tbuckley/cabot-search huggingface dataset:
Synergistic Action of Cyclophosphamide and 1,3-Bis(2-Chloroethyl)-1-Nitrosourea on a Transplanted Murine Lymphoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: F. A. Valeriote, W. R. Bruce, B. E. Meeker
Journal: JNCI Journal of the National Cancer Institute (1968)

Dose-survival curves for lymphoma cells in the spleen and liver of tumor-bearing mice after treatment with cyclophosphamide (CY) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were obtained. These curves, measured through 8 decades of survival with the endpoint dilution assay of Hewitt, revealed that the reasons for the failure of these two drugs to cure animals with advanced lymphoma were different. Whereas BCNU was limited by host toxicity at doses that might have effected a cure, CY was limited by the presence of a CY-insensitive population of cells in the liver and the spleen of the host following treatment. Seventy percent of mice with advanced lymphoma could be cured of their malignancy by combinations of these two drugs. A similar synergistic action of a number of other chemotherapeutic agents in conjunction with either CY or BCNU was also demonstrated.
Active Inhibition of Plasma Cell Development in Resting B Cells by Microphthalmia-associated Transcription Factor
Authors: Ling Lin, Andrea J. Gerth, Stanford L. Peng
Journal: The Journal of Experimental Medicine (2004)

B cell terminal differentiation involves development into an antibody-secreting plasma cell, reflecting the concerted activation of proplasma cell transcriptional regulators, such as Blimp-1, IRF-4, and Xbp-1. Here, we show that the microphthalmia-associated transcription factor (Mitf) is highly expressed in naive B cells, where it antagonizes the process of terminal differentiation through the repression of IRF-4. Defective Mitf activity results in spontaneous B cell activation, antibody secretion, and autoantibody production. Conversely, ectopic Mitf expression suppresses the expression of IRF-4, the plasma cell marker CD138, and antibody secretion. Thus, Mitf regulates B cell homeostasis by suppressing the antibody-secreting fate.
Tumor Escape Mechanism Governed by Myeloid-Derived Suppressor Cells
Authors: Srinivas Nagaraj, Dmitry I. Gabrilovich
Journal: Cancer Research (2008)

Abstract T-cell nonresponsiveness is a critical factor in immune escape and myeloid-derived suppressor cells play a major role in organizing this phenomenon. Recent findings indicate that myeloid-derived suppressor cells can induce antigen-specific CD8+ T-cell tolerance through a posttranslation mechanism which involves modification (nitration) of CD8 and the T-cell receptor itself on the T-cell surface. Elucidation of this mechanism of T-cell tolerance offers new opportunities for therapeutic corrections of immune escape in cancer. [Cancer Res 2008;68(8):2561–63]
Ischaemic colitis and the contraceptive pill.
Authors: M Lea Thomas, P B Cotton
Journal: BMJ (1971)

27which classes of hyperlipoproteinaemia are best treated with a combination or with clofibrate alone.It is, however, quite clear that its greatest potential use is for the treatment of the type II pattern, which is, in general, affected little by clofibrate alone and only moderately by cholestyramine.We are indebted to Dr. W.
Screening for Hypothyroidism in Sleep Apnea
Authors: NEIL M. SKJODT, RAJ ATKAR, PAUL A. EASTON
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Primary sleep apnea–hypopnea syndrome (obstructive sleep apnea [OSA]) and hypothyroidism have many signs and symptoms in common. The overlap in clinical presentation, and the sleep-disordered breathing that can accompany hypothyroidism, create a significant risk of misdiagnosis of sleep apnea among patients referred to sleep clinic who have undiagnosed hypothyroidism. We determined the point prevalence of hypothyroidism in our sleep clinic patients with newly diagnosed sleep-disordered breathing. Of 290 sequential patients referred to sleep clinic, 200 (69%) patients judged at high risk for OSA underwent polysomnography (PSG) and biochemical screening for hypothyroidism. Of these, 124 (62%) were judged to have sleep apnea. This included three patients (1.5% of patients undergoing PSG or 2.4% of those judged to have OSA) who were also discovered to have previously undiagnosed hypothyroidism. These three patients with "secondary" sleep apnea were treated with thyroxine therapy alone, and followed with sequential sleep studies and serum thyroid hormone assays; symptoms, sleep-disordered breathing, nocturnal hypoxia, and thyroid deficiency resolved simultaneously. We conclude that biochemical screening for hypothyroidism is required to prevent inadvertent misdiagnosis of hypothyroid sleep-disordered breathing as primary sleep apnea, and that it is a cost-effective component of the investigation of sleep apnea.
Visual acuity outcomes of patients 50 years of age and older with high myopia and untreated choroidal neovascularization
Authors: Homayoun Tabandeh, Harry W Flynn, Ingrid U Scott, Mary L Lewis, Philip J Rosenfeld, Francisco Rodriguez, Alvaro Rodriguez, Lawrence J Singerman, Joyce Schiffman
Journal: Ophthalmology (1999)

To evaluate visual outcomes of untreated submacular choroidal neovascularization (CNV) in patients 50 years of age and older with high myopia.Retrospective observational case series.Twenty-two eyes in 22 patients were studied. All were 50 years of age and older with myopia of 6.0 diopters (D) or greater or an axial length of 25.5 mm or greater. Patients had untreated CNV documented by clinical examination and fluorescein angiography at two medical centers between 1986 and 1997.Demographic and clinical data were abstracted from patients' medical records.Visual acuity at 1 year after CNV diagnosis.The study included 22 eyes of 22 patients (mean age, 63.1 years; mean refraction, -11.0 D). Baseline visual acuity (VA) in the study eye was 20/40 or greater in 2 (9%) patients, 20/50 to 20/150 in 9 (41%) patients, and 20/200 or less in 11 (50%) patients. Drusen were present in seven (32%) eyes, and lacquer cracks were noted in ten (45%) eyes. Mean refractive error was -7.0 D for patients with drusen and -12.5 D for patients without drusen. Choroidal neovascularization was less than 0.25 disc diameters (DD) in 11 (50%) eyes, 0.25 to 0.5 DD in 5 (23%) eyes, and greater than 0.5 DD in 6 (27%) eyes. Visual acuity in the study eye 1 year after CNV diagnosis was 20/40 or greater in 3 (14%) patients, 20/50 to 20/150 in 3 (14%) patients, and 20/200 or less in 16 (73%) eyes. The presence of drusen was significantly associated with older age and a lower degree of myopia but was not associated with size of the CNV or visual acuity outcome.When compared to patients younger than 50 years of age with high myopia and CNV reported in previous publications, the patients in the current series generally have poorer visual outcomes.
The requirement for C3 receptors on the precursors of 19S and 7S antibody-forming cells.
Authors: D W Mason
Journal: The Journal of Experimental Medicine (1976)

The main conclusion from this study is that C3 receptors are not required for the generation from B cells of a thymus-dependent 7S antibody response. The requirement for C3 receptors on the precursors of antibody-forming cells was studied in an adoptive transfer system using thoracic duct lymphocytes (TDL) from primed rats as a source of precursors and irradiated recipients as hosts. 7S precursors were found in both the CR+ and the CR- fractions of TDL and it was established that the response transferred by CR- cells did not arise from either a raidoresistant B cell in the host or from CR+ cells contaminating the CR- population. Thus, the C3 receptor is not obligatory for B-cell-T-cell cooperation in the 7S response. The precursors of 19S antibody-forming cells were found only in the CR+ subpopulation. The CR-Ig+ subpopulation was shown to contain all the B blasts in rat TDL and a very small number (approximately 1% of all TDL) of small lymphocytes. This latter population contained the CR- 7S precursors and contributed approximately 20% of the total adoptive secondary 7S response transferred by CR+ and CR- subpopulations combined. This observation suggests that the percentage of rat TDL committed to carry 7S memory is small, a conclusion which is confirmed and extended in the following paper.
Complement and Its Receptors: New Insights into Human Disease
Authors: V. Michael Holers
Journal: Annual Review of Immunology (2014)

Although new activation and regulatory mechanisms are still being identified, the basic architecture of the complement system has been known for decades. Two major roles of complement are to control certain bacterial infections and to promote clearance of apoptotic cells. In addition, although inappropriate complement activation has long been proposed to cause tissue damage in human inflammatory and autoimmune diseases, whether this is indeed true has been uncertain. However, recent studies in humans, especially those using newly available biological therapeutics, have now clearly demonstrated the pathophysiologic importance of the complement system in several rare diseases. Beyond these conditions, recent genetic studies have strongly supported an injurious role for complement in a wide array of human inflammatory, degenerative, and autoimmune diseases. This review includes an overview of complement activation, regulatory, and effector mechanisms. It then focuses on new understandings gained from genetic studies, ex vivo analyses, therapeutic trials, and animal models as well as on new research opportunities.
Immunobiology of pleural inflammation: potential implications for pathogenesis, diagnosis and therapy
Authors: C Kroegel, VB Antony
Journal: European Respiratory Journal (1997)

Although infectious, inflammatory and neoplastic diseases frequently involve the pleural space and walls, little is known about the immunological and molecular mechanisms underlying pleural disorders. This article provides an overview of recent insights into immunobiological processes likely to play a role in the pathogenesis of pleural disorders. Pleural involvement in certain diseases is associated with the infiltration of a number of different types of immune cells, such as neutrophils, eosinophils or lymphocytes, in various proportions depending on both the course and the aetiology of the underlying disease. In addition to infiltrating cells, mesothelial cells have been demonstrated to actively participate in pleural inflammation via release of various mediators and proteins, including platelet-derived growth factor (PDGF), interleukin-8, monocyte chemotactic peptide (MCP-1), nitric oxide (NO), collagen, antioxidant enzymes and the plasminogen activation inhibitor (PAI). Furthermore, several inflammatory mediators have been detected at increased concentrations within pleural effusions, including lipid mediators, cytokines and proteins (adenosine deaminase, lysosyme, eosinophil-derived cationic proteins, and products of the coagulation cascade). The presence of these mediators underline the concept of pleural inflammation, and certain cytokines seem to characterize a specific aetiology of pleurisy. The understanding of these processes and the sequence of events leading to pleural loculation, pleural adhesion or repair are likely to provide the basis for early therapeutic intervention and reduce pleural-associated morbidity.
Réutilisation de matériel médical stérile à usage unique dans les hôpitaux danois - l'impact d'un rapport décourageant cette pratique
Authors: M Christensen, M Meyer, O. B Jepsen
Journal: Eurosurveillance (1999)

L’etendue de la pratique consistant a reutiliser du materiel medical sterile  a usage unique  a fait recemment l’objet d’une etude dans 100 hopitaux au Danemark, en Finlande, en Norvege et en Suede (1). La meme methodologie avait ete utilisee lors d’une etude menee, deux ans plus tot, dans les seuls hopitaux danois. Il a donc ete possible de comparer les resultats des hopitaux danois ayant participe aux deux enquetes et d’evaluer si la publication des conclusions de la premiere, qui recommandait que le le materiel medical jetable ne soit jamais reutilise, avait ete suivie de changements des pratiques et des politiques dans ce domaine.
Intestinal transplantation in children with chronic intestinal pseudo-obstruction
Authors: L Sigurdsson, J Reyes, S A Kocoshis, G Mazariegos, K M Abu-Elmagd, J Bueno, C Di Lorenzo
Journal: Gut (1999)

Children with chronic intestinal pseudo-obstruction (CIPO) often require total parenteral nutrition (TPN) which puts them at risk of liver failure and recurrent line infections. Intestinal transplantation has become a therapeutic option for TPN dependent children with intestinal failure who are failing management with TPN.To investigate the outcome of children with CIPO referred for intestinal transplantation.A retrospective review was carried out of records and diagnostic studies from 27 patients with CIPO referred for intestinal transplantation.Five children were not listed for transplantation: two because of parental decision, two because of suspicion of Munchausen syndrome by proxy, and one because he tolerated enteral nutrition. Six are still TPN dependent and awaiting transplantation. Eight children died awaiting transplantation. Eight children underwent transplantation. Three died (two months, seven months, and four years after transplant). Five children are alive with a median follow up of 2.6 years (range two months to six years). All transplanted children were able to tolerate full enteral feedings. The postoperative course was complicated by dumping syndrome, Munchausen syndrome by proxy, narcotic withdrawal, and uncovering of achalasia. Conclusion-Intestinal transplantation may be a life saving procedure in children with CIPO. Early referral and thorough pretransplant evaluation are keys to successful transplantation.
Effects of brain natriuretic peptide on forearm vasculature: comparison with atrial natriuretic peptide
Authors: K van der Zander
Journal: Cardiovascular Research (1999)

Objective: The aim of the present study was to determine the vasoactive effects of brain natriuretic peptide (BNP) as compared to those of atrial natriuretic peptide (ANP) in normal man. Methods: Ten healthy male subjects (median age 21 (20–23) year) were studied twice. In the first study equimolar doses (1, 3, and 10 pmol/dl/min) of both BNP and ANP (in random order and double blind) were infused into the brachial artery of the non-dominant arm with a 1-h wash-out period in between. In the second study two BNP (n=5) or ANP (n=5) dose–response curves were performed in order to assess the repeatability of the BNP/ANP infusions. To this end, BNP and ANP were infused in the same equimolar doses as in the first protocol. Forearm blood flow (FBF) was determined by venous occlusion plethysmography before and during infusions. Results: BNP increased the FBF ratio (infused/contralateral arm) by 6%, 17%, and 48%, respectively (p<0.05), while ANP increased the FBF ratio by 4%, 58%, and 133% (p<0.001). The slopes of the BNP dose–response curves differed significantly from those of the ANP curves (18.1 versus 43.2; p=0.022). No differences were observed between the repeated dose–response curves of either BNP or ANP. Conclusions: The present data demonstrate that BNP induces a dose-dependent vasodilatation in man. On a molar basis, however, this vasodilatation is significantly less than the vasodilatation induced by ANP. These differences may be related to differences in natriuretic-peptide-receptor affinity. Furthermore, our data show that the vasoactive effects of both BNP and ANP are repeatable in time.
Epstein-Barr Virus Infections: Biology, Pathogenesis, and Management
Authors: Stephen E. Straus
Journal: Annals of Internal Medicine (1993)

Epstein-Barr virus (EBV) encodes genes that ensure its persistence in human B lymphocytes. Some of the genes encourage B-cell proliferation; others are poised to evade or defeat immune recognition. Immune restraints on the virus, however, are typically so effective that most infections are never symptomatic. In contrast, acute infectious mononucleosis, a self-limited lymphoproliferative illness, is common in adolescents and young adults. Unbridled proliferative illnesses arise when cellular immunity is grossly defective. Treatment of EBV-associated syndromes is largely supportive. Antiviral drugs have no proven role except in patients with oral hairy leukoplakia. Vaccine development is technically feasible but is not considered a high priority for developed nations.
London health service faces serious financial problems and cuts of 5bn by 2017
Authors: A. O'Dowd
Journal: BMJ (2010)

Doctors’ leaders have warned that London is facing the most severe healthcare financial problems of anywhere in England, as NHS budget cuts will bite hardest in the capital.

The BMA published a report this week warning that London is heading towards “a major financial and organisational crisis” that will mean the closure or downgrading of hospital services.

Real term cuts of £5bn (€5.7bn; $8.2bn) to primary care trusts’ funding by 2017 are now being envisaged, says the report, which was commissioned by the BMA and written by John Lister, information director at the campaigning organisation London Health Emergency.

In preparing the report Mr Lister …
A model based on age, sex, and morbidity to explain variation in UK general practice prescribing: cohort study
Authors: R. Z Omar, C. O'Sullivan, I. Petersen, A. Islam, A. Majeed
Journal: BMJ (2008)

<b>Objective</b> To examine whether patient level morbidity based measure of clinical case mix explains variations in prescribing in general practice. <b>Design</b> Retrospective study of a cohort of patients followed for one year. <b>Setting</b> UK General Practice Research Database. <b>Participants</b> 129 general practices, with a total list size of 1 032 072. <b>Main outcome measures</b> Each patient was assigned a morbidity group on the bases of diagnoses, age, and sex using the Johns Hopkins adjusted clinical group case mix system. Multilevel regression models were used to explain variability in prescribing, with age, sex, and morbidity as predictors. <b>Results</b> The median number of prescriptions issued annually to a patient is 2 (90% range 0 to 18). The number of prescriptions issued to a patient increases with age and morbidity. Age and sex explained only 10% of the total variation in prescribing compared with 80% after including morbidity. When variation in prescribing was split between practices and within practices, most of the variation was at the practice level. Morbidity explained both variations well. <b>Conclusions</b> Inclusion of a diagnosis based patient morbidity measure in prescribing models can explain a large amount of variability, both between practices and within practices. The use of patient based case mix systems may prove useful in allocation of budgets and therefore should be investigated further when examining prescribing patterns in general practices in the UK, particularly for specific therapeutic areas.
Imaging gastrointestinal tumours using vascular endothelial growth factor-165 (VEGF165) receptor scintigraphy
Authors: S. Li, M. Peck-Radosavljevic, O. Kienast, J. Preitfellner, G. Hamilton, A. Kurtaran, C. Pirich, P. Angelberger, R. Dudczak
Journal: Annals of Oncology (2003)
CD10 and CD34 in fetal and adult human hair follicles: dynamic changes in their immunohistochemical expression during embryogenesis and hair cycling
Authors: E. Poblet, F. Jiménez
Journal: British Journal of Dermatology (2008)

CD10 and CD34 have been detected in both epithelial and mesenchymal components of anagen human hair follicles.To analyse the expression of CD10 and CD34 in human hair follicle development as well as in different phases of the hair cycle.Fetal and adult hair follicles at different stages of the hair cycle were examined by immunohistochemistry for CD10 and CD34.In fetal follicles, CD10 is expressed by the cells of the placodes, and CD34 by the mesenchymal cells of the dermal condensate. As the follicle matures, CD10 can be seen in the matrix cells, inner root sheath and dermal sheath. In adult follicles, the expression of CD10 in the follicular epithelium is present in anagen follicles, but tends to disappear in catagen, and is not detected in telogen. The CD10 positivity of the dermal sheath is more intense in catagen than in anagen follicles. CD34 immunostaining of the external root sheath was seen in adult anagen follicles but not in fetal follicles. This staining of the anagen outer sheath tends to disappear in catagen and is not detected in telogen.CD10 and CD34 are not proteins constantly present in a specific cell type of the hair follicle, but are proteins that can be expressed by both epithelial and mesenchymal cells depending on the stage of development and hair cycle. The distribution of the immunoreactivity to CD10 in the placode and CD34 in the dermal condensate suggests a role of these proteins in initial stages of hair formation.
Orthology Inference in Nonmodel Organisms Using Transcriptomes and Low-Coverage Genomes: Improving Accuracy and Matrix Occupancy for Phylogenomics
Authors: Ya Yang, Stephen A. Smith
Journal: Molecular Biology and Evolution (2014)

Orthology inference is central to phylogenomic analyses. Phylogenomic data sets commonly include transcriptomes and low-coverage genomes that are incomplete and contain errors and isoforms. These properties can severely violate the underlying assumptions of orthology inference with existing heuristics. We present a procedure that uses phylogenies for both homology and orthology assignment. The procedure first uses similarity scores to infer putative homologs that are then aligned, constructed into phylogenies, and pruned of spurious branches caused by deep paralogs, misassembly, frameshifts, or recombination. These final homologs are then used to identify orthologs. We explore four alternative tree-based orthology inference approaches, of which two are new. These accommodate gene and genome duplications as well as gene tree discordance. We demonstrate these methods in three published data sets including the grape family, Hymenoptera, and millipedes with divergence times ranging from approximately 100 to over 400 Ma. The procedure significantly increased the completeness and accuracy of the inferred homologs and orthologs. We also found that data sets that are more recently diverged and/or include more high-coverage genomes had more complete sets of orthologs. To explicitly evaluate sources of conflicting phylogenetic signals, we applied serial jackknife analyses of gene regions keeping each locus intact. The methods described here can scale to over 100 taxa. They have been implemented in python with independent scripts for each step, making it easy to modify or incorporate them into existing pipelines. All scripts are available from https://bitbucket.org/yangya/phylogenomic_dataset_construction.