tbuckley/cabot-search huggingface dataset:
Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials
Authors: Paul W Noble, Carlo Albera, Williamson Z Bradford, Ulrich Costabel, Marilyn K Glassberg, David Kardatzke, Talmadge E King, Lisa Lancaster, Steven A Sahn, Javier Szwarcberg, Dominique Valeyre, Roland M du Bois
Journal: The Lancet (2011)
Sleep and synaptic homeostasis
Authors: Giulio Tononi, Chiara Cirelli
Journal: Behavioral and Brain Sciences (2005)

We propose that sleep is linked to synaptic homeostasis. Specifically, we propose that: (1) Wakefulness is associated with synaptic potentiation in cortical circuits; (2) synaptic potentiation is tied to the homeostatic regulation of slow wave activity; (3) slow wave activity is associated with synaptic downscaling; and (4) synaptic downscaling is tied to several beneficial effects of sleep, including performance enhancement.
Incoagulability of Blood After Accidental Haemorrhage
Authors: H. C. Moore
Journal: BMJ (1954)

precipitating causes on a soil already prepared.Put in another way, the affective manifestation of anxiety and depression might seem to be some sort of preformed cere- bral function occurring in the personality type and poten- tially manifesting itself when the right precipitating factor came along.Malamud et atl. ( 1941 take a similar view, and feel that in the "development of the psychoses the pre-morbid personality and catastrophic occurrences before the onset of the illness are of outstanding importance."From a purely practical point of view, exhaustive evaluation of any physical anomalies seen in association with this type of illness, even if, as in these cases, the whole background seems to be characteristic of involutional depression, is clearly of the utmost importance. SummaryFour cases of agitated depression are noted, all of which were associated with organic disease.The depression, its symptoms, signs, and time of occur- rence, together with the pre-morbid personality of the patient, were characteristic of the involutional type of illness.The significance of this association is discussed.I am grateful to Dr. R. E.
Somatostatin Analogs in Cancer Management: Edited by C Scarpignato. Nantes: Parma, 2001, US$97.50, pp 198. ISBN 3 8055 7035 X
Authors: S J Mather
Journal: Gut (2002)

It may be common practice to publish book versions of journal supplements but this is the first such example to reach the desk of this reviewer (reprint of Chemotherapy 2001: 47 :supplement 2). In this age of instant electronic information retrieval the idea of producing such a hard copy version seems rather retrogressive, but for frequent referral it is still easier and quicker to reach for a book from the shelf than to suffer the vagaries of Internet access. But is this a book that needs to be at one’s fingertips?

The book consists of a preface and …
The Impact of Coronary Artery Disease on the Coronary Vasomotor Response to Nonionic Contrast Media
Authors: Ugo Limbruno, Anna Sonia Petronio, Giovanni Amoroso, Roberto Baglini, Giovanni Paterni, Antonella Merelli, Rita Mariotti, None Raffaele De Caterina, Mario Mariani
Journal: Circulation (2000)

Coronary artery disease (CAD) alters the vasomotor response to a variety of pharmacological agents. We tested the hypothesis that CAD also has an impact on the coronary vasomotor response to radiologic contrast media.We performed quantitative coronary angiography in 42 patients without angiographic evidence of CAD and 38 patients with CAD in the left coronary artery. Angiographically smooth coronary segments (n=235) were analyzed for changes on luminal diameters and coronary venous oxygen saturation in response to 3 media: the nonionic dimer iodixanol, the nonionic monomer iopromide, and the ionic agent ioxaglate. In subjects without CAD, we assessed the effects of intracoronary administration of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine and of the cyclooxygenase inhibitor indomethacin on such changes. Iodixanol induced coronary vasodilation in subjects without CAD (8.8+/-8.6%, P<0.001). Patients with CAD exhibited no significant diameter changes in segments >/=20 mm apart from a stenosis (4.7+/-9.4%, P=NS) and significant constriction in segments <20 mm from a stenosis (-3.8+/-4.6%, P<0. 05). Similar results were obtained with iopromide, but no changes were found with ioxaglate. All contrast media induced transient (<35 seconds) increases in coronary venous oxygen saturation in all subjects. Indomethacin, but not N(G)-monomethyl-L-arginine, blunted the vasodilating effect of iodixanol and iopromide (by 80% and 76%, respectively; P<0.001).Nonionic contrast media induce a vasodilatory response in normal vessels not by a mechanism involving increased flow or endothelial nitric oxide synthesis, but rather by depending on preserved vascular cyclooxygenase activity. CAD changes normal epicardial vasodilatory response into vasoconstriction.
RABL6A Promotes G1–S Phase Progression and Pancreatic Neuroendocrine Tumor Cell Proliferation in an Rb1-Dependent Manner
Authors: Jussara Hagen, Viviane P. Muniz, Kelly C. Falls, Sara M. Reed, Agshin F. Taghiyev, Frederick W. Quelle, Francoise A. Gourronc, Aloysius J. Klingelhutz, Heather J. Major, Ryan W. Askeland, Scott K. Sherman, Thomas M. O'Dorisio, Andrew M. Bellizzi, James R. Howe, Benjamin W. Darbro, Dawn E. Quelle
Journal: Cancer Research (2014)

Mechanisms of neuroendocrine tumor (NET) proliferation are poorly understood, and therapies that effectively control NET progression and metastatic disease are limited. We found amplification of a putative oncogene, RABL6A, in primary human pancreatic NETs (PNET) that correlated with high-level RABL6A protein expression. Consistent with those results, stable silencing of RABL6A in cultured BON-1 PNET cells revealed that it is essential for their proliferation and survival. Cells lacking RABL6A predominantly arrested in G1 phase with a moderate mitotic block. Pathway analysis of microarray data suggested activation of the p53 and retinoblastoma (Rb1) tumor-suppressor pathways in the arrested cells. Loss of p53 had no effect on the RABL6A knockdown phenotype, indicating that RABL6A functions independent of p53 in this setting. By comparison, Rb1 inactivation partially restored G1 to S phase progression in RABL6A-knockdown cells, although it was insufficient to override the mitotic arrest and cell death caused by RABL6A loss. Thus, RABL6A promotes G1 progression in PNET cells by inactivating Rb1, an established suppressor of PNET proliferation and development. This work identifies RABL6A as a novel negative regulator of Rb1 that is essential for PNET proliferation and survival. We suggest RABL6A is a new potential biomarker and target for anticancer therapy in PNET patients.
Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis.
Authors: J Vilaseca, A Salas, F Guarner, R Rodriguez, M Martinez, J R Malagelada
Journal: Gut (1990)

Eicosanoids are modulators of defensive and inflammatory processes in the gut mucosa, and may be involved in the pathogenesis of chronic inflammatory lesions of the bowel. As omega-3 fatty acids compete with the omega-6 as precursors of eicosanoid synthesis, we compared the effects of dietary supplementation with either sunflower (source of omega-6) or cod liver (source of omega-3) oil on the development of chronic granulomatous lesions in the rat colon. After four weeks on the supplemented diets, plasma omega-6 fatty acid content was significantly higher in the sunflower group, while omega-3 fatty acids predominated in the cod liver group. Inflammatory colitis was then induced by intracolonic administration of trinitrobenzene sulphonic acid. Luminal eicosanoid release, as measured by radioimmunoassay of intracolonic dialysis fluid, increased significantly after the challenge in both groups. Generation of prostaglandin E2 (PGE2) and leucotriene B4 (LTB4) peaked by day 3 and thereafter declined; thromboxane B2 (TXB2), instead, continued to increase from day 3 to 20 in sunflower fed rats, whereas this change was blunted in cod liver animals. The rats were killed 20, 30, or 50 days after the induction of colitis, and the colonic lesions were scored macroscopically (adhesions to surrounding tissues, strictures, ulcerations, and wall thickness) and histologically (ulceration, inflammation, depth of the lesions, and fibrosis). In cod liver animals, the damage score was markedly reduced by day 30, and inflammation and ulceration were almost absent by day 50. In conclusion, a fish oil diet prevents the increase in thromboxane in the chronic state of inflammation and shortens the course of the colonic disease by diminishing both the severity of the lesions and their progression to chronicity.
Single germline VH and V kappa genes encode predominating antibody variable regions elicited in strain A mice by immunization with p-azophenylarsonate.
Authors: L J Wysocki, T Gridley, S Huang, A G Grandea, M L Gefter
Journal: The Journal of Experimental Medicine (1987)

We have cloned and sequenced the predominant germline V kappa gene segment expressed by B cells of strain A origin that synthesize antibodies with specificity for Ars. In hybridomas synthesizing anti-Ars antibodies, this V kappa gene segment (V kappa IdCR) has been found exclusively associated with the J kappa 1 gene segment without exhibiting junctional sequence variation. Sequence comparisons of the germline V kappa IdCR gene with expressed derivatives reveals that the latter frequently contain somatically introduced amino acid replacements. Taken together with results of previous structural analyses, these results show that the predominant population of IdCR+ V regions elicited in the secondary immune response is encoded by one or two combinations of V gene segments, has little junctional diversity, and is extensively diversified by somatic mutation in both heavy and light chains.
Long-term Angiotensin-Converting Enzyme Inhibition With High-Dose Enalapril Retards Nitrate Tolerance in Large Epicardial Arteries and Prevents Rebound Coronary Vasoconstriction In Vivo
Authors: Thomas Münzel, Eberhard Bassenge
Journal: Circulation (1996)

Background Rebound myocardial ischemia develops in patients with unstable or stable angina pectoris after sudden cessation of nitroglycerin therapy. Long-term nitroglycerin infusion is associated with increases in plasma renin activity and catecholamine release rates, both of which may lead to excess angiotensin II and α-adrenergic–mediated vasoconstriction, particularly on withdrawal of nitroglycerin. Methods and Results Chronically instrumented dogs were treated for 5 days with nitroglycerin (1.5 μg·kg −1 ·min −1 IV) alone or in combination with the angiotensin-converting enzyme (ACE) inhibitor enalapril (0.1 mg/kg two times daily or 1 mg/kg). With long-term nitroglycerin therapy, the left anterior circumflex artery was maximally dilated 4 hours after the start of nitroglycerin infusion (9.5±0.6%) and returned to baseline levels within the third day of treatment (baseline, 2.52±0.07 mm; day 3, 2.55±0.07 mm; P =NS), indicating a complete loss of nitroglycerin-induced coronary vasodilatation. Nitroglycerin infusion also was accompanied by a transient increase in plasma renin activity. Sudden withdrawal of nitroglycerin infusion caused a progressive constriction of the left anterior circumflex artery, which peaked 4 hours after nitroglycerin infusion cessation (−7.8±0.2%). This occurred in the absence of elevated plasma renin activity. Concomitant treatment with high-dose enalapril (1 mg·kg −1 ·d −1 ) markedly reduced the degree of tolerance and prevented the rebound constriction on cessation of nitroglycerin therapy. Conclusions Long-term ACE inhibition with high-dose enalapril reduces nitroglycerin tolerance and prevents rebound vasoconstriction in coronary arteries. These phenomena were not associated with an activated circulating renin-angiotensin system. This observation suggests that during long-term nitroglycerin treatment, intrinsic abnormalities of the vascular smooth muscle may have developed that are suppressed by concomitant ACE inhibitor therapy. The present study also favors a combination of nitroglycerin and ACE inhibitors to maintain nitrate sensitivity of the vasculature during long-term nitroglycerin treatment.
Review and expert opinion on prevention and treatment of infliximab-related infusion reactions
Authors: L.L.A. Lecluse, G. Piskin, J.R. Mekkes, J.D. Bos, M.A. de Rie
Journal: British Journal of Dermatology (2008)

Infliximab (Remicade; Schering-Plough, Kenilworth, NJ, U.S.A.) is a chimeric monoclonal antibody that acts as a tumour necrosis factor-alpha inhibitor. Infliximab is registered for the treatment of rheumatoid arthritis, psoriatic arthritis, Crohn disease, ulcerative colitis, ankylosing spondylitis and plaque-type psoriasis. Like other foreign protein-derived agents, infliximab may lead to infusion reactions during and after infusion. Infusion reactions occur in 3-22% of patients with psoriasis treated with infliximab. Most of these reactions are mild or moderate and only few are severe. Nevertheless, they may lead to discontinuation of treatment. As infliximab for psoriasis is prescribed as a last resort and is in most cases very effective, discontinuation of treatment is undesirable. With proper care and prevention of the infusion reactions the need to discontinue treatment with infliximab can be diminished. The objective of this article is to present a guideline for the management of infliximab-related infusion reactions, based on the best available evidence. This guideline can be used in patients with psoriasis as well as in dermatology patients receiving infliximab for off-label indications such as hidradenitis suppurativa or pyoderma gangrenosum.
Coordination of PGC-1β and iron uptake in mitochondrial biogenesis and osteoclast activation
Authors: Kiyo-aki Ishii, Toshio Fumoto, Kazuhiro Iwai, Sunao Takeshita, Masako Ito, Nobuyuki Shimohata, Hiroyuki Aburatani, Shigeru Taketani, Christopher J Lelliott, Antonio Vidal-Puig, Kyoji Ikeda
Journal: Nature Medicine (2009)
Individualized Treatment for Alcohol Withdrawal
Authors: Richard Saitz
Journal: JAMA (1994)

<h3>Objective.</h3> —To assess the effect of an individualized treatment regimen on the intensity and duration of medication treatment for alcohol withdrawal. <h3>Design.</h3> —A randomized double-blind, controlled trial. <h3>Setting.</h3> —An inpatient detoxification unit in a Veterans Affairs medical center. <h3>Patients.</h3> —One hundred one patients admitted for the treatment of alcohol withdrawal who could give informed consent and had no history of seizures or medication use that might alter the clinical course of withdrawal. <h3>Intervention.</h3> —Patients were randomized to either a standard course of chlordiazepoxide four times daily with additional medication as needed (fixed-schedule therapy) or to a treatment regimen that provided chlordiazepoxide only in response to the development of the signs and symptoms of alcohol withdrawal (symptomtriggered therapy). The need for administration of "as-needed" medication was determined using a validated measure of the severity of alcohol withdrawal. <h3>Main Outcome Measures.</h3> —Duration of medication treatment and total chlordiazepoxide administered. <h3>Results.</h3> —The median duration of treatment in the symptom-triggered group was 9 hours compared with 68 hours in the fixed-schedule group (<i>P</i>&lt;.001). The symptom-triggered group received 100 mg of chlordiazepoxide, and the fixed-schedule group received 425 mg (<i>P</i>&lt;.001). There were no significant differences in the severity of withdrawal during treatment or in the incidence of seizures or delirium tremens. <h3>Conclusions.</h3> —Symptom-triggered therapy individualizes treatment, decreases both treatment duration and the amount of benzodiazepine used, and is as efficacious as standard fixed-schedule therapy for alcohol withdrawal. (<i>JAMA</i>. 1994;272:519-523)
668. Non-Viral Gene Delivery for Ocular Diseases with Compacted DNA Nanoparticles
Authors: Rafal Farjo, Jeff Skaggs, Alexander B. Quiambao, Mark J. Cooper, Muna I. Naash
Journal: Molecular Therapy (2005)

Top of pageAbstract
Our objective is to develop an effective and robust therapeutic vector system which can be utilized in the treatment of genetically-based blinding diseases. In the present study we have evaluated the ability of compacted DNA nanoparticles to transfect mouse ocular tissues in vivo. EGFP expression plasmids transcriptionally-controlled by the CMV promoter were compacted into neutral-charged DNA nanoparticles (having a diameter < 15 nm) using polyethylene glycol-substituted lysine peptides and injected subretinally or intravitreally into the eyes of adult BALB/c mice. Both delivery routes were examined in order to target photoreceptors, RPE, and optic nerve cells (subretinal) or inner retinal cells (intravitreal). In a set of control animals, naked plasmid DNA was injected at the same concentration as the nanoparticles or a mock injection was performed. After 2 days post-injection, mice were euthanized and the retinas were assayed for EGFP expression by quantitative real-time RT-PCR (qRT-PCR) and immunohistochemistry. Significant levels of EGFP expression were obtained by either subretinal or intravitreal delivery of the compacted DNA nanoparticles. Immunohistochemistry demonstrated the ability of these nanoparticles to transfect and express EGFP in vivo at extraordinarily high efficiencies. After subretinal injection, EGFP was detected in almost 100% of the photoreceptors and abundant expression was observed in the inner nuclear layer, RPE, and optic nerve. By qRT-PCR, EGFP mRNA levels were comparable in abundance to rhodopsin mRNA. Mice injected intravitreally showed very efficient EGFP expression in the cells of the inner retina, including the ganglion cell layer. After either subretinal or intravitreal delivery, minimal or no expression of EGFP was detected with naked plasmid or mock-injected controls. Ocular delivery of the DNA nanoparticles did not induce any apparent toxicity. Compacted DNA nanoparticles can efficiently target post-mitotic cells of the retina and yield high levels of transgene expression. Transfection of different retinal cell layers can be achieved by the route of delivery. This non-viral system is a safe and very effective tool for ocular gene therapy. Further studies are underway utilizing this technology to rescue several well characterized animal models of retinal disease.
Papillon-Lefèvre syndrome patient reveals species-dependent requirements for neutrophil defenses
Authors: Ole E. Sørensen, Stine N. Clemmensen, Sara L. Dahl, Ole Østergaard, Niels H. Heegaard, Andreas Glenthøj, Finn Cilius Nielsen, Niels Borregaard
Journal: Journal of Clinical Investigation (2014)

Papillon-Lefèvre syndrome (PLS) results from mutations that inactivate cysteine protease cathepsin C (CTSC), which processes a variety of serine proteases considered essential for antimicrobial defense. Despite serine protease-deficient immune cell populations, PLS patients do not exhibit marked immunodeficiency. Here, we characterized a 24-year-old woman who had suffered from severe juvenile periodontal disease, but was otherwise healthy, and identified a homozygous missense mutation in CTSC indicative of PLS. Proteome analysis of patient neutrophil granules revealed that several proteins that normally localize to azurophil granules, including the major serine proteases, elastase, cathepsin G, and proteinase 3, were absent. Accordingly, neutrophils from this patient were incapable of producing neutrophil extracellular traps (NETs) in response to ROS and were unable to process endogenous cathelicidin hCAP-18 into the antibacterial peptide LL-37 in response to ionomycin. In immature myeloid cells from patient bone marrow, biosynthesis of CTSC and neutrophil serine proteases appeared normal along with initial processing and sorting to cellular storage. In contrast, these proteins were completely absent in mature neutrophils, indicating that CTSC mutation promotes protease degradation in more mature hematopoietic subsets, but does not affect protease production in progenitor cells. Together, these data indicate CTSC protects serine proteases from degradation in mature immune cells and suggest that neutrophil serine proteases are dispensable for human immunoprotection.
A Typographic Error.
Authors: Elliott R. King
Journal: JAMA (1896)

Muscatine,Iowa, Dec. 24, 1895. <h3>To the Editor:</h3> —As I was reading an article in the issue of December 21, p. 1090 of theJournal, I came across this word, " tribaism," in second column, line 41. I could not find its meaning from any books at my command nor from any of my "Roman friends." I am yours fraternally, <h3>Answer:</h3> —The word was misprinted by the omission of the letter "d." It should have been printed<i>tribadism</i>.
CARBOHYDRATE AND LYMPHOID STUDIES IN SCHIZOPHRENIA
Authors: HARRY FREEMAN, FRED ELMADJIAN
Journal: American Journal of Psychiatry (1950)

A series of studies have been carried out in schizophrenic patients and normal controls that indicate that (1) there is a reduction of tolerance to glucose in this psychosis; (2) the response of the adrenal cortex to stimulation by the ingestion of glucose is generally deficient as exemplified by measurements of various blood and urinary variables known to be pertinent to adreno-cortical activation.
Thalassemia Major: Molecular and Clinical Aspects
Authors: ARTHUR W. NIENHUIS
Journal: Annals of Internal Medicine (1979)

Thalassemia major is a severe and transfusion-dependent anemia that occurs in persons homozygous for a mutation that affects the capacity for synthesis of the β- globin subunit of hemoglobin. Characterization of the molecular defects that cause β- thalassemia is providing insight into the mechanism of globin gene regulation. Newer approaches to the management of thalassemia major include more effective chelation by use of subcutaneous desferrioxamine and attempts to obtain young erythrocytes with a longer potential for survival in recipient patients. Development of more effective chelators that may be given orally is an ongoing effort. Noninvasive evaluation of cardiac structure and function in patients with thalassemia major suggests that myocardial iron deposits begin at an early age, causing functional impairment long before the onset of clinical symptoms. Prevention or reversal of these cardiac abnormalities remains the goal of chelation therapy.
Euthanasia Is Not the Answer: A Hospice Physician's View
Authors: Burton C. Einspruch
Journal: JAMA (1993)

In the summer of 1992,I read, among other books about euthanasia, Derek Humphrey's controversialFinal Exit. It is an unapologetic and somewhat bizarrely forthright how-to book on ending one's life. Humphrey, a news reporter, states simply that his goal was to actually give dying people printed guidance on how to end their lives if their suffering was unbearable!  Just as divorce has increased dramatically among the elderly, so has suicide. Suicidal wishes would be acted upon much more frequently if individuals had the physical capacity, awareness, and access to end their lives. Recent publicity has focused on an American practitioner and author, Dr Jack Kevorkian (The Goodness of a Planned Death), whose invention of a death machine to end the life of an Alzheimer's patient has received considerable support and far less condemnation from the public.  ... 'where cure is not possible, care is still needed'...   The medical community has not,