tbuckley/cabot-search huggingface dataset:
Practical strategies for management of fatigue and sleep disorders in people with brain tumors
Authors: T. S. Armstrong, M. R. Gilbert
Journal: Neuro-Oncology (2012)

It makes me feel good to know that I'm not the only [one] having fatigue and no energy.I can't get my positive mind and my fatigued body on the same page.Frustrating.I used to be a jet before cancer, and I am still adapting to being a sailboat after diagnosis.I just want to do more, like my old self.
Response of the cerebral circulation in baboons to changing perfusion pressure after indomethacin.
Authors: J D Pickard, L A MacDonell, E T MacKenzie, A M Harper
Journal: Circulation Research (1977)

An earlier study has demonstrated that indomethacin, a prostaglandin synthesis inhibitor, blocks the cerebrovascular response to hypercapnia. This response is believed to be mediated by a lowering of pH in the cerebral interstitial fluid. Should autoregulation of cerebral blood flow (CBF) to changing perfusion pressure also be mediated by a changing interstitial pH (the "metabolic" theory), then indomethacin should impair autoregulation. This hypothesis was tested in anesthetized baboons. CBF was measured by the intracarotid 133Xe clearance technique; the preparation and the indomethacin protocol were identical to those of our previous investigation. Arterial pressure was increased by the intravenous infusion of angiotensin and decreased by controlled hemorrhage. Indomethacin was given by continuous infusion into the internal carotid artery. Although it reduced resting CBF, the cerebrovascular response to changing perfusion pressure was unchanged. Because indomethacin affects the response to changing CO2 but not that to changing perfusion pressure, the mechanisms for these two reactions presumably are different and it is improbable that changing interstitial pH is responsible for autoregulation in the cerebral circulation.
Synergistic Antitumor Activity of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Gefitinib and IFN-α in Head and Neck Cancer Cells <i>In vitro</i> and <i>In vivo</i>
Authors: Francesca Bruzzese, Elena Di Gennaro, Antonio Avallone, Stefano Pepe, Claudio Arra, Michele Caraglia, Pierosandro Tagliaferri, Alfredo Budillon
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Epidermal growth factor receptor (EGFR) overexpression has been implicated in the development of head and neck squamous cell carcinomas (HNSCC) and represents a potential therapeutic target for this disease. We have reported previously that growth inhibitory concentrations of IFN-α enhance the expression and activity of EGFR and that this effect could represent an escape mechanism to the growth inhibition and apoptotic cell death induced by IFN-α. In this study, we investigate whether the combination of IFN-α and gefitinib (Iressa, AstraZeneca Pharmaceuticals, Macclesfield, United Kingdom), a selective EGFR tyrosine kinase inhibitor, might have a cooperative antitumor effect on HNSCC-derived cell lines. Experimental Design: The interaction of IFN-α and gefitinib was evaluated in vitro on HNSCC-derived cell lines by median drug effect analysis calculating a combination index with CalcuSyn software and in vivo by using HNSCC xenografts in nude mice. The mechanism of gefitinib and IFN-α interactions was also studied by analysis of cell cycle kinetics, apoptosis assays, and Western blotting of EGFR signal transduction components. Results: Simultaneous exposure to gefitinib and IFN-α produced synergistic antiproliferative and proapoptotic effects compared with single drug treatment. Furthermore, daily treatment of gefitinib (50 mg/kg p.o.) in combination with an IFN-α regimen (50,000 units s.c. three times weekly) induced tumor growth delay and increased survival rate on established HNSCC xenografts in nude mice. Moreover, the concomitant treatment with gefitinib suppressed the stimulation of extracellular signal-regulated kinase phosphorylation/activity induced by IFN-α both in vitro and in vivo. Conclusion: The observed cooperative antitumor effects could be, at least in part, explained by the inhibition exerted by gefitinib of an IFN-α-induced EGF-dependent survival pathway, which involves extracellular signal-regulated kinase activation. These results provide a rationale for the clinical evaluation of gefitinib in combination with IFN-α in HNSCC.
National cross sectional survey to determine whether the decision to delivery interval is critical in emergency caesarean section
Authors: Jane Thomas, Shantini Paranjothy, David James
Journal: BMJ (2004)

Abstract Objective To examine the association between decision to delivery interval and maternal and baby outcomes. Design National cross sectional survey. Setting Maternity units in England and Wales. Subjects reviewed 17 780 singleton births (99% of all births) delivered by emergency caesarean section in England and Wales between 1 May 2000 and 31 July 2000. Main outcome measures Association between decision to delivery interval and baby outcomes (Apgar scores of &lt; 7 and &lt; 4 at five minutes and stillbirth) and maternal outcomes (requirement for special care additional to routine care after caesarean section and where care was provided). Results Compared with babies delivered within 15 minutes, there was no difference in maternal or baby outcome for decision to delivery interval between 16 and 75 minutes. After 75 minutes, however, there was a significantly higher odds of a five minute Apgar score of &lt; 7 (odds ratio 1.7, 95% confidence interval 1.2 to 2.4), and 50% increase in odds of special care additional to routine care for mothers. Conclusion A decision to delivery interval of 30 minutes is not an absolute threshold for influencing baby outcome. Decision to delivery intervals of more than 75 minutes are associated with poorer maternal and baby outcomes and should be avoided.
Complete Sequences of the Highly Rearranged Molluscan Mitochondrial Genomes of the Scaphopod Graptacme eborea and the Bivalve Mytilus edulis
Authors: Jeffrey L. Boore, Monica Medina, Lewis A. Rosenberg
Journal: Molecular Biology and Evolution (2004)

We have determined the complete sequence of the mitochondrial genome of the scaphopod mollusk Graptacme eborea (14,492 nts) and completed the sequence of the mitochondrial genome of the bivalve mollusk Mytilus edulis (16,740 nts). (The name Graptacme eborea is a revision of the species formerly known as Dentalium eboreum.) G. eborea mtDNA contains the 37 genes that are typically found and has the genes divided about evenly between the two strands, but M. edulis contains an extra trnM and is missing atp8, and it has all genes on the same strand. Each has a highly rearranged gene order relative to each other and to all other studied mtDNAs. G. eborea mtDNA has almost no strand skew, but the coding strand of M. edulis mtDNA is very rich in G and T. This is reflected in differential codon usage patterns and even in amino acid compositions. G. eborea mtDNA has fewer noncoding nucleotides than any other mtDNA studied to date, with the largest noncoding region only 24 nt long. Phylogenetic analysis using 2,420 aligned amino acid positions of concatenated proteins weakly supports an association of the scaphopod with gastropods to the exclusion of Bivalvia, Cephalopoda, and Polyplacophora, but it is generally unable to convincingly resolve the relationships among major groups of the Lophotrochozoa, in contrast to the good resolution seen for several other major metazoan groups.
A Comparison of Aripiprazole, Methylphenidate, and Placebo for Amphetamine Dependence
Authors: Jari Tiihonen, Kimmo Kuoppasalmi, Jaana Föhr, Pekka Tuomola, Outi Kuikanmäki, Helena Vorma, Petteri Sokero, Jari Haukka, Esa Meririnne
Journal: American Journal of Psychiatry (2007)

Problems related to illegal amphetamine use have become a major public health issue in many developed countries. To date, evidence on the effectiveness of psychosocial treatments has remained modest, and no pharmacotherapy has proven effective for amphetamine dependence.Individuals meeting DSM-IV criteria for intravenous amphetamine dependence (N=53) were randomly assigned to receive aripiprazole (15 mg/day), slow-release methylphenidate (54 mg/day), or placebo for 20 weeks. The study was terminated prematurely due to unexpected results of interim analysis. An intention-to-treat analysis was used. The primary outcome measure was the proportion of amphetamine-positive urine samples.Patients allocated to aripiprazole had significantly more amphetamine-positive urine samples than patients in the placebo group (odds ratio=3.77, 95% CI=1.55-9.18), whereas patients who received methylphenidate had significantly fewer amphetamine-positive urine samples than patients who had received placebo (odds ratio=0.46, 95% CI=0.26-0.81).Methylphenidate is an effective treatment for reducing intravenous drug use in patients with severe amphetamine dependence.
Multicenter Validation of the Diagnostic Accuracy of a Blood-Based Gene Expression Test for Assessing Obstructive Coronary Artery Disease in Nondiabetic Patients
Authors: Steven Rosenberg, Michael R. Elashoff, Philip Beineke, Susan E. Daniels, James A. Wingrove, Whittemore G. Tingley, Philip T. Sager, Amy J. Sehnert, May Yau, William E. Kraus, L. Kristin Newby, Robert S. Schwartz, Szilard Voros, Stephen G. Ellis, Naeem Tahirkheli, Ron Waksman, John McPherson, Alexandra Lansky, Mary E. Winn, Nicholas J. Schork, Eric J. Topol
Journal: Annals of Internal Medicine (2010)

Background: Diagnosing obstructive coronary artery disease (CAD) in at-risk patients can be challenging and typically requires both noninvasive imaging methods and coronary angiography, the gold standard. Previous studies have suggested that peripheral blood gene expression can indicate the presence of CAD. Objective: To validate a previously developed 23-gene, expression-based classification test for diagnosis of obstructive CAD in nondiabetic patients. Design: Multicenter prospective trial with blood samples obtained before coronary angiography. (ClinicalTrials.gov registration number: NCT00500617) Setting: 39 centers in the United States. Patients: An independent validation cohort of 526 nondiabetic patients with a clinical indication for coronary angiography. Measurements: Receiver-operating characteristic (ROC) analysis of classifier score measured by real-time polymerase chain reaction, additivity to clinical factors, and reclassification of patient disease likelihood versus disease status defined by quantitative coronary angiography. Obstructive CAD was defined as 50% or greater stenosis in 1 or more major coronary arteries by quantitative coronary angiography. Results: The area under the ROC curve (AUC) was 0.70 ± 0.02 (P < 0.001); the test added to clinical variables (Diamond–Forrester method) (AUC, 0.72 with the test vs. 0.66 without; P = 0.003) and added somewhat to an expanded clinical model (AUC, 0.745 with the test vs. 0.732 without; P = 0.089). The test improved net reclassification over both the Diamond–Forrester method and the expanded clinical model (P < 0.001). At a score threshold that corresponded to a 20% likelihood of obstructive CAD (14.75), the sensitivity and specificity were 85% and 43% (yielding a negative predictive value of 83% and a positive predictive value of 46%), with 33% of patient scores below this threshold. Limitation: Patients with chronic inflammatory disorders, elevated levels of leukocytes or cardiac protein markers, or diabetes were excluded. Conclusion: A noninvasive whole-blood test based on gene expression and demographic characteristics may be useful for assessing obstructive CAD in nondiabetic patients without known CAD. Primary Funding Source: CardioDx.
Plasmacytoid Dendritic Cells: Recent Progress and Open Questions
Authors: Boris Reizis, Anna Bunin, Hiyaa S. Ghosh, Kanako L. Lewis, Vanja Sisirak
Journal: Annual Review of Immunology (2011)

Plasmacytoid dendritic cells (pDCs) are specialized in rapid and massive secretion of type I interferon (IFN-α/β) in response to foreign nucleic acids. Combined with their antigen presentation capacity, this powerful functionality enables pDCs to orchestrate innate and adaptive immune responses. pDCs combine features of both lymphocytes and classical dendritic cells and display unique molecular adaptations to nucleic acid sensing and IFN production. In the decade since the identification of the pDC as a distinct immune cell type, our understanding of its molecular underpinnings and role in immunity has progressed rapidly. Here we review select aspects of pDC biology including cell fate establishment and plasticity, specific molecular mechanisms of pDC function, and the role of pDCs in T cell responses, antiviral immunity, and autoimmune diseases. Important unresolved questions remain in these areas, promising exciting times in pDC research for years to come.
Refining the staging evaluation of pineal region germinoma using neuroendoscopy and the presence of preoperative diabetes insipidus
Authors: Alyssa T. Reddy, John C. Wellons, Jeffrey C. Allen, John B. Fiveash, Hussein Abdullatif, Karen W. Braune, Paul A. Grabb
Journal: Neuro-Oncology (2004)

Treatment strategies for CNS germinoma are currently evolving. Current approaches include reducing the volume and dose of radiation by adding pre-irradiation chemotherapy. Very accurate staging is necessary with such an approach to prevent failures. Eight consecutive patients with pineal germinoma at one institution underwent endoscopic surgery for tumor biopsy, direct visualization of the third ventricular region, and third ventriculostomy for those with hydrocephalus. All patients were treated with 4 cycles of chemotherapy. Conformal field radiation therapy followed, with the dose to the tumor bed dependent on the response to chemotherapy. Patients who had MRI, endoscopic, or cerebrospinal fluid evidence of multicentric or disseminated disease also received craniospinal radiation. Six patients had diabetes insipidus (DI) at presentation. All 6 had tumor studding the floor of the third ventricle on endoscopic visualization, while only 4 of those patients had MRI evidence of disease in that region. All patients have completed therapy and are alive, with no evidence of disease at median follow-up of 31.5 months from diagnosis. Direct endoscopic visualization of the third ventricular region may be more sensitive than MRI for evaluating the presence of suprasellar disease and appears to add important information. This parameter should be added to the staging evaluation when feasible. In this series, the presence of DI was 100% predictive of suprasellar disease, even when the MRI was negative for involvement of that region. Patients should be evaluated for DI as part of the initial staging, and if it is present, the patients should be treated for suprasellar disease regardless of MRI findings.
Kinetic Analysis of Plasma Insulin Disappearance in Nonketotic Diabetic Patients and in Normal Subjects
Authors: Renzo Navalesi, Alessandro Pilo, Eleuterio Ferrannini, Paolo Cecchetti, Antonio Masoni
Journal: Journal of Clinical Investigation (1978)

The studies so far reported on the metabolic clearance rate of insulin in human diabetes mellitus have given conflicting results, probably because they have been conducted on few patients and have used a variety of experimental techniques and data treatments. We investigated the kinetics of insulin distribution and degradation in 35 normal subjects and in 42 nonketotic, nonobese, overtly diabetic patients, of whom 26 were above 40 yr old and 16 were 40 yr old or less at diagnosis. The design of the study combined (a) the use of a tracer to perturb minimally the steady state and to avoid glucose infusion; (b) the preparation of purified [125I]-monoiodoinsulin, which has a metabolic behavior similar to that of native insulin; and (c) noncompartmental analysis of the plasma immunoprecipitable 125I-insulin disappearance curves, which were recorded for 2 h after pulse i.v. injection of the tracer.
Control of Hereditary Disorders
Authors: I H Porter
Journal: Annual Review of Public Health (1982)

Genetics is the study of biological variations, and medical genetics is the study of those variations that result in, or predispose to, disease. Although at first blush these definitions seem straightforward, they are, in fact, quite contrary to the present perceptions of what genetics is all about. To the pediatrician it is about birth defects and syndromes, to the internist it is about arcane metabolic and morphological disorders, and to the US Sur­ geon General it appears to be summed up in his phrase search and de­ stroy. Screening and antenatal diagnosis of genetic abnormalities are mainly in the province of pediatricians and obstetricians. Patients referred to genetics clinics are usually children with dysmorphic syndromes and developmental abnormalities. This and the likely over-representation of pediatricians among medical geneticists at the medical school may lead to the impression by students and faculty that medical genetics is mainly concerned with developmental defects. This obscures the comprehensive scope of genetics. The genes are a source of differences in structural and metabolic properties that account not only for overt disease but also for predisposition to disease under particular conditions of living. Such observations, as the relationships between human leukocyte antigen (HLA) typing and autoimmune disease, low-density lipoprotein receptor variation and heart attacks, or serum levels of pepsinogen I and peptic ulcer, are a few examples of the many hereditary properties that may be risk factors for the diseases of middle and later life (1). The lack of interest among those concerned with preventive medicine is probably related to the preoccupation of medical geneticists with rare con-
Nrf2 Enhances Cell Proliferation and Resistance to Anticancer Drugs in Human Lung Cancer
Authors: Shinsuke Homma, Yukio Ishii, Yuko Morishima, Tadahiro Yamadori, Yosuke Matsuno, Norihiro Haraguchi, Norihiro Kikuchi, Hiroaki Satoh, Tohru Sakamoto, Nobuyuki Hizawa, Ken Itoh, Masayuki Yamamoto
Journal: Clinical Cancer Research (2009)

NF-E2-related factor 2 (Nrf2), a key transcription regulator for antioxidant and detoxification enzymes, is abundantly expressed in cancer cells. In this study, therefore, the role of Nrf2 in cancer cell proliferation and resistance to anticancer drugs was investigated.We used three human lung cancer cell lines with different degrees of Nrf2 activation: Nrf2 was highly activated in A549 cells, slightly activated in NCI-H292 cells, and not activated in LC-AI cells under unstimulated conditions.A549 cells showed higher resistance to cisplatin compared with NCI-H292 and LC-AI cells. The resistance to cisplatin was significantly inhibited in A549 but not in NCI-H292 or LC-AI cells by knockdown of Nrf2 with its specific small interfering RNA (Nrf2-siRNA). The cell proliferation was also most prominently inhibited in A549 cells by treatment with Nrf2-siRNA. In A549 cells, the expression of self-defense genes, such as antioxidant enzymes, phase II detoxifying enzymes, and drug efflux pumps, was significantly reduced by Nrf2-siRNA concomitant with a reduction of the cellular glutathione level. The degree of DNA crosslink and apoptosis after treatment with cisplatin was significantly elevated in A549 cells by Nrf2-siRNA. Knockdown of Nrf2 arrested the cell cycle at G(1) phase with a reduction of the phosphorylated form of retinoblastoma protein in A549 and NCI-H292 cells but not in LC-AI cells.These results indicate that the Nrf2 system is essential for both cancer cell proliferation and resistance to anticancer drugs. Thus, Nrf2 might be a potential target to enhance the effect of anticancer drugs.
External validity of randomised controlled trials in idiopathic pulmonary fibrosis
Authors: M. Thomeer
Journal: European Respiratory Journal (2006)

To the Editors: 

I would like to comment on the editorial by Johnson and Raghu 1, which was published in the November issue of the European Respiratory Journal . In a very clear way, the authors overviewed the use of outcome measures in clinical trials of idiopathic pulmonary fibrosis (IPF).

I would like to propose some concerns, …
LTP and learning: Let's stay together
Authors: Robert D. Hawkins
Journal: Behavioral and Brain Sciences (1997)

The hypothesis that there is a 1:1 correspondence between LTP and learning is simplistic, and the correlation approach to testing it is therefore too limited. The alternative hypothesis that LTP plays a role in arousal is consistent with activity-dependent neuromodulation, but ignores the Hebbian properties of LTP. LTP may involve both types of mechanisms, suggesting a possible synthesis of the two hypotheses.
EU could help make patients better informed
Authors: R. Watson
Journal: BMJ (2003)

<h3>ABSTRACT</h3> <h3>Purpose</h3> Approximately 7% of men suffer from infertility worldwide and sperm abnormalities are the major cause. Though genetic defects are thought to underlie a substantial fraction of all male infertility cases, the actual molecular bases are usually undetermined. Because the consequences of most genetic variants in populations are unknown, this complicates genetic diagnosis even after genome sequencing of patients. Some patients with ciliopathies, including primary ciliary dyskinesia (PCD) and Bardet-Biedl syndrome (BBS), also suffer from infertility because sperm flagella, which share several characteristics with cilia, are also affected in these patients. <h3>Methods</h3> To identify infertility-causing genetic variants in human populations, we used <i>in silico</i> predictions to identify potentially deleterious SNP (single nucleotide polymorphism) alleles of <i>RABL2A</i>, a gene essential for normal cilia and flagella function. Candidate variants were assayed for protein stability <i>in vitro</i>, and the destabilizing variants were modeled in mice using CRISPR/Cas9-mediated genome editing. The resulting mice were characterized phenotypically for reproductive and developmental defects. <h3>Results</h3> Two of the SNP alleles, <i>Rabl2</i><sup><i>L119F</i></sup> (rs80006029) and <i>Rabl2</i><sup><i>V158F</i></sup> (rs200121688), destabilized the protein. Mice bearing these alleles exhibited PCD- and BBS-associated disorders including male infertility, early growth retardation, excessive weight gain in adulthood, heterotaxia, pre-axial polydactyly, neural tube defects (NTD) and hydrocephalus. <h3>Conclusion</h3> Our study identified and validated pathogenicity of two variants causing ciliopathies and male infertility in human populations, and identified phenotypes not previously described for null alleles of <i>Rabl2</i>.
Discrepancies in Epstein—Barr virus association at presentation and relapse of classical Hodgkin’s disease: Impact on pathogenesis
Authors: A.Y. Nerurkar, P. Vijayan, V. Srinivas, C.S. Soman, K.A. Dinshaw, S.H. Advani, I. Magrath, K. Bhatia, K.N. Naresh
Journal: Annals of Oncology (2000)
THE FUNCTIONS OF THE SKIN
Authors: M. S. PEMBREY
Journal: British Journal of Dermatology (1910)

Journal Article THE FUNCTIONS OF THE SKIN Get access M. S. PEMBREY, M.A., M.D. M. S. PEMBREY, M.A., M.D. Lecturer in Physiology, Guy's Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 22, Issue 5, 1 May 1910, Pages 156–161, https://doi.org/10.1111/j.1365-2133.1910.tb16620.x Published: 01 May 1910