerging therapies targeting the molecularly distinct GCB and non-GCB/ABC subtypes of diffuse large B-cell lymphoma (DLBCL) have created the need to develop an accurate subtyping assay for routine use. We investigated the potential of QuantiGene Plex (QGP)-branched DNA signal amplification assay-for DLBCL subtyping. We performed in silico analysis of public DLBCL datasets to develop and validate a naïve Bayes classifier, and migrated the resulting 21-gene classifier to QGP and real-time quantitative PCR (qPCR) assays. Forty DLBCL formalin-fixed, paraffin-embedded tumors of known subtype (20 per subtype by gene expression profiling of paired fresh-frozen tissues) were reclassified, and results for QGP (on 38/40 for 21/21 targets) and qPCR (on 40/40 samples for 19/21 targets) compared for recapitulation of microarray data and classification accuracy. The 21-gene bayesian classifier achieved mean area under the curve values >0.9 on independent validation. QGP showed a higher correlation with microarray data (mean R(2) = 0.66 ± 0.05 versus 0.34 ± 0.07; P QGP (85.7% versus 47.4%). The QGP protocol was rapid and simple to perform, at a cost similar to qPCR. These promising preliminary results strongly support ongoing work to develop a QGP companion diagnostic assay for DLBCL subtyping.

  14. Modification of the anabaseine pyridine nucleus allows achieving binding and functional selectivity for the α3β4 nicotinic acetylcholine receptor subtype.

    Science.gov (United States)

    Matera, Carlo; Quadri, Marta; Sciaccaluga, Miriam; Pomè, Diego Yuri; Fasoli, Francesca; De Amici, Marco; Fucile, Sergio; Gotti, Cecilia; Dallanoce, Clelia; Grazioso, Giovanni

    2016-01-27

    We report the design, synthesis and pharmacological screening of a group of analogues of anabaseine 2, a naturally occurring unselective nicotinic agonist. The novel nAChR ligands 5-15 were planned following a molecular modeling analysis which suggested the replacement of the pyridine ring of 2 with a 3-substituted benzene ring as a means to gain selectivity for the α3β4 nAChR subtype. Overall, from binding experiments, the synthesized compounds showed high values of α3β4 affinity and α3β4 vs α4β2 selectivity, although they poorly discriminated the homomeric α7 subtype. The three analogues 6, 12 and 13 were also evaluated in electrophysiological assays, and 12 [6-(3-iodophenyl)-2,3,4,5-tetrahydropyridine] emerged as a rather interesting nicotinic ligand. Indeed, in addition to a noteworthy affinity (Ki = 4.7 nM) for the α3β4 subtype and to an excellent α3β4 vs α4β2 subtype selectivity (806-fold), compound 12 selectively activated the α3β4 nAChR (EC50 = 7.4 μM) while eliciting a negligible response at the α7 subtype and no effect at the α4β2 subtype.

  15. Can Diabetes Change the Intrinsic Subtype Specificity of Breast Cancer?

    Science.gov (United States)

    2008-09-01

    TITLE: Can Diabetes Change the Intrinsic Subtype Specificity of Breast Cancer ? PRINCIPAL INVESTIGATOR: Harikrishna Nakshatri, B.V.Sc., PhD Kasi R... Diabetes Change the Intrinsic Subtype Specificity of 5a. CONTRACT NUMBER Breast Cancer 5b. GRANT NUMBER W81XWH-07-1-0651...as in type II diabetes , to disrupt GATA- 3:FOXA1:ERα network. Insulin induced the expression of T-bet in MCF-7 breast cancer cells and MCF-7 cells

  16. The biological effects of five feline IFN-alpha subtypes.

    Science.gov (United States)

    Baldwin, Susan L; Powell, Tim D; Sellins, Karen S; Radecki, Steven V; Cohen, J John; Milhausen, Michael J

    2004-06-01

    IFN-alpha has been shown to induce both antiviral and antiproliferative activities in animals. This report describes the biological activity of five recently identified feline IFN-alpha subtypes expressed in the Chinese hamster ovary (CHO) cell line (rfeIFN-alpha1[CHO], rfeIFN-alpha2[CHO], rfeIFN-alpha3[CHO], rfeIFN-alpha5[CHO] and rfeIFN-alpha6[CHO]) and the feIFN-alpha6 subtype expressed in and purified from Pichia pastoris (rfeIFN-alpha6[P. pastoris]). The rfeIFN-alpha[CHO] subtypes were tested for antiviral activity against either Vesicular stomatitis virus (VSV) or feline calicivirus (FCV) infected feline embryonic fibroblast cell line (AH927) or Crandell feline kidney cell line (CRFK). Antiviral activity was induced against both VSV and FCV infected AH927 cells and VSV infected CRFK cells by all five of the rfeIFN-alpha[CHO] subtypes and rfeIFN-alpha6[P. pastoris]. In addition, the IFN-alpha inducible Mx gene (associated with antiviral activity) was upregulated in vivo 24 h following treatment with rfeIFN-alpha6[P. pastoris], compared to baseline levels seen prior to treatment. All of the rfeIFN-alpha[CHO] subtypes and rfeIFN-alpha6[P. pastoris] exhibited antiproliferative activity in the FeT-J cell line (an IL-2 independent feline T-cell line). Both necrosis and apoptosis were observed in rfeIFN-alpha6[P. pastoris]-treated FeT-J cells. The rfeIFN-alpha3[CHO] subtype consistently exhibited lower antiviral and antiproliferative activity compared to that observed with the other four rfeIFN-alpha[CHO] subtypes. In summary, this paper demonstrates that five previously described feIFN-alpha subtypes induce both antiviral and antiproliferative activities in vitro and are capable of upregulating the feMx gene in vivo.

  17. Heterogeneity of muscarinic receptor subtypes in cerebral blood vessels

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    Garcia-Villalon, A.L.; Krause, D.N.; Ehlert, F.J.; Duckles, S.P. (Department of Pharmacology, College of Medicine, University of California, Irvine (USA))

    1991-07-01

    The identity and distribution of muscarinic cholinergic receptor subtypes and associated signal transduction mechanisms was characterized for the cerebral circulation using correlated functional and biochemical investigations. Subtypes were distinguished by the relative affinities of a panel of muscarinic antagonists, pirenzepine, AF-DX 116 (11-2-((2-(diethylaminomethyl)- 1-piperidinyl)acetyl)-5,11-dihydro-6H- pyrido(2,3-b)(1,4)benzodiazepine-6-one), hexahydrosiladifenidol, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methobromide, dicyclomine, para-fluoro-hexahydrosiladifenidol and atropine. Muscarinic receptors characterized by inhibition of (3H)quinuclidinylbenzilate binding in membranes of bovine pial arteries were of the M2 subtype. In contrast pharmacological analysis of (3H)-quinuclidinylbenzilate binding in bovine intracerebral microvessels suggests the presence of an M4 subtype. Receptors mediating endothelium-dependent vasodilation in rabbit pial arteries were of the M3 subtype, whereas muscarinic receptors stimulating endothelium-independent phosphoinositide hydrolysis in bovine pial arteries were of the M1 subtype. These findings suggest that characteristics of muscarinic receptors in cerebral blood vessels vary depending on the type of vessel, cellular location and function mediated.

  18. 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.

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

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    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

  20. Phylogeography, phylodynamics and transmission chains of bovine viral diarrhea virus subtype 1f in Northern Italy.

    Science.gov (United States)

    Cerutti, Francesco; Luzzago, Camilla; Lauzi, Stefania; Ebranati, Erika; Caruso, Claudio; Masoero, Loretta; Moreno, Ana; Acutis, Pier Luigi; Zehender, Gianguglielmo; Peletto, Simone

    2016-11-01

    Bovine viral diarrhea virus (BVDV) type 1 in Italy is characterized by high genetic diversity, with at least 20 subtypes. Subtype 1f is endemic in a restricted geographic area, meaning that it has local distribution. We investigated the population dynamics of BVDV-1f in Northern Italy and characterized the transmission chains of a subset of samples from Piedmont and Aosta Valley regions. A total of 51 samples from 1966 to 2013 were considered and 5' UTR sequences were used for phylogeography. A subset of 12 samples was selected for Npro gene sequencing and further characterization of the transmission chains using both molecular and epidemiological data. Phylogeography estimated the root of BVDV-1f tree in Veneto in 1965. Four significant subclades included sequences clustering by region: Lombardy (n=3), Lombardy and Emilia-Romagna (n=7), Piedmont (n=17), Piedmont and Aosta Valley (n=21). The Piedmont-only subclade has a ladder-like branching structure, while the Piedmont and Aosta Valley subclade has a nearly complete binary structure. In the subset, the outbreak reconstruction identified one sample from Piedmont as the most probable source of infection for the Aosta Valley cases. An ad hoc questionnaire submitted to public veterinarians revealed connections between sampled and non-sampled farms by means of trades, exhibitions and markets. According to the phylogeography, BVDV-1f moved westward, entering from Veneto, and spreading to Lombardy and Emilia-Romagna in the early 1990s, and finally to Piedmont and Aosta Valley in the first decade of 2000s. Both phylogeographic analyses on the whole dataset and on the selection of Npro dataset pointed out that subtype 1f entered Aosta Valley from Piedmont. The integration of molecular and epidemiological data revealed connections between farms, and such approach should be considered in any control plan. In Aosta Valley, the study showed that BVDV1f can be controlled only monitoring the introduction of cattle from Piedmont

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

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    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

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

    Science.gov (United States)

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

    2016-06-01

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

  3. Reemergence of dengue virus type-3 (subtype-III in India: Implications for increased incidence of DHF & DSS

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    Tewari KN

    2006-07-01

    Full Text Available Abstract Background Dengue virus infection has recently taken endemic proportion in India implicating all the four known dengue serotypes. There was a major dengue outbreak in northern India including Delhi in October- December, 2003 and again in 2004. We have carried out a detailed investigation of the 2004 outbreak by Serosurveillance, RT-PCR, nested PCR, virus isolation and genotyping. We also report the molecular epidemiological investigation of these outbreaks. Results The serological investigation of 162 suspected serum samples using an in-house dengue dipstick ELISA revealed 11%-IgM, 51%-IgG and 38%-both IgM and IgG antibody positivity. The RT-PCR analysis revealed presence of dengue RNA in 17 samples. Further subtyping and genotyping by nested PCR and nucleotide sequencing of C-prM gene junction revealed the association of subtype III of dengue virus type 3 in the outbreak. Conclusion The sudden shifting and dominance of the dengue virus serotype-3 (subtype III replacing the earlier circulating serotype-2 (subtype IV is a point of major concern and may be attributed to increased incidence of DHF and DSS in India.

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

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    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.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Kotagal, Vikas

    2016-06-01

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

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

    Science.gov (United States)

    Masuda, Shinobu

    2012-05-01

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

  8. [New molecular classification of colorectal cancer, pancreatic cancer and stomach cancer: Towards "à la carte" treatment?].

    Science.gov (United States)

    Dreyer, Chantal; Afchain, Pauline; Trouilloud, Isabelle; André, Thierry

    2016-01-01

    This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion). In gastric adenocarcinoma, 4 groups were established: subtype "EBV" (9%, high frequency of PIK3CA mutations, hypermetylation and amplification of JAK2, PD-L1 and PD-L2), subtype "MSI" (22%, high rate of mutation), subtype "genomically stable tumor" (20%, diffuse histology type and mutations of RAS and genes encoding integrins and adhesion proteins including CDH1) and subtype "tumors with chromosomal instability" (50%, intestinal type, aneuploidy and receptor tyrosine kinase amplification). In pancreatic adenocarcinomas, a classification in four sub-groups has been proposed, stable subtype (20%, aneuploidy), locally rearranged subtype (30%, focal event on one or two chromosoms), scattered subtype (36%,200 structural variation events, defects in DNA maintenance). Although currently away from the care of patients, these classifications open the way to "à la carte" treatment depending on molecular biology.

  9. Diagnosis and subtypes of adolescent antisocial personality disorder.

    Science.gov (United States)

    Jones, Meredith; Westen, Drew

    2010-04-01

    The present study examined the application of the Antisocial Personality Disorder (APD) diagnosis to adolescents and investigated the possibility of subtypes of APD adolescents. As part of a broader study of adolescent personality in clinically-referred patients, experienced clinicians provided personality data on a randomly selected patient in their care using the SWAP-II-A personality pathology instrument. Three hundred thirteen adolescents met adult DSM-IV diagnostic criteria for APD. To characterize adolescents with the disorder, we aggregated the data to identify the items most descriptive and distinctive of APD adolescents relative to other teenagers in the sample (N = 950). Q-factor analysis identified five personality subtypes: psychopathic-like, socially withdrawn, impulsive-histrionic, emotionally dysregulated, and attentionally dysregulated. The five subtypes differed in predictable ways on a set of external criteria related to global adaptive functioning, childhood family environment, and family history of psychiatric illness. Both the APD diagnosis and the empirically derived APD subtypes provided incremental validity over and above the DSM-IV disruptive behavior disorders in predicting global adaptive functioning, number of arrests, early-onset severe externalizing pathology, and quality of peer relationships. Although preliminary, these results provide support for the use of both APD and personality-based subtyping systems in adolescents.

  10. Immunogenicity of a recombinant measles HIV-1 subtype C vaccine.

    Science.gov (United States)

    Stebbings, Richard; Li, Bo; Lorin, Clarisse; Koutsoukos, Marguerite; Février, Michèle; Mee, Edward T; Page, Mark; Almond, Neil; Tangy, Frédéric; Voss, Gérald

    2013-12-09

    The HIV epidemic is greatest in Sub-Saharan Africa and India where HIV-1 subtype C is predominant. To control the spread of HIV in these parts of the world a preventive HIV-1 subtype C vaccine is urgently required. Here we report the immunogenicity of a candidate HIV-1 subtype C vaccine delivered by a recombinant measles vector carrying an insert encoding HIV-1 subtype C Gag, RT and Nef (MV1-F4), in MHC-typed non-human primates. HIV-1 specific cytokine secreting CD4+ and CD8+ T cell responses were detected in 15 out of 16 vaccinees. These HIV-specific T cell responses persisted in lymphoid tissues. Anti-HIV-1 antibody responses were detected in 15 out of 16 vaccinees and titres were boosted by a second immunisation carried out 84 days later. These findings support further exploration of the MV1-F4 vector as a candidate HIV-1 subtype C vaccine or as part of a wider vaccine strategy.

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

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    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

  12. Molecular heterogeneity in glioblastoma: potential clinical implications

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    Nicole Renee Parker

    2015-03-01

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

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

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    Marcelo Pinto Pereira

    2013-09-01

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

  14. 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.

  15. Psychosocial and Adaptive Deficits Associated With Learning Disability Subtypes.

    Science.gov (United States)

    Backenson, Erica M; Holland, Sara C; Kubas, Hanna A; Fitzer, Kim R; Wilcox, Gabrielle; Carmichael, Jessica A; Fraccaro, Rebecca L; Smith, Amanda D; Macoun, Sarah J; Harrison, Gina L; Hale, James B

    2015-01-01

    Children with specific learning disabilities (SLD) have deficits in the basic psychological processes that interfere with learning and academic achievement, and for some SLD subtypes, these deficits can also lead to emotional and/or behavior problems. This study examined psychosocial functioning in 123 students, aged 6 to 11, who underwent comprehensive evaluations for learning and/or behavior problems in two Pacific Northwest school districts. Using concordance-discordance model (C-DM) processing strengths and weaknesses SLD identification criteria, results revealed working memory SLD (n = 20), processing speed SLD (n = 30), executive SLD (n = 32), and no disability groups (n = 41). Of the SLD subtypes, repeated measures MANOVA results revealed the processing speed SLD subtype exhibited the greatest psychosocial and adaptive impairment according to teacher behavior ratings. Findings suggest processing speed deficits may be behind the cognitive and psychosocial disturbances found in what has been termed "nonverbal" SLD. Limitations, implications, and future research needs are addressed.

  16. Groin hernia subtypes are associated in patients with bilateral hernias

    DEFF Research Database (Denmark)

    Burcharth, Jakob; Andresen, Kristoffer; Pommergaard, Hans-Christian;

    2015-01-01

    for a DIH. Females and males operated for a unilaterally indirect inguinal hernia (IIH) had HRs of 6.93 (CI 95% 3.66-13.11) and 1.89 (CI95% 1.24-2.88) for being contralaterally operated for an IIH. The same tendency was seen for femoral hernias. CONCLUSIONS: All hernia subtypes were bilaterally associated......BACKGROUND: To investigate the relation between groin hernia subtypes in patients operated for bilateral hernias. METHODS: With data from the Danish Hernia Database, we identified all patients operated for primary groin hernias from 1998 to 2012. Within this cohort all patients that were...... bilaterally operated were analyzed. Risk factors for bilateral groin hernia operation as well as the relationship between groin hernia subtypes bilaterally, were analyzed using multivariate Cox proportional hazards analysis and Kappa statistics. RESULTS: A total of 108, 775 persons with primary groin hernia...

  17. Regular Expression Subtyping for XML Query and Update Languages

    CERN Document Server

    Cheney, James

    2008-01-01

    XML database query languages such as XQuery employ regular expression types with structural subtyping. Subtyping systems typically have two presentations, which should be equivalent: a declarative version in which the subsumption rule may be used anywhere, and an algorithmic version in which the use of subsumption is limited in order to make typechecking syntax-directed and decidable. However, the XQuery standard type system circumvents this issue by using imprecise typing rules for iteration constructs and defining only algorithmic typechecking, and another extant proposal provides more precise types for iteration constructs but ignores subtyping. In this paper, we consider a core XQuery-like language with a subsumption rule and prove the completeness of algorithmic typechecking; this is straightforward for XQuery proper but requires some care in the presence of more precise iteration typing disciplines. We extend this result to an XML update language we have introduced in earlier work.

  18. Therapeutic response to benzodiazepine in panic disorder subtypes

    Directory of Open Access Journals (Sweden)

    Alexandre Martins Valença

    Full Text Available CONTEXT: This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam, a benzodiazepine. OBJECTIVES: To evaluate the clinical efficacy of clonazepam in a fixed dosage (2 mg/day, compared to placebo, in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes. TYPE OF STUDY: Randomized study with clonazepam and placebo. SETTING: Outpatient Anxiety and Depression Unit of the Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. PARTICIPANTS: 34 patients with a diagnosis of panic disorder with agoraphobia, between 18 and 55 years old. PROCEDURES: Administration of clonazepam or placebo for 6 weeks, in panic disorder patients, after they were classified within two subtypes of panic disorder: respiratory and non-respiratory. MAIN MEASUREMENTS: Changes in the number of panic attacks in comparison with the period before the beginning of the study; Hamilton Anxiety Scale; Global Clinical Impression Scale; and Patient's Global Impression scale. RESULTS: In the group that received clonazepam, by the end of the 6th week there was a statistically significant clinical improvement, shown by the remission of panic attacks (p < 0.001 and decrease in anxiety (p = 0.024. In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder, regarding the therapeutic response to clonazepam. CONCLUSION: Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder, suggesting there is no difference in the therapeutic response between the two subtypes.

  19. 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.

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

    Science.gov (United States)

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

    2016-02-01

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

  1. 5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials

    OpenAIRE

    Pithadia, Anand B.; Jain, Sunita M.

    2009-01-01

    5-hydroxytryptamine (5-HT) has become one of the most investigated and complex biogenic amines. The main receptors and their subtypes, e.g., 5-HTI (5-HT1A, 5-HT1B, 5-HTID, 5-HTIE and 5-HT1F), 5-HT2 (5-HT2A, 5-HT2B and 5-HT2C), 5-HT3, 5-HT4, 5-HT5 (5-HT5A, 5-HT5B), 5-HT6 and 5-HT7 have been identified. Specific drugs which are capable of either selectively stimulating or inhibiting these receptor subtypes are being designed. This has generated therapeutic potentials of 5-HT receptor modulators...

  2. HLA-DR4 subtype frequencies in rheumatoid arthritis indicate that DRB1 is the major susceptibility locus within the HLA class II region

    Energy Technology Data Exchange (ETDEWEB)

    Wordsworth, B.P.; Bell, J.I. (Univ. of Oxford (England)); Lanchbury, J.S.S.; Sakkas, L.I.; Welsh, K.I.; Panayi, G.S. (Guy' s Hospital, London (England))

    1989-12-01

    Susceptibility to rheumatoid arthritis (RA) may be due to the presence of shared functional epitopes common the HLA-DR {beta} chains of several RA-associated haplotypes. The authors have obtained direct evidence for this hypothesis by using the polymerase chain reaction and sequencing the DRB1 and DQB1 genes from RA patients. A highly conserved epitope present on DR {beta} chains of DR4 and DR1 haplotypes was found in 83% of 149 patients with classical or definite RA but was found in only 46% of 100 control individuals. Two Dw subtypes of DR4 (Dw4 and Dw14) were associated with disease susceptibility but two other subtypes (Dw10 and Dw13) were not. Sequence differences between these subtypes implicate those residues around the putative antigen binding site of the DR {beta} molecule in the pathogenesis of RA. These data provide a basis for understanding host susceptibility to RA at a molecular level.

  3. Prognosis of early breast cancer by immunohistochemistry defined intrinsic sub-types in patients treated with adjuvant chemotherapy in the NEAT/BR9601 trial.

    Science.gov (United States)

    Ali, Alaa M; Provenzano, Elena; Bartlett, John M S; Abraham, Jean; Driver, Kristy; Munro, Alison F; Twelves, Christopher; Poole, Christopher J; Hiller, Louise; Dunn, Janet A; Earl, Helena M; Caldas, Carlos; Pharoah, Paul D

    2013-09-15

    Breast cancer can be classified into molecular sub-types that have distinct survival patterns. We evaluated the prognostic significance of breast cancer sub-types in a cohort of women taking part in the NEAT and BR9601 clinical trials comparing cyclophosphamide, methotrexate and fluorouracil (CMF) with ECMF (epirubicin and CMF). Furthermore, we evaluated whether the sub-types were predictive of the added benefit of epirubicin in these trials. Tumour tissue microarrays were stained and scored for ER, PR, HER2, EGFR and CK5/6. These were used to classify the tumours into six intrinsic sub-types. We used Cox regression to compare overall survival (OS), breast cancer-specific survival (BCSS) and relapse-free survival (RFS) in the different sub-groups. We also compared the effect of ECMF with CMF by sub-group. Immunohistochemistry data were available for 1,725 cases of whom 805 were luminal 1-basal negative. Median follow-up time was 7 years. The luminal 1-basal negative tumours were associated with the best prognosis in five years after surgery and the HER2-like tumours were associated with the poorest prognosis. There was little evidence for significant heterogeneity of this effect by tumour sub-type (OS p = 0.40, BCSS p = 0.53 RFS p = 0.50) - the largest additional benefit of epirubicin was in women with tumours of the 5-negative phenotype (OS HR = 0.39 95% CI: 0.21-0.73) and the smallest was in Luminal 1-basal negative tumours (OS HR = 0.86 95% CI: 0.64-1.16). We confirmed that breast cancer sub-types show distinct behaviour with differences in short- and long-term survival. The benefit of ECMF over CMF was statistically similar in all disease sub-types.

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

    Science.gov (United States)

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

    2011-01-01

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

  5. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer

    NARCIS (Netherlands)

    Wang, Kai; Yuen, Siu Tsan; Xu, Jiangchun; Lee, Siu Po; Yan, Helen H N; Shi, Stephanie T; Siu, Hoi Cheong; Deng, Shibing; Chu, Kent Man; Law, Simon; Chan, Kok Hoe; Chan, Annie S Y; Tsui, Wai Yin; Ho, Siu Lun; Chan, Anthony K W; Man, Jonathan L K; Foglizzo, Valentina; Ng, Man Kin; Chan, April S; Ching, Yick Pang; Cheng, Grace H W; Xie, Tao; Fernandez, Julio; Li, Vivian S W; Clevers, Hans; Rejto, Paul A; Mao, Mao; Leung, Suet Yi

    2014-01-01

    Gastric cancer is a heterogeneous disease with diverse molecular and histological subtypes. We performed whole-genome sequencing in 100 tumor-normal pairs, along with DNA copy number, gene expression and methylation profiling, for integrative genomic analysis. We found subtype-specific genetic and e

  6. A new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification.

    Science.gov (United States)

    Guérin, Maxime; Thariat, Juliette; Ouali, Mounia; Bouvier, Corinne; Decouvelaere, Anne-Valérie; Cassagnau, Elisabeth; Aubert, Sébastien; Lepreux, Sébastien; Coindre, Jean-Michel; Valmary-Degano, Séverine; Larousserie, Frédérique; Meilleroux, Julie; Projetti, Fabrice; Stock, Nathalie; Galant, Christine; Marie, Béatrice; Peyrottes, Isabelle; de Pinieux, Gonzague; Gomez-Brouchet, Anne

    2016-04-01

    In contrast to long bone osteosarcoma, mandibular osteosarcoma is highly heterogeneous and morphologically overlaps with benign tumors, obscuring diagnosis and treatment selection. Molecular characterization is difficult due to the paucity of available specimens of this rare disease. We aimed to characterize the spectrum of mandibular osteosarcoma using immunohistochemistry and molecular techniques (quantitative polymerase chain reaction and sequencing) and compare them with benign fibro-osseous lesions. Forty-nine paraffin-embedded mandible osteosarcoma tissue samples were collected retrospectively and compared with 10 fibrous dysplasia and 15 ossifying fibroma cases. These were analyzed for molecular markers thought to differ between the different diseases and subtypes: MDM2 (murine double-minute type 2) overexpression, GNAS (guanine nucleotide-binding protein/α subunit) mutations, and amplification of MDM2 and/or RASAL1 (RAS protein activator like 1). Five fibroblastic high-grade osteosarcoma subtypes showed MDM2 amplification, including 2 with a microscopic appearance of high-grade osteosarcoma with part low-grade osteosarcoma (differentiated/dedifferentiated osteosarcoma) and MDM2 overexpression. The other 3 contained a coamplification of MDM2 and RASAL1, a signature also described for juvenile ossifying fibroma, with no overexpression of MDM2. These were of the giant cell-rich high-grade osteosarcoma, with areas mimicking juvenile ossifying fibroma (ossifying fibroma-like osteosarcoma). Our results show that some diagnosed high-grade osteosarcomas are differentiated/dedifferentiated osteosarcomas and harbor an overexpression and amplification of MDM2. In addition, juvenile ossifying fibromas can potentially evolve into giant cell-rich high-grade osteosarcomas and are characterized by a RASAL1 amplification (osteosarcoma with juvenile ossifying fibroma-like genotype). Thus, the presence of a RASAL1 amplification in ossifying fibroma may indicate a requirement

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

    Directory of Open Access Journals (Sweden)

    Marie Le Mercier

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

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

    Directory of Open Access Journals (Sweden)

    Christopher M Bryant

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

  9. 联合射频电波刀治疗的改良大汗腺清除术临床效果观察%Therapeutic effect of modified apocrine gland removal surgery with the combination of high radiofrequency knife for axillary osmidrosis

    Institute of Scientific and Technical Information of China (English)

    韩飞; 黎晴

    2013-01-01

    Objective To compare the therapeutic effect of traditional and modified apocrine gland removal surgery with the combination of high radiofrequency knife for axillary osmidrosis.Methods 105 cases(210 sides) were randomly divided into traditional group A(38 cases,76 sides) and modified group B(67 cases,134 sides).The wound healing and complications were recorded.The clinical effect was followed up for 6-12 months after operation.Results No flap necrosis happened in both groups.The cure rate was 82.89% (63/76)) and 92.54% (124/134) in group A and B,respectively,which was significantly different (P < 0.05).The effective rate of hair removal in group A and B was 42.1%,59.7% (P < 0.05).There is no markedly difference between the two groups in postoperative hematoma(P >0.05).The recurrence rate in group A and B was 9.21% and 1.49% respectively,with a statistically difference between them (P < 0.05).Conclusions Modified apocrine gland removal surgery with the combination of high radiofrequency knife can expose the apocrine gland better and the gland,as well as hair,can be removed in the most.The residue hair and recurrency of osmidrosis are very lower.%目的 探讨联合射频电波刀治疗的改良大汗腺清除术和大汗腺清除术治疗腋臭的疗效差异.方法 将105例210侧腋臭患者,随机分为两组,A组(38例,76侧)采用大汗腺清除术治疗,B组(67例,134侧)采用联合射频电波刀的改良大汗腺清除术治疗,观察两组切口愈合及并发症情况,并于术后6个月至1年比较两组的临床疗效.结果 两组术后均未发生皮瓣坏死等严重并发症.腋臭治愈率A、B两组分别为82.89% (63/76)和92.54%(124/134),差异有统计学意义(P<0.05);腋毛明显减少的有效率A、B两组分别为42.1%和59.7%,差异有统计学意义(P<0.05);两组术后血肿发生率则无统计学意义(P>0.05).两组复发率比较,A组为9.21%,B组为1.49%,差异有统计学意义(P<0

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    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 illnesses...

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

    Science.gov (United States)

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

    2014-03-01

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

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

    Science.gov (United States)

    Mayberry, Megan L.; Espelage, Dorothy L.

    2007-01-01

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

  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. Preoperative subtyping of meningiomas by perfusion MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hao [University Medical Center Groningen, University of Groningen (Netherlands); Shanghai Jiaotong University affiliated First People' s Hospital, Department of Radiology, Shanghai (China); Department of Radiology, University of Groningen (Netherlands); Roediger, Lars A.; Oudkerk, Matthijs [University Medical Center Groningen, University of Groningen (Netherlands); Department of Radiology, University of Groningen (Netherlands); Shen, Tianzhen [Fudan University Huashan Hospital, Department of Radiology, Shanghai (China); Miao, Jingtao [Shanghai Jiaotong University affiliated First People' s Hospital, Department of Radiology, Shanghai (China)

    2008-10-15

    This paper aims to evaluate the value of perfusion magnetic resonance (MR) imaging in the preoperative subtyping of meningiomas by analyzing the relative cerebral blood volume (rCBV) of three benign subtypes and anaplastic meningiomas separately. Thirty-seven meningiomas with peritumoral edema (15 meningothelial, ten fibrous, four angiomatous, and eight anaplastic) underwent perfusion MR imaging by using a gradient echo echo-planar sequence. The maximal rCBV (compared with contralateral normal white matter) in both tumoral parenchyma and peritumoral edema of each tumor was measured. The mean rCBVs of each two histological subtypes were compared using one-way analysis of variance and least significant difference tests. A p value less than 0.05 indicated a statistically significant difference. The mean rCBV of meningothelial, fibrous, angiomatous, and anaplastic meningiomas in tumoral parenchyma were 6.93{+-}3.75, 5.61{+-}4.03, 11.86{+-}1.93, and 5.89{+-}3.85, respectively, and in the peritumoral edema 0.87{+-}0.62, 1.38{+-}1.44, 0.87{+-}0.30, and 3.28{+-}1.39, respectively. The mean rCBV in tumoral parenchyma of angiomatous meningiomas and in the peritumoral edema of anaplastic meningiomas were statistically different (p<0.05) from the other types of meningiomas. Perfusion MR imaging can provide useful functional information on meningiomas and help in the preoperative diagnosis of some subtypes of meningiomas. (orig.)

  16. Psychosocial and Adaptive Deficits Associated with Learning Disability Subtypes

    Science.gov (United States)

    Backenson, Erica M.; Holland, Sara C.; Kubas, Hanna A.; Fitzer, Kim R.; Wilcox, Gabrielle; Carmichael, Jessica A.; Fraccaro, Rebecca L.; Smith, Amanda D.; Macoun, Sarah J.; Harrison, Gina L.; Hale, James B.

    2015-01-01

    Children with specific learning disabilities (SLD) have deficits in the basic psychological processes that interfere with learning and academic achievement, and for some SLD subtypes, these deficits can also lead to emotional and/or behavior problems. This study examined psychosocial functioning in 123 students, aged 6 to 11, who underwent…

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

    Science.gov (United States)

    Telzrow, Cathy F.; And Others

    1983-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Serrano Ducelina

    2009-04-01

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

  2. Prehospital Identification of Stroke Subtypes in Chinese Rural Areas

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  3. 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.

  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.

  5. Prognosis of metastatic breast cancer subtypes: the hormone receptor/HER2-positive subtype is associated with the most favorable outcome.

    Science.gov (United States)

    Lobbezoo, Dorien J A; van Kampen, Roel J W; Voogd, Adri C; Dercksen, M Wouter; van den Berkmortel, Franchette; Smilde, Tineke J; van de Wouw, Agnes J; Peters, Frank P J; van Riel, Johanna M G H; Peters, Natascha A J B; de Boer, Maaike; Borm, George F; Tjan-Heijnen, Vivianne C G

    2013-10-01

    Contrary to the situation in early breast cancer, little is known about the prognostic relevance of the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) in metastatic breast cancer. The objectives of this study were to present survival estimates and to determine the prognostic impact of breast cancer subtypes based on HR and HER2 status in a recent cohort of metastatic breast cancer patients, which is representative of current clinical practice. Patients diagnosed with metastatic breast cancer between 2007 and 2009 were included. Information regarding patient and tumor characteristics and treatment was collected. Patients were categorized in four subtypes based on the HR and HER2 status of the primary tumor: HR positive (+)/HER2 negative (-), HR+/HER2+, HR-/HER2+ and triple negative (TN). Survival was estimated using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic impact of breast cancer subtype, adjusted for possible confounders. Median follow-up was 21.8 months for the 815 metastatic breast cancer patients included; 66 % of patients had the HR+/HER2- subtype, 8 % the HR-/HER2+ subtype, 15 % the TN subtype and 11 % the HR+/HER2+ subtype. The longest survival was observed for the HR+/HER2+ subtype (median 34.4 months), compared to 24.8 months for the HR+/HER2- subtype, 19.8 months for the HR-/HER2+ subtype and 8.8 months for the TN subtype (P < 0.0001). In the multivariate analysis, subtype was an independent prognostic factor, as were initial site of metastases and metastatic-free interval. The HR+/HER2+ subtype was associated with the longest survival after diagnosis of distant metastases.

  6. Robust Identification of Alzheimer's Disease subtypes based on cortical atrophy patterns.

    Science.gov (United States)

    Park, Jong-Yun; Na, Han Kyu; Kim, Sungsoo; Kim, Hyunwook; Kim, Hee Jin; Seo, Sang Won; Na, Duk L; Han, Cheol E; Seong, Joon-Kyung

    2017-03-09

    Accumulating evidence suggests that Alzheimer's disease (AD) is heterogenous and can be classified into several subtypes. Here, we propose a robust subtyping method for AD based on cortical atrophy patterns and graph theory. We calculated similarities between subjects in their atrophy patterns throughout the whole brain, and clustered subjects with similar atrophy patterns using the Louvain method for modular organization extraction. We applied our method to AD patients recruited at Samsung Medical Center and externally validated our method by using the AD Neuroimaging Initiative (ADNI) dataset. Our method categorized very mild AD into three clinically distinct subtypes with high reproducibility (>90%); the parietal-predominant (P), medial temporal-predominant (MT), and diffuse (D) atrophy subtype. The P subtype showed the worst clinical presentation throughout the cognitive domains, while the MT and D subtypes exhibited relatively mild presentation. The MT subtype revealed more impaired language and executive function compared to the D subtype.

  7. Robust Identification of Alzheimer’s Disease subtypes based on cortical atrophy patterns

    Science.gov (United States)

    Park, Jong-Yun; Na, Han Kyu; Kim, Sungsoo; Kim, Hyunwook; Kim, Hee Jin; Seo, Sang Won; Na, Duk L.; Han, Cheol E.; Seong, Joon-Kyung; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Liu, Enchi; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; DeCarli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven G.; Shen, Li; Kelley, Faber; Kim, Sungeun; Nho, Kwangsik; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Doody, Rachelle S.; Villanueva Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; de Toledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; D’Agostino II, Daniel; Kielb, Stephanie; Galvin, James E.; Pogorelec, Dana M.; Cerbone, Brittany; Michel, Christina A.; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Wong, Terence Z.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc Adams Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz Arrastia, Ramon; King, Richard; Weiner, Myron; Martin Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H. S.; Lu, Po H.; Bartzokis, George; Graff Radford, Neill R.; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Farlow, Martin R.; Marie Hake, Ann; Matthews, Brandy R.; Herring, Scott; Hunt, Cynthia; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging Yuek; Feldman, Howard; Mudge, Benita; Assaly, Michele; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Marsel Mesulam, Marek; Lipowski, Kristine; Kuo Wu, Chuang; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Lynn Johnson, Patricia; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Hudson, Leon; Fletcher, Evan; Carmichael, Owen; Olichney, John; Kittur, Smita; Borrie, Michael; Lee, T. Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Santulli, Robert B.; Kitzmiller, Tamar J.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabether; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Smith, Karen Elizabeth; Relkin, Norman; Chaing, Gloria; Raudin, Lisa; Smith, Amanda; Fargher, Kristin; Raj, Balebail Ashok

    2017-01-01

    Accumulating evidence suggests that Alzheimer’s disease (AD) is heterogenous and can be classified into several subtypes. Here, we propose a robust subtyping method for AD based on cortical atrophy patterns and graph theory. We calculated similarities between subjects in their atrophy patterns throughout the whole brain, and clustered subjects with similar atrophy patterns using the Louvain method for modular organization extraction. We applied our method to AD patients recruited at Samsung Medical Center and externally validated our method by using the AD Neuroimaging Initiative (ADNI) dataset. Our method categorized very mild AD into three clinically distinct subtypes with high reproducibility (>90%); the parietal-predominant (P), medial temporal-predominant (MT), and diffuse (D) atrophy subtype. The P subtype showed the worst clinical presentation throughout the cognitive domains, while the MT and D subtypes exhibited relatively mild presentation. The MT subtype revealed more impaired language and executive function compared to the D subtype. PMID:28276464

  8. 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

    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...

  9. Cognitive subtypes in non-affected siblings of schizophrenia patients : characteristics and profile congruency with affected family members

    NARCIS (Netherlands)

    Quee, P. J.; Alizadeh, B. Z.; Aleman, A.; van den Heuvel, E. R.

    2014-01-01

    Background Although cognitive subtypes have been suggested in schizophrenia patients, similar analyses have not been carried out in their non-affected siblings. Subtype classification may provide more insight into genetically driven variation in cognitive function. We investigated cognitive subtypes

  10. Cognitive subtypes in non-affected siblings of schizophrenia patients : characteristics and profile congruency with affected family members

    NARCIS (Netherlands)

    Quee, P J; Alizadeh, B Z; Aleman, A; van den Heuvel, E R

    2014-01-01

    BACKGROUND: Although cognitive subtypes have been suggested in schizophrenia patients, similar analyses have not been carried out in their non-affected siblings. Subtype classification may provide more insight into genetically driven variation in cognitive function. We investigated cognitive subtype

  11. 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.

  12. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  14. Concurrent and prognostic utility of subtyping anorexia nervosa along dietary and negative affect dimensions.

    Science.gov (United States)

    Forbush, Kelsie T; Hagan, Kelsey E; Salk, Rachel H; Wildes, Jennifer E

    2017-03-01

    Bulimia nervosa can be reliably classified into subtypes based on dimensions of dietary restraint and negative affect. Community and clinical studies have shown that dietary-negative affect subtypes have greater test-retest reliability and concurrent and predictive validity compared to subtypes based on the Diagnostic and Statistical Manual of Mental Disorders (DSM). Although dietary-negative affect subtypes have shown utility for characterizing eating disorders that involve binge eating, this framework may have broader implications for understanding restrictive eating disorders.

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

    Science.gov (United States)

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

    2016-01-01

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

  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. Genome-wide analysis for identification of adaptive diversification between hepatitis C virus subtypes 1a and 1b.

    Science.gov (United States)

    Li, Yan; Wang, Ruirui; Du, Xiaogang; Zhang, Mingwang; Xie, Meng

    2016-07-01

    Hepatitis C virus (HCV) is a major cause of liver disease and has been estimated to infect approximately 2%-3% of the world's population. HCV genotype 1 is the subject of intense research and clinical investigations because of its worldwide prevalence and poor access to treatment for patients in developing countries and marginalized populations. The predominant subtypes 1a and 1b of HCV genotype 1 present considerable differences in epidemiological features. However, the genetic signature underlying such phenotypic functional divergence is still an open question. Here, we performed a genome-wide evolutionary study on HCV subtypes 1a and 1b. The results show that adaptive selection has driven the diversification between these subtypes. Furthermore, the major adaptive divergence-related changes have occurred on proteins E1, NS4B, NS5A, and NS5B. Structurally, a number of adaptively selected sites cluster in functional regions potentially relevant to (i) membrane attachment and (ii) the interactions with viral and host cell factors and the genome template. These results might provide helpful hints about the molecular determinants of epidemiological divergence between HCV 1a and 1b.

  18. The homeodomain-containing transcription factors Arx and Pax4 control enteroendocrine subtype specification in mice.

    Directory of Open Access Journals (Sweden)

    Anthony Beucher

    Full Text Available Intestinal hormones are key regulators of digestion and energy homeostasis secreted by rare enteroendocrine cells. These cells produce over ten different hormones including GLP-1 and GIP peptides known to promote insulin secretion. To date, the molecular mechanisms controlling the specification of the various enteroendocrine subtypes from multipotent Neurog3(+ endocrine progenitor cells, as well as their number, remain largely unknown. In contrast, in the embryonic pancreas, the opposite activities of Arx and Pax4 homeodomain transcription factors promote islet progenitor cells towards the different endocrine cell fates. In this study, we thus investigated the role of Arx and Pax4 in enteroendocrine subtype specification. The small intestine and colon of Arx- and Pax4-deficient mice were analyzed using histological, molecular, and lineage tracing approaches. We show that Arx is expressed in endocrine progenitors (Neurog3(+ and in early differentiating (ChromograninA(- GLP-1-, GIP-, CCK-, Sct- Gastrin- and Ghrelin-producing cells. We noted a dramatic reduction or a complete loss of all these enteroendocrine cell types in Arx mutants. Serotonin- and Somatostatin-secreting cells do not express Arx and, accordingly, the differentiation of Serotonin cells was not affected in Arx mutants. However, the number of Somatostatin-expressing D-cells is increased as Arx-deficient progenitor cells are redirected to the D-cell lineage. In Pax4-deficient mice, the differentiation of Serotonin and Somatostatin cells is impaired, as well as of GIP and Gastrin cells. In contrast, the number of GLP-1 producing L-cells is increased concomitantly with an upregulation of Arx. Thus, while Arx and Pax4 are necessary for the development of L- and D-cells respectively, they conversely restrict D- and L-cells fates suggesting antagonistic functions in D/L cell allocation. In conclusion, these finding demonstrate that, downstream of Neurog3, the specification of a subset of

  19. Peroxisome proliferator-activated receptor subtype- and cell-type-specific activation of genomic target genes upon adenoviral transgene delivery

    DEFF Research Database (Denmark)

    Nielsen, Ronni; Grøntved, Lars; Stunnenberg, Hendrik G

    2006-01-01

    Investigations of the molecular events involved in activation of genomic target genes by peroxisome proliferator-activated receptors (PPARs) have been hampered by the inability to establish a clean on/off state of the receptor in living cells. Here we show that the combination of adenoviral...... delivery and chromatin immunoprecipitation (ChIP) is ideal for dissecting these mechanisms. Adenoviral delivery of PPARs leads to a rapid and synchronous expression of the PPAR subtypes, establishment of transcriptional active complexes at genomic loci, and immediate activation of even silent target genes...

  20. 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.

  1. Differential drug resistance acquisition in HIV-1 of subtypes B and C.

    Directory of Open Access Journals (Sweden)

    Esmeralda A J M Soares

    Full Text Available BACKGROUND: Subtype C is the most prevalent HIV-1 subtype in the world, mainly in countries with the highest HIV prevalence. However, few studies have evaluated the impact of antiretroviral therapy on this subtype. In southern Brazil, the first developing country to offer free and universal treatment, subtypes B and C co-circulate with equal prevalence, allowing for an extensive evaluation of this issue. METHODS AND FINDINGS: Viral RNA of 160 HIV-1+ patients was extracted, and the protease and reverse transcriptase genes were sequenced, subtyped and analyzed for ARV mutations. Sequences were grouped by subtype, and matched to type (PI, NRTI and NNRTI and time of ARV exposure. Statistical analyses were performed to compare differences in the frequency of ARV-associated mutations. There were no significant differences in time of treatment between subtypes B and C groups, although they showed distinct proportions of resistant strains at different intervals for two of three ARV classes. For PI, 26% of subtype B strains were resistant, compared to only 8% in subtype C (p = 0.0288, Fisher's exact test. For NRTI, 54% of subtype B strains were resistant versus 23% of subtype C (p = 0.0012. Differences were significant from 4 years of exposure, and remained so until the last time point analyzed. The differences observed between both subtypes were independent of time under rebound viremia in cases of virologic failure and of the number of HAART regimens used by treated patients. CONCLUSIONS: Our results pointed out to a lower rate of accumulation of mutations conferring resistance to ARV in subtype C than in subtype B. These findings are of crucial importance for current initiatives of ARV therapy roll-out in developing countries, where subtype is C prevalent.

  2. Synchronized diurnal and circadian expressions of four subtypes of melatonin receptor genes in the diencephalon of a puffer fish with lunar-related spawning cycles.

    Science.gov (United States)

    Ikegami, Taro; Motohashi, Eiji; Doi, Hiroyuki; Hattori, Atsuhiko; Ando, Hironori

    2009-10-02

    Multiple subtypes of melatonin receptors are expressed in neural and peripheral tissues to mediate melatonin actions on the regulation of circadian rhythms in vertebrates. To elucidate molecular basis of "circa" rhythms in the grass puffer Takifugu niphobles, which spawns synchronously with semilunar cycles, tissue distribution of four melatonin receptor subtype mRNAs (Mel(1a) 1.4, Mel(1a) 1.7, Mel(1b), and Mel(1c)) were examined, and diurnal and circadian changes in their absolute amounts were examined in the retina, diencephalon, and optic tectum. Mel(1a) 1.4, Mel(1a) 1.7, and Mel(1b) mRNAs were widely distributed in various brain regions, retina, pituitary, and peripheral tissues, whereas Mel(1c) mRNA was mainly detected in the nervous tissues and pituitary. All subtype genes showed diurnal expressions with one or two peaks during nighttime. When the fish were reared under constant darkness, the retinal expressions of Mel(1a) 1.7, Mel(1b), and Mel(1c) genes were markedly diminished but still showed circadian variations. In contrast, increased and synchronized expressions of the four subtype genes were noticeable with one peak at circadian time 18 in the diencephalon. The circadian expression profiles in the optic tectum were different among the subtypes. The present results suggest that melatonin receptor gene expression is regulated by circadian clock and light, but the effects of light are different among the tissues. The synchronized expressions of the four subtype genes in the diencephalon may be related to the exertion of reproductive rhythmicity in this puffer species.

  3. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

    Science.gov (United States)

    Peck, Michael W.; Smith, Theresa J.; Anniballi, Fabrizio; Austin, John W.; Bano, Luca; Bradshaw, Marite; Cuervo, Paula; Cheng, Luisa W.; Derman, Yagmur; Dorner, Brigitte G.; Fisher, Audrey; Hill, Karen K.; Kalb, Suzanne R.; Korkeala, Hannu; Lindström, Miia; Lista, Florigio; Lúquez, Carolina; Mazuet, Christelle; Pirazzini, Marco; Popoff, Michel R.; Rossetto, Ornella; Rummel, Andreas; Sesardic, Dorothea; Singh, Bal Ram; Stringer, Sandra C.

    2017-01-01

    Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future. PMID:28106761

  4. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

    Directory of Open Access Journals (Sweden)

    Michael W. Peck

    2017-01-01

    Full Text Available Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.

  5. 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

  6. Complete genome amplification of Equine influenza virus subtype 2

    OpenAIRE

    Sguazza, G. H.; Fuentealba, N. A.; Tizzano, Marco Antonio; Galosi, Cecilia Mónica; Pecoraro, M. R.

    2009-01-01

    This work reports a method for rapid amplification of the complete genome of equine influenza virus subtype 2 (H3N8). A ThermoScriptTM reverse transcriptase instead of the avian myeloblastosis virus reverse transcriptase or Moloney murine leukemia virus reverse transcriptase was used. This enzyme has demonstrated higher thermal stability and is described as suitable to make long cDNA with a complex secondary structure. The product obtained by this method can be cloned, used in later...

  7. Brain metastases free survival differs between breast cancer subtypes

    Science.gov (United States)

    Berghoff, A; Bago-Horvath, Z; De Vries, C; Dubsky, P; Pluschnig, U; Rudas, M; Rottenfusser, A; Knauer, M; Eiter, H; Fitzal, F; Dieckmann, K; Mader, R M; Gnant, M; Zielinski, C C; Steger, G G; Preusser, M; Bartsch, R

    2012-01-01

    Background: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. Methods: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan–Meier method and compared with the log-rank test. Results: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34–16.66) compared with 18 months (95% CI: 14.46–21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71–44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). Conclusion: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes. PMID:22233926

  8. Maltreatment and psychopathy subtypes in high-risk adolescent females

    OpenAIRE

    Coupland, Ruth Louise

    2011-01-01

    Psychopathy is often viewed as a unitary construct, however, research with adults and adolescent males has revealed two heterogeneous subtypes. Primary psychopathy is presumed to have biological underpinnings and is associated with low levels of anxiety and psychological distress. In contrast, secondary psychopathy is believed to result from exposure to adversity, including childhood maltreatment, and is associated with emotional reactivity, impulsivity, and comorbid psychological problems. T...

  9. Clinical investigation of set-shifting subtypes in anorexia nervosa.

    Science.gov (United States)

    Abbate-Daga, Giovanni; Buzzichelli, Sara; Marzola, Enrica; Amianto, Federico; Fassino, Secondo

    2014-11-30

    While evidence continues to accumulate on the relevance of cognitive inflexibility in anorexia nervosa (AN), its clinical correlates remain unclear. We aimed at examining the relationship between set-shifting and clinical variables (i.e., eating psychopathology, depression, and personality) in AN. Ninety-four individuals affected by AN and 59 healthy controls (HC) were recruited. All participants were assessed using: Eating Disorders Inventory-2 (EDI-2), Temperament and Character Inventory (TCI), Beck Depression Inventory (BDI), and Wisconsin Card Sorting Test (WCST). The AN group scored worse than HCs on set-shifting. According to their neuropsychological performances, AN patients were split into two groups corresponding to poor (N=30) and intact (N=64) set-shifting subtypes. Interoceptive awareness, impulse regulation, and maturity fears on the EDI-2 and depression on the BDI differed across all groups (HC, intact, and poor set-shifting subtype). Self-directedness on the TCI differed significantly among all groups. Cooperativeness and reward dependence differed instead only between HC and AN poor set-shifting subtype. After controlling for depression, only interoceptive awareness remained significant with reward dependence showing a trend towards statistical significance. These findings suggest that multiple clinical variables may be correlated with set-shifting performances in AN. The factors contributing to impaired cognitive inflexibility could be more complex than heretofore generally considered.

  10. 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.

  11. Strategies for subtyping influenza viruses circulating in the Danish pig population

    DEFF Research Database (Denmark)

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona;

    2010-01-01

    Influenza viruses are endemic in the Danish pig population and the dominant circulating subtypes are H1N1, a Danish H1N2 reassortant, and H3N2. Here we present our current and future strategies for influenza virus subtyping. For diagnostic and surveillance of influenza subtypes circulating...... in the Danish pig population functional and rapid subtyping assays are required. The conventional RT-PCR influenza subtyping assays developed by Chiapponi et al. (2003) have been implemented and used for typing of influenza viruses found positive in a pan influenza A real time RT-PCR assay. The H1 and N1 assays...... assays based on RT-PCR and subsequent sequencing were implemented for the four subtypes H1, H3, N1, and N2. The assays were based on primer sets published by the WHO, but slightly modified for improved detection of Danish subtype variants. Sequencing of circulating influenza viruses is beneficial since...

  12. The prevalence and prognostic significance of KRAS mutation subtypes in lung adenocarcinomas from Chinese populations

    Directory of Open Access Journals (Sweden)

    Zheng DF

    2016-02-01

    Full Text Available Difan Zheng,1,2,* Rui Wang,1,2,* Yang Zhang,1,2 Yunjian Pan,1,2 Xinghua Cheng,3 Chao Cheng,1,2 Shanbo Zheng,1,2 Hang Li,1,2 Ranxia Gong,1,2 Yuan Li,2,4 Xuxia Shen,2,4 Yihua Sun,1,2 Haiquan Chen1–3,51Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Shanghai Chest Hospital, Shanghai Jiao Tong University, 4Department of Pathology, Fudan University Shanghai Cancer Center, 5Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workBackground: We performed this retrospective study to identify the prevalence of KRAS mutation in Chinese populations and make a comprehensive investigation of the clinicopathological features of KRAS mutation in these patients.Patients and methods: Patients from 2007 to 2013 diagnosed with primary lung adenocarcinoma who received a radical resection were examined for KRAS, EGFR, HER2, BRAF mutations, and ALK, RET, and ROS1 fusions. Clinicopathological features, including sex, age, tumor–lymph node–metastasis stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed.Result: KRAS mutation was detected in 113 of 1,368 patients. Nine different subtypes of KRAS mutation were identified in codon 12, codon 13, and codon 61. KRAS mutation was more frequently found in male patients and former/current smoker patients. Tumors with KRAS mutation had poorer differentiation. Invasive mucinous adenocarcinoma predominant and solid predominant subtypes were more frequent in KRAS mutant patients. No statistical significance was found in relapse-free survival or overall survival between patients with KRAS mutation and patients with other mutations.Conclusion: In Chinese populations, we identified KRAS mutation in 8.3% (113/1,368 of the patients with lung adenocarcinoma. KRAS mutation defines a molecular subset of

  13. Cloning, functional expression, and characterization of the human prostaglandin E2 receptor EP2 subtype.

    Science.gov (United States)

    Bastien, L; Sawyer, N; Grygorczyk, R; Metters, K M; Adam, M

    1994-04-22

    A cDNA clone encoding the human prostaglandin (PG) E2 receptor EP2 subtype has been isolated from a human lung cDNA library. The 1.9-kilobase pair cDNA, hEP2, encodes for a 488-amino acid protein with a predicted molecular mass of 53,115 and has the seven putative transmembrane domains characteristic of G protein-coupled receptors. The specific binding of [3H]PGE2 to COS cell membranes transfected with the hEP2 cDNA was of high affinity with an equilibrium dissociation constant (Kd) of 1 nM and the rank order of potency for prostaglandins in competition for [3H]PGE2 specific binding was PGE1 = PGE2 > iloprost > PGF2 alpha > PGD2. In competition studies using more selective prostanoid-receptor agonist and antagonists, the [3H]PGE2 specific binding was competed by MB28767, an EP3 agonist, but not by the EP1-preferring antagonists AH6809 and SC19220, or by the EP2 agonist butaprost. Electrophysiological studies of Xenopus oocytes co-injected with hEP2 and cystic fibrosis transmembrane conductance regulator (cAMP-activated Cl- channel) cDNAs detected PGE2-specific inward Cl- currents, demonstrating that the hEP2 cDNA encoded a functional receptor which produced an increase in cAMP levels. Thus, we have cloned the human EP2 receptor subtype which is functionally coupled to increase in cAMP. Northern blot analysis showed that hEP2 is expressed as a 3.8-kilobase mRNA in a number of human tissues with the highest expression levels present in the small intestine.

  14. 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.

  15. Reviewing the history of HIV-1: spread of subtype B in the Americas.

    Directory of Open Access Journals (Sweden)

    Dennis Maletich Junqueira

    Full Text Available The dispersal of HIV-1 subtype B (HIV-1B is a reflection of the movement of human populations in response to social, political, and geographical issues. The initial dissemination of HIV-1B outside Africa seems to have included the passive involvement of human populations from the Caribbean in spreading the virus to the United States. However, the exact pathways taken during the establishment of the pandemic in the Americas remain unclear. Here, we propose a geographical scenario for the dissemination of HIV-1B in the Americas, based on phylogenetic and genetic statistical analyses of 313 available sequences of the pol gene from 27 countries. Maximum likelihood and bayesian inference methods were used to explore the phylogenetic relationships between HIV-1B sequences, and molecular variance estimates were analyzed to infer the genetic structure of the viral population. We found that the initial dissemination and subsequent spread of subtype B in the Americas occurred via a single introduction event in the Caribbean around 1964 (1950-1967. Phylogenetic trees present evidence of several primary outbreaks in countries in South America, directly seeded by the Caribbean epidemic. Cuba is an exception insofar as its epidemic seems to have been introduced from South America. One clade comprising isolates from different countries emerged in the most-derived branches, reflecting the intense circulation of the virus throughout the American continents. Statistical analysis supports the genetic compartmentalization of the virus among the Americas, with a close relationship between the South American and Caribbean epidemics. These findings reflect the complex establishment of the HIV-1B pandemic and contribute to our understanding between the migration process of human populations and virus diffusion.

  16. Reviewing the history of HIV-1: spread of subtype B in the Americas.

    Science.gov (United States)

    Junqueira, Dennis Maletich; de Medeiros, Rúbia Marília; Matte, Maria Cristina Cotta; Araújo, Leonardo Augusto Luvison; Chies, Jose Artur Bogo; Ashton-Prolla, Patricia; Almeida, Sabrina Esteves de Matos

    2011-01-01

    The dispersal of HIV-1 subtype B (HIV-1B) is a reflection of the movement of human populations in response to social, political, and geographical issues. The initial dissemination of HIV-1B outside Africa seems to have included the passive involvement of human populations from the Caribbean in spreading the virus to the United States. However, the exact pathways taken during the establishment of the pandemic in the Americas remain unclear. Here, we propose a geographical scenario for the dissemination of HIV-1B in the Americas, based on phylogenetic and genetic statistical analyses of 313 available sequences of the pol gene from 27 countries. Maximum likelihood and bayesian inference methods were used to explore the phylogenetic relationships between HIV-1B sequences, and molecular variance estimates were analyzed to infer the genetic structure of the viral population. We found that the initial dissemination and subsequent spread of subtype B in the Americas occurred via a single introduction event in the Caribbean around 1964 (1950-1967). Phylogenetic trees present evidence of several primary outbreaks in countries in South America, directly seeded by the Caribbean epidemic. Cuba is an exception insofar as its epidemic seems to have been introduced from South America. One clade comprising isolates from different countries emerged in the most-derived branches, reflecting the intense circulation of the virus throughout the American continents. Statistical analysis supports the genetic compartmentalization of the virus among the Americas, with a close relationship between the South American and Caribbean epidemics. These findings reflect the complex establishment of the HIV-1B pandemic and contribute to our understanding between the migration process of human populations and virus diffusion.

  17. Duration of cross-protection between subtypes A and B avian pneumovirus in turkeys.

    Science.gov (United States)

    Van de Zande, S; Nauwynck, H; Naylor, C; Pensaert, M

    2000-07-29

    The degree and duration of clinical and virological cross-protection between avian pneumovirus subtypes A and B were examined in two-week-old pneumovirus antibody-free turkeys. The turkeys were inoculated with either a virulent subtype A (Belgian isolate A/T6/96), a virulent subtype B (Belgian isolate B/T9/96), an attenuated subtype A or an attenuated subtype B, and challenged homologously and heterologously with virulent avian pneumovirus two, five and 11 weeks after inoculation. Birds inoculated with virulent A or B virus showed typical respiratory signs from three to seven days after inoculation. After challenge, no clinical signs were observed in any of the groups, and no virus was isolated from the turkeys that had been initially inoculated with a virulent strain. Virulent virus was recovered from the birds that had been initially inoculated with attenuated subtypes and challenged five and/or 11 weeks later with a heterologous virulent strain. Birds challenged after five weeks showed a serological booster reaction only when they had been inoculated initially with a virulent or attenuated subtype B and challenged with subtype A. Seroconversion was observed in all the groups challenged after 11 weeks except when they had been inoculated initially with attenuated subtype B and challenged with subtype B.

  18. 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.

  19. 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; Van Wart, Audra; Kuhlman, Sandra J; Wilson, Nathan R; Huang, Z Josh; Sur, Mriganka

    2010-09-09

    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 band-pass 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.

  20. Salmonella serotyping and molecular subtyping analysis on diarrhea cases in Hongkou District of Shanghai, in 2010-2012 ZHANG Jing1,SHEN Jing1,TANG Yi-ling1,CHEN Zhen1,YAO Hong1,WANG%上海市虹口区2010-2012年腹泻病例沙门菌监测及分子型特征

    Institute of Scientific and Technical Information of China (English)

    张静; 沈静; 唐漪灵; 陈真; 姚红; 王斌; 汤显; 陈洪友; 许学斌

    2015-01-01

    Objective ] To study the molecular characteristics and antibiotic resistance of Salmonella diarrhea cases in sentinel hospitals through active surveillance system conducted by public health laboratory. [ Methods] Two sentinel hospitals were chosen for collection of stool specimens from food-borne infectious diarrhea cases and for Salmonella separation and detection immediately following serotyping and antimicrobial susceptible test ( AST ) on those isolates .Moreover , pulsed field gel electrophoresis ( PFGE) was used for the genetic homology analysis . [ Results] A total of 2 579 diarrhea specimens were collected and analyzed from 2010 to 2012, with 185 Salmonella isolates, covering 23 different serotypes (annual positive rates were 9.1%, 6.8%, 5.1%, with an average 7.2%).Salmonella enterica serovar Enteritidis(S.Enteritidis) and Typhimurium(S.Typhimurium) were the most common serotypes, of which 68.9% cases were seen in those aged 21 to 60 and 21.4% cases in those over 60 years old. 27.7%-96.9%S.Enteritidis and 2.6%-63.2% S.Typhimurium(P all <0.05) proved resistant to Nalidixic acid, Sultisoxazole, Streptomycin, Sulfamethoxydiazine, Gentamicinand Tetracycline. PFGE analysis on 22 S.Enteritidis strains showed 11 different clusters , while 20 S.Typhimurium strians showed 6. [Conclusion] S.Enteritidis and S.Typhimurium are the most common Salmonella serotypes, and molecular typing indicates the existence of clustering and sporadic outbreaks caused by dominance clones . We should be alert to early warnings on potential outbreaks of multiple-drug-resistant ( MDR ) S.Enteritidis.Active surveillance system based on public health laboratory should play an important role in the control of food-borne infectious diseases .%[目的]研究基于公共卫生实验室主动监测哨点医院沙门菌腹泻及优势菌型的耐药性和分子型特征。[方法]选择辖区内2家医院作为主动监测哨点,甄别食源性感染性腹泻的病

  1. 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.

  2. Leptomeningeal disease and breast cancer: the importance of tumor subtype.

    Science.gov (United States)

    Abouharb, Sausan; Ensor, Joe; Loghin, Monica Elena; Katz, Ruth; Moulder, Stacy L; Esteva, Francisco J; Smith, Benjamin; Valero, Vicente; Hortobagyi, Gabriel N; Melhem-Bertrandt, Amal

    2014-08-01

    Breast cancer (BC) is one of the most common tumors to involve the leptomeninges. We aimed to characterize clinical features and outcomes of patients with LMD based on BC subtypes. We retrospectively reviewed records of 233 patients diagnosed with LMD from BC between 1997 and 2012. Survival was estimated by the Kaplan-Meier method and significant differences in survival were determined by Cox proportional hazards or log-rank tests. Of 190 patients with BC subtype available, 67 (35 %) had hormone receptor positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative BC, 56 (29 %) had HER2+BC, and 67 (35 %) had triple-negative BC (TNBC). Median age at LMD diagnosis was 50 years. Median overall survival (OS) from LMD diagnosis was 4.4 months for HER2+BC (95 % CI 2.8, 6.9), 3.7 months (95 % CI 2.4, 6.0) for HR+/HER2-BC, and 2.2 months (95 % CI 1.5, 3.0) for TNBC (p = 0.0002). Older age was associated with worse outcome (p LMD were more likely to receive systemic therapy (ST) (p = 0.001). Use of intrathecal therapy (IT) (52 %) was similar (p = 0.35). Both IT (p LMD carries a dismal prognosis. Modest survival differences by tumor subtype were seen. Patients with HER2+BC had the best outcome. There is an urgent need to develop effective treatment strategies.

  3. 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.

  4. CRISPR adaptation in Escherichia coli subtypeI-E system.

    Science.gov (United States)

    Kiro, Ruth; Goren, Moran G; Yosef, Ido; Qimron, Udi

    2013-12-01

    The CRISPRs (clustered regularly interspaced short palindromic repeats) and their associated Cas (CRISPR-associated) proteins are a prokaryotic adaptive defence system against foreign nucleic acids. The CRISPR array comprises short repeats flanking short segments, called 'spacers', which are derived from foreign nucleic acids. The process of spacer insertion into the CRISPR array is termed 'adaptation'. Adaptation allows the system to rapidly evolve against emerging threats. In the present article, we review the most recent studies on the adaptation process, and focus primarily on the subtype I-E CRISPR-Cas system of Escherichia coli.

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

    Science.gov (United States)

    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.

    2015-01-01

    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

  6. Applicable advances in the molecular pathology of glioblastoma.

    Science.gov (United States)

    Ranjit, Melissa; Motomura, Kazuya; Ohka, Fumiharu; Wakabayashi, Toshihiko; Natsume, Atsushi

    2015-07-01

    Comprising more than 80% of malignant brain tumors, glioma has proven to be a daunting cause of mortality in a vast majority of the human population. Progressive and extensive research on malignant glioma has substantially enhanced our understanding of glioma cell biology and molecular pathology. Subtypes of glioma such as astrocytoma and oligodendroglioma are currently grouped together into one pathological class, where they show many differences in histology and molecular etiology. This indicates that it may be beneficial to consider a new and radical subclassification. Thus, we summarize recent developments in glioblastoma multiforme (GBM) subtypes, immunohistochemical analyses useful for diagnoses and the biological evaluation and therapeutic implications of gliomas in this review.

  7. [Visual detection of H1 subtype and identification of N1, N2 subtype of avian influenza virus by reverse transcription loop-mediated isothermal amplification assay].

    Science.gov (United States)

    Peng, Yi; Xie, Zhi-Xun; Guo, Jie; Zhou, Chen-Yu; Liu, Jia-Bo; Pang, Yao-Shan; Deng, Xian-Wen; Xie, Zhi-Qin; Xie, Li-Ji; Fan, Qing; Luo, Si-Si

    2013-03-01

    In order to visually detect H1, N1 and N2 subtype of avian influenza virus (AIV), three reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays were developed. According to the sequences of AIV gene available in GenBank, three degenerate primer sets specific to HA gene of H1 subtype AIV, NA gene of N1 and N2 subtype AIV were designed, and the reaction conditions were optimized. The results showed that all the assays had no cross-reaction with other subtype AIV and other avian respiratory pathogens, and the detection limit was higher than that of conventional RT-PCR. These assays were performed in water bath within 50 minutes. Without opening tube, the amplification result could be directly determined by inspecting the color change of reaction system as long as these assays were fin-ished. Fourteen specimens of H1N1 subtype and eight specimens of H1N2 subtype of AIV were identified from the 120 clinical samples by RT-LAMP assays developed, which was consistent with that of virus isolation. These results suggested that the three newly developed RT-LAMEP assays were simple, specific and sensitive and had potential for visual detection of H1, N1 and N2 subtype of AIV in field.

  8. Genetic and Epigenetic Determinants of Lung Cancer Subtype: Adenocarcinoma to Small Cell Conversion

    Science.gov (United States)

    2015-08-01

    AWARD NUMBER: W81XWH-14-1-0223 TITLE: Genetic and Epigenetic Determinants of Lung Cancer Subtype: Adenocarcinoma to Small Cell Conversion...COVERED 1Aug2014 - 31Jul2015 4. TITLE AND SUBTITLE Genetic and Epigenetic Determinants of Lung Cancer Subtype: 5a. CONTRACT NUMBER W81XWH-14-1-0223...same patient will provide substantial insight into the determinants of subtype specificity. Preliminary data on one such case demonstrates a

  9. Evidence of multiple introductions of HIV-1 subtype C in Angola.

    Science.gov (United States)

    Afonso, Joana Morais; Morgado, Mariza G; Bello, Gonzalo

    2012-10-01

    HIV-1 subtype C is the most prevalent group M clade in southern Africa and some eastern African countries. Subtype C is also the most frequent subtype in Angola (southwestern Africa), with an estimated prevalence of 10-20%. In order to better understand the origin of the HIV-1 subtype C strains circulating in Angola, 31 subtype C pol sequences of Angolan origin were compared with 1950 subtype C pol sequences sampled in other African countries. Phylogenetic analyses reveal that the Angolan subtype C sequences were distributed in 16 different lineages that were widely dispersed among other African strains. Ten subtype C Angolan lineages were composed by only one sequence, while the remaining six clades contain between two and seven sequences. Bayesian phylogeographic analysis indicates that most Angolan clades probably originated in different southern African countries with the exception of one lineage that most likely originated in Burundi. Evolutionary analysis suggests that those Angolan subtype C clades composed by ≥ 2 sequences were introduced into the country between the late 1970s and the mid 2000s. The median estimated time frame for the origin of those Angolan lineages coincides with periods of positive migration influx in Angola that were preceded by phases of negative migratory outflow. These results demonstrate that the Angolan subtype C epidemic resulted from multiple introductions of subtype C viruses mainly imported from southern African countries over the last 30years, some of which have been locally disseminated establishing several autochthonous transmission networks. This study also suggests that population mobility between Angola and southern African countries during civil war (1974-2002) may have played a key role in the emergence of the Angolan subtype C epidemic.

  10. Rapid Subtyping of Dengue Virus Serotypes 1 and 4 by Restriction Site-Specific PCR

    OpenAIRE

    Marize P Miagostovich; dos Santos, Flavia B.; Gutiérrez, C. Milena; Riley, Lee W.; Harris, Eva

    2000-01-01

    We previously reported a simple subtyping method, restriction site-specific PCR (RSS-PCR), for dengue virus serotypes 2 and 3; here we describe its application for subtyping dengue virus serotypes 1 and 4. Three major RSS-PCR types were observed for dengue virus serotype 1 and two types were observed for dengue virus serotype 4, in agreement with previous strain classifications based on sequence analysis. Because of its simplicity, this method is amenable to rapid subtyping and application to...

  11. Molecular epidemiology of human immunodeficiency virus-infected individuals in Medellin, Colombia.

    Science.gov (United States)

    Sanchez, Gloria I; Bautista, Christian T; Eyzaguirre, Lindsay; Carrion, Gladys; Arias, Sonia; Sateren, Warren B; Negrete, Monica; Montano, Silvia M; Sanchez, Jose L; Carr, Jean K

    2006-04-01

    To study the molecular epidemiology of human immunodeficiency virus type 1 (HIV-1) strains in Medellín, Colombia, 115 HIV-1-positive individuals who were recruited from an HIV outpatient hospital (Universitario San Vicente de Paul) during the period from July 2001 to January 2002 were genotyped. All samples were analyzed by envelope heteroduplex mobility assay and found to be subtype B. Twenty-four samples were randomly selected for sequencing of the protease and the reverse transcriptase regions; all isolates were found to be subtype B. Phylogenetic analysis of seven nearly full-length genomes showed that all samples were subtype B. This study shows that the HIV epidemic in Colombia continues to be dominated by the subtype B virus. The predominance of subtype B genotypes of HIV-1 strains in Medellín resembles what is seen in the nearby countries of Peru, Ecuador, and Venezuela.

  12. Phytoestrogens from Psoralea corylifolia reveal estrogen receptor-subtype selectivity.

    Science.gov (United States)

    Xin, D; Wang, H; Yang, J; Su, Y-F; Fan, G-W; Wang, Y-F; Zhu, Y; Gao, X-M

    2010-02-01

    The seed of Psoralea corylifolia L. (PCL), a well-known traditional Chinese medicine, has been applied as a tonic or an aphrodisiac agent and commonly used as a remedy for bone fracture, osteomalacia and osteoporosis in China. In our study, the estrogen receptor subtype-selective activities of the extracts and compounds derived from PCL were analyzed using the HeLa cell assay. The different fractions including petroleum ether, CH(2)Cl(2) and EtOAc fractions of the EtOH extract of PCL showed significant activity in activating either ERalpha or ERbeta whereas the n-BuOH fraction showed no estrogenic activity. Further chromatographic purification of the active fractions yielded seven compounds including the two coumarins isopsoralen and psoralen, the four flavonoids isobavachalcone, bavachin, corylifol A and neobavaisoflavone, and the meroterpene phenol, bakuchiol. In reporter gene assay, the two coumarins (10(-8)-10(-5)M) acted as ERalpha-selective agonists while the other compounds (10(-9)-10(-6)M) activated both ERalpha and ERbeta. The estrogenic activities of all compounds could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ER. Only psoralen and isopsoralen as ERalpha agonists promoted MCF-7 cell proliferation significantly. Although all the compounds have estrogenic activity, they may exert different biological effects. In conclusion, both ER subtype-selective and nonselective activities in compounds derived from PCL suggested that PCL could be a new source for selective estrogen-receptor modulators.

  13. 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.

  14. ONE-CLASS DETECTION OF CELL STATES IN TUMOR SUBTYPES

    Science.gov (United States)

    SOKOLOV, ARTEM; PAULL, EVAN O.; STUART, JOSHUA M.

    2016-01-01

    The cellular composition of a tumor greatly influences the growth, spread, immune activity, drug response, and other aspects of the disease. Tumor cells are usually comprised of a heterogeneous mixture of subclones, each of which could contain their own distinct character. The presence of minor subclones poses a serious health risk for patients as any one of them could harbor a fitness advantage with respect to the current treatment regimen, fueling resistance. It is therefore vital to accurately assess the make-up of cell states within a tumor biopsy. Transcriptome-wide assays from RNA sequencing provide key data from which cell state signatures can be detected. However, the challenge is to find them within samples containing mixtures of cell types of unknown proportions. We propose a novel one-class method based on logistic regression and show that its performance is competitive to two established SVM-based methods for this detection task. We demonstrate that one-class models are able to identify specific cell types in heterogeneous cell populations better than their binary predictor counterparts. We derive one-class predictors for the major breast and bladder subtypes and reaffirm the connection between these two tissues. In addition, we use a one-class predictor to quantitatively associate an embryonic stem cell signature with an aggressive breast cancer subtype that reveals shared stemness pathways potentially important for treatment. PMID:26776204

  15. 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.

  16. Different subtypes of impulsivity differentiate uncontrolled eating and dietary restraint.

    Science.gov (United States)

    Leitch, Margaret A; Morgan, Michael J; Yeomans, Martin R

    2013-10-01

    The current study explored the relationship between three subtypes of impulsivity (Reflection Impulsivity, Impulsive Choice, and Impulsive Action) and measures of uncontrolled eating (TFEQ-D) and restraint (TFEQ-R). Eighty women classified as scoring higher or lower on TFEQ-D and TFEQ-R completed the Matching Familiar Figures Test (MFFT20), Delay Discounting Task (DDT), a Go No Go task, Balloon Analogue Risk Task (BART), and the Barrett Impulsivity Scale-11 (BIS-11). To test whether these relationships were affected by enforced controls overeating, half of the participants fasted the night before and ate breakfast in the laboratory before testing and half had no such control. Women scoring higher on the TFEQ-D were significantly more impulsive on the MFFT20 and BIS-11 overall but not on DDT, Go No Go or BART. Women scoring higher on TFEQ-R were significantly less impulsive on the Go No Go task but did not differ on other measures. The eating manipulation modulated responses on the BART and BIS-11 non-planning scale depending on TFEQ-D classification. These results confirm recent data that high scores on TFEQ-D are related to impulsivity, but imply this relates more to Reflection Impulsivity rather than Impulsive Choice or Action. In contrast restrained eating was associated with better inhibitory control. Taken together, these results suggest that subtypes of impulsivity further differentiate uncontrolled eating and restraint, and suggest that a poor ability to reflect on decisions may underlie some aspects of overeating.

  17. Neglect subtypes, race, and poverty: individual, family, and service characteristics.

    Science.gov (United States)

    Jonson-Reid, Melissa; Drake, Brett; Zhou, Pan

    2013-02-01

    Recent child maltreatment research has highlighted the very different context of poverty for Black and White children. Neglect is the most common form of maltreatment and strongly associated with poverty. Neglect is, however, not a unitary construct. We lack an understanding of whether reporting of and responding to different types of neglect may vary by poverty, race, or the intersection of the two. Administrative census, child welfare, welfare, health, and education data were used to examine how family and community poverty factors associate with various subtypes of neglect and subsequent case dispositions for Black and White children. Black children reported to child welfare reside in far poorer communities than Whites, even after taking into account family income (Aid to Families with Dependent Children [AFDC]/Temporary Aid to Needy Families [TANF]). Black children were more commonly reported and substantiated for severe and basic needs neglect. Community poverty indicators had a different relationship to report disposition for Black as compared to White children after controlling for neglect subtypes, child and family characteristics. Implications for practice and policy are discussed.

  18. 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: o C1 = children at risk (having considerable difficulty with jumping and minor difficulty with manual dexterity and simultaneous coding); o C2 = children on the mean (all cognitive-motor scores close to the mean); o C3 = free from cognitive-motor problems (all scores above average); o C4 = manual dexterity, planning and simultaneous coding difficulties; o C5 = manual dexterity, dynamic balance, and planning difficulties; o C6 = generalized cognitive-motor dysfunction (all scores considerably below average). 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.

  19. Sensory subtypes and anxiety in older children and adolescents with autism spectrum disorder.

    Science.gov (United States)

    Uljarević, Mirko; Lane, Alison; Kelly, Amanda; Leekam, Susan

    2016-10-01

    This study aimed to identify sensory subtypes in older children and adolescents with Autism Spectrum Disorders (ASD) and examine the relationship of sensory subtypes with anxiety levels in this group. Mothers of 57 children and adolescents with ASD aged 11-17 years (Mean age = 14 years. 2.4 months, SD = 1.81) completed the short sensory profile and Spence anxiety scales. Model-based cluster analysis was applied to sensory profile scores to identify sensory subtypes. Three sensory subtypes, sensory adaptive (N = 19), sensory moderate (N = 29) and sensory severe (N = 9) were identified. The results indicated that the differences between the subtypes were well characterised by the severity of sensory symptoms and were not attributable to sensory modality or varying types of sensory-related behaviors. Children and adolescents from the adaptive subtype had significantly lower anxiety scores when compared with other two subtypes. There were no differences between subtypes based on chronological age, expressive language, or severity of autism diagnostic features as measured by the social communication questionnaire (SCQ total score). This is the first study to identify the existence of sensory subtypes among older children and adolescents with ASD and explore their association with anxiety levels. Autism Res 2016, 9: 1073-1078. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  20. Multiplex PCR followed by restriction length polymorphism analysis for the subtyping of bovine herpesvirus 5 isolates

    OpenAIRE

    Maidana; Morano, C.D.; Cianfrinid; de Campos, F.; Roehe, P.M.; Siedler, B.; G. De Stefano; Mauroy, Axel; Thiry, Etienne; Romera, S. A.

    2013-01-01

    Abstract Background: Several types and subtypes of bovine herpesviruses 1 and 5 (BoHV-1 and BoHV-5) have been associated to different clinical conditions of cattle, making type/subtype differentiation essential to understand the pathogenesis and epidemiology of BoHV infections. BoHV-5 subtyping is currently carried out by BstEII restriction enzyme analysis (REA) of the complete virus genome. This method allowed the description of three subtypes, one of which is the most widespread while ...

  1. Immunological responses to envelope glycoprotein 120 from subtypes of human immunodeficiency virus type 1.

    Science.gov (United States)

    Gilljam, G; Svensson, A; Ekström, A; Wahren, B

    1999-07-01

    The outer envelope glycoprotein (gp120) from subtypes A-E of HIV-1 was purified using a specific high mannose-binding lectin, Galanthus nivalis agglutinin. All isolates were grown in peripheral blood lymphocyte cells in order to avoid selection in cell lines. A comparison of the reactivities of the envelope proteins was made using sera from patients infected with the different subtypes. In this study, the B and C subtype envelope glycoproteins showed the strongest immunological reactivity, when reacted with sera from patients infected with the same subtype of virus. On the other hand, sera of patients infected with subtype A or C virus had the strongest and broadest reactivities, to envelope glycoproteins of many subtypes. The purified gp120 proteins from all five subtypes stimulated mononuclear cells from HIV-1 (subtype B)-infected patients, indicating conserved T cell-activating epitopes. The immunological reactivities indicate that strong antigenicity does not always predict the broadest immunogenicity of an envelope glycoprotein. Glycoprotein 120 from foreign subtypes may serve to induce strong cross-reactive immune responses.

  2. 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

    lines, sequencing and cloning. Structural modeling was performed using a crystal structure of gp120-CD4-X5. Phylogenetic analysis was done using subtype-A, subtype-B and subtype-C sequences from blood and cervix of 37 infected women and database sequences. RESULTS: We identified two envelope motifs...... 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...

  3. Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration.

    Directory of Open Access Journals (Sweden)

    Rami Kantor

    2005-04-01

    Full Text Available BACKGROUND: The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. METHODS AND FINDINGS: To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80% of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. CONCLUSION: Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

  4. Distribution of neprilysin and deposit patterns of Abeta subtypes in the brains of aged squirrel monkeys (Saimiri sciureus).

    Science.gov (United States)

    Chambers, James K; Kuribayashi, Hiroyuki; Ikeda, Shu-Ichi; Une, Yumi

    2010-06-01

    Beta-amyloid (Abeta) is deposited in the parenchyma and blood vessel walls of the senescent brain, and forms lesions termed senile plaques (SPs) and cerebral amyloid angiopathy (CAA). Since in Alzheimer's disease (AD) excessive Abeta is linked to cognitive deterioration, the mechanisms of degradation and clearance of Abeta are now being researched for use in AD therapy. We conducted an immunohistochemical study of the patterns of deposition of two Abeta subtypes (Abeta40 and Abeta42) and the distribution of the Abeta degrading enzyme neprilysin (NEP) in the brains of aged squirrel monkeys, a species known to develop CAA and SPs. Abeta deposits were observed mainly in the cerebral cortex of five older monkeys, and were absent in monkeys under 12 years of age. NEP expression was observed in the caudate nucleus, putamen, globus pallidus, substantia nigra and the molecular layer of the dentate gyrus, and thus exhibited a distribution complementary to those of CAA and SPs in cerebral cortex and hippocampus. It is known that CAA is more prominent than SPs in squirrel monkey brains. However, we confirmed that Abeta40 is deposited predominantly in the arterioles of the meninges and penetrates vertically into the cerebral cortex, whereas Abeta42 is deposited predominantly in the capillaries of the cerebral cortex. These distinct patterns of deposition of Abeta subtypes are likely related to the difference in biochemical character of these two subtypes. We have demonstrated for the first time the distribution of NEP in the brain of a non-human primate, the squirrel monkey, which appears useful for research on AD treatment.

  5. Subtyping Animal Influenza Virus with General Multiplex RT-PCR and Liquichip High Throughput (GMPLex)

    Institute of Scientific and Technical Information of China (English)

    Zhi-feng Qin; Bing Cheng; Zhou-xi Ruan; Ying-zuo Bi; Joseph J Giambrone; Hong-zhuan Wu; Jie Sun; Ti-kang Lu; Shao-ling Zeng; Qun-yi Hua; Qing-yan Ling; Shu-kun Chen; Jian-qiang Lv; Cai-hong Zhang

    2012-01-01

    This study developed a multiplex RT-PCR integrated with luminex technology to rapidly subtype simultaneously multiple influenza viruses.Primers and probes were designed to amplify NS and M genes of influenza A viruses HA gene of H1,H3,H5,H7,H9 subtypes,and NA gene of the N1 and N2 subtypes.Universal super primers were introduced to establish a multiplex RT-PCR (GM RT-PCR).It included three stages of RT-PCR amplification,and then the RT-PCR products were further tested by LiquiChip probe,combined to give an influenza virus (Ⅳ) rapid high throughput subtyping test,designated as GMPLex.The IV GMPLex rapid high throughput subtyping test presents the following features:high throughput,able to determine the subtypes of 9 target genes in H1,H3,H5,H7,H9,N1,and N2 subtypes of the influenza A virus at one time; rapid,completing the influenza subtyping within 6 hours; high specificity,ensured the specificity of the different subtypes by using two nested degenerate primers and one probe,no cross reaction occurring between the subtypes,no non-specific reactions with other pathogens and high sensitivity.When used separately to detect the product of single GM RT-PCR for single H5 or N1 gene,the GMPLex test showed a sensitivity of 105(=280ELD50) forboth tests and the Luminex qualitative ratio results were 3.08 and 3.12,respectively.When used to detect the product of GM RT-PCR for HSN1 strain at the same time,both showed a sensitivity of 10-4(=2800 ELD50).The GMPLex rapid high throughput subtyping test can satisfy the needs of influenza rapid testing.

  6. Different frequencies of drug resistance mutations among HIV-1 subtypes circulating in China: a comprehensive study.

    Directory of Open Access Journals (Sweden)

    Hongshuai Sui

    Full Text Available The rapid spreading of HIV drug resistance is threatening the overall success of free HAART in China. Much work has been done on drug-resistant mutations, however, most of which were based on subtype B. Due to different genetic background, subtypes difference would have an effect on the development of drug-resistant mutations, which has already been proved by more and more studies. In China, the main epidemic subtypes are CRF07_BC, CRF08_BC, Thai B and CRF01_AE. The depiction of drug resistance mutations in those subtypes will be helpful for the selection of regimens for Chinese. In this study, the distributions difference of amino acids at sites related to HIV drug resistance were compared among subtype B, CRF01_AE, CRF07_BC and CRF08_BC strains prevalent in China. The amino acid composition of sequences belonging to different subtypes, which were obtained from untreated and treated individuals separately, were also compared. The amino acids proportions of 19 sites in RT among subtype B, CRF01_AE and CRF08_BC have significant difference in drug resistance groups (chi-square test, p<0.05. Genetic barriers analysis revealed that sites 69, 138, 181, 215 and 238 were significantly different among subtypes (Kruskal Wallis test, p<0.05. All subtypes shared three highest prevalent drug resistance sites 103, 181 and 184 in common. Many drug resistant sites in protease show surprising high proportions in almost all subtypes in drug-naïve patients. This is the first comprehensive study in China on different development of drug resistance among different subtypes. The detailed data will lay a foundation for HIV treatment regimens design and improve HIV therapy in China.

  7. Preparation of quadri-subtype influenza virus-like particles using bovine immunodeficiency virus gag protein

    Energy Technology Data Exchange (ETDEWEB)

    Tretyakova, Irina; Hidajat, Rachmat; Hamilton, Garrett; Horn, Noah; Nickols, Brian; Prather, Raphael O. [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States); Tumpey, Terrence M. [Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Atlanta, GA (United States); Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States)

    2016-01-15

    Influenza VLPs comprised of hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins have been previously used for immunological and virological studies. Here we demonstrated that influenza VLPs can be made in Sf9 cells by using the bovine immunodeficiency virus gag (Bgag) protein in place of M1. We showed that Bgag can be used to prepare VLPs for several influenza subtypes including H1N1 and H10N8. Furthermore, by using Bgag, we prepared quadri-subtype VLPs, which co-expressed within the VLP the four HA subtypes derived from avian-origin H5N1, H7N9, H9N2 and H10N8 viruses. VLPs showed hemagglutination and neuraminidase activities and reacted with specific antisera. The content and co-localization of each HA subtype within the quadri-subtype VLP were evaluated. Electron microscopy showed that Bgag-based VLPs resembled influenza virions with the diameter of 150–200 nm. This is the first report of quadri-subtype design for influenza VLP and the use of Bgag for influenza VLP preparation. - Highlights: • BIV gag protein was configured as influenza VLP core component. • Recombinant influenza VLPs were prepared in Sf9 cells using baculovirus expression system. • Single- and quadri-subtype VLPs were prepared by using BIV gag as a VLP core. • Co-localization of H5, H7, H9, and H10 HA was confirmed within quadri-subtype VLP. • Content of HA subtypes within quadri-subtype VLP was determined. • Potential advantages of quadri-subtype VLPs as influenza vaccine are discussed.

  8. 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.

  9. Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling

    NARCIS (Netherlands)

    R.G.W. Verhaak (Roel); B.J. Wouters (Bas); C.A.J. Erpelinck (Claudia); S. Abbas (Saman); H.B. Beverloo (Berna); S. Lugthart (Sanne); B. Löwenberg (Bob); H.R. Delwel (Ruud); P.J.M. Valk (Peter)

    2009-01-01

    textabstractWe examined the gene expression profiles of two independent cohorts of patients with acute myeloid leukemia [n=247 and n=214 (younger than or equal to 60 years)] to study the applicability of gene expression profiling as a single assay in prediction of acute myeloid leukemia-specific mol

  10. Molecular alterations in gastric cancer with special reference to the early-onset subtype

    NARCIS (Netherlands)

    Skierucha, Małgorzata; Milne, Anya Na; Offerhaus, G Johan A; Polkowski, Wojciech P; Maciejewski, Ryszard; Sitarz, Robert

    2016-01-01

    Currently, gastric cancer (GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the pro-carcinogenic activity of important genes. These

  11. Glycoprotein C Gene Based Molecular Subtyping of a Bovine Herpesvirus -1 Isolate from Uttar Pradesh, India

    OpenAIRE

    2012-01-01

    Bovine herpesvirus -1 (BHV-1) is the etiological agent of many clinical syndromes in cattle which causes huge economic losses to the animal husbandry sector annually. Since the first report of its presence in India in 1976, the disease is considered to be endemic in the country. In the present study, a case of keratoconjunctivitis in a cow was investigated to find out the underlying cause of the condition. The clinical material (ocular swab) was tested by BHV-1 glycoprotein D gene specific PC...

  12. 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.

  13. Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

    Directory of Open Access Journals (Sweden)

    Rosa Dolz-Marco

    2014-01-01

    Full Text Available Purpose: To report corneal findings in a familial case of the crystalline subtype of pre- Descemetic corneal dystrophy. Case Report: A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion: To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti΄s dystrophy and monoclonal gammopathy.

  14. Subtypes of Pathological Gambling with Concurrent Illegal Behaviors.

    Science.gov (United States)

    Granero, Roser; Fernández-Aranda, Fernando; Aymamí, Neus; Gómez-Peña, Mónica; Fagundo, Ana Beatriz; Sauchelli, Sarah; Del Pino-Gutiérrez, Amparo; Moragas, Laura; Savvidou, Lamprini G; Islam, Mohammed A; Tàrrega, Salomé; Menchón, José M; Jiménez-Murcia, Susana

    2015-12-01

    The aims of this study are: to explore empirical clusters in a sample of individuals with a gambling disorder (GD) according to the presence of illegal behaviors, to describe the subgroups at a clinical level and to examine whether a temporal change has taken place across the last 9 years. The sample consisted of 378 patients with a GD who consecutively received outpatient treatment, and who reported the presence of the DSM-IV criteria "presence of illegal behavior". Two-step clustering procedure revealed the existence of four empirical groups, which differed in both sociodemographic and clinical profiles. The patients, who have committed illegal acts due to their gambling behavior, are a heterogeneous group in which it is possible to identify different subtypes, based on sociodemographic, psychopathological, clinical and personality characteristics.

  15. 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.

  16. Diversity of Blastocystis subtypes in dogs in different geographical settings

    DEFF Research Database (Denmark)

    Wang, Wenqi; Cuttell, Leigh; Bielefeldt-Ohmann, Helle

    2013-01-01

    Background: Blastocystis is a ubiquitous, globally distributed intestinal protist infecting humans and a wide range of animals. Several studies have shown that Blastocystis is a potentially zoonotic parasite. A 1996 study reported a 70% Blastocystis prevalence in Brisbane pound dogs while another...... study found that pet dogs/cats of 11 symptomatic Blastocystis infected patients harboured at least one Blastocystis subtype (ST) in common with the patient. These results raised the possibility that dogs might be natural hosts of Blastocystis. In this study, we aimed to investigate this hypothesis...... by estimating the prevalence of Blastocystis carriage and characterising the diversity of STs in dogs from three different environmental settings and comparing these STs with the range that humans harbour. Methods: Two hundred and forty faecal samples from dogs from three different geographical regions...

  17. 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

    of dyspeptic patients with or without Helicobacter pylori infection, and to determine the 5-HT receptor subtypes functionally involved. Biopsies from the second part of duodenum were obtained from 43 dyspeptic patients during routine endoscopy. Biopsies were mounted in modified Ussing chambers with air suction......: ketanserin, ondansetron, or SB-204070 (1-butyl-4 piperidinmethyl-8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-carboxylate HCl). Histological examination was performed on duodenal biopsies. Helicobacter urease testing and histological examination determined Helicobacter pylori infection. 5-HT induced a dose......-dependent and bumetanide-sensitive short-circuit current, which was independent of the presence of Helicobacter pylori infection. All the three 5-HT receptor antagonists failed to significantly effect basal and 5-HT-induced short-circuit current. Our results indicate that in human duodenum 1) 5-HT is a potent stimulator...

  18. Memory processes in learning disability subtypes of children born preterm.

    Science.gov (United States)

    McCoy, Thomasin E; Conrad, Amy L; Richman, Lynn C; Nopoulos, Peg C; Bell, Edward F

    2013-01-01

    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 or visual memory performances between language and perceptual-motor learning disability groups. Within-group comparisons revealed that both learning disability groups performed significantly lower on a task of immediate memory when the mode of stimulus presentation and mode of response were visual.

  19. 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

    growth factor receptor 2 subtypes had similar median survival duration and mortality risk. Patients with triple-negative breast cancer had a median survival duration of only 9.9 months. CONCLUSION: Patients with spinal metastases with ER/HR (-) status and triple-negative breast cancer could be 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...... hazards regression model unadjusted and adjusted by age were used. RESULTS: Patients with ER-negative (-) breast cancer had 11 months shorter median survival duration (10.6 vs. 21.5 mo) and 48% higher mortality risk (P=0.03) than those with ER-positive (+) breast cancer. Patients with PgR (-) status had...

  20. Antisocial personality disorder--stable and unstable subtypes.

    Science.gov (United States)

    Ullrich, Simone; Coid, Jeremy

    2010-04-01

    There have been criticisms that the criteria for antisocial personality disorder (ASPD) are over-dependent on criminal behavior. This study aimed to identify unrelated criteria of social and behavioral problems and instability, and to investigate their associations in a representative household sample of adults in the UK. Approximately one third of adults with ASPD did not fulfill any of the criteria for instability. They were less aggressive and involved in illegal activities but expressed less remorse for their behaviors. Instability in ASPD was mediated primarily through comorbid anxiety disorders and borderline personality disorder. The concept of Secondary Psychopathy, which has not generally been applied to ASPD, demonstrated many similarities to the unstable subtype.

  1. Subtyping Ageism: Policy Issues in Succession and Consumption.

    Science.gov (United States)

    North, Michael S; Fiske, Susan T

    2013-01-01

    Ageism research tends to lump "older people" together as one group, as do policy matters that conceptualize everyone over-65 as "senior." This approach is problematic primarily because it often fails to represent accurately a rapidly growing, diverse, and healthy older population. In light of this, we review the ageism literature, emphasizing the importance of distinguishing between the still-active "young-old" and the potentially more impaired "old-old" (Neugarten, 1974). We argue that ageism theory has disproportionately focused on the old-old and differentiate the forms of age discrimination that apparently target each elder subgroup. In particular, we highlight the young-old's plights predominantly in the workplace and tensions concerning succession of desirable resources; by contrast, old-old predicaments likely center on consumption of shared resources outside of the workplace. For both social psychological researchers and policymakers, accurately subtyping ageism will help society best accommodate a burgeoning, diverse older population.

  2. Incidence of dementia and major subtypes in Europe

    DEFF Research Database (Denmark)

    Fratiglioni, L; Launer, L J; Andersen, K;

    2000-01-01

    The authors examined the association of incident dementia and subtypes with age, sex, and geographic area in Europe. Incidence data from eight population-based studies carried out in seven European countries were compared and pooled. The pooled data included 835 mild to severe dementia cases and 42......,996 person-years of follow-up. In all studies a higher proportion of cases were diagnosed with AD (60 to 70% of all demented cases) than vascular dementia (VaD). The incidence of dementia and AD continued to increase with age up to age 85 years, after which rates increased in women but not men....... There was a large variation in VaD incidence across studies. In the pooled analysis, the incidence rates increased with age without any substantial difference between men and women. Surprisingly, higher incidence rates of dementia and AD were found in the very old in northwest countries than in southern countries...

  3. Neurocognitive impairment in the deficit subtype of schizophrenia.

    Science.gov (United States)

    Fervaha, Gagan; Agid, Ofer; Foussias, George; Siddiqui, Ishraq; Takeuchi, Hiroyoshi; Remington, Gary

    2016-08-01

    Schizophrenia is a heterogeneous disorder characterized by numerous diverse signs and symptoms. Individuals with prominent, persistent, and idiopathic negative symptoms are thought to encompass a distinct subtype of schizophrenia. Previous work, including studies involving neuropsychological evaluations, has supported this position. The present study sought to further examine whether deficit patients are cognitively distinct from non-deficit patients with schizophrenia. A comprehensive neurocognitive battery including tests of verbal memory, vigilance, processing speed, reasoning, and working memory was administered to 657 patients with schizophrenia. Of these, 144 (22 %) patients were classified as deficit patients using a proxy identification method based on severity, persistence over time, and possible secondary sources (e.g., depression) of negative symptoms. Deficit patients with schizophrenia performed worse on all tests of cognition relative to non-deficit patients. These patients were characterized by a generalized cognitive impairment on the order of about 0.4 standard deviations below that of non-deficit patients. However, when comparing deficit patients to non-deficit patients who also present with negative symptoms, albeit not enduring or primary, no group differences in cognitive performance were found. Furthermore, a discriminant function analysis classifying patients into deficit/non-deficit groups based on cognitive scores demonstrated only 62.3 % accuracy, meaning over one-third of individuals were misclassified. The deficit subtype of schizophrenia is not markedly distinct from non-deficit schizophrenia in terms of neurocognitive performance. While deficit patients tend to have poorer performance on cognitive tests, the magnitude of this effect is relatively modest, translating to over 70 % overlap in scores between groups.

  4. GABA(A) receptor subtype selective cognition enhancers.

    Science.gov (United States)

    Maubach, Karen

    2003-08-01

    Currently the treatment of Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) is largely unrealised, with no preventive or curative therapies. The marketed acetylcholinesterase inhibitors (eg. donepezil, Aricept) are directed toward temporary symptomatic relief from impaired cognition, but have prominent adverse effects with minimal efficacy. In pursuit of novel cognition enhancers, the observation that classical benzodiazepines (BZ, eg. diazepam) are amnesic, coupled with the preservation of GABA(A) receptors in brain areas most affected by AD, highlighted the GABA(A) receptor as a potential therapeutic target. In contrast to the amnesic BZ agonists, the BZ inverse agonists (eg. DMCM) which attenuate GABA(A) receptor function, have been shown to improve performance in animal models of learning and memory. Unfortunately, such non-selective ligands also induce anxiety and convulsions. More recently, novel ligands have been developed (eg. 6,6-dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one) that demonstrate binding selectivity and high inverse agonism for the alpha5 GABA(A) receptor subtype, which is preferentially located in the hippocampus, a region of the brain associated with learning and memory. Pre-clinical results are encouraging, since these alpha5 selective inverse agonists enhance memory in animal models, such as spatial learning in the Morris water-maze, but are devoid of the adverse effects associated with activity at other GABA(A) receptor subtypes in other brain regions. If the efficacy and safety profiles of alpha5 inverse agonists in humans prove to be similar to those seen in pre-clinical studies, these compounds would offer significant benefit to AD and MCI patients.

  5. Recent advances in the molecular pharmacology of the alpha 1-adrenergic receptors.

    Science.gov (United States)

    Guarino, R D; Perez, D M; Piascik, M T

    1996-08-01

    This review is intended to discuss recent developments in the molecular pharmacology of the alpha 1-adrenergic receptor (alpha 1-AR) subtypes. After a brief historical development, we will focus on the more contemporary issues having to do with this receptor family. Emphasis will be put on recent data regarding the cloning, nomenclature, signalling mechanisms, and genomic organization of the alpha 1-AR subtypes. We will also highlight recent mutational studies that identify key amino acid residues involved in ligand binding, as well as the role of the alpha 1-AR subtypes in regulating physiologic processes.

  6. Folic acid supplementation influences the distribution of neural tube defect subtypes : A registry-based study

    NARCIS (Netherlands)

    Bergman, J. E. H.; Otten, E.; Verheij, J. B. G. M.; de Walle, H. E. K.

    2016-01-01

    Periconceptional folic acid (FA) reduces neural tube defect (NTD) risk, but seems to have a varying effect per NTD subtype. We aimed to study the effect of FA supplementation on NTD subtype distribution using data from EUROCAT Northern Netherlands. We included all birth types with non-syndromal NTDs

  7. Variation in Campylobacter MLST Subtypes Detected from Chickens on Three Different Plating Media

    Science.gov (United States)

    The objective of this study was to compare subtypes of Campylobacter jejuni and coli detected on three discreet selective Campylobacter plating media to determine if different media select for different subtypes. Fifty ceca and fifty carcasses (n=100, representing 50 flocks) were collected from the...

  8. 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...

  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. Predictors of Stability of Attention-Deficit/Hyperactivity Disorder Subtypes from Childhood to Young Adulthood

    Science.gov (United States)

    Todd, Richard D.; Huang, Hongyan; Todorov, Alexandre A.; Neuman, Rosalind J.; Reiersen, Angela M.; Henderson, Cynthia A.; Reich, Wendy C.

    2008-01-01

    A 5-year prospective study attempts to determine the predictors of stability of attention-deficit/hyperactivity disorder (ADHD) subtypes from childhood to young adulthood. The results conclude that population-defined ADHD subtype criteria indicate improved diagnostic stability over 5 years.

  11. Nitrogen substitution modifies the activity of cytisine on neuronal nicotinic receptor subtypes.

    Science.gov (United States)

    Carbonnelle, Eric; Sparatore, Fabio; Canu-Boido, Caterina; Salvagno, Cristian; Baldani-Guerra, Barbara; Terstappen, Georg; Zwart, Ruud; Vijverberg, Henk; Clementi, Francesco; Gotti, Cecilia

    2003-06-20

    Cytisine very potently binds and activates the alpha 3 beta 4 and alpha 7 nicotinic subtypes, but only partially agonises the alpha 4 beta 2 subtype. Although with a lower affinity than cytisine, new cytisine derivatives with different substituents on the basic nitrogen (CC1-CC8) bind to both the heteromeric and homomeric subtypes, with higher affinity for brain [3H]epibatidine receptors. The cytisine derivatives were tested on the Ca(2+) flux of native or transfected cell lines expressing the rat alpha 7, or human alpha 3 beta 4 or alpha 4 beta 2 subtypes using Ca(2+) dynamics in conjunction with a fluorescent image plate reader. None elicited any response at doses of up to 30-100 microM, but all inhibited agonist-induced responses. Compounds CC5 and CC7 were also electrophysiologically tested on oocyte-expressed rat alpha 4 beta 2, alpha 3 beta 4 and alpha 7 subtypes. CC5 competitively antagonised the alpha 4 beta 2 and alpha 3 beta 4 subtypes with similar potency, whereas CC7 only partially agonised them with maximum responses of respectively 3% and 11% of those of 1 mM acetylcholine. Neither compound induced any current in the oocyte-expressed alpha 7 subtype, and both weakly inhibited acetylcholine-induced currents. Adding chemical groups of a different class or size to the basic nitrogen of cytisine leads to compounds that lose full agonist activity on the alpha 3 beta 4 and alpha 7 subtypes.

  12. Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test

    Directory of Open Access Journals (Sweden)

    Valença A.M.

    2002-01-01

    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.

  13. Development of an abbreviated version of the delirium motor subtyping scale (DMSS-4)

    NARCIS (Netherlands)

    Meagher, D; Adamis, D; Leonard, M; Trzepacz, P; Grover, S; Jabbar, F; Meehan, K; O'Connor, M; Cronin, C; Reynolds, P; Fitzgerald, J; O'Regan, N; Timmons, S; Slor, C; de Jonghe, J; de Jonghe, A; van Munster, B C; de Rooij, S E; Maclullich, A

    2014-01-01

    BACKGROUND: Delirium is a common neuropsychiatric syndrome with considerable heterogeneity in clinical profile. Identification of clinical subtypes can allow for more targeted clinical and research efforts. We sought to develop a brief method for clinical subtyping in clinical and research settings.

  14. Structural basis for ether-a-go-go-related gene K+ channel subtype-dependent activation by niflumic acid.

    Science.gov (United States)

    Fernandez, David; Sargent, John; Sachse, Frank B; Sanguinetti, Michael C

    2008-04-01

    Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridinecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K(+) channel subtypes expressed in Xenopus laevis oocytes using two-electrode voltage-clamp techniques. NFA acted from the extracellular side of the membrane to differentially enhance ERG channel currents independent of channel state. At 1 mM, NFA shifted the half-point for activation by -6, -18, and -11 mV for ERG1, ERG2, and ERG3 channels, respectively. The half-point for channel inactivation was shifted by +5 to +9 mV by NFA. The structural basis for the ERG subtype-specific response to NFA was explored with chimeric channels and site-directed mutagenesis. The molecular determinants of enhanced sensitivity of ERG2 channels to NFA were isolated to an Arg and a Thr triplet in the extracellular S3-S4 linker.

  15. Cloning, structural characterization, and chromosomal localization of the gene encoding the human prostaglandin E(2) receptor EP2 subtype.

    Science.gov (United States)

    Smock, S L; Pan, L C; Castleberry, T A; Lu, B; Mather, R J; Owen, T A

    1999-09-17

    Northern blot analysis of human placental RNA using a probe to the 5' end of the human prostaglandin E(2) (PGE(2)) EP2 receptor subtype coding region revealed the existence of a high abundance, low molecular weight transcript. To investigate the origin of this transcript, and its possible relationship to the human EP2 mRNA, we have cloned and characterized the gene encoding the human PGE(2) EP2 receptor subtype, identified transcriptional initiation and termination sites in two tissues (spleen and thymus), and determined its chromosomal localization. The human EP2 gene consists of two exons separated by a large intron, utilizes a common initiation site in both spleen and thymus at 1113 bp upstream of the translation initiation site, and has 3' transcript termini at 1140 bp and 1149 bp downstream of the translation stop site in spleen and thymus respectively. Southern and fluorescence in situ hybridization analysis demonstrated the human EP2 gene to be a single copy gene located in band 22 of the long arm of chromosome 14 (14q22). Though our initial interest in this gene was to investigate potential differential splicing of the human EP2 gene in placenta, this work demonstrates that the atypical transcript observed in placenta probably arises from a distinct, yet related, gene. Knowledge of the sequence, structure, and transcription events associated with the human EP2 gene will enable a broader understanding of its regulation and potential role in normal physiology and disease.

  16. 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

  17. A single subtype of avian pneumovirus circulates among Minnesota turkey flocks.

    Science.gov (United States)

    Dar, Arshud M; Munir, Shirin; Goyal, Sagar M; Kapur, Vivek

    2002-09-01

    The recent emergence of avian pneumovirus (APV) infection among US turkey flocks has resulted in a major economic threat to the turkey industry. In order to elucidate the molecular epidemiology of APV, comparative sequence analysis of the fusion (F) protein gene of APV was performed for 3 cell culture-adapted isolates and 10 APV positive clinical samples recovered from US turkey flocks. Relatively modest levels of nucleotide and amino acid sequence divergence were identified, suggesting the prevalence of a single lineage of APV among US turkey flocks. Additionally, numerous polymorphisms were identified that were only represented in the clinical samples but not in the in vitro propagated isolates of APV. Phylogenetic analyses confirm that the subtype of APV circulating in the upper Midwestern United States is evolutionarily related to, but distinct from, European APV subgroups A and B. Overall, the results of the present investigation suggest that there has been only a single recent introduction of APV into US turkey populations in the upper Midwestern United States.

  18. Muscarinic M3 receptor subtype gene expression in the human heart.

    Science.gov (United States)

    Hellgren, I; Mustafa, A; Riazi, M; Suliman, I; Sylvén, C; Adem, A

    2000-01-20

    The heart is an important target organ for cholinergic function. In this study, muscarinic receptor subtype(s) in the human heart were determined using reverse transcription-polymerase chain reaction. Our results demonstrated muscarinic receptor M2 and M3 subtype RNA in left/right atria/ventricles of donor hearts. Receptor autoradiography analysis using selective muscarinic ligands indicated an absence of M1 receptor subtype in the human heart. The level of muscarinic receptor binding in atria was two to three times greater than in ventricles. Our results suggest that muscarinic receptors in the human heart are of the M2 and M3 subtypes. This is the first report of M3 receptors in the human myocardium.

  19. Specific trauma subtypes improve the predictive validity of the Harvard Trauma Questionnaire in Iraqi refugees.

    Science.gov (United States)

    Arnetz, Bengt B; Broadbridge, Carissa L; Jamil, Hikmet; Lumley, Mark A; Pole, Nnamdi; Barkho, Evone; Fakhouri, Monty; Talia, Yousif Rofa; Arnetz, Judith E

    2014-12-01

    Trauma exposure contributes to poor mental health among refugees, and exposure often is measured using a cumulative index of items from the Harvard Trauma Questionnaire (HTQ). Few studies, however, have asked whether trauma subtypes derived from the HTQ could be superior to this cumulative index in predicting mental health outcomes. A community sample of recently arrived Iraqi refugees (N = 298) completed the HTQ and measures of posttraumatic stress disorder (PTSD) and depression symptoms. Principal components analysis of HTQ items revealed a 5-component subtype model of trauma that accounted for more item variance than a 1-component solution. These trauma subtypes also accounted for more variance in PTSD and depression symptoms (12 and 10%, respectively) than did the cumulative trauma index (7 and 3%, respectively). Trauma subtypes provided more information than cumulative trauma in the prediction of negative mental health outcomes. Therefore, use of these subtypes may enhance the utility of the HTQ when assessing at-risk populations.

  20. 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.

  1. Molecular Typing in Public Health Laboratories: From an Academic Indulgence to an Infection Control Imperative

    OpenAIRE

    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...

  2. 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.

  3. 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

  4. 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.

  5. Cognitive subtypes in non-affected siblings of patients with schizophrenia : Characteristics and profile congruency with affected family member

    NARCIS (Netherlands)

    Quee, P.J.; Alizadeh, B.Z.; Aleman, A.; van den Heuvel, E.R.

    2013-01-01

    Introduction: Although cognitive subtypes have been suggested in schizophrenia patients, similar analyses have not been carried out in their unaffected siblings. Subtype classification may provide more insight into genetically driven variation in cognitive function. Objectives/aims: To investigate c

  6. Genetic identification of Entamoeba polecki subtype 3 from pigs in Japan and characterisation of its pathogenic role in ulcerative colitis.

    Science.gov (United States)

    Matsubayashi, Makoto; Murakoshi, Naoko; Komatsu, Tetsuya; Tokoro, Masaharu; Haritani, Makoto; Shibahara, Tomoyuki

    2015-12-01

    To date, three Entamoeba spp. (E. suis, zoonotic E. polecki and E. histolytica) have been identified in pigs, but their pathogenicity and molecular classification have not been fully determined. Examination and pathological analysis of pigs (n=3) with diarrhoea was conducted and revealed the presence of Entamoeba organisms. We performed a genetic analysis of the isolate using the small-subunit ribosomal RNA (SSU rRNA) gene region to identify the species. A severe ulcerative colitis was observed histopathologically with inflammatory cells, including macrophages and neutrophils, infiltrating the mucous membranes of the cecum and colon. Many Entamoeba trophozoites were found at the erosion site or at ulcerative lesions. Pathogenic viruses or bacteria were not detected. The SSU rRNA sequence of the Entamoeba isolate was found to be completely homologous to that of E. polecki subtype 3.

  7. Utility of neurophysiological criteria in Guillain Barre΄ syndrome: Subtype spectrum from a tertiary referral hospital in India

    OpenAIRE

    Alexander, M.; A T Prabhakar; S Aaron; M. Thomas; Mathew, V; Patil, A. K.

    2011-01-01

    Background: The Guillain Barre′ syndrome (GBS) is a heterogeneous disease with various subtypes, the prevalence of which would depend on the geographic region. Recognition of these subtypes is of clinical importance since each subtype has an independent pathogenesis and different type of pathology and prognosis. Objectives: To study the various subtypes of GBS using the various published electrophysiological criteria. Design: Retrospective descriptive study. Materials and Methods: In a tertia...

  8. 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.

  9. 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.

  10. 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

  11. Bilateral vestibular hypofunction: Insights in etiologies, clinical subtypes and diagnostics

    Directory of Open Access Journals (Sweden)

    F. eLucieer

    2016-03-01

    Full Text Available Objective:To evaluate the different etiologies and clinical subtypes of bilateral vestibular hypofunction (BVH and the value of diagnostic tools in the diagnostic process of BVH.Materials and methods: A retrospective case review was performed on 154 patients diagnosed with BVH in a tertiary referral center, between 2013 and 2015. Inclusion criteria comprised 1 imbalance and/or oscillopsia during locomotion, and 2 summated slow phase velocity of nystagmus of less than 20 degrees per second during bithermal caloric tests.Results:The definite etiology of BVH was determined in 47% of the cases and the probable etiology in 22%. In 31%, the etiology of BVH remained idiopathic. BVH resulted from more than 20 different etiologies. In the idiopathic group, the percentage of migraine was significantly higher compared to the non-idiopathic group (50% versus 11%, p<0.001. Among all patients, 23.4% were known with autoimmune disorders in their medical history. All 4 clinical subtypes (recurrent vertigo with BVH, rapidly progressive BVH, slowly progressive BVH and slowly progressive BVH with ataxia were found in this population. Slowly progressive BVH with ataxia comprised only 4.5% of the cases. The head impulse test was abnormal in 94% of the cases. The torsion swing test was abnormal in 66%. Bilateral normal hearing to moderate hearing loss was found in 49%. Blood tests did not often contribute to the determination of the etiology of the disease. Abnormal cerebral imaging was found in 21 patients.Conclusion:BVH is a heterogeneous condition with various etiologies and clinical characteristics. Migraine seems to play a significant role in idiopathic BVH and auto-immunity could be a modulating factor in the development of BVH. The distribution of etiologies of BVH probably depends on the clinical setting. In the diagnostic process of BVH, the routine use of some blood tests can be reconsidered and a low-threshold use of audiometry and cerebral imaging is

  12. 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

  13. Analysis of the Differentiation of Kenyon Cell Subtypes Using Three Mushroom Body-Preferential Genes during Metamorphosis in the Honeybee (Apis mellifera L..

    Directory of Open Access Journals (Sweden)

    Shota Suenami

    Full Text Available 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.

  14. Predicting Subtype Selectivity for Adenosine Receptor Ligands with Three-Dimensional Biologically Relevant Spectrum (BRS-3D)

    Science.gov (United States)

    He, Song-Bing; Ben Hu; Kuang, Zheng-Kun; Wang, Dong; Kong, De-Xin

    2016-11-01

    Adenosine receptors (ARs) are potential therapeutic targets for Parkinson’s disease, diabetes, pain, stroke and cancers. Prediction of subtype selectivity is therefore important from both therapeutic and mechanistic perspectives. In this paper, we introduced a shape similarity profile as molecular descriptor, namely three-dimensional biologically relevant spectrum (BRS-3D), for AR selectivity prediction. Pairwise regression and discrimination models were built with the support vector machine methods. The average determination coefficient (r2) of the regression models was 0.664 (for test sets). The 2B-3 (A2B vs A3) model performed best with q2 = 0.769 for training sets (10-fold cross-validation), and r2 = 0.766, RMSE = 0.828 for test sets. The models’ robustness and stability were validated with 100 times resampling and 500 times Y-randomization. We compared the performance of BRS-3D with 3D descriptors calculated by MOE. BRS-3D performed as good as, or better than, MOE 3D descriptors. The performances of the discrimination models were also encouraging, with average accuracy (ACC) 0.912 and MCC 0.792 (test set). The 2A-3 (A2A vs A3) selectivity discrimination model (ACC = 0.882 and MCC = 0.715 for test set) outperformed an earlier reported one (ACC = 0.784). These results demonstrated that, through multiple conformation encoding, BRS-3D can be used as an effective molecular descriptor for AR subtype selectivity prediction.

  15. 75 FR 69046 - Notice of Determination of the High Pathogenic Avian Influenza Subtype H5N1 Status of Czech...

    Science.gov (United States)

    2010-11-10

    ... Pathogenic Avian Influenza Subtype H5N1 Status of Czech Republic and Sweden AGENCY: Animal and Plant Health... the highly pathogenic avian influenza (HPAI) subtype H5N1 status of the Czech Republic and Sweden... status of the Czech Republic and Sweden relative to highly pathogenic avian influenza (HPAI) subtype...

  16. Cognitive subtypes in non-affected siblings of schizophrenia patients: characteristics and profile congruency with affected family members.

    NARCIS (Netherlands)

    Quee, P.J.; Alizadeh, B.Z.; Aleman, A.; van den Heuvel, E.R.; GROUP Investigators, [No Value

    2014-01-01

    Although cognitive subtypes have been suggested in schizophrenia patients, similar analyses have not been carried out in their non-affected siblings. Subtype classification may provide more insight into genetically driven variation in cognitive function. We investigated cognitive subtypes in sibling

  17. Differences in conformational stability of the two alpha domains of the disease-associated and non-disease-associated subtypes of HLA-B27.

    Science.gov (United States)

    Rana, Manish Kumar; Luthra-Guptasarma, Manni

    2017-01-01

    The MHC Class I molecule, HLA-B27, is strongly linked with development of the inflammatory arthritic disease, ankylosing spondylitis (AS); whereas the B*2705 subtype shows strong association, B*2709 is not associated with disease, even though the two subtypes differ in only a single residue at position 116. Currently, attention is focused on the misfolding propensities of these two subtypes, including studies of disulfide-linked dimers and non-covalently formed high molecular weight (HMW) aggregates. Using mutants retaining only a single cysteine at positions C67 or C164, and using a cysteine-reactive, environment-sensitive, fluorescence probe (acrylodan), we find that within the same overall population of identical single-cysteine HLA-B27 molecules, there exist sub-populations which (a) possess free cysteines which react with acrylodan, (b) form disulfide-linked dimers, and (c) form HMW aggregates. Further, using acrylodan fluorescence, we find (d) that the α1 and α2 domains unfold independently of each other in HMW aggregates, (e) that these two domains of B*2709 are less stable to chemical and thermal denaturation than the corresponding domains of B*2705, suggesting easier clearance of misfolded molecules in the former, and (f) C67 is much more exposed in B*2705 than in B*2709, which could potentially explain how B*2705 more easily forms C67-mediated disulfide-bonded dimers.

  18. A DNA methylation-based definition of biologically distinct breast cancer subtypes.

    Science.gov (United States)

    Stefansson, Olafur A; Moran, Sebastian; Gomez, Antonio; Sayols, Sergi; Arribas-Jorba, Carlos; Sandoval, Juan; Hilmarsdottir, Holmfridur; Olafsdottir, Elinborg; Tryggvadottir, Laufey; Jonasson, Jon G; Eyfjord, Jorunn; Esteller, Manel

    2015-03-01

    In cancer, epigenetic states are deregulated and thought to be of significance in cancer development and progression. We explored DNA methylation-based signatures in association with breast cancer subtypes to assess their impact on clinical presentation and patient prognosis. DNA methylation was analyzed using Infinium 450K arrays in 40 tumors and 17 normal breast samples, together with DNA copy number changes and subtype-specific markers by tissue microarrays. The identified methylation signatures were validated against a cohort of 212 tumors annotated for breast cancer subtypes by the PAM50 method (The Cancer Genome Atlas). Selected markers were pyrosequenced in an independent validation cohort of 310 tumors and analyzed with respect to survival, clinical stage and grade. The results demonstrate that DNA methylation patterns linked to the luminal-B subtype are characterized by CpG island promoter methylation events. In contrast, a large fraction of basal-like tumors are characterized by hypomethylation events occurring within the gene body. Based on these hallmark signatures, we defined two DNA methylation-based subtypes, Epi-LumB and Epi-Basal, and show that they are associated with unfavorable clinical parameters and reduced survival. Our data show that distinct mechanisms leading to changes in CpG methylation states are operative in different breast cancer subtypes. Importantly, we show that a few selected proxy markers can be used to detect the distinct DNA methylation-based subtypes thereby providing valuable information on disease prognosis.

  19. Personality subtypes in male patients with eating disorder: validation of a classification approach.

    Science.gov (United States)

    Claes, Laurence; Fernandez-Aranda, Fernando; Jiménez-Murcia, Susana; Agüera, Zaida; Granero, Roser; Sánchez, Isabel; Menchón, Jose Manuel

    2012-10-01

    In the present study, we investigated personality subtypes and their correlates in a sample of 132 male patients with eating disorder (ED). All patients filled out the Temperament and Character Inventory-Revised, the Eating Disorder Inventory-2, and the Symptom Checklist-90-Revised. Three personality subtypes emerged. Cluster 1, the adaptive-like subtype, was characterized by a high prevalence of eating-disorder-not-otherwise-specified and low levels of ED and general psychopathology. Cluster 2, the average or socially detached subtype, showed a high prevalence of eating-disorder-not-otherwise-specified, more social problems, less motivation for treatment, and an intermediate position on the psychopathology dimension between patients of clusters 1 and 3. Finally, cluster 3, the maladaptive subtype, was characterized the highest prevalence of bulimia nervosa and the highest scores on ED and general psychopathology. Our data support the presence of the 3 personality subtypes in male patients with ED. Future studies need to address whether patients of different subtypes differ with respect to therapy outcome.

  20. Immunohistochemical characterization of molecular classification of breast carcinoma and its relation with Ki-67

    Directory of Open Access Journals (Sweden)

    Shabnam Karangadan

    2016-01-01

    Full Text Available Background: Breast carcinoma is the leading cause of cancer deaths in women. Molecular classification of breast carcinoma along with Ki-67 index is considered a better predictive factor for prognosis and treatment than routine histopathology. Aims: To classify breast carcinoma into the four molecular subtypes defined by immunohistochemical expression of triple markers: Luminal A (estrogen receptor/progesterone receptor-positive [ER/PR+] and human epidermal growth factor receptor 2 HER2/neu, luminal B (ER/PR + and HER2/neu+, triple negative (ER/PR − and HER2/neu−, and HER2 positive (ER/PR−, HER2/neu+, and to correlate the expression of ER, PR, HER2/neu, and classification with Ki-67. Materials and Methods: The present study includes sixty breast carcinoma cases studied over a 3-year period. The expression patterns of ER, PR, HER2/neu, and Ki-67 were studied. Clinical features, pathologic features such as size, grade, and lymph node status, and correlation with Ki-67 of the four subtypes were compared. Results: Out of sixty cases, most common molecular subtype was triple negative (40.00% followed by luminal B (23.33%. Most of the tumors showed low proliferative index (low Ki-67; however, triple negative and HER2 positive subtype showed high proliferative index. Most common histological subtype was ductal carcinoma which was mainly triple negative. All medullary carcinoma cases were triple negative. One case of lobular carcinoma and mucinous carcinoma each was HER2 positive and luminal B, respectively. Single case of carcinoma of male breast was luminal B subtype. Conclusion: Correlation of molecular classification with age, histological grade, and Ki-67 was statistically significant (P < 0.05. ER/PR also correlated with histological grade and Ki-67 (P < 0.01. These results emphasize the fact that molecular subtypes correlate with prognosis and aid in targeted therapy.

  1. GABA A/Bz receptor subtypes as targets for selective drugs.

    Science.gov (United States)

    Da Settimo, F; Taliani, S; Trincavelli, M L; Montali, M; Martini, C

    2007-01-01

    The gamma-aminobutyric acid type A (GABA(A)) receptors are the major inhibitory neuronal receptors in the mammalian brain. Their activation by GABA opens the intrinsic ion channel, enabling chloride flux into the cell with subsequent hyperpolarization. Several GABA(A) receptor subunit isoforms have been cloned, the major isoform containing alpha, beta, and gamma subunits, and a regional heterogeneity associated with distinct physiological effects has been suggested. As a variety of allosteric ligands can modulate GABA-gated conductance changes through binding to distinct sites, the development of subtype-selective ligands may lead to the selective treatment of GABA system-associated pathology. In particular, the best characterized binding site is the benzodiazepine site (BzR), localized at the alpha/gamma subunit interface, in which the alpha subunit is the main determinant of BzR ligand action selectivity. The alpha1-containing BzR have been proposed to be responsible for the sedative action; the alpha2 and/or the alpha3 subtypes have been suggested to mediate the anxiolytic activity and the myorelaxation effects, and the alpha5 subtype has been associated with cognition processes. The discovery of alpha-selective subtype ligands may help in the specific treatment of anxiety, sleep disorders, convulsions and memory deficits with fewer side effects. Selectivity may be achieved by two approaches: selective affinity or selective efficacy. Selective affinity needs a compound to bind with a higher affinity to one receptor subtype compared with another, whereas subtype-selective efficacy relies on a compound binding to all subtypes, but having different efficacies at various subtypes. The status of BzR ligands, subdivided on the basis of their main chemical structural features, is reviewed in relation to structure-activity relationships which determine their affinity or efficacy selectivity for a certain BzR subtype.

  2. 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

  3. Study Points to Genetic Subtypes of Esophageal Cancer

    Science.gov (United States)

    A Cancer Currents blog post about a study by The Cancer Genome Atlas Research Network that identified distinct genetic and molecular changes in esophageal cancers that could improve their classification and identify potential new treatments.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wagerle, L.C.; Delivoria-Papadopoulos, M.

    1987-06-01

    The purpose of this study was to identify the ..cap alpha..-adrenergic receptor subtype mediating cerebral vasoconstriction during sympathetic nerve stimulation in the newborn piglet. The effect of ..cap alpha../sub 1/- and ..cap alpha../sub 2/-antagonists prazosin and yohimbine on the cerebrovascular response to unilateral electrical stimulation (15 Hz, 15 V) of the superior cervical sympathetic trunk was studied in 25 newborn piglets. Regional cerebral blood flow was measured with tracer microspheres. Sympathetic stimulation decreased blood flow to the ipsilateral cerebrum hippocampus, choroid plexus, and masseter muscle. ..cap alpha../sub 1/-Adrenergic receptor blockade with prazosin inhibited the sympathetic vasoconstriction in the cerebrum, hippocampus, and masseter muscle and abolished it in the choroid plexus. ..cap alpha../sub s/-Adrenergic receptor blockade with yohimbine had no effect. Following the higher dose of yohimbine, however, blood flow to all brain regions was increased by approximately two-fold, possibly due to enhanced cerebral metabolism. These data demonstrate that vascular ..cap alpha../sub 1/-adrenergic receptors mediate vasoconstriction to neuroadrenergic stimulation in cerebral resistance vessels in the newborn piglet.

  5. Oxidatively Modified Proteins in the Serous Subtype of Ovarian Carcinoma

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    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.

  6. Subtypes of GABAergic neurons project axons in the neocortex

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    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.

  7. Homicide-Complex Suicide: A Rare Subtype of Dyadic Death

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    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.

  8. 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.

  9. Optimizing prophylactic treatment of migraine: Subtypes and patient matching

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    Michel Dib

    2008-09-01

    Full Text Available Michel DibFédération du système nerveux central, Hôpital de la Salpêtrière, Assistance Publique- Hôpitaux de Paris, FranceAbstract: Advances in our understanding of the pathophysiology of migraine have resulted in important breakthroughs in treatment. For example, understanding of the role of serotonin in the cerebrovascular circulation has led to the development of triptans for the acute relief of migraine headaches, and the identification of cortical spreading depression as an early central event associated wih migraine has brought renewed interest in antiepileptic drugs for migraine prophylaxis. However, migraine still remains inadequately treated. Indeed, it is apparent that migraine is not a single disease but rather a syndrome that can manifest itself in a variety of pathological conditions. The consequences of this may be that treatment needs to be matched to particular patients. Clinical research needs to be devoted to identifying which sort of patients benefit best from which treatments, particularly in the field of prophylaxis. We propose four patterns of precipitating factors (adrenergic, serotoninergic, menstrual, and muscular which may be used to structure migraine prophylaxis. Finally, little is known about long-term outcome in treated migraine. It is possible that appropriate early prophylaxis may modify the long-term course of the disease and avoid late complications.Keywords: migraine, diagnosis, treatment, prophylaxis, subtypes

  10. Subtypes of Ovarian Cancer and Ovarian Cancer Screening

    Science.gov (United States)

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2017-01-01

    Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC) and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS) did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed. PMID:28257098

  11. Externalizing and internalizing subtypes of posttraumatic psychopathology and anger expression.

    Science.gov (United States)

    Castillo, Diane T; Joseph, Jeremy S; Tharp, Andra T; C'de Baca, Janet; Torres-Sena, Lorraine M; Qualls, Clifford; Miller, Mark W

    2014-02-01

    Subtypes of posttraumatic psychopathology were replicated and extended in 254 female veterans with posttraumatic stress disorder (PTSD). Cluster analyses on Minnesota Multiphasic Personality Inventory-2 and Personality Psychopathology Five scales (Harkness, McNulty, & Ben-Porath, ) yielded internalizing and externalizing psychopathology dimensions, with a third low psychopathology group (simple PTSD). Externalizers were higher than the internalizers and the simple PTSD groups on the antisocial, substance, and aggression scales; internalizers were higher on depression and anxiety scales. Further validation included an independent measure of psychopathology to examine anger (Buss-Durkee Hostility Inventory, [BDHI]; Buss & Durkee, ). Externalizers were higher on extreme behavioral anger scales (assault and verbal hostility); and externalizers and internalizers were higher than the simple PTSD subjects on other anger scales. Positive correlations between the BDHI scales and the PTSD symptom of "irritability and anger outbursts" were found across scales in the total sample (range: r = .19-.36), on the assault scale in externalizers (r = .59), and the verbal hostility scale in both internalizers (r = .30) and simple PTSD (r = .37) groups, suggesting the broad utility of the symptom in the diagnosis. The results demonstrate the generalizability of the internalizing/externalizing typology to the female veteran population and highlight clinically relevant distinctions in anger expression within PTSD.

  12. T Cell Transcriptomes Describe Patient Subtypes in Systemic Lupus Erythematosus.

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    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.

  13. 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

  14. Quality of life and mild cognitive impairment in early Parkinson's disease: does subtype matter?

    Science.gov (United States)

    Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Khoo, Tien K; Breen, David P; Barker, Roger A; Collerton, Daniel; Taylor, John-Paul; Burn, David J

    2014-01-01

    We evaluated the association between mild cognitive impairment (MCI) subtypes and quality of life (QoL) in 219 newly diagnosed Parkinson's disease (PD) patients without dementia. Participants completed neuropsychological tests of attention, executive function, visuospatial function, memory, and language, and reported QoL using the Parkinson's Disease Questionnaire. Impairments were most common in executive function, memory and attention. MCI subtypes were classified according to Movement Disorder Society Task Force criteria. More severe cognitive impairment was associated with poorer quality of life (p = 0.01), but subtype of impairment was not (p > 0.10), suggesting that the nature of cognitive impairment is less significant than its severity.

  15. 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.;

    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....

  16. Identifying Cancer Subtypes from miRNA-TF-mRNA Regulatory Networks and Expression Data.

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    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

  17. Subtype-specific reduction of olfactory bulb interneurons in Pax6 heterozygous mutant mice.

    Science.gov (United States)

    Haba, Hasumi; Nomura, Tadashi; Suto, Fumikazu; Osumi, Noriko

    2009-09-01

    Interneurons in the olfactory bulb (OB) play essential roles in the processing of olfactory information. They are classified into several subpopulations by the expression of different neurochemical markers. Here we focused on a transcription factor Pax6, and examined its expression and function in distinct subtypes of OB interneurons. We identified Pax6 expression in specific subtypes of interneurons in the external plexiform layer (EPL). The number of these interneuron subtypes was dramatically decreased in Pax6 heterozygous mutant mice. These results indicate that Pax6 is required for differentiation and/or maintenance of EPL interneurons in the adult mouse OB.

  18. Isolation and identification of highly pathogenic avian influenza virus subtype H5N1 from emus from the Ein Gedi oasis by the Dead Sea.

    Science.gov (United States)

    Amnon, Inbar; Shkoda, Irina; Lapin, Ekaterina; Raibstein, Israel; Rosenbluth, Ezra; Nagar, Sagit; Perk, Shimon; Bellaiche, Michel; Davidson, Irit

    2011-09-01

    An avian influenza virus (AIV), A/Emu/Israel/552/2010/(H5N1), was isolated from a dead emu that was found in the Ein Gedi oasis near the Dead Sea. The virus molecular characterization was performed by reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR using AIV subtype-specific primers. The virus was of high pathogenicity, according to its intravenous pathogenicity index of 2.85 and the nucleotide sequencing at the cleavage site of the hemagglutinin gene, GERRRKKR, which is typical for highly pathogenic chicken influenza A viruses.

  19. MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data

    Science.gov (United States)

    Mencoboni, Manlio; Grosso, Federica; Ceresoli, Giovanni Luca; Lunardi, Francesca; Vuljan, Stefania Edith; Bertorelle, Roberta; Sacchetto, Valeria; Ciminale, Vincenzo; Rea, Federico; Favaretto, Adolfo; Conte, PierFranco; Calabrese, Fiorella

    2015-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited treatment options. Sarcomatoid/biphasic mesotheliomas are characterized by more aggressive behaviour and a poorer prognosis compared with the epithelioid subtype. To date prognostic and tailored therapeutic biomarkers are lacking. The present study analyzed the expression levels of MDM2 and HIF1alpha in different histologic subtypes from chemonaive MPM patients. Diagnostic biopsies of MPM patients from four Italian cancer centers were centrally collected and analyzed. MDM2 and HIF1alpha expression levels were investigated through immunohistochemistry and RT-qPCR. Pathological assessment of necrosis, inflammation and proliferation index was also performed. Molecular markers, pathological features and clinical characteristics were correlated to overall survival (OS) and progression free survival (PFS). Sixty MPM patients were included in the study (32 epithelioid and 28 non-epithelioid). Higher levels of MDM2 (p < 0.001), HIF1alpha (p = 0.013), necrosis (p = 0.013) and proliferation index (p < 0.001) were seen mainly in sarcomatoid/biphasic subtypes. Higher levels of inflammation were significantly associated with epithelioid subtype (p = 0.044). MDM2 expression levels were correlated with HIF1alpha levels (p = 0.0001), necrosis (p = 0.008) and proliferation index (p = 0.009). Univariate analysis showed a significant correlation of non-epithelioid histology (p = 0.04), high levels of necrosis (p = 0.037) and proliferation index (p = 0.0002) with shorter PFS. Sarcomatoid/biphasic and epithelioid mesotheliomas showed different MDM2 and HIF1alpha expression levels and were characterized by different levels of necrosis, proliferation and inflammation. Further studies are warranted to confirm a prognostic and predictive role of such markers and features. PMID:26544728

  20. MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data.

    Science.gov (United States)

    Pasello, Giulia; Urso, Loredana; Mencoboni, Manlio; Grosso, Federica; Ceresoli, Giovanni Luca; Lunardi, Francesca; Vuljan, Stefania Edith; Bertorelle, Roberta; Sacchetto, Valeria; Ciminale, Vincenzo; Rea, Federico; Favaretto, Adolfo; Conte, PierFranco; Calabrese, Fiorella

    2015-12-08

    Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited treatment options. Sarcomatoid/biphasic mesotheliomas are characterized by more aggressive behaviour and a poorer prognosis compared with the epithelioid subtype. To date prognostic and tailored therapeutic biomarkers are lacking. The present study analyzed the expression levels of MDM2 and HIF1alpha in different histologic subtypes from chemonaive MPM patients. Diagnostic biopsies of MPM patients from four Italian cancer centers were centrally collected and analyzed. MDM2 and HIF1alpha expression levels were investigated through immunohistochemistry and RT-qPCR. Pathological assessment of necrosis, inflammation and proliferation index was also performed. Molecular markers, pathological features and clinical characteristics were correlated to overall survival (OS) and progression free survival (PFS). Sixty MPM patients were included in the study (32 epithelioid and 28 non-epithelioid). Higher levels of MDM2 (p sarcomatoid/biphasic subtypes. Higher levels of inflammation were significantly associated with epithelioid subtype (p = 0.044). MDM2 expression levels were correlated with HIF1alpha levels (p = 0.0001), necrosis (p = 0.008) and proliferation index (p = 0.009). Univariate analysis showed a significant correlation of non-epithelioid histology (p = 0.04), high levels of necrosis (p = 0.037) and proliferation index (p = 0.0002) with shorter PFS. Sarcomatoid/biphasic and epithelioid mesotheliomas showed different MDM2 and HIF1alpha expression levels and were characterized by different levels of necrosis, proliferation and inflammation. Further studies are warranted to confirm a prognostic and predictive role of such markers and features.

  1. Towards a brief definition of burnout syndrome by subtypes: Development of the "Burnout Clinical Subtypes Questionnaire" (BCSQ-12

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    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

  2. Immunity raised by recent European subtype 1 PRRSV strains allows better replication of East European subtype 3 PRRSV strain Lena than that raised by an older strain

    DEFF Research Database (Denmark)

    Trus, Ivan; Frydas, Ilias S.; Reddy, Vishwanatha R. A. P.

    2016-01-01

    Stable spatial distribution of porcine reproductive and respiratory syndrome (PRRSV)-1 subtypes in Europe is accompanied by a strong population immunity induced by local PRRSV strains. In the present study, it was examined if the immunity induced by three West European subtype 1 PRRSV strains (2007...... isolate 07V063 and 2013 isolates 13V091 and 13V117) offers protection against the highly virulent East European subtype 3 PRRSV strain Lena. The number of fever days was greater (p ...: 8.3). Reduction of respiratory disease, nasal shedding (mean AUC and mean peak values) and viremia (mean AUC and mean peak values) was more pronounced in 07V063-immune (p strains caused priming of the Lena...

  3. HIV subtype is not associated with dementia among individuals with moderate and advanced immunosuppression in Kampala, Uganda

    Science.gov (United States)

    Sacktor, Ned; Nakasujja, Noeline; Redd, Andrew D.; Manucci, Jordyn; Laeyendecker, Oliver; Wendel, Sarah K.; Porcella, Stephen F; Martens, Craig; Bruno, Daniel; Skolasky, Richard L.; Okonkwo, Ozioma C.; Robertson, Kevin; Musisi, Seggane; Katabira, Elly; Quinn, Thomas C.

    2014-01-01

    Background HIV-associated neurocognitive disorders (HAND) are a common neurological manifestation of HIV infection. A previous study suggested that HIV dementia may be more common among patients with subtype D virus than among those with subtype A virus among HIV+ individuals with advanced immunosuppression. We conducted a study to evaluate the frequency of HIV dementia, and the association of HIV dementia with HIV subtype and compartmentalization among HIV+ individuals with moderate and advanced immunosuppression (CD4 lymphocyte count >150 cells/μL and < 250 cells/μL). Methods The study enrolled 117 antiretroviral naïve HIV+ individuals in Kampala, Uganda. HIV+ individuals received neurological, neuropsychological testing, and functional assessments, and gag and gp41 regions were subtyped. Subjects were considered infected with a specific subtype if both regions analyzed were from the same subtype. Results 41% of the HIV+ individuals had HIV dementia (mean CD4 lymphocyte count= 233 cells/μL). 67 individuals had subtype A, 25 individuals had subtype D, 24 individuals were classified as A/D recombinants, and one individual had subtype C. There was no difference in the frequency of HIV dementia when stratified by HIV subtype A and D and no association with compartmentalization between the cerebrospinal fluid and peripheral blood. Conclusions These results suggest that HIV dementia is common in HIV+ individuals in Uganda. There was no association between HIV subtype and dementia among HIV+ individuals with moderate and advanced immunosuppression. Future studies should be performed to confirm these results. PMID:24515303

  4. Executive function profile of Chinese boys with attention-deficit hyperactivity disorder: different subtypes and comorbidity.

    Science.gov (United States)

    Shuai, Lan; Chan, Raymond C K; Wang, Yufeng

    2011-03-01

    This study examined the executive function (EF) profile of Chinese boys with attention-deficit hyperactivity disorder (ADHD) using a large sample. Executive function performance within the ADHD subtypes and the effects of comorbidity were also investigated. Five hundred Chinese boys (375 with ADHD and 125 controls) aged 6-15 completed a battery of EF tests. Boys with all types of ADHD performed worse in all of the EF tests than age- and intelligence quotient-matched healthy controls. The boys with the inattention ADHD subtype and the combined subtype showed similar impairments across different EF tasks, whereas the boys with the hyperactive-impulsive ADHD subtype primarily displayed deficits in theory of mind and visual memory. Comorbid oppositional defiant disorder/conduct disorder had no additional influence on the EF characteristics of the boys with ADHD only, whereas comorbid learning disorder increased the severity of inhibition and shifting impairments.

  5. Variation of types of alcoholism: review and subtypes identified in Han Chinese.

    Science.gov (United States)

    Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Lu, Ru-Band

    2014-01-03

    Alcoholism, as it has been hypothesized, is caused by a highly heterogeneous genetic load. Since 1960, many reports have used the bio-psycho-social approach to subtype alcoholism; however, no subtypes have been genetically validated. We reviewed and compared the major single-gene, multiple-gene, and gene-to-gene interaction studies on alcoholism published during the past quarter-century, including many recent studies that have made contributions to the subtyping of alcoholism. Four subtypes of alcoholism have been reported: [1] pure alcoholism, [2] anxiety/depression alcoholism, [3] antisocial alcoholism, and [4] mixed alcoholism. Most of the important studies focused on three genes: DRD2, MAOA, and ALDH2. Therefore, our review focuses on these three genes.

  6. Interpersonal Subtypes of Anxiety Disorder Patients: Relationship to Assessment and Treatment Variables.

    Science.gov (United States)

    Pitman, Seth R; Hilsenroth, Mark J

    2016-07-01

    We attempted to replicate earlier findings of interpersonal subtypes in patients with anxiety disorder (Psychotherapy. 2011;48:304-310) and examine whether these subtypes are characterized by different types of pathology and respond differently to treatment. Interpersonal problems were measured by the Inventory of Interpersonal Problems (Inventory of Interpersonal Problems Manual. San Antonio, TX: Psychological Cooperation; 2000) in a sample of 31 patients with anxiety disorder. Results demonstrated the existence of 4 interpersonal subtypes. The subtypes did not differ in severity of anxiety and global levels of symptoms at pretreatment or in Reliable Change Index of anxiety symptoms over the course of treatment. However, they were significantly different in terms of overall interpersonal problems (p = 0.004). Regarding treatment variables, half of the patients in the nonassertive cluster discontinued treatment prematurely. The number of psychotherapy sessions attended was significantly different across the 4 clusters (p = 0.04), with socially avoidant patients attending significantly greater number of sessions.

  7. GDE2 regulates subtype-specific motor neuron generation through inhibition of Notch signaling.

    Science.gov (United States)

    Sabharwal, Priyanka; Lee, Changhee; Park, Sungjin; Rao, Meenakshi; Sockanathan, Shanthini

    2011-09-22

    The specification of spinal interneuron and motor neuron identities initiates within progenitor cells, while motor neuron subtype diversification is regulated by hierarchical transcriptional programs implemented postmitotically. Here we find that mice lacking GDE2, a six-transmembrane protein that triggers motor neuron generation, exhibit selective losses of distinct motor neuron subtypes, specifically in defined subsets of limb-innervating motor pools that correlate with the loss of force-generating alpha motor neurons. Mechanistically, GDE2 is expressed by postmitotic motor neurons but utilizes extracellular glycerophosphodiester phosphodiesterase activity to induce motor neuron generation by inhibiting Notch signaling in neighboring motor neuron progenitors. Thus, neuronal GDE2 controls motor neuron subtype diversity through a non-cell-autonomous feedback mechanism that directly regulates progenitor cell differentiation, implying that subtype specification initiates within motor neuron progenitor populations prior to their differentiation into postmitotic motor neurons.

  8. Chest imaging of H7N9 subtype of human avian influenza

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    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.

  9. Folic acid supplementation influences the distribution of neural tube defect subtypes: A registry-based study.

    Science.gov (United States)

    Bergman, J E H; Otten, E; Verheij, J B G M; de Walle, H E K

    2016-01-01

    Periconceptional folic acid (FA) reduces neural tube defect (NTD) risk, but seems to have a varying effect per NTD subtype. We aimed to study the effect of FA supplementation on NTD subtype distribution using data from EUROCAT Northern Netherlands. We included all birth types with non-syndromal NTDs born in 1997-2012. By Fisher's exact test we analyzed possible differences in NTD subtype distribution between a correct FA supplementation group and incorrect FA supplementation group. We found proportionally fewer cervical/thoracic spina bifida cases and more lumbar/sacral spina bifida cases in the correct FA supplementation group, irrespective of the presence of the main NTD risk factors. The effect on NTD subtype distribution was only seen when FA supplementation was started before conception. We conclude that FA not only prevents the occurrence of a significant proportion of NTDs, but might also decrease the severity of NTDs, as long as supplementation is started before conception.

  10. Serum testosterone levels and symptom-based depression subtypes in men

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    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.

  11. Clinical, electrophysiological subtypes and antiganglioside antibodies in childhood Guillain-Barré syndrome

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    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

  12. Subtyping demoralization in the medically ill by cluster analysis

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    Chiara Rafanelli

    2013-03-01

    Full Text Available Background and Objectives: There is increasing interest in the issue of demoralization, particularly in the setting of medical disease. The aim of this investigation was to use both DSM-IV comorbidity and the Diagnostic Criteria for Psychosomatic Research (DCPR in order to characterize demoralization in the medically ill. Methods: 1700 patients were recruited from 8 medical centers in the Italian Health System and 1560 agreed to participate. They all underwent a cross-sectional assessment with DSM-IV and DCPR structured interviews. 373 patients (23.9% received a diagnosis of demoralization. Data were submitted to cluster analysis. Results: Four clusters were identified: demoralization and comorbid depression; demoralization and comorbid somatoform/adjustment disorders; demoralization and comorbid anxiety; demoralization without any comorbid DSM disorder. The first cluster included 2