tbuckley/cabot-search huggingface dataset:
OCCURRENCE OF FOCAL THREE-DIMENSIONAL PROLIFERATION IN CULTURED HUMAN CELLS AFTER PROLONGED INFECTION WITH HERPES SIMPLEX VIRUS
Authors: Harry C. Hinze, Duard L. Walker
Journal: The Journal of Experimental Medicine (1961)

The occurrence of focal three-dimensional proliferation was observed in human conjunctiva cells in culture after prolonged infection with herpes simplex virus at 30 degrees C. and in KB cells infected with herpes virus at 37 degrees C. for several months in the presence of pooled human serum. This atypical growth pattern consisted of many discrete piles of cells 15 to 20 cells thick scattered over a monolayer of cells. Three-dimensional growth appeared only in the presence of 10 to 20 per cent of selected human sera. When horse serum was substituted for human serum growth was in an ordinary monolayer. The abnormal growth pattern of this cell line (C-4 line) has remained stable through continuous culture for over 2 years and was observed consistently in each of 25 clones isolated from the parent culture. Repeated tests for the presence of persisting infectious virus and for herpes virus antigen in the cells were negative. Comparison of the C-4 cell line with control conjunctiva cells revealed no significant difference in multiplication rate or in range of viral susceptibility, but the C-4 line was found to be more sensitive to ultraviolet irradiation.
Microfibrils of blood platelets: their relationship to microtubules and the contractile protein
Authors: Dorothea Zucker-Franklin
Journal: Journal of Clinical Investigation (1969)

Human blood platelets were subjected to osmotic shock, brief sonication, pressure homogenization, or treatment with adenosine diphosphate (ADP). These procedures demonstrated an abundance of cytoplasmic microfibrils. The fibrils resembled those found on electron microscopy of partially purified thrombosthenin, the actomyosin-like protein isolated from platelets, and they also appeared to resemble the myofilaments of smooth muscle. Similar fibrils were not found in leukocytes studied under identical conditions. Treatment with colchicine (2 x 10(-5) mole/liter) resulted in the disappearance of microtubules but did not affect the morphology of the microfibrils or interfere with platelet-dependent clot retraction. Thus, microfibrils rather than microtubules may represent the morphologic counterpart of the contractile protein. Brief osmotic shock at low temperature or treatment with 10(-4) M ADP caused the marginal band of microtubules to be replaced by a bundle of intertwining microfibrils. The apparent inter-conversion of microtubules and microfibrils under a variety of conditions led to the hypothesis that fibrils and tubules consist of similar subunits whose degree of polymerization might be dependent on local cytoplasmic forces. Furthermore, on the basis of these observations, it is postulated that the contractile properties of the cells may be vested in the microfibrils, whereas the tubules may serve to maintain the highly asymmetric shape characteristic of circulating and irreversibly aggregated platelets.
Ranitidine, aspirin, food, and the stomach.
Authors: A. T. Cole, S. Brundell, N. Hudson, A. B. Hawthorne, Y. R. Mahida, C. J. Hawkey
Journal: BMJ (1992)

Mal de debarquement, or "land sickness," is a transient sensation of tumbling, swinging, unsteadiness, and disequilibrium reported by passengers and crew after returning to land from long sea voyages.Although mal de debarquement is mentioned in classic texts on seasickness,' 2 there are no specific studies concerning the nature and extent of this phenomenon.A computer search of the literature yielded only one publication dealing with persistent (not transient) mal de de- barquement.3We report a survey of the incidence of mal de debarquement and its relation to experience at sea and susceptibility to seasickness. Subjects, methods, and resultsThe information was collected by means of question- naires distributed among 234 healthy crew members of seagoing vessels (300-500 tonnes).Subjects were aged 18-38 (mean 20 5) years and had 1-150 months' experience at sea (mean 17 (SD 18) months).None had a history of any disease which might cause vertigo or disequilibrium.The occurrence and frequency of mal de debarque- ment were graded on a four point scale (very often, occasionally, only once, never).Latency from disembarkment to the onset of symptoms, duration of symptoms, and additional causative factors such as rough seas and length of voyage were also recorded.Present susceptibility to seasickness was graded on an eight point scale (not susceptible to very susceptible) according to Wiker et al.4"Other parameters of susceptibility, such as nausea and vomiting during most recent voyages in rough seas and susceptibility to seasickness in the past,2 were also graded.One hundred and seventy one subjects (73%) reported having experienced mal de debarquement, 20 (9%) very often, 86 (37%) occasionally, and 65 (28%) Kendall correlation coefficients Occurrence of mal de debarquement p Value No Experience at sea
Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma
Authors: Pranabashis Haldar, Christopher E. Brightling, Beverley Hargadon, Sumit Gupta, William Monteiro, Ana Sousa, Richard P. Marshall, Peter Bradding, Ruth H. Green, Andrew J. Wardlaw, Ian D. Pavord
Journal: New England Journal of Medicine (2009)

Exacerbations of asthma are associated with substantial morbidity and mortality and with considerable use of health care resources. Preventing exacerbations remains an important goal of therapy. There is evidence that eosinophilic inflammation of the airway is associated with the risk of exacerbations.We conducted a randomized, double-blind, placebo-controlled, parallel-group study of 61 subjects who had refractory eosinophilic asthma and a history of recurrent severe exacerbations. Subjects received infusions of either mepolizumab, an anti-interleukin-5 monoclonal antibody (29 subjects), or placebo (32) at monthly intervals for 1 year. The primary outcome measure was the number of severe exacerbations per subject during the 50-week treatment phase. Secondary outcomes included a change in asthma symptoms, scores on the Asthma Quality of Life Questionnaire (AQLQ, in which scores range from 1 to 7, with lower values indicating more severe impairment and a change of 0.5 unit considered to be clinically important), forced expiratory volume in 1 second (FEV(1)) after use of a bronchodilator, airway hyperresponsiveness, and eosinophil counts in the blood and sputum.Mepolizumab was associated with significantly fewer severe exacerbations than placebo over the course of 50 weeks (2.0 vs. 3.4 mean exacerbations per subject; relative risk, 0.57; 95% confidence interval [CI], 0.32 to 0.92; P=0.02) and with a significant improvement in the score on the AQLQ (mean increase from baseline, 0.55 vs. 0.19; mean difference between groups, 0.35; 95% CI, 0.08 to 0.62; P=0.02). Mepolizumab significantly lowered eosinophil counts in the blood (P<0.001) and sputum (P=0.002). There were no significant differences between the groups with respect to symptoms, FEV(1) after bronchodilator use, or airway hyperresponsiveness. The only serious adverse events reported were hospitalizations for acute severe asthma.Mepolizumab therapy reduces exacerbations and improves AQLQ scores in patients with refractory eosinophilic asthma. The results of our study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population. (Current Controlled Trials number, ISRCTN75169762.)
Interaction of Viruses and Bacteria in Host-Parasite Relations
Authors: Lowell Glasgow
Journal: New England Journal of Medicine (1972)

IT is apparent that we become colonized (or "infected") with only a small fraction of the many micro-organisms to which we are exposed, and that a still smaller percentage of such host-parasite interaction ever results in disease. The factors that determine "who amongst us are chosen" remain poorly defined. The concept that viruses may predispose to bacterial infections has long been accepted by both physicians and the lay public. At the beginning of the century, Metchnikoff noted that respiratory disorders, "a cold, for example," could alter host resistance, resulting in a "more or less marked susceptibility."1 Young and his co-workers . . .
Effectiveness, efficiency, and leadership
Authors: T. Groves
Journal: BMJ (2009)

After years of investment to bring the NHS into line with the European Union average for healthcare funding, the money is drying up. That’s hardly surprising, given the global financial crisis and the UK’s national debt. But what will it mean for patients, doctors, and other healthcare workers? Between four and 10 years of austerity, according to Chris Ham (doi:10.1136/bmj.b1760), and Nicholas Timmins (doi:10.1136/bmj.b1754), as they review the Chancellor of the Exchequer’s recent budget statement and its implications for the NHS.

Chris Ham likens the coming funding freeze to bereavement and warns against magical thinking. He means that politicians shouldn’t depend on the private sector …
Abstract 2400: Epithelial-mesenchymal transition in hepatocellular carcinoma leads to downregulation of adaptive immunity via COX-2 pathway
Authors: Olorunseun O. Ogunwobi, Chen Liu
Journal: Cancer Research (2012)

Abstract The immune system targets pre-malignant and malignant cells and can attenuate or eliminate carcinogenesis. Epithelial-mesenchymal transition (EMT) is known to promote tumor progression in hepatocellular carcinoma (HCC). It is, however, unknown whether EMT promotes HCC by dysregulating the immune system. A clear understanding of the mechanisms underlying immune evasion in HCC may reveal targets that can be exploited for immunotherapy. In this study, we have used the murine HCC cell line 1MEA that we have successfully used to establish a syngeneic mouse model of aggressive HCC. The cells were exposed to TGFβ-1 (2ng/ml) and EGF (50ng/ml), two well-established inducers of EMT in HCC. Induction of EMT was confirmed by analysis of the gene expression profiles of E-cadherin, albumin, fibronectin and collagen I. Effects on clonogenicity were analyzed using colony formation assays. Effects on adaptive immunity were examined by analyzing gene and protein expression of major histocompatibility complexes I and II (MHC I and MHC II). The role of cyclooxygenase-2 (COX-2) was determined by examining the effect of the selective COX-2 inhibitor, celecoxib (1μM). Exposure to TGFβ-1 and EGF led to downregulation of E-cadherin and albumin and upregulation of fibronectin and collagen I. TGFβ-1 and EGF both promoted increased clonogenicity. Interestingly, exposure to TGFβ-1 and EGF both resulted in significant downregulation of both gene and protein expression of MHC I and MHC II. However, pre-treatment of cells with celecoxib significantly reversed these effects. Consequently, we conclude that EMT induction in HCC is associated with downregulation of adaptive immunity in a manner dependent on the COX-2 pathway. Immunotherapeutic targeting of COX-2 may, therefore, be a useful strategy for HCC management. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2400. doi:1538-7445.AM2012-2400
Five-year Survival of Patients with Hepatocellular Carcinoma Treated with Laparoscopic Microwave Coagulation Therapy
Authors: S. Seki, H. Sakaguchi, S. Iwai, H. Kadoya, S. Kabayashi, T. Kitada, H. Fujii, T. Tanaka
Journal: Endoscopy (2005)

Background and Study Aim: Hepatocellular carcinomas (HCCs) that are located near the liver surface are difficult to treat with percutaneous locoregional therapies, so we have performed laparoscopic microwave coagulation therapy (LMCT) for these HCCs. We assessed the long-term survival of patients with HCCs treated with LMCT, the factors related to their survival, and the rates and causes of local and distant recurrences. Patients and Methods: Participants were 68 patients with HCC treated in the past 8 years with LMCT under local or general anesthesia. LMCT was done using microwave electrodes with tips ranging from 15 to 45 mm in length; the effectiveness of LMCT was confirmed using contrast-enhanced computed tomography (CT) within 2 weeks of the LMCT procedure while patients were still in hospital, and within 1 - 3 months after the procedure in an outpatient setting; and the follow-up study was performed periodically by CT, ultrasonography, or magnetic resonance imaging (MRI) in addition to estimation of alpha fetoprotein. Factors contributing to survival were analyzed statistically.
711 5-LIPOXYGENASE ACTIVATING PROTEIN, FLAP, SIGNALS ADIPOSE TISSUE INFLAMMATION AND STEATOGENIC POTENTIAL IN OBESITY
Authors: R. Horrillo, A. González-Périz, M. Martínez-Clemente, M. López-Parra, N. Ferré, E. Titos, E. Morán-Salvador, V. Arroyo, J. Clária
Journal: Journal of Hepatology (2009)
Primary Mesenteric Vein Thrombosis Associated With Antithrombin III Deficiency
Authors: Frank R. Arko, C. Thomas Jewell, Paul Dainer, William A. J. MacLeod
Journal: JAMA (1979)

PRIMARY mesenteric vein thrombosis associated with hereditary antithrombin III (AT III) deficiency has recently been reported as a new clinical entity.<sup>1</sup>Primary mesenteric vein thrombosis is a result of abnormal coagulation, whereas most cases of mesenteric vein occlusions are secondary to some other disease process. This case report of a patient who had segmental infarction, recurrent infarction, postresection morbidity, and clinical evidence of hypercoagulability depicts and reemphasizes the diagnostic and therapeutic difficulties encountered by the surgeon who must deal with this problem. <h3>Report of a Case</h3> A 47-year-old man was first seen with a six-day history of midepigastric pain and nausea. Pain was strikingly intensified by food ingestion. History disclosed deep-vein thrombosis in the left leg, for which the patient had received anticoagulant therapy three years previously. Family history disclosed that the patient's father died of peritonitis, which, according to the patient, was secondary to a "blood clot to
S11 Expression of Tenascin-C Regulates Airway Smooth Muscle Derived Matrix Metalloproteinase-1 in Asthma
Authors: NK Rogers, D Clements, TW Harrison, D Shaw, SR Johnson
Journal: Thorax (2012)

<h3>Background</h3> Collagenases are differentially regulated in conditions of lung remodelling. Literature documents the capacity of extracellular matrix (ECM) proteins to induce collagenase expression. The current study aims to characterise ECM regulation of the collagenase matrix metalloproteinase-1 (MMP-1) in human airway smooth muscle (ASM) cells, and the applicability of this mechanism to remodelling. <h3>Methods</h3> ASM cells were derived from patients with and without asthma and cultured with ECM proteins for 24 hours. MMP-1 gene expression was quantitated by Real-time PCR, with secreted protein and activity levels assessed by ELISA, Western Blotting and fluorometric activity assay. Pathways mediating MMP-1 induction were mapped using a phosphoprotein array, specific inhibitors and blocking antibodies. Tenascin-C and MMP-1 expression were studied in endobronchial biopsies from patients with and without asthma by immunohistochemistry. <h3>Results</h3> Tenascin–C increased MMP-1 mRNA, protein and activity in a dose and time dependent manner. Tenascin-C phosphorylated MAPK intermediates ERK and P38, and inhibitors to these intermediates attenuated MMP-1 induction. Blocking antibodies showed this response was mediated by the β1 and β3 integrins. Control tissue showed minimal tenascin-C and MMP-1 expression, but strong co-localising Tenascin-C and MMP-1 expression in the subepithelial layer and to a lesser extent in ASM bundles. ASM cells from patients with asthma had elevated basal levels of MMP-1, which was further increased by Tenascin-C stimulation. <h3>Discussion</h3> Tenascin-C upregulates expression and activity of MMP-1 via the β1 and β3 integrin subunits and MAPK signalling in ASM cells. These proteins were increased in lung remodelling diseases, with overlapping localisation. The functional consequences of this observation needs to be evaluated in vivo, however, this could potentially yield a new target for therapeutic in airway remodelling.
Extended prescribing by UK nurses and pharmacists
Authors: Sam Richmond
Journal: BMJ (2005)

Editor—As a consultant neonatologist in a neonatal intensive care unit I am delighted that the Department of Health has at last seen sense with respect to nurse prescribing.1 This now means that the neonatal nurse practitioners who form 40% of our first line “medical” team on the unit will have almost the same prescribing powers as the senior house officers who form the remaining 60%. If, in the context of a hospital, the department extended this permission to “controlled” and unlicensed drugs I would be even more pleased.​pleased.




Figure 1



Credit: PETER MENZEL/SPL




What currently stands in the way of this progress is article 12 of the Prescription Only Medicines (Human Use) Order 1997, which forbids any pharmacist from supplying any prescription only medicine except in accordance with the written directions of a doctor or dentist in the course of the business of the hospital.

Currently a dentist or a consultant pathologist can legally prescribe drugs for the babies in our neonatal intensive care unit purely by virtue of their medical or dental qualification and despite their total lack of neonatal experience (I mean no disrespect here, I am merely using these as examples). At the same time, the neonatal nurse practitioners, each with many years of senior neonatal nurse experience followed by 12 months' nurse practitioner training and a further six months' closely supervised practical experience, cannot legally do the same.

Senior house officers joining our unit have little idea about prescribing in neonatal intensive care despite many years of medical training. The quality of their prescribing is the responsibility of those in clinical charge of the unit, who must lay down appropriate guidance. If this guidance is appropriate then prescribing will be safe and effective; if it is not it will not be.
THE TREATMENT OF PERNICIOUS ANEMIA WITH SWINE STOMACH
Authors: H. MILTON CONNER
Journal: JAMA (1930)

Castle and Locke<sup>1</sup>have demonstrated that meat fed to normal persons and recovered by vomiting, and then fed to patients with pernicious anemia, contains some material that produces the same effect on the blood of patients with pernicious anemia as that which was shown by Minot and Murphy to result from the administration of liver. Practically all cases of pernicious anemia are accompanied by achylia, and I<sup>2</sup>have shown that approximately 26 per cent of a large series of relatives of patients suffering from pernicious anemia have achlorhydria. Because of these facts, I decided to try the effect of feeding the raw and cooked stomach of a meat-producing animal to patients with pernicious anemia. By consultation with Mann and Feldman<sup>3</sup>of the Mayo Foundation, it was found that the stomach of swine resembles the stomach of human beings much more closely than does that of bovine animals
PDGF-C Is a Proinflammatory Cytokine that Mediates Renal Interstitial Fibrosis
Authors: Frank Eitner, Eva Bu[Combining Diaeresis]cher, Claudia van Roeyen, Uta Kunter, Song Rong, Claudia Seikrit, Luigi Villa, Peter Boor, Linda Fredriksson, Gudrun Ba[Combining Diaeresis]ckstro[Combining Diaeresis]m, Ulf Eriksson, Arne O[Combining Diaeresis]stman, Ju[Combining Diaeresis]rgen Floege, Tammo Ostendorf
Journal: Journal of the American Society of Nephrology (2008)

<h3>Abstract</h3> Drug intake is known to be under the influence of social context. We have recently shown that presence of a peer influences drug intake in both rats and humans. Whether or not social acoustic communications between the peers play a role during cocaine or sucrose self-administration (SA) was investigated here, using playback of ultrasonic vocalizations (USV) at 50- and 22-kHz, conveying respectively positive and negative internal affective states in adult rats. To assess the neurobiological substrate of a potential USV influence on drug and food intake, we tested the effects of subthalamic nucleus (STN) lesions, given its role in emotional and motivational processes. In sham-control rats, playback of USV associated with positive affective states induced long-term decreased cocaine consumption, while USV associated with negative affective states induced short-term increase. Interestingly, no effect of USV playback was observed on sucrose intake, whatever the frequency. STN lesions abolished the influence of USV on cocaine intake, highlighting the influence of STN in emotional processes induced by USV emitted by a peer. These results show how acoustic social communication is important to regulate drug intake in rats and how STN modulation could interfere with addiction processes.
Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes
Authors: Budhaditya Mazumdar, Arup Banerjee, Keith Meyer, Ranjit Ray
Journal: Hepatology (2011)

Our previous studies demonstrated that hepatitis C virus (HCV) envelope glycoproteins 1 and 2 (E1 and E2) display distinct reactivity to different cell-surface molecules. In this study, we characterized the interaction of E1 and E2 with apolipoproteins in facilitating virus entry. The results suggested a higher neutralization of vesicular stomatitis virus (VSV)/HCV E1-G pseudotype infectivity by antibodies to apolipoprotein E (ApoE) than apolipoprotein B (ApoB), with VSV/HCV E2-G pseudotype infectivity remaining largely unaffected. Neutralization of cell-culture-grown HCV infectivity by antiserum to ApoE and, to a lesser extent, by ApoB further verified their involvement in virus entry. HCV E1, but not E2, displayed binding with ApoE and ApoB by enzyme-linked immunosorbent assay. Binding of E1 with apolipoproteins were further supported by coimmunoprecipitation from human hepatocytes expressing E1. Rabbit antiserum to a selected E1 ectodomain-derived peptide displayed ∼ 50% neutralization of E1-G pseudotype infectivity. Furthermore, E1 ectodomain-derived synthetic peptides significantly inhibited the interaction of E1 with both the apolipoproteins. Investigation on the role of low-density lipoprotein receptor (LDL-R) as a hepatocyte surface receptor for virus entry suggested a significant reduction in E1-G pseudotype plaque numbers (∼ 70%) by inhibiting LDL-R ligand-binding activity using human proprotein convertase subtilisin/kexin type 9 and platelet factor-4, whereas they had a minimal inhibitory effect on the E2-G pseudotype.
Glucose Levels and Risk of Dementia
Authors: Paul K. Crane, Rod Walker, Rebecca A. Hubbard, Ge Li, David M. Nathan, Hui Zheng, Sebastien Haneuse, Suzanne Craft, Thomas J. Montine, Steven E. Kahn, Wayne McCormick, Susan M. McCurry, James D. Bowen, Eric B. Larson
Journal: New England Journal of Medicine (2013)

Diabetes is a risk factor for dementia. It is unknown whether higher glucose levels increase the risk of dementia in people without diabetes.