tbuckley/cabot-search huggingface dataset:
Simultaneous transcription of duplicated var2csa gene copies in individual Plasmodium falciparum parasites
Authors: Kim J M Brolin, Ulf Ribacke, Sandra Nilsson, Johan Ankarklev, Kirsten Moll, Mats Wahlgren, Qijun Chen
Journal: Genome biology (2009)

Single nucleotide polymorphisms are common in duplicated genes, causing functional preservation, alteration or silencing. The Plasmodium falciparum genes var2csa and Pf332 are duplicated in the haploid genome of the HB3 parasite line. Whereas the molecular function of Pf332 remains to be elucidated, VAR2CSA is known to be the main adhesin in placental parasite sequestration. Sequence variations introduced upon duplication of these genes provide discriminative possibilities to analyze allele-specific transcription with a bearing towards understanding gene dosage impact on parasite biology. We demonstrate an approach combining real-time PCR allelic discrimination and discriminative RNA-FISH to distinguish between highly similar gene copies in P. falciparum parasites. The duplicated var2csa variants are simultaneously transcribed, both on a population level and intriguingly also in individual cells, with nuclear co-localization of the active genes and corresponding transcripts. This indicates transcriptional functionality of duplicated genes, challenges the dogma of mutually exclusive var gene transcription and suggests mechanisms behind antigenic variation, at least in respect to the duplicated and highly similar var2csa genes. Allelic discrimination assays have traditionally been applied to study zygosity in diploid genomes. The assays presented here are instead successfully applied to the identification and evaluation of transcriptional activity of duplicated genes in the haploid genome of the P. falciparum parasite. Allelic discrimination and gene or transcript localization by FISH not only provide insights into transcriptional regulation of genes such as the virulence associated var genes, but also suggest that this sensitive and precise approach could be used for further investigation of genome dynamics and gene regulation.
Assessing Tobacco Use by Cancer Patients and Facilitating Cessation: An American Association for Cancer Research Policy Statement
Authors: Benjamin A. Toll, Thomas H. Brandon, Ellen R. Gritz, Graham W. Warren, Roy S. Herbst
Journal: Clinical Cancer Research (2013)

When diagnosed with cancer, patients can immediately make a meaningful positive impact on their health by stopping their tobacco use. Scientific evidence clearly shows that tobacco use in patients with cancer leads to poorer outcomes. The specific biological processes driving tobacco consumption's interference in cancer therapy are the subject of continuing research, but the evidence is clear that tobacco use in patients with cancer leads to decreased treatment efficacy and safety, decreased survival, decreased quality of life, increased treatment-related toxicity, and increased risk of cancer recurrence and second primary tumors. Data suggest that tobacco cessation can improve outcomes and survival in patients with cancer, yet full execution of evidence-based cessation interventions is infrequent in oncology settings. Therefore, both improved provision of cessation assistance to all patients with cancer who use tobacco or have recently quit and further study of the deleterious effects of tobacco use and benefits of tobacco cessation on cancer progression and treatment are needed and recommended by the American Association for Cancer Research. Progress on both fronts begins with universal assessment and documentation of tobacco use as a standard of quality cancer care regardless of treatment setting and will be further facilitated through the development of reliable, valid, and standard measures of tobacco use, incorporation of evidence-based procedures into quality and accreditation procedures, and the development of appropriate training, clinical infrastructure, and incentives for delivery of tobacco cessation interventions.
The Brain as a Target for Steroid Hormone Action
Authors: Bruce S. McEwen, Paula G. Davis, Bruce Parsons, Donald W. Pfaff
Journal: Annual Review of Neuroscience (1979)

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
ACTIVATION OF PEPTIC ULCER BY NICOTINIC ACID
Authors: William B. Parsons
Journal: JAMA (1960)

Side-reactions encountered when patients take substantial doses (3.0 to 7.5 Gm.) of nicotinic acid per day are exemplified in the histories of five patients who were being treated for hypercholesteremia. In addition to the underlying vascular disease present in every case, two patients were known to have had peptic ulcers before, two had had other upper gastrointestinal symptoms, and one showed signs of previous duodenal ulceration. After prolonged administration (up to 124 weeks in one case) of nicotinic acid, all developed symptoms and signs of active ulcers. When the nicotinic acid was administered in the form of tablets containing a buffer the gastrointestinal difficulties subsided promptly. The use of buffered preparations of nicotinic acid is suggested when long-term administration is necessary.
Service Utilization and Cost of Community Care for Discharged State Hospital Patients: A 3-Year Follow-Up Study
Authors: Aileen B. Rothbard, Eri Kuno, Arie P. Schinnar, Trevor R. Hadley, Roland Turk
Journal: American Journal of Psychiatry (1999)

This study examined the mental health service utilization and costs of 321 discharged state hospital patients during a 3-year follow-up period compared with costs if the patients had remained in the hospital.The study subjects were long-stay patients discharged from Philadelphia State Hospital after 1988. A longitudinal integrated database on all mental health and medical services reimbursed by Medicaid and Medicare as well as state- and county-funded services was used to construct service utilization and unit cost measures.During the 3-year period after discharge, 20%-30% of the patients required rehospitalization an average of 76-91 days per year. The percentage of rehospitalized patients decreased over time, but the number of hospital days increased. All of the discharged patients received case management services, and a majority also received outpatient mental health care (66%-70%) and residential services (75%) throughout the follow-up period. The total treatment cost per person was approximately $60,000 a year after controlling for inflation, with costs rising slightly over the 3-year period. The estimated cost of state hospitalization, with the use of 1992 estimates, would have been $130,000 per year if the patients had remained institutionalized.This analysis suggests that most former long-stay patients are able to live in residential settings while receiving community outpatient treatment and intensive case management services at a reduced cost. There is no indication of cost shifting from the psychiatric to the health care sector; however, some cost shifting from the state mental health agency to the Medicaid program has occurred, since most psychiatric hospital care now takes place in community hospitals.
Complexity and Diversity of Mammalian Adenylyl Cyclases
Authors: R K Sunahara, C W Dessauer, A G Gilman
Journal: The Annual Review of Pharmacology and Toxicology (1996)

Molecular cloning has permitted identification of several novel isoforms of mammalian adenylyl cyclase; these proteins now comprise a family of at least 10. All of the membrane-bound enzymes are activated by the alpha subunit of G alpha, a receptor-regulated, heterotrimeric guanine nucleotide-binding protein, and by the diterpene forskolin. Certain cyclases are also activated by Ca(2+)-calmodulin, while some are inhibited by the alpha subunits of the three Gi proteins. The discovery of new isoforms has also revealed unanticipated mechanisms of regulation, including activation or inhibition by the G-protein beta gamma subunit complex, inhibition by G(o) alpha, inhibition by Ca2+, and phosphorylation by protein kinases C and A. The effects of activators are often highly synergistic or conditional, suggesting function of these enyzmes as coincidence detectors. The plethora of receptors, G proteins, and adenylyl cyclases permits assembly of very complex signaling systems with a wide variety of integrative characteristics.
A Study of Defibrillating Agents on Perfused Rabbit Hearts
Authors: M. N. J. DIRKEN, F. GEVERS, H. HEEMSTRA, E. H. HUIZING
Journal: Circulation Research (1955)

Cooling the myocardium is an effective method for abolishing ventricular fibrillation. Using this method as a reference a comparison between five other methods for cardiac resuscitation is made using the Langendorff preparation of the rabbit's heart.
Seliciclib (CYC202, R-Roscovitine) Induces Cell Death in Multiple Myeloma Cells by Inhibition of RNA Polymerase II–Dependent Transcription and Down-regulation of Mcl-1
Authors: David E. MacCallum, Jean Melville, Sheelagh Frame, Kathryn Watt, Sian Anderson, Athos Gianella-Borradori, David P. Lane, Simon R. Green
Journal: Cancer Research (2005)

Seliciclib (CYC202, R-roscovitine) is a cyclin-dependent kinase (CDK) inhibitor that competes for the ATP binding site on the kinase. It has greatest activity against CDK2/cyclin E, CDK7/cyclin H, and CDK9/cyclin T. Seliciclib induces apoptosis from all phases of the cell cycle in tumor cell lines, reduces tumor growth in xenografts in nude mice and is currently in phase II clinical trials. This study investigated the mechanism of cell death in multiple myeloma cells treated with seliciclib. In myeloma cells treated in vitro, seliciclib induced rapid dephosphorylation of the carboxyl-terminal domain of the large subunit of RNA polymerase II. Phosphorylation at these sites is crucial for RNA polymerase II-dependent transcription. Inhibition of transcription would be predicted to exert its greatest effect on gene products where both mRNA and protein have short half-lives, resulting in rapid decline of the protein levels. One such gene product is the antiapoptotic factor Mcl-1, crucial for the survival of a range of cell types including multiple myeloma. As hypothesized, following the inhibition of RNA polymerase II phosphorylation, seliciclib caused rapid Mcl-1 down-regulation, which preceded the induction of apoptosis. The importance of Mcl-1 was confirmed by short interfering RNA, demonstrating that reducing Mcl-1 levels alone was sufficient to induce apoptosis. These results suggest that seliciclib causes myeloma cell death by disrupting the balance between cell survival and apoptosis through the inhibition of transcription and down-regulation of Mcl-1. This study provides the scientific rationale for the clinical development of seliciclib for the treatment of multiple myeloma.
Mechanism of early contractile failure during hypoxia in intact ferret heart: evidence for modulation of maximal Ca2+-activated force by inorganic phosphate.
Authors: H Kusuoka, M L Weisfeldt, J L Zweier, W E Jacobus, E Marban
Journal: Circulation Research (1986)

We tested the hypothesis that accumulation of H+ or inorganic phosphate (Pi) is responsible for the early contractile failure of hypoxia by measuring maximal Ca2+-activated pressure and 31P nuclear magnetic resonance spectra in Langendorff-perfused ferret hearts at 30 degrees C. Maximal Ca2+-activated pressure was identified by the saturation of pressure with respect to [Ca2+]o observed during tetani as [Ca2+]o was increased to 15 mM in HEPES-buffered, 100% O2-bubbled perfusate and during hypoxia induced by bubbling with room air or with 100% N2. Tetani were produced by pacing at 8-12 Hz following exposure to ryanodine (1-5 microM), an inhibitor of Ca2+ release from the sarcoplasmic reticulum, and were elicited once a minute to measure maximal Ca2+-activated pressure during acquisition of nuclear magnetic resonance spectra. An inverse correlation was observed between [Pi] and maximal Ca2+-activated pressure (r = -0.87 mean, n = 12), with an average decline of 8.6% in pressure per 1 mumol/g wet wt. increase in [Pi]. Intracellular pH (pHi) showed no significant correlation with maximal Ca2+-activated pressure (r = 0.49 mean, n = 12). Two other protocols, pacing at variable rates and gated measurements at two different times during the tetanus, were also used to correlate [Pi], pHi, and maximal Ca2+-activated pressure. These protocols confirmed the highly significant correlation between [Pi] and maximal Ca2+-activated pressure, as well as the lack of correlation with pHi. Acidosis induced by NH4Cl (20 mM) or by bubbling with 95% O2/5% CO2 was associated with less than 20% depression of maximal Ca2+-activated pressure in the pHi range down to 6.8, but much greater depression at lower pHi. The data are consistent with depression of maximal Ca2+-activated force during the early phase of hypoxia by Pi but not by H+.
An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt’s lymphoma: results of United Kingdom Lymphoma Group LY06 study
Authors: G.M. Mead, M.R. Sydes, J. Walewski, A. Grigg, C.S. Hatton, P. Norbert, C. Guarnaccia, M.S. Lewis, J. McKendrick, S.P. Stenning, D. Wright
Journal: Annals of Oncology (2002)
Effects of High-Dose Atorvastatin on Cerebrovascular Events in Patients With Stable Coronary Disease in the TNT (Treating to New Targets) Study
Authors: David D. Waters, John C. LaRosa, Philip Barter, Jean-Charles Fruchart, Antonio M. Gotto, Roddy Carter, Andrei Breazna, John J.P. Kastelein, Scott M. Grundy
Journal: Journal of the American College of Cardiology (2006)
Optical Imaging Modalities for Biomedical Applications
Authors: Atam P. Dhawan, Brian D'Alessandro, Xiaolei Fu
Journal: IEEE Reviews in Biomedical Engineering (2010)

Optical photographic imaging is a well known imaging method that has been successfully translated into biomedical applications such as microscopy and endoscopy. Although several advanced medical imaging modalities are used today to acquire anatomical, physiological, metabolic, and functional information from the human body, optical imaging modalities including optical coherence tomography, confocal microscopy, multiphoton microscopy, multispectral endoscopy, and diffuse reflectance imaging have recently emerged with significant potential for non-invasive, portable, and cost-effective imaging for biomedical applications spanning tissue, cellular, and molecular levels. This paper reviews methods for modeling the propagation of light photons in a biological medium, as well as optical imaging from organ to cellular levels using visible and near-infrared wavelengths for biomedical and clinical applications.
Rheumatology outpatient training
Authors: I. N BRUCE;, J. MCDONAGH
Journal: Annals of the Rheumatic Diseases (1998)

The leader by McDonagh regarding outpatient training for rheumatology specialist registrars is a timely and important commentary.1 Having done most of my training in the United Kingdom, for the past two years I have spent time at the University of Toronto, Division of Rheumatology. This experience provides some observations that are relevant to the current debate.

It is impossible to avoid the differences in the organisation of health services and postgraduate medical education in the UK and Canada. These have a significant impact on training. The NHS is consultant-led with a high dependency on doctors at the senior house officer and registrar grades to provide the service. Many outpatients are therefore seen by doctors who may have little or no previous experience in rheumatology. Because of the pressure of numbers and resultant time constraints mistakes in management as well as potentially unnecessary follow ups can go unchecked. The Canadian health care system is consultant-based. Specialists work on a fee for service basis and are required to see each patient. Clinics are organised in …
Defective control of ribosomal RNA processing in stimulated leukemic lymphocytes
Authors: Arnold D. Rubin
Journal: Journal of Clinical Investigation (1971)

The kinetics of ribosomal RNA transcription and processing were assessed in chronic lymphocytic leukemia (CLL) lymphocytes during the initial phases of their delayed response to phytohemagglutinin. When compared to cultures of normal lymphocytes, CLL cultures developed normal augmentations in 45S rRNA precursor transcription and cleavage after a 1 hr incubation with PHA. However, failure to conserve 18S RNA subunits persisted in the CLL cultures. Subsequently the PHA-induced progressive rise in 45S RNA transcription became aborted and the over-all rate of RNA synthesis lagged far behind the levels attained by normal cultures incubated with PHA for 48 hr. CLL cultures responding to PHA in a delayed fashion exhibited efficient conservation of 18S RNA at 168 hr. In normal cultures, PHA-induced conservation of 18S RNA appeared to be independent of any effect on 45S ribosomal RNA precursor transcription. Therefore, the sluggish growth response of CLL lymphocytes was associated with a defect in one of the important mechanisms regulating assembly of new ribosomes.
Role of the renin-angiotensin system in the control of vasopressin secretion in conscious dogs.
Authors: V L Brooks, L C Keil, I A Reid
Journal: Circulation Research (1986)

The present studies were designed to evaluate the physiological significance of angiotensin II in the control of vasopressin secretion in conscious dogs. They demonstrated that exogenous angiotensin II (10 ng/kg per min) increased vasopressin secretion more when the pressor effect of angiotensin II was abolished. The fact that endogenous angiotensin II levels are normally increased without an increase in arterial pressure suggests that angiotensin II may play a greater role in the control of vasopressin secretion than was previously thought. The present study also evaluated the role of endogenous angiotensin II in the control of vasopressin secretion during sodium depletion, a state in which angiotensin II levels are elevated. Intracarotid infusion of a low dose of the angiotensin II antagonist, saralasin, decreased plasma vasopressin concentration, suggesting that endogenous angiotensin II acts in an area of the brain perfused by the carotid arteries to stimulate vasopressin secretion in sodium-deprived dogs. Finally, the present experiments evaluated the role of angiotensin II in baroreceptor reflex control of vasopressin secretion. Baroreflex function was assessed by examining the relationship between the change in blood pressure and the log of the change in vasopressin secretion over a range of blood pressure levels. Exogenous angiotensin II (10 ng/kg per min) altered baroreflex function by causing a shift of this relationship to a higher pressure level in sodium-replete dogs. In sodium-depleted dogs, inhibition of the renin-angiotensin system with saralasin or captopril produced an opposite shift. These results suggest that endogenous angiotensin II may be necessary for the maintenance of normal baroreflex control of vasopressin secretion during sodium depletion. Collectively, these results support the hypothesis that endogenous angiotensin II plays a role in the control of vasopressin secretion.
An activated mutant BRAF kinase domain is sufficient to induce pilocytic astrocytoma in mice
Authors: Jan Gronych, Andrey Korshunov, Josephine Bageritz, Till Milde, Manfred Jugold, Dolores Hambardzumyan, Marc Remke, Christian Hartmann, Hendrik Witt, David T.W. Jones, Olaf Witt, Sabine Heiland, Martin Bendszus, Eric C. Holland, Stefan Pfister, Peter Lichter
Journal: Journal of Clinical Investigation (2011)

Pilocytic astrocytoma (PA) is the most common type of primary brain tumor in children and the second most frequent cancer in childhood. Children with incompletely resected PA represent a clinically challenging patient cohort for whom conventional adjuvant therapies are only moderately effective. This has produced high clinical demand for testing of new molecularly targeted treatments. However, the development of new therapeutics for PA has been hampered by the lack of an adequate in vivo tumor model. Recent studies have identified activation of MAPK signaling, mainly by oncogenic BRAF activation, as a hallmark genetic event in the pathogenesis of human PA. Using in vivo retroviral somatic gene transfer into mouse neural progenitor cells, we have shown here that ectopic expression of the activated BRAF kinase domain is sufficient to induce PA in mice. Further in vitro analyses demonstrated that overexpression of activated BRAF led to increased proliferation of primary mouse astrocytes that could be inhibited by treatment with the kinase inhibitor sorafenib. Our in vivo model for PA shows that the activated BRAF kinase domain is sufficient to induce PA and highlights its role as a potential therapeutic target.
Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein
Authors: Richard E. Clark, I. Anthony Dodi, Seran C. Hill, Jennie R. Lill, Geraldine Aubert, Andrew R. Macintyre, Jose Rojas, Audrey Bourdon, Philip L. R. Bonner, Lihui Wang, Stephen E. Christmas, Paul J. Travers, Colin S. Creaser, Robert C. Rees, J. Alejandro Madrigal
Journal: Blood (2001)
ANASTOMOSIS OF THE VAS DEFERENS
Authors: W. I. D. C. Wheeler
Journal: BMJ (1914)

ANASTOMOSIS OF THE.-VAS DEFERENS.[FEB. 7, 19I4 Certainly thle dermnatitis in botlh pellagra and zeism has some strong points in commoni, but when their respective positions are considered in full, and those of zeism com- pared witlh the beautiful coloured drawing of pellagra wlhiclh appeared in the JOURNAL of JUly 5t11, 1913, their dlifferences are even iilore striking tllan their similarities.M)i--lOns Symptoiiis.Pellagra (Box).Zeism.
Effect of irradiation on hepatic natural killer cells
Authors: Karin Vanderkerken, Luc Bouwens, Peter Kuppen, Wilfried De Neve, Kit Van Den Berg, Marijke Baekeland, Eddie Wisse
Journal: Hepatology (1994)

The rat liver contains a population of natural killer cells consisting of two morphologically and functionally different subsets, a low-density and a high-density fraction. In this work we describe the influence of low-dose radiation on hepatic natural killer activity. The effect on the cytotoxicity against YAC-1 lymphoma and CC531 colon adenocarcinoma tumor cells was measured in chromium-51 assays, and morphological changes were analyzed by means of electron microscopy. The low-density natural killer fraction showed increased cytotoxicity against YAC-1 which was associated with an increased binding of natural killer cells to the YAC-1 tumor cells shortly after irradiation. These phenomena were paralleled by an increased number of multivesicular bodies and cytoplasmic granules with an electron-lucent halo. In contrast, the other hepatic natural killer cell fraction, the high-density natural killer cells, did not show increased cytotoxicity, binding or morphological alterations. The radiation-stimulated lysis of YAC-1 cells was also observed when in vivo irradiated cells were isolated and tested immediately for in vitro lysis of YAC-1 cells. Sixteen hours after in vitro or in vivo irradiation, the cytotoxicity of hepatic natural killer cells against YAC-1 was no longer enhanced. The cytolysis of and binding of hepatic natural killer cells to CC531 colon adenocarcinoma cells was not stimulated by in vitro irradiation. From these experiments, we conclude that low-dose radiation stimulates the cytotoxicity of hepatic low-density natural killer cells against YAC-1 lymphoma cells immediately after irradiation as the result of enhanced binding of the cells to the tumor cells, in addition to the synthesis of new cytotoxic granules.