tbuckley/cabot-search huggingface dataset:
Soy, Isoflavones, and Breast Cancer Risk in Japan
Authors: Seiichiro Yamamoto, Tomotaka Sobue, Minatsu Kobayashi, Satoshi Sasaki, Shoichiro Tsugane
Journal: JNCI Journal of the National Cancer Institute (2003)

Although isoflavones, such as those found in soy, have been shown to inhibit breast cancer in laboratory studies, associations between consumption of isoflavone-containing foods and breast cancer risk have been inconsistent in epidemiologic studies. We evaluated the relationship between isoflavone consumption and breast cancer risk among women in the Japan Public Health Center-Based Prospective Study on Cancer and Cardiovascular Diseases (JPHC Study).In January 1990, 21 852 Japanese female residents (aged 40-59 years) from four public health center areas completed a self-administered questionnaire, which included items about the frequency of soy consumption. Through December 1999 and 209 354 person-years of follow-up, 179 women were diagnosed with breast cancer. Cox proportional hazards regression was used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer in relation to consumption of miso soup, soyfoods, and estimated isoflavones. All statistical tests were two-sided.Consumption of miso soup and isoflavones, but not of soyfoods, was inversely associated with the risk of breast cancer. The associations did not change substantially after adjustment for potential confounders, including reproductive history, family history, smoking, and other dietary factors. Compared with those in the lowest quartile of isoflavone intake, the adjusted RRs for breast cancer for women in the second, third, and highest quartiles were 0.76 (95% CI = 0.47 to 1.2), 0.90 (95% CI = 0.56 to 1.5), and 0.46 (95% CI = 0.25 to 0.84), respectively (P(trend) =.043). The inverse association was stronger in postmenopausal women (P(trend) =.006).In a population-based, prospective cohort study in Japan, frequent miso soup and isoflavone consumption was associated with a reduced risk of breast cancer.
Inhibition of Epstein-Barr virus (EBV) release from the P3HR-1 Burkitt's lymphoma cell line by a monoclonal antibody against a 200,000 dalton EBV membrane antigen.
Authors: T Sairenji, P S Reisert, R C Spiro, T Connolly, R E Humphreys
Journal: The Journal of Experimental Medicine (1985)

In raising murine hybridoma antibodies against Epstein-Barr virus (EBV)-induced membrane antigens (MA), we found one antibody that blocked the release of infectious EBV from cultured P3HR-1 cells. This monoclonal antibody (mAb) recognized a 200 kD, phosphonoacetic acid-sensitive (late) MA, and did not directly neutralize virus without complement. When this mAb was added to 33 degrees C-cultured, spontaneously EBV-producing P3HR-1 cells, the intracellular expression of viral capsid antigen and infectious virus was not inhibited, but the appearance of infectious virus in the culture medium was significantly reduced. The duration of this suppression was dependent upon the concentration of the mAb, an effect being observed to a 1:4 X 10(5) titer of the ascites mAb preparation. A more acute effect of suppression of EBV release was observed in a second model of 12-o-tetradecanoyl phorbol-13-acetate and n-butyrate induction of EBV in 37 degrees C-cultured P3HR-1 cells. Again, intracellular infectious virus production was not inhibited, but the level of infectious virus in the culture medium was significantly reduced as early as 1 and 2 d of culture with antibody. This effect was reversed within 31 h after replacement of mAb-containing medium with fresh medium. This description of antibody-mediated inhibition of EBV release might lead to the characterization of another form of immune defense for the control of EBV infections.
Arabidopsis replacement histone variant H3.3 occupies promoters of regulated genes
Authors: Huan Shu, Miyuki Nakamura, Alexey Siretskiy, Lorenzo Borghi, Izabel Moraes, Thomas Wildhaber, Wilhelm Gruissem, Lars Hennig
Journal: Genome biology (2014)

Abstract Background Histone variants establish structural and functional diversity of chromatin by affecting nucleosome stability and histone-protein interactions. H3.3 is an H3 histone variant that is incorporated into chromatin outside of S-phase in various eukaryotes. In animals, H3.3 is associated with active transcription and possibly maintenance of transcriptional memory. Plant H3 variants, which evolved independently of their animal counterparts, are much less well understood. Results We profile the H3.3 distribution in Arabidopsis at mono-nucleosomal resolution using native chromatin immunoprecipitation. This results in the precise mapping of H3.3-containing nucleosomes, which are not only enriched in gene bodies as previously reported, but also at a subset of promoter regions and downstream of the 3′ ends of active genes. While H3.3 presence within transcribed regions is strongly associated with transcriptional activity, H3.3 at promoters is often independent of transcription. In particular, promoters with GA motifs carry H3.3 regardless of the gene expression levels. H3.3 on promoters of inactive genes is associated with H3K27me3 at gene bodies. In addition, H3.3-enriched plant promoters often contain RNA Pol II considerably upstream of the transcriptional start site. H3.3 and RNA Pol II are found on active as well as on inactive promoters and are enriched at strongly regulated genes. Conclusions In animals and plants, H3.3 organizes chromatin in transcribed regions and in promoters. The results suggest a function of H3.3 in transcriptional regulation and support a model that a single ancestral H3 evolved into H3 variants with similar sub-functionalization patterns in plants and animals.
Patterns and Predictors of Treatment Contact After First Onset of Psychiatric Disorders
Authors: R C Kessler, M Olfson, P A Berglund
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The authors used self-report data to study patterns and predictors of treatment contact after the first onset of DSM-III-R mood, anxiety, and addictive disorders. METHOD: Data from the National Comorbidity Survey, a general population survey of 8,098 respondents, were used. Disorders were assessed by using a modified version of the Composite International Diagnostic Interview. Age at onset and age at first treatment contact were assessed retrospectively. RESULTS: There was great variation across disorders in lifetime probability of treatment contact. Most treatment contact was delayed; the median delay time was between 6 and 14 years across the disorders considered here. Probability of treatment contact was inversely related to age at onset and increased in younger cohorts. The effects of sociodemographic variables were modest and inconsistent across disorders. CONCLUSIONS: The majority of people with the disorders considered here eventually make treatment contact. However, delay was pervasive. Further research is needed on the determinants of delay and on the low probability of lifetime treatment contact among people with early-onset psychiatric disorders. (Am J Psychiatry 1998; 155:62–69)
Overcoming the Response Plateau in Multiple Myeloma: A Novel Bortezomib-Based Strategy for Secondary Induction and High-Yield CD34+ Stem Cell Mobilization
Authors: Ruben Niesvizky, Tomer M. Mark, Maureen Ward, David S. Jayabalan, Roger N. Pearse, Megan Manco, Jessica Stern, Paul J. Christos, Lena Mathews, Tsiporah B. Shore, Faiza Zafar, Karen Pekle, Zhaoying Xiang, Scott Ely, Donna Skerret, Selina Chen-Kiang, Morton Coleman, Maureen E. Lane
Journal: Clinical Cancer Research (2013)

Abstract Purpose: This phase II study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible patients with myeloma who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Experimental Design: Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells after bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. Results: The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; postmobilization response rate was 96%, including 48% ≥VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 106 cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation; 5-year overall survival rate was 76.4%. Grade ≥3 adverse events included thrombocytopenia (13%), hand–foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Conclusion: Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield. Clin Cancer Res; 19(6); 1534–46. ©2013 AACR.
Paleoecology and the overlap of homeotic genes for isocortex evolution
Authors: Danilo Arruda Furtado
Journal: Behavioral and Brain Sciences (2003)

Two issues in synapsid brain evolution are discussed: the presumed structure and function of the brain of the Synapsida/Diapsida common ancestral, and the enlargement of dorsal telencephalon. Ecological niches possibly occupied by some Carboniferous tetrapods are considered in order to speculate about evolution of major telencephalic sectors. An alternative interpretation of isocortical origins, based on differences in Pax-6 expression, is suggested for discussion.
International Consensus Study of Antipsychotic Dosing
Authors: David M Gardner, Andrea L Murphy, Heather O'Donnell, Franca Centorrino, Ross J Baldessarini
Journal: American Journal of Psychiatry (2010)

Objective Potency equivalents for anti­psychotic drugs are required to guide clinical dosing and for designing and interpreting research studies. Available dosing guidelines are limited by the methods and data from which they were generated. Method With a two-step Delphi method, the authors surveyed a diverse group of international clinical and research experts, seeking consensus regarding antipsychotic dosing. The authors determined median clinical dosing equivalents and recommended starting, target range, and maximum doses for 61 drugs, adjusted for selected clinical circumstances. Results Participants (N=43) from 18 countries provided dosing recommendations regarding treatment of psychotic disorders for 37 oral agents and 14 short-acting and 10 long-acting parenteral agents. With olanzapine 20 mg/day as reference, estimated clinical equivalency ratios of oral agents ranged from 0.025 for sulpiride to 10.0 for trifluperidol. Seventeen patient and treatment characteristics, including age, hepatic and renal function, illness stage and severity, sex, and diagnosis, were associated with dosing modifications. Conclusions In the absence of adequate prospective, randomized drug-drug comparisons, the present findings provide broad, international, expert consensus-based recommendations for most clinically employed antipsychotic drugs. They can support clinical practice, trial design, and interpretation of comparative antipsychotic trials.
HEMOPOIETIC COLONY STUDIES
Authors: N. S. Wolf, J. J. Trentin
Journal: The Journal of Experimental Medicine (1968)

In heavily irradiated mice, bone marrow regeneration of either endogenous or exogenous origin was shown to occur in discrete foci comparable to the more intensively studied spleen colonies. The number of endogenous bone marrow colonies was inversely related to dose of whole body X-irradiation. Endogenous marrow colonies were found after higher doses of irradiation than were endogenous spleen colonies. Most of them were granulocytic in nature. Exogenous bone marrow colonies in lethally irradiated mice injected with bone marrow cells were proportional in number to the dose of cells injected, appeared at a time comparable to spleen colonies like which, at 7 or 8 days, they were of single differentiated cell line, either granuloid or erythroid or megakaryocytic, with a small percentage of "mixed" colonies. Whereas erythroid colonies outnumber granuloid colonies in spleen, either in situ or subcutaneously transplanted (E:G colony ratio of about 3.5), granuloid colonies outnumber erythroid in bone marrow (E:G colony ratio of about 0.7). The characteristic E:G colony ratios of spleen and marrow appear more likely to be the result of a hemopoietic organ stromal influence on pluripotent colony forming units (CFU's) than of selective lodgment of committed (unipotent) granuloid and erythroid CFU's in bone marrow and spleen, respectively, as indicated by the following. Bone marrow stem cells (CFU) which had reseeded the marrow cavity of irradiated primary recipients 18-24 hr earlier, were reharvested and retransplanted intravenously into irradiated secondary hosts. The E:G colony ratio of the colonies formed in the spleen of the secondary hosts was typical of primary spleen colonies (2.8), that of the colonies formed in the marrow cavity was typical of bone marrow colonies (0.6). Pieces of marrow stroma containing reseeded CPU's from the contralateral femur of these same primary recipients were implanted by trocar directly into the spleens of other irradiated secondary recipients. Those CPU's that developed in the intrasplenic-implanted marrow stroma yielded an. E:G colony ratio of 0.1. Those that migrated into the contiguous and remote portions of the spleen gave E:G colony ratios of 2.9 and 2.4, respectively. Irradiated marrow stroma and normal spleen CPU's (a 1 mm cube of spleen) were loaded into the same trocar and implanted directly into the spleens of irradiated mice. The spleen CFU's that migrated into the implanted marrow stroma yielded five granuloid and two mixed colonies. The larger number that developed in the host spleen yielded an E:G colony ratio of 2.9 or higher. Of those 19 mixed colonies that bridged the junction of spleen and implanted marrow stroma in each of the above two experiments, in every case, the erythroid portion of the colony was in the splenic stroma, the granuloid portion was in the marrow stroma.
Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications
Authors: Lingyun Wu, Rui Wang
Journal: Pharmacological Reviews (2005)

Over the last decade, studies have unraveled many aspects of endogenous production and physiological functions of carbon monoxide (CO). The majority of endogenous CO is produced in a reaction catalyzed by the enzyme heme oxygenase (HO). Inducible HO (HO-1) and constitutive HO (HO-2) are mostly recognized for their roles in the oxidation of heme and production of CO and biliverdin, whereas the biological function of the third HO isoform, HO-3, is still unclear. The tissue type-specific distribution of these HO isoforms is largely linked to the specific biological actions of CO on different systems. CO functions as a signaling molecule in the neuronal system, involving the regulation of neurotransmitters and neuropeptide release, learning and memory, and odor response adaptation and many other neuronal activities. The vasorelaxant property and cardiac protection effect of CO have been documented. A plethora of studies have also shown the importance of the roles of CO in the immune, respiratory, reproductive, gastrointestinal, kidney, and liver systems. Our understanding of the cellular and molecular mechanisms that regulate the production and mediate the physiological actions of CO has greatly advanced. Many diseases, including neurodegenerations, hypertension, heart failure, and inflammation, have been linked to the abnormality in CO metabolism and function. Enhancement of endogenous CO production and direct delivery of exogenous CO have found their applications in many health research fields and clinical settings. Future studies will further clarify the gasotransmitter role of CO, provide insight into the pathogenic mechanisms of many CO abnormality-related diseases, and pave the way for innovative preventive and therapeutic strategies based on the physiologic effects of CO.
Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/ -catenin signalling pathway
Authors: L. Fu, C. Zhang, L.-Y. Zhang, S.-S. Dong, L.-H. Lu, J. Chen, Y. Dai, Y. Li, K. L. Kong, D. L. Kwong, X.-Y. Guan
Journal: Gut (2011)

Interaction between neoplastic and stromal cells plays an important role in tumour progression. It was recently found that WNT2 was frequently overexpressed in fibroblasts isolated from tumour tissue tumour fibroblasts (TF) compared with fibroblasts from non-tumour tissue normal fibroblasts in oesophageal squamous cell carcinoma (OSCC). This study aimed to investigate the effect of TF-secreted Wnt2 in OSCC development via the tumour-stroma interaction.Quantitative PCR, western blotting, immunohistochemistry and immunofluorescence were used to study the expression pattern of Wnt2 and its effect on the Wnt/β-catenin pathway. A Wnt2-secreting system was established in Chinese hamster ovary cells and its conditioned medium was used to study the role of Wnt2 in cell proliferation and invasion.Expression of Wnt2 could only be detected in TF but not in OSCC cancer cell lines. In OSCC tissues, Wnt2(+) cells were mainly detected in the boundary between stroma and tumour tissue or scattered within tumour tissue. In this study, Wnt2-positive OSCC was defined when five or more Wnt2(+) cells were observed in 200× microscopy field. Interestingly, Wnt2-positive OSCC (22/51 cases) was significantly associated with lymph node metastases (p=0.001), advanced TNM stage (p=0.001) and disease-specific survival (p<0.0001). Functional study demonstrated that secreted Wnt2 could promote oesophageal cancer cell growth by activating the Wnt/β-catenin signalling pathway and subsequently upregulated cyclin D1 and c-myc expression. Further study found that Wnt2 could enhance cell motility and invasiveness by inducing epithelial-mesenchymal transition.TF-secreted Wnt2 acts as a growth and invasion-promoting factor through activating the canonical Wnt/β-catenin signalling pathway in oesophageal cancer cells.
Combining rapid diagnostic tests and dried blood spot assays for point-of-care testing of human immunodeficiency virus, hepatitis B and hepatitis C infections in Burkina Faso, West Africa
Authors: D. Kania, A.M. Bekalé, N. Nagot, A.-M. Mondain, L. Ottomani, N. Meda, M. Traoré, J.B. Ouédraogo, J. Ducos, P. Van de Perre, E. Tuaillon
Journal: Clinical Microbiology and Infection (2013)
Influence of Androgen Suppression Therapy for Prostate Cancer on the Frequency and Timing of Fatal Myocardial Infarctions
Authors: Anthony V. D'Amico, James W. Denham, Juanita Crook, Ming-Hui Chen, Samuel Z. Goldhaber, David S. Lamb, David Joseph, Keen-Hun Tai, Shawn Malone, Charles Ludgate, Allison Steigler, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2007)

We evaluated whether the timing of fatal myocardial infarction (MI) was influenced by the administration of androgen suppression therapy (AST).The study cohort comprised 1,372 men who were enrolled onto three randomized trials between February 1995 and June 2001. In the three trials, the men were randomly assigned to receive radiation therapy with 0 versus 3 versus 6, 3 versus 8, or 0 versus 6 months of AST. Fine and Gray's regression was used to determine the clinical factors associated with the time to fatal MI, and estimates of time to fatal MI were calculated using a cumulative incidence method. When comparing the cumulative incidence estimates using Gray's k-sample P values, increased weight was ascribed to the earlier data because recovery of testosterone is expected for most men within 2 years after short-course AST.Men age 65 years or older who received 6 months of AST experienced shorter times to fatal MIs compared with men in this age group who did not receive AST (P = .017) and men younger than 65 years (P = .016). No significant difference (P = .97) was observed in the time to fatal MIs in men age 65 years or older who received 6 to 8 months of AST compared with 3 months of AST.The use of AST is associated with earlier onset of fatal MIs in men age 65 years or older who are treated for 6 months compared with men who are not treated with AST.
The role of the natural environment in the emergence of antibiotic resistance in Gram-negative bacteria
Authors: Elizabeth MH Wellington, Alistair BA Boxall, Paul Cross, Edward J Feil, William H Gaze, Peter M Hawkey, Ashley S Johnson-Rollings, Davey L Jones, Nicholas M Lee, Wilfred Otten, Christopher M Thomas, A Prysor Williams
Journal: The Lancet Infectious Diseases (2013)
Autologous Cardiomyotissue Implantation Promotes Myocardial Regeneration, Decreases Infarct Size, and Improves Left Ventricular Function
Authors: Joanna J. Wykrzykowska, Audrey Rosinberg, Seung U. Lee, Pierre Voisine, Guifu Wu, Evan Appelbaum, Munir Boodhwani, Frank W. Sellke, Roger J. Laham
Journal: Circulation (2010)

Cell therapy for myocardial infarction (MI) may be limited by poor cell survival and lack of transdifferentiation. We report a novel technique of implanting whole autologous myocardial tissue from preserved myocardial regions into infarcted regions.Fourteen rats were used to optimize cardiomyotissue size with peritoneal wall implantation (300 μm identified as optimal size). Thirty-nine pigs were used to investigate cardiomyotissue implantation in MI induced by left anterior descending balloon occlusion (10 animals died; male-to-female transplantation for tracking with in situ hybridization for Y chromosome, n=4 [2 donors and 2 MI animals]; acute MI implantation cohort at 1 hour, n=13; and healed MI implantation at 2 weeks, n=12). Assessment included echocardiography, magnetic resonance imaging, hemodynamics, triphenyltetrazolium chloride staining, and histological and molecular analyses. Tracking studies demonstrated viable implants with donor cells interspersed in the adjacent myocardium with gap junctions and desmosomes. In the acute MI cohort, treated animals compared with controls had improved perfusion by magnetic resonance imaging (1.2±0.01 versus 0.86±0.05; P<0.01), decreased MI size (magnetic resonance imaging: left ventricle, 2.2±0.5% versus 5.4±1.5%, P=0.04; triphenyltetrazolium chloride: anterior wall, 10.3±4.6% versus 28.9±5.8%, P<0.03), and improved contractility (dP/dt, 1235±215 versus 817±817; P<0.05). In the healed MI cohort, treated animals had less decline in ejection fraction between 2 and 4 week assessment (-3±4% versus -13±-4%; P<0.05), less decline in ±dP/dt, and smaller MI (triphenyltetrazolium chloride, 21±11% versus 3±8%; P=0.006) than control animals. Infarcts in the treated animals contained more mdr-1(+) cells and fewer c-kit(+) cells with a trend for decreased expression of matrix metalloproteinase-2 and increased expression of tissue inhibitor of metalloproteinase-2.Autologous cardiomyotissue implanted in an MI area remains viable, exhibits electromechanical coupling, decreases infarct size, and improves left ventricular function.
The ASH Choosing Wisely® campaign: five hematologic tests and treatments to question
Authors: Lisa K. Hicks, Harriet Bering, Kenneth R. Carson, Judith Kleinerman, Vishal Kukreti, Alice Ma, Brigitta U. Mueller, Sarah H. O'Brien, Marcelo Pasquini, Ravindra Sarode, Lawrence Solberg, Adam E. Haynes, Mark A. Crowther
Journal: Blood (2013)