tbuckley/cabot-search huggingface dataset:
Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance
Authors: Noemi Soto-Nieves, Irene Puga, Brian T. Abe, Sanmay Bandyopadhyay, Ian Baine, Anjana Rao, Fernando Macian
Journal: The Journal of Experimental Medicine (2009)

In T cells, anergy can be induced after T cell receptor engagement in the absence of costimulation. Under these conditions, the expression of a specific set of anergy-associated genes is activated. Several lines of evidence suggest that nuclear factor of activated T cells (NFAT) proteins may regulate the expression of many of those genes; however, the nature of the complexes responsible for the induction of this new program of gene expression is unknown. Here, we show that transcriptional complexes formed by NFAT homodimers are directly responsible for the activation of at least two anergy-inducing genes, Grail and Caspase3. Our data shows that Grail expression is activated by direct binding of NFAT dimers to the Grail promoter at two different sites. Consequently, a mutant NFAT protein with impaired ability to dimerize is not able to induce an unresponsive state in T cells. Our results not only identify a new biological function for NFAT dimers but also reveal the different nature of NFAT-containing complexes that induce anergy versus those that are activated during a productive immune response. These data also establish a basis for the design of immunomodulatory strategies that specifically target each type of complex.
Coronary pressure-flow relationships. Controversial issues and probable implications.
Authors: F J Klocke, R E Mates, J M Canty, A K Ellis
Journal: Circulation Research (1985)

On the basis of the material discussed, our current assessments of the controversial points mentioned at the beginning of this article may be summarized as follows: Pf = 0, the minimum back pressure to coronary flow associated with a measurable conductance, is indeed greater than coronary outflow pressure (and usually left ventricular diastolic pressure, as well). Pf = 0 needs to be taken into account in attempts to determine coronary driving pressure. In maximally vasodilated beds, Pf = 0 derived from diastolic pressure-flow relationships exceeds coronary outflow pressure by at least a few mm Hg. Pf = 0 varies with coronary outflow and/or diastolic ventricular cavity pressure. When left ventricular preload is elevated, Pf = 0 exceeds outflow pressure by increasing amounts. Pf = 0 appears to be systematically higher and pressure-dependent in beds in which vasomotor tone is operative. An improved understanding of the nature of, and basis for, time-dependent changes in resistance and/or Pf = 0 during long diastoles in nonvasodilated beds is needed. The contour of pressure-flow relationships which are free of reactive effects is curvilinear rather than linear. The degree of curvilinearity is substantial and can change with interventions. Curvilinearity is accentuated at lower pressures and may reflect changes in the number of perfused vascular channels as well as the caliber of individual channels. Capacitive effects need to be dealt with quantitatively in studies of pressure-flow relationships. Values of the capacitance which is involved in these effects vary with both pressure and tone. Capacitive flow also depends upon the instantaneous rate of change of pressure, which has not usually been defined in published studies. Although intramyocardial capacitance is large and plays an important role in systolic-diastolic flow interactions, a controlling role in diastolic coronary arterial pressure-flow relationships has not been established experimentally. In vasodilated beds, in-flow remains remarkably constant for several seconds after the brief transient associated with a step-change in the level of constant pressure perfusion during a long diastole. Calculations of coronary vascular resistance (by whatever method) remain of limited value, particularly when changes in response to an intervention are modest. Because of the curvilinear diastolic pressure-flow relationship, resistance is pressure-dependent and, at any given pressure, is probably best defined by establishing the slope of a diastolic pressure-flow curve which is free of reactive effects.(ABSTRACT TRUNCATED AT 400 WORDS)
Guidelines for the management of lichen sclerosus
Authors: S.M. Neill, F.M. Tatnall, N.H. Cox
Journal: British Journal of Dermatology (2002)

Summary These guidelines for the management of lichen sclerosus have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.
Endothelial cells present an innate resistance to glucocorticoid treatment: implications for therapy of primary vasculitis
Authors: Paola Koenen, Katarzyna Barczyk, Marc Wolf, Johannes Roth, Dorothee Viemann
Journal: Annals of the Rheumatic Diseases (2011)

Background In contrast to other chronic inflammatory diseases glucocorticoids alone do not maintain sufficient remission in primary vasculitis. The reasons for this therapeutic failure remain unclear. Objectives To investigate the molecular effects glucocorticoids exert on endothelial cells (EC) and to elucidate the molecular pathways responsible. Methods A comparative approach was used to treat human micro and macrovascular EC as well as monocytes long and short term with glucocorticoids or glucocorticoids and tumour necrosis factor alpha (TNFα). Gene expression changes were analysed applying microarray technology, sophisticated bioinformatic work-up and quantitative reverse transcription PCR. Glucocorticoid receptor translocation processes were traced by cell fractionation assays and immunofluorescence microscopy. Results In EC glucocorticoids completely failed to inhibit the expression of immune response genes both after sole glucocorticoid exposure and glucocorticoid treatment of a TNFα-induced proinflammatory response. In contrast, an impressive downregulation of proinflammatory genes was seen in monocytes. The study demonstrated that the glucocorticoid receptor is comparably expressed in EC and monocytes, and demonstrated good translocation of ligand-bound glucocorticoid receptor allowing genomic glucocorticoid actions. Refined gene expression analysis showed that in EC transactivation takes place and causes glucocorticoid side effects on growth and metabolism whereas transrepression-mediated anti-inflammatory effects as in monocytes are missing. Insufficient induction of SAP30, an important constituent of the Sin3A-histone deacetylase complex, in EC suggests impairment of transrepression due to co-repressor absence. Conclusions The impressive unresponsiveness of EC to anti-inflammatory glucocorticoid effects is associated with deficiencies downstream of glucocorticoid receptor translocation not affecting transactivation but transrepression. The findings provide the first molecular clues to the poor benefit of glucocorticoid treatment in patients with primary vasculitis.
The impact of endocrine disrupters on the female reproductive system
Authors: P. Nicolopoulou-Stamati
Journal: Human Reproduction Update (2001)

Over the last decades, many tonnes of man-made chemicals have been produced and released into the environment. Many of these chemical substances have the ability to modulate the action of hormones and are called endocrine disrupters. Cell receptors that have been pure receptors for thousands of years have (due to industrialization), become susceptible to the action of exogenous chemicals. The balance of the endocrine system is very important in the human body especially in females because the menstrual cycle and fertility are very sensitive to hormone imbalances. This review considers the mode of exposure and action of endocrine disrupters and focuses on their impact on the female reproductive system, including female hormone concentrations, menstrual cycle, fertility, spontaneous abortion and the development of endometriosis. An attempt is made to elucidate the impact of endocrine disrupters on the female reproductive system, while admitting that most scientific data come from experimental animals and the conclusions cannot be applied to humans easily. The aim is to present available information, highlighting the impact of endocrine disrupters on the female reproductive system, in order to stimulate re-evaluation in identifying hormone disorders.
Insulin resistance and depressive symptoms in middle aged men: findings from the Caerphilly prospective cohort study
Authors: Debbie A Lawlor, Yoav Ben-Shlomo, Shah Ebrahim, George Davey Smith, Stephen A Stansfeld, John W G Yarnell, John E J Gallacher
Journal: BMJ (2005)

Insulin resistance may protect against depression, possibly through an effect on circulating free fatty acid concentrations and brain serotonin concentration, 1 2 although a recent study contradicted these findings. 3Studies to date have either used indirect measures of insulin resistance, 1 or they have been cross sectional. 2 3We assessed the association of insulin resistance with depressive symptoms in a prospective cohort.
Acute Phosphate Nephropathy following Oral Sodium Phosphate Bowel Purgative
Authors: Glen S. Markowitz, M. Barry Stokes, Jai Radhakrishnan, Vivette D. D’Agati
Journal: Journal of the American Society of Nephrology (2005)

The findings of diffuse tubular injury with abundant tubular calcium phosphate deposits on renal biopsy are referred to as nephrocalcinosis, a condition typically associated with hypercalcemia. During the period from 2000 to 2004, 31 cases of nephrocalcinosis were identified among the 7349 native renal biopsies processed at Columbia University. Among the 31 patients, 21 presented with acute renal failure (ARF), were normocalcemic, and had a history of recent colonoscopy preceded by bowel cleansing with oral sodium phosphate solution (OSPS) or Visicol. Because the precipitant was OSPS rather than hypercalcemia, these cases are best termed <i>acute phosphate nephropathy.</i> The cohort of 21 patients with APhN was predominantly female (81.0%) and white (81.0%), with a mean age of 64.0 yr. Sixteen of the 21 patients had a history of hypertension, 14 (87.5%) of whom were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. The mean baseline serum creatinine was 1.0 mg/dl, available within 4 mo of colonoscopy in 19 (90.5%) patients. Patients presented with ARF and a mean creatinine of 3.9 mg/dl at a median of 1 mo after colonoscopy. In a few patients, ARF was discovered within 3 d of colonoscopy, at which time hyperphosphatemia was documented. Patients had minimal proteinuria, normocalcemia, and bland urinary sediment. At follow-up (mean 16.7 mo), four patients had gone on to require permanent hemodialysis. The remaining 17 patients all have developed chronic renal insufficiency (mean serum creatinine, 2.4 mg/dl). Acute phosphate nephropathy is an underrecognized cause of acute and chronic renal failure. Potential etiologic factors include inadequate hydration (while receiving OSPS), increased patient age, a history of hypertension, and concurrent use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.
Risks and outcomes of idiopathic pneumonia syndrome after nonmyeloablative and conventional conditioning regimens for allogeneic hematopoietic stem cell transplantation
Authors: Takahiro Fukuda, Robert C. Hackman, Katherine A. Guthrie, Brenda M. Sandmaier, Michael Boeckh, Michael B. Maris, David G. Maloney, H. Joachim Deeg, Paul J. Martin, Rainer F. Storb, David K. Madtes
Journal: Blood (2003)
A Susceptibility Locus at Chromosome 3p21 Linked to Familial Nasopharyngeal Carcinoma
Authors: Wei Xiong, Zhao Yang Zeng, Jia Hui Xia, Kun Xia, Shou Rong Shen, Xiao Ling Li, Dong Xu Hu, Chen Tan, Juan Juan Xiang, Jie Zhou, Hao Deng, Song Qing Fan, Wei Fang Li, Rong Wang, Ming Zhou, Shi Guo Zhu, Hong Bin Lü, Jun Qian, Bi Cheng Zhang, Jie Ru Wang, Jian Ma, Bing Yi Xiao, He Huang, Qiu Hong Zhang, Yan Hong Zhou, Xiao Min Luo, Hou De Zhou, Yi Xin Yang, He Ping Dai, Guo Yin Feng, Qian Pan, Ling Qian Wu, Lin He, Gui Yuan Li
Journal: Cancer Research (2004)

Abstract Nasopharyngeal carcinoma (NPC) poses one of the serious health problems in southern Chinese, with an incidence rate ranging from 15 to 50/100,000. Chromosome translocation t(1;3) and frequent loss of heterogeneity on short arms of chromosome 3 and 9 have been reported to be associated with NPC, and a genome-wide scan identified an NPC susceptibility locus on chromosome 4p15.1-q12 recently. In our study, we collected samples from 18 families at high risk of NPC from the Hunan province in southern China, genotyped with a panel of polymorphic markers on short arms of chromosomes 3, 9, and 4p15.1-q12. A locus on 3p21 was identified to link to NPC with a maximum logarithm of odds for linkage score of 4.18. Fine mapping located the locus to a 13.6-cM region on 3p21.31-21.2, where a tumor suppressor gene cluster resided. Our findings identified a novel locus for NPC and provided a map location for susceptibility genes candidates. In contrast to a recent study, no significant evidence for NPC linkage to chromosomes 4 and 9 was observed.
Plasma Alkylresorcinols, Biomarkers of Whole-Grain Wheat and Rye Intake, and Incidence of Colorectal Cancer
Authors: Cecilie Kyrø, Anja Olsen, Rikard Landberg, Guri Skeie, Steffen Loft, Per Åman, Max Leenders, Vincent K. Dik, Peter D. Siersema, Tobias Pischon, Jane Christensen, Kim Overvad, Marie-Christine Boutron-Ruault, Guy Fagherazzi, Vanessa Cottet, Tilman Kühn, Jenny Chang-Claude, Heiner Boeing, Antonia Trichopoulou, Christina Bamia, Dimitrios Trichopoulos, Domenico Palli, Vittorio Krogh, Rosario Tumino, Paolo Vineis, Salvatore Panico, Petra H. Peeters, Elisabete Weiderpass, Toril Bakken, Lene Angell Åsli, Marcial Argüelles, Paula Jakszyn, María-José Sánchez, Pilar Amiano, José María Huerta, Aurelio Barricarte, Ingrid Ljuslinder, Richard Palmqvist, Kay-Tee Khaw, Nick Wareham, Timothy J. Key, Ruth C. Travis, Pietro Ferrari, Heinz Freisling, Mazda Jenab, Marc J. Gunter, Neil Murphy, Eilo Riboli, Anne Tjønneland, H.B(as). Bueno-de-Mesquita
Journal: JNCI Journal of the National Cancer Institute (2013)

Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations. The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored. High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher). High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer.
Emergency Laparotomy Immediately After Coronary Bypass
Authors: Aaron Lucas
Journal: JAMA (1980)

Eight patients required emergency laparotomy in the immediate postoperative period after coronary artery bypass (CAB). Cardiac complications were few and minor. Sepsis was the major cause of mortality. In the two patients who died, delay in operative management contributed to their deaths. The lack of cardiac causes of morbidity and mortality in our series and others suggests that a stable postoperative coronary bypass patient represents a better surgical risk than the same patient preoperatively. Therefore, aggressive management, including early laparotomy, for suspected intra-abdominal pathology after CAB is recommended to avoid uncontrollable sepsis and death.
The effect of cryopreservation on the genome of gametes and embryos: principles of cryobiology and critical appraisal of the evidence
Authors: Julia Kopeika, Alan Thornhill, Yacoub Khalaf
Journal: Human Reproduction Update (2014)

BACKGROUNDCryopreservation has been extensively used in assisted reproductive technology, agriculture and conservation programmes for endangered species. The literature reports largely positive results regarding the survival of frozen–thawed cells and clinical outcomes. Nonetheless, it is unclear whether or not cryopreservation of sperm, oocytes and embryos causes any disruption in their genetic integrity. Drawing on the available published evidence, this review paper describes in detail the physical and biochemical factors of cryopreservation that could potentially affect genomic integrity.
Potential for lung sound monitoring during bronchial provocation testing.
Authors: A B Bohadana, R Peslin, H Uffholtz, G Pauli
Journal: Thorax (1995)

BACKGROUND--The use of lung sound monitoring during bronchial provocation testing has not been clearly demonstrated. The appearance of wheeze and changes in inspiratory breath sound intensity have been analysed and related to changes in spirometric parameters and to airways hyperresponsiveness. METHODS--Lung sounds were recorded in 38 patients undergoing a routine carbachol airway challenge (CAC) test. Spirometric testing was performed before and after the inhalation of each of five cumulative doses of 320 micrograms carbachol; a fall in forced expiratory volume in one second (FEV1) by 20% or more was considered as significant. Lung sound analysis was carried out using a computerised system. RESULTS--The CAC test was positive (CAC+) in 21 patients and negative (CAC-) in 17. At the final stage of the challenge, wheeze was identified in 10 positive patients (48%) and in one negative patient (6%); in non-wheezers the inspiratory breath sound intensity decreased significantly from baseline in 11 CAC+ patients (mean (SD) change -35 (24%)) but not in 16 CAC- patients (mean (SD) change 5 (24%)). In all non-wheezers a linear relationship was found between breath sound intensity and the squared inspiratory airflow (r = 0.53-0.92) which became looser after the inhalation of carbachol. CONCLUSION--When unertaking bronchial provocation testing the accurate identification of wheeze may prove useful in avoiding or shortening the test because of the presumed relationship between wheeze and airways hyperresponsiveness. Changes in breath sound intensity may also be useful, but further studies are required to define the threshold for significant changes in this index.
Impaired Heart Contractility in Apelin Gene–Deficient Mice Associated With Aging and Pressure Overload
Authors: Keiji Kuba, Liyong Zhang, Yumiko Imai, Sara Arab, Manyin Chen, Yuichiro Maekawa, Michael Leschnik, Andreas Leibbrandt, Mato Markovic, Julia Schwaighofer, Nadine Beetz, Renata Musialek, G. Greg Neely, Vukoslav Komnenovic, Ursula Kolm, Bernhard Metzler, Romeo Ricci, Hiromitsu Hara, Arabella Meixner, Mai Nghiem, Xin Chen, Fayez Dawood, Kit Man Wong, Renu Sarao, Eva Cukerman, Akinori Kimura, Lutz Hein, Johann Thalhammer, Peter P. Liu, Josef M. Penninger
Journal: Circulation Research (2007)

Apelin constitutes a novel endogenous peptide system suggested to be involved in a broad range of physiological functions, including cardiovascular function, heart development, control of fluid homeostasis, and obesity. Apelin is also a catalytic substrate for angiotensin-converting enzyme 2, the key severe acute respiratory syndrome receptor. The in vivo physiological role of Apelin is still elusive. Here we report the generation of Apelin gene–targeted mice. Apelin mutant mice are viable and fertile, appear healthy, and exhibit normal body weight, water and food intake, heart rates, and heart morphology. Intriguingly, aged Apelin knockout mice developed progressive impairment of cardiac contractility associated with systolic dysfunction in the absence of histological abnormalities. We also report that pressure overload induces upregulation of Apelin expression in the heart. Importantly, in pressure overload–induced heart failure, loss of Apelin did not significantly affect the hypertrophy response, but Apelin mutant mice developed progressive heart failure. Global gene expression arrays and hierarchical clustering of differentially expressed genes in hearts of banded Apelin −/y and Apelin +/y mice showed concerted upregulation of genes involved in extracellular matrix remodeling and muscle contraction. These genetic data show that the endogenous peptide Apelin is crucial to maintain cardiac contractility in pressure overload and aging.
A distance difference matrix approach to identifying transcription factors that regulate differential gene expression
Authors: Pieter De Bleser, Bart Hooghe, Dominique Vlieghe, Frans van Roy
Journal: Genome biology (2007)

We introduce a method that considers target genes of a transcription factor, and searches for transcription factor binding sites (TFBSs) of secondary factors responsible for differential responses among these targets. Based on the distance difference matrix concept, the method simultaneously integrates statistical overrepresentation and co-occurrence of TFBSs. Our approach is validated on datasets of differentially regulated human genes and is shown to be highly effective in detecting TFBSs responsible for the observed differential gene expression.
The Classification of Dopamine Receptors: Relationship to Radioligand Binding
Authors: I Creese, D R Sibley, M W Hamblin, S E Leff
Journal: Annual Review of Neuroscience (1983)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More