tbuckley/cabot-search huggingface dataset:
Chick Ovalbumin Upstream Promoter-Transcription Factors (COUP-TFs): Coming of Age*
Authors: Sophia Y. Tsai, Ming-Jer Tsai
Journal: Endocrine Reviews (1997)

I. Introduction II.The COUP-TF Gene Family A. Homology to other members of the steroid/thyroid hormone receptor superfamily B. Sequence homology within the COUP-TF gene family III.Biochemical Characteristics A. DNA-binding sites B. Molecular mechanism of COUP-TFs action 1.Competition for occupancy of the binding sites 2. Competition for RXR 3. Active repression 4. Transrepression 5.The role of COUP-TFs in transactivation IV.Expression Patterns of COUP-TFs During Development A. Expression patterns in zebrafish and Xenopus B. Expression patterns in mouse and chick V. Physiological Function of COUP-TFs A. Ectopic expression of svp in Drosophila B. Ectopic expression of COUP-TFI in Xenopus embryos C. Loss of function of COUP-TFI in mice D. Loss of function of COUP-TFII in mice VI.
Because I'm worth it
Authors: R. Mayer
Journal: BMJ (2008)

This personal view is published posthumously. Robert Mayer died on 21 March 2008, aged 48. (See Obituary, doi:10.1136/bmj.a1215.) Below, his widow adds her thoughts I’m listening to the consumer programme You and Yours on BBC Radio 4, like you do when you have too much time on your hands and an inadequate concentration span for anything purposeful. The programme is about the cost of new anticancer drugs and whether or not the NHS can afford them “at a price that we the taxpayer can afford,” as England’s cancer tsar, Mike Richards, says. I was given a diagnosis of metastatic pancreatic adenocarcinoma four months ago, and I’ve been thinking a lot recently about how much I cost the NHS. Now that I am a patient as well as an “expensive” GP, perhaps I might be, how shall we say . . . a little too pricey now? Of course, cancer doesn’t come cheaply. If you look at my medical record, you will see that very little had been spent on me until I got cancer. A few prescriptions, tonsils and adenoids taken out when I was 7—probably unnecessary by today’s standards—and one haemorrhoid injected. A few hundred pounds all in. With an eye to the future, and because we may not be too far away from this scenario, I’ve done a few back of the envelope calculations of what my treatment might cost.
Soluble interleukin 2 receptor in acute viral hepatitis and chronic liver disease
Authors: Christian Müller, Peter Knoflach, Christoph C. Zielinski
Journal: Hepatology (1989)

Serum levels of soluble interleukin 2 receptor were determined in patients with acute viral hepatitis and patients with various chronic liver diseases. In addition, the ability of peripheral blood mononuclear cells of patients with alcoholic cirrhosis to generate soluble interleukin 2 receptor following mitogenic stimulation was studied in vitro. Serum soluble interleukin 2 receptor concentrations in all patients with acute viral hepatitis were found to be significantly elevated (1,319 +/- 527 units per ml) during the first week after onset of disease, as compared to healthy control individuals (375 +/- 102 units per ml; p less than 0.0005) and declined toward normal levels during the course of the illness. Similarly, patients suffering from chronic liver disease such as alcoholic liver cirrhosis (1,172 +/- 507 units per ml), primary biliary cirrhosis (619 +/- 190 units per ml) or chronic active HBsAg+ hepatitis (941 +/- 357 units per ml) showed increased serum soluble interleukin 2 receptor concentrations (p less than 0.0005 vs. controls, respectively). In vitro mitogen stimulation of peripheral mononuclear cells derived from patients with alcoholic cirrhosis resulted in a soluble interleukin 2 receptor production not different from that seen in healthy individuals, suggesting that elevated soluble interleukin 2 receptor serum levels seen in this disease are not the result of an increased synthesis by circulating lymphocytes. Due to the ability of soluble interleukin 2 receptor to bind free interleukin 2--thus making it a potential immunoregulatory molecule--its high serum levels could explain some of the immunologic abnormalities observed in acute and chronic liver disease.
Ada3 Requirement for HAT Recruitment to Estrogen Receptors and Estrogen-Dependent Breast Cancer Cell Proliferation
Authors: Aleksandra Germaniuk-Kurowska, Alo Nag, Xiangshan Zhao, Manjari Dimri, Hamid Band, Vimla Band
Journal: Cancer Research (2007)

Abstract We have previously shown that evolutionarily conserved alteration/deficiency in activation (Ada) protein associates with and promotes estrogen receptor (ER)–mediated target gene expression. Here, we examined the role of endogenous Ada3 to recruit histone acetyl transferases (HAT) to an ER-responsive promoter and its role in estrogen-dependent cell proliferation and malignant phenotype. Using a combination of glycerol gradient cosedimentation and immunoprecipitation analyses, we show that Ada3, ER, and three distinct HATs [p300, (p300/CBP-associated factor) PCAF, and general control nonrepressed 5 (Gcn5)] are present in a complex. Using chromatin immunoprecipitation analysis, we show that short hairpin RNA (shRNA)–mediated knockdown of Ada3 in ER-positive breast cancer cells significantly reduced the ligand-dependent recruitment of p300, PCAF, and Gcn5 to the ER-responsive pS2 promoter. Finally, we use shRNA knockdown to show that Ada3 is critical for estrogen-dependent proliferation of ER-positive breast cancer cell lines in two-dimensional, as well as three-dimensional, culture. Knockdown of Ada3 in ER-positive MCF-7 cells induced reversion of the transformed phenotype in three-dimensional culture. Thus, our results show an important role of Ada3 in HAT recruitment to estrogen-responsive target gene promoters and for estrogen-dependent proliferation of breast cancer cells. [Cancer Res 2007;67(24):11789–97]
IL-12 as an adjuvant for the induction of immune responses against hepatitis C viral antigens
Authors: JJ Lasarte, N. Casares, A. López-Díaz de Cerio, J. Ruiz, O. Cheng, X. Xiaoming, O. Bruña, F. Borrás-Cuesta, J. Prieto
Journal: Journal of Hepatology (1998)
The oxygenation variations related to prone positioning during mechanical ventilation: a clinical comparison between ARDS and non-ARDS hypoxemic patients
Authors: Christophe Venet, Stephane Guyomarc'h, Christine Migeot, Monique Bertrand, Pierre Gery, Dominique Page, Regine Vermesch, Jean Bertrand, Fabrice Zeni
Journal: Intensive Care Medicine (2001)
Elements of Medical Statistics
Authors: C. C. Li
Journal: JAMA (1964)

This little book presents, in a very condensed form, a large collection of statistical methods to test the significance of difference between two or more treatments. It has certainly covered a great deal of ground within 111 pages of text. The author assures his medical readers, "It is not necessary to be an expert mathematician in order to use and interpret statistics intelligently, any more than it is necessary to be an electronic engineer in order to use an electrocardiograph properly." The chapter topics will show the scope of the book: (1) introduction, (2) frequency distributions, (3) probability, (4) tests of significance, (5) basic principles of trial design, (6) correlation and regression, (7) analysis of variance, (8) crossover trials, (9) analysis of covariance. Appropriate methods have been given for data in four different scales: categorical, ordinal, interval, and ratio. There are some apparent misprints (p 22, p 117). Certain statements
The Dénouement of the Supreme Court's ACA Drama
Authors: Renée M. Landers
Journal: New England Journal of Medicine (2012)

Interview with Professors Renée Landers and John McDonough on the implications of the Supreme Court’s ruling on the Affordable Care Act. (33:32)Download The Supreme Court has sent the debate about the Affordable Care Act's expansion of health insurance coverage back to the political process, while setting out competing philosophies on the reach of federal power and the Court's role in policing limits on federal action.
Effectiveness and cost effectiveness of compression bandages should be shown
Authors: P. J Franks, C. J Moffatt
Journal: BMJ (1998)

EDITOR—Fletcher et al report their systematic review of compression treatment for venous leg ulcers.1 As researchers who perform randomised trials of compression bandages, we echo their concern that the quality of research is poor in this area.

A particular concern of ours is that, unlike pharmaceuticals, bandages (which are classified as medical devices), do not need to undergo rigorous clinical testing to establish effectiveness before being released on to the market. Moreover, provided …
Early CD8 T-cell memory precursors and terminal effectors exhibit equipotent in vivo degranulation
Authors: Yevgeniy Yuzefpolskiy, Florian M. Baumann, Vandana Kalia, Surojit Sarkar
Journal: Cellular and Molecular Immunology (2014)

Early after priming, effector CD8 T cells are distinguished into memory precursor and short-lived effector cell subsets (MPECs and SLECs). Here, we delineated a distinct in vivo heterogeneity in killer cell lectin-like receptor G1 (KLRG-1) expression, which was strongly associated with diverse MPEC and SLEC fates. These in vivo MPECs and SLECs expressed equivalent levels of cytotoxic molecules and effector cytokines. Using a unique in vivo degranulation assay, we found that the MPECs and SLECs similarly encountered infected target cells and elaborated equivalent levels of cytotoxicity in vivo. These data provide direct in vivo evidence that memory-fated cells pass through a robust effector phase. Additionally, the preferential localization of the MPECs in the lymph nodes, where a lesser degree of cytotoxicity was elaborated, suggests that the MPECs may be protected from excessive stimulation and terminal differentiation by virtue of their differential tissue localization. These data provide novel mechanistic insights into the linear decreasing potential model of memory differentiation.
Functional analysis of a novel glioma antigen, EFTUD1
Authors: Katsuya Saito, Yukihiko Iizuka, Shigeki Ohta, Satoshi Takahashi, Kenta Nakamura, Hideyuki Saya, Kazunari Yoshida, Yutaka Kawakami, Masahiro Toda
Journal: Neuro-Oncology (2014)

A cDNA library made from 2 glioma cell lines, U87MG and T98G, was screened by serological identification of antigens by recombinant cDNA expression (SEREX) using serum from a glioblastoma patient. Elongation factor Tu GTP binding domain containing protein 1 (EFTUD1), which is required for ribosome biogenesis, was identified. A cancer microarray database showed overexpression of EFTUD1 in gliomas, suggesting that EFTUD1 is a candidate molecular target for gliomas. EFTUD1 expression in glioma cell lines and glioma tissue was assessed by Western blot, quantitative PCR, and immunohistochemistry. The effect on ribosome biogenesis, cell growth, cell cycle, and induction of apoptosis and autophagy in glioma cells during the downregulation of EFTUD1 was investigated. To reveal the role of autophagy, the autophagy-blocker, chloroquine (CQ), was used in glioma cells downregulating EFTUD1. The effect of combining CQ with EFTUD1 inhibition in glioma cells was analyzed. EFTUD1 expression in glioma cell lines and tissue was higher than in normal brain tissue. Downregulating EFTUD1 induced G1 cell-cycle arrest and apoptosis, leading to reduced glioma cell proliferation. The mechanism underlying this antitumor effect was impaired ribosome biogenesis via EFTUD1 inhibition. Additionally, protective autophagy was induced by glioma cells as an adaptive response to EFTUD1 inhibition. The antitumor effect induced by the combined treatment was significantly higher than that of either EFTUD1 inhibition or CQ alone. These results suggest that EFTUD1 represents a novel therapeutic target and that the combination of EFTUD1 inhibition with autophagy blockade may be effective in the treatment of gliomas.
Percutaneous Vascular Stent Implantation as Treatment for Central Vascular Obstruction Due to Fibrosing Mediastinitis
Authors: Erin L. Albers, Meredith E. Pugh, Kevin D. Hill, Li Wang, James E. Loyd, Thomas P. Doyle
Journal: Circulation (2011)

Fibrosing Mediastinitis (FM) is a rare complication of infection with Histoplasma capsulatum that can lead to obstruction of pulmonary and systemic vasculature and large airways, often resulting in significant morbidity and mortality. Medical therapy is ineffective, and surgical intervention is often not feasible. Stent implantation offers a potential treatment for vascular obstruction due to FM, but this has not been well studied.We conducted a retrospective review of all patients undergoing cardiac catheterization for FM. Anatomic site of stenosis and hemodynamic information before and after intervention, as well as clinical presentation and follow-up data, were recorded. From 1996 to 2008, 58 patients underwent cardiac catheterization for FM, with intervention performed in 40 (69%). A total of 77 stents were used to relieve 59 lesions (pulmonary artery=26, pulmonary vein=21, and superior vena cava=12). Significant reduction in pressure gradients (P<0.001) and increase in vessel caliber (P<0.001) were seen at all locations. Symptomatic recurrent stenosis requiring further intervention occurred in 11 patients (28%). Median time to recurrence was 115 months. Thirty-two (87%) of 37 patients for whom follow-up was available reported symptomatic improvement after stent placement.related complications occurred in 14 patients (24%). Overall mortality was 19%, with the majority of deaths in patients with bilateral disease. Among patients with bilateral disease, intervention was associated with improved survival at 5 years.Percutaneous vascular stent implantation is an effective therapy for central vascular obstruction due to FM, providing significant relief of anatomic obstruction and sustained clinical improvement.
Postprandial Hyperglycemia and Glycemic Variability
Authors: Eberhard Standl, Oliver Schnell, Antonio Ceriello
Journal: Diabetes Care (2011)

The aim of this article is to evaluate the pros and cons of a specific impact of postprandial hyperglycemia and glycemic variability on the--mainly cardiovascular (CV)--complications of diabetes, above and beyond the average blood glucose (BG) as measured by HbA(1c) or fasting plasma glucose (FPG). The strongest arguments in favor of this hypothesis come from impressive pathophysiological studies, also in the human situation. Measures of oxidative stress and endothelial dysfunction seem to be especially closely related to glucose peaks and even more so to fluctuating high and low glucose concentrations and can be restored to normal by preventing those glucose peaks or wide glucose excursions. The epidemiological evidence, which is more or less confined to postprandial hyperglycemia and postglucose load glycemia, is also rather compelling in favor of the hypothesis, although certainly not fully conclusive as there are also a number of conflicting results. The strongest cons are seen in the missing evidence as derived from randomized prospective intervention studies targeting postprandial hyperglycemia longer term, i.e., over several years, and seeking to reduce hard CV end points. In fact, several such intervention studies in men have recently failed to produce the intended beneficial outcome results. As this evidence by intervention is, however, key for the ultimate approval of a treatment concept in patients with diabetes, the current net balance of attained evidence is not in favor of the hypothesis here under debate, i.e., that we should care about postprandial hyperglycemia and glycemic variability. The absence of a uniformly accepted standard of how to estimate these parameters adds a further challenge to this whole debate.
PPARα governs glycerol metabolism
Authors: David Patsouris, Stéphane Mandard, Peter J. Voshol, Pascal Escher, Nguan Soon Tan, Louis M. Havekes, Wolfgang Koenig, Winfried März, Sherrie Tafuri, Walter Wahli, Michael Müller, Sander Kersten
Journal: Journal of Clinical Investigation (2004)

Glycerol, a product of adipose tissue lipolysis, is an important substrate for hepatic glucose synthesis. However, little is known about the regulation of hepatic glycerol metabolism. Here we show that several genes involved in the hepatic metabolism of glycerol, i.e., cytosolic and mitochondrial glycerol 3-phosphate dehydrogenase (GPDH), glycerol kinase, and glycerol transporters aquaporin 3 and 9, are upregulated by fasting in wild-type mice but not in mice lacking PPARα. Furthermore, expression of these genes was induced by the PPARα agonist Wy14643 in wild-type but not PPARα−null mice. In adipocytes, which express high levels of PPARγ, expression of cytosolic GPDH was enhanced by PPARγ and β/δ agonists, while expression was decreased in PPARγ+/– and PPARβ/δ–/– mice. Transactivation, gel shift, and chromatin immunoprecipitation experiments demonstrated that cytosolic GPDH is a direct PPAR target gene. In line with a stimulating role of PPARα in hepatic glycerol utilization, administration of synthetic PPARα agonists in mice and humans decreased plasma glycerol. Finally, hepatic glucose production was decreased in PPARα-null mice simultaneously fasted and exposed to Wy14643, suggesting that the stimulatory effect of PPARα on gluconeogenic gene expression was translated at the functional level. Overall, these data indicate that PPARα directly governs glycerol metabolism in liver, whereas PPARγ regulates glycerol metabolism in adipose tissue.
UG, the L1, and questions of evidence
Authors: Lydia White
Journal: Behavioral and Brain Sciences (1996)

Abstract Epstein, Flynn, and Martohardjono's presentation of the principal approaches to UG access in L2 acquisition is misleading; they have neglected the possibility that the L1 grammar forms the learner's initial representation of the L2, with subsequent modifications constrained by UG. Furthermore, their experimental data are open to several interpretations and are consistent with a number of different positions in the field.
Effect of neomycin on exchangeable pools of cholesterol in the steady state
Authors: Paul Samuel, Charles M. Holtzman, Edward Meilman, William Perl
Journal: Journal of Clinical Investigation (1968)

Five patients received cholesterol-7α-3H intravenously during control periods. Specific activity of total serum cholesterol was determined serially during the 1st wk and weekly thereafter. 28-59 wk after the injection of the tracer, when no further radioactivity could be detected in serum cholesterol, 2 g of oral neomycin was given daily to four patients for the remainder of the experiment. Average total serum cholesterol concentrations were reduced by 20, 21, 26, and 29%, respectively, in these subjects. The fifth patient, given placebo, had no change in serum cholesterol. After a period of 12-26 wk of medication the intravenous injection of cholesterol-7α-3H was repeated, and while neomycin or placebo administration was continued, serum cholesterol specific activity was again determined serially during the 1st wk and weekly thereafter for 23-42 wk. The data were subjected to a two-compartment analysis. During the administration of neomycin, half-times of the cholesterol radio-activity decay curves were decreased in two patients and remained unchanged in two subjects. The size of the "intermediate" pool of cholesterol decreased in each patient during the administration of neomycin by 33, 36, 40, and 44%, respectively. The absolute decrease was much larger in each case than the concomitant reduction of serum cholesterol. There was no significant change in the data during the administration of placebo in one patient. The size of the "intermediate" pool can be calculated by compartmental analysis from the cholesterol decay curves. For the "slow" pool size and the other kinetic parameters only ranges of values can be deduced from the present experiment.
Congenital Cytomegalovirus Infection
Authors: Sergio Stagno, David W. Reynolds, Eng-Shang Huang, Shirley D. Thames, Richard J. Smith, Charles A. Alford
Journal: New England Journal of Medicine (1977)

The overall prevalence of congenital cytomegalovirus infection among the offspring of a highly immune young female population was 2.4 per cent (23 of 939). To ascertain whether the presence of anticytomegalovirus antibodies protects the developing fetus, we examined the offspring of 239 prospectively studied women. Despite substantial levels of preconceptional antibodies, intrauterine cytomegalovirus infection occured in seven of 208 (3.4 per cent) seroimmune women. Three neonates with congenital infection were born to 31 initially seronegative women. All the congenitally infected infants had subclinical involvement. Maternal humoral immunity may not protect the fetus against congenital cytomegalovirus infection. Neutralization kinetics and restriction enzyme analysis with endonucleases (EcoR-1 and HinD 111) demonstrated antigenic and genetic homology between viral strains isolated from two siblings consecutively infected in utero, indicating that repeat maternal infection with the same virus is transmissible to sequential products of conception.
Alterations in cardiac myosin isozymes associated with aging and chronic hypertension: their modulation with nifedipine
Authors: V. Raizada, D. Pathak, T. M Blomquist, R. Minser, B. Woodfin
Journal: Cardiovascular Research (1993)

Objective: Pressure induced left ventricular hypertrophy is associated with alterations in distribution of cardiac myosin isozymes. This study evaluated the influence of aging, superimposed chronic hypertension on aging, and treatment with nifedipine on cardiac myosin isozyme proportions. Methods: Myosin isozyme (V1, V2, and V3) proportions were investigated by pyrophosphate gel electrophoresis, and left ventricular to body weight ratio was studied in two subgroups each of hypertensive and normotensive rats, with and without nifedipine treatment. Nifedipine treatment was started at 48 weeks and concluded at 60 weeks. Results: For all four groups, the V1 level was the lowest (range 15%-24%), V3 was the highest (47%-60%), and V2 was intermediate (25%-29%). The left ventricular weight to body weight ratio was 25% higher (p < 0.001) in the untreated old hypertensive v old rats, but V1 level was of the same magnitude in both these groups. The left ventricular weight to body weight ratio was 18% lower (p < 0.001) in the old hypertensive treated v untreated rats. The V1 level was higher in both treated groups; old normotensive as well as old hypertensive rats. The changes in V1 were not statistically correlated with arterial pressure and left ventricular to body weight ratio. Conclusions: The profound decrease in V1 myosin isozyme proportion acquired with aging is not accentuated by superimposed chronic hypertension. The aging process, and not the left ventricular hypertrophy by itself, seems to be the principal determinant of the myosin isozyme shift. The myosin isozyme shift that occurs with aging is not fixed, and can be partially reversed or prevented by nifedipine. Cardiovascular Research 1993;27:1869-1872