tbuckley/cabot-search huggingface dataset:
OC-025 Alisporivir inhibition of cellular cyclophilins disrupts hepatitis B virus (HBV) replication and this effect is further enhanced in combination with direct antiviral targeting HBV-DNA polymerase in vitro
Authors: S Chokshi, S Phillips, A Riva, N Naoumov
Journal: Gut (2012)

<h3>Introduction</h3> Cyclophilins are intracellular proteins with enzymatic activity—peptidyl-prolyl-isomerase that plays a major role in the life cycle of Hepatitis C virus. By targeting host cyclophilins Alisporivir (DEB025) exerts potent anti-HCV activity in vitro and in clinical studies. We have recently shown in vitro that cyclophilin inhibition with Alisporivir or NIM811 also interferes with HBV replication, with Alisporivir having a greater effect than NIM811. To elucidate the underlying mechanisms, in the present study we compared in vitro the effects on HBV replication of Alisporivir alone, Alisporivir in combination with a potent antiviral targeting HBV-DNA polymerase, and in cells after selective knockdown of individual cyclophilins. <h3>Methods</h3> Stably (HepG2215) and transiently (HUH-7) transfected cells, producing full HBV virions and HBsAg particles, were treated with different Alisporivir concentrations (0.25/1.0/5.0/20 ug/ml) alone, Telbivudine alone, or combinations of Alisporivir and Telbivudine. To determine the involvement of individual cyclophilins, HepG2215 cells were transfected with siRNA-specific for cyclophilin (Cyp) A, C or D and additionally treated with Alisporivir. Cytoplasmic extracts and supernatants were harvested at baseline; 24, 48 and 72 h post-treatment. The kinetics of antiviral activity was assessed by quantitation of intracellular and secreted HBV-DNA (real-time qPCR) and HBsAg levels (ELISA). <h3>Results</h3> Alisporivir treatment resulted in dose-dependent reduction of intracellular and secreted HBV-DNA from HepG2215 and HUH-7 cells at all time points, by 70% (p=0.004) and 63% (p&lt;0.001), respectively, compared with untreated controls. The combination of Alisporivir and Telbivudine had greater effects in reducing intracellular (p=0.001) and secreted (p=0.028) HBV-DNA, and &gt;3-fold reduction of HBsAg vs either Alisporivir or Telbivudine alone. CypA, C or D expression was markedly reduced after transfection with corresponding siRNA, which was associated with significant decrease of HBV-DNA and HBsAg levels (p&lt;0.001). Alisporivir treatment of cells silenced for CypA, C or D further reduced HBV-DNA and HBsAg levels, with greater antiviral effects in CypC or CypD silenced cells, compared with CypA silenced cells (p&lt;0.001). <h3>Conclusion</h3> These results suggest that Alisporivir interferes with multiple sites of HBV replication and has synergistic antiviral activity with direct antiviral targeting viral DNA polymerase, such as Telbivudine. <h3>Competing interests</h3> None declared.
Level of Adenosine Diphosphate Receptor P2Y12 Blockade During Percutaneous Coronary Intervention Predicts the Extent of Endothelial Injury, Assessed by Circulating Endothelial Cell Measurement
Authors: Laurent Bonello, Karim Harhouri, Florence Sabatier, Laurence Camoin-Jau, Laurent Arnaud, Karine Baumstarck-Barrau, Omar Ait-Mokhtar, François Roubille, Christophe Piot, Nathalie Lesavre, Franck Paganelli, Françoise Dignat-George
Journal: Journal of the American College of Cardiology (2010)
Psychopharmacology: A Biochemical and Behavioral Approach
Authors: Frank J. Ayd
Journal: JAMA (1977)

A quarter century has passed since modern psychopharmacology was inaugurated by the advent of chlorpromazine and reserpine. During this time the number of psychoactive drugs has escalated annually, and the clinical and research literature on psychopharmacology has increased exponentially. Thousands of papers have been published on neuropharmacology (drug-neurochemical interactions), behavioral pharmacology (drug-behavior interactions), and clinical psychopharmacology (effectiveness and toxicity of drugs in humans). This has created a need for an authoritative, concise, but comprehensive review of the experimental literature, a need amply fulfilled by this well-written volume. The contents are restricted to basic biochemical, behavioral, and neuropharmacologic data obtained from animal studies of psychomotor stimulants, antidepressants, antianxiety agents, antipsychotics, analgesics, and hallucinogens. Lithium is the only important psychoactive drug omitted. This book consists of three sections. The first covers behavior methods for assessing drug action, and pharmacologic and biochemical methods in psychopharmacology. The second section is devoted to the pharmacologic
More research is not needed
Authors: C. J Wright
Journal: BMJ (2009)

The conclusions of the editorial on prostate specific antigen for detecting early prostate cancer published with the paper and analysis article are incongruous.1 2 3 Having summarised all the evidence to date on the validity of screening using prostate specific antigen, the conclusions seemingly ignore most of it and call for more research.

The more time we spend conducting more research the more …
Reactive arthritis associated with Campylobacter jejuni enteritis.
Authors: J H Berden, H L Muytjens, L B van de Putte
Journal: BMJ (1979)

Intracranial section of the glossopharyngeal and upper roots of the vagus nerves has been recommended, the cardiac dysrhythmia being controlled with atropine, isoprenaline, or transvenous pacemaker.Carbamazepine is known to relieve the pain of uncomplicated glossopharyngeal neuralgia.2In our first patient the combination of carbamazepine and demand pacemaker abolished both pain and syncope within hours.The pacemaker was later withdrawn.In the second patient both neuralgia and syncope were suppressed by carbamazepine for one year.By its inhibitory effect or. brain stem reflex activity carbamazepine appears not only to be an effective treatment for the pain of glosso- pharyngeal neuralgia but also to control the more dangerous brady- cardia and asystole.
Denial of pregnancy – a literature review and discussion of ethical and legal issues
Authors: Angela Jenkins, Simon Millar, James Robins
Journal: Journal of the Royal Society of Medicine (2011)

Denial of pregnancy is an important condition that is more common than expected, with an incidence at 20 weeks gestation of approximately 1 in 475. The proportion of cases persisting until delivery is about 1 in 2500, a rate similar to that of eclampsia. Denial of pregnancy poses adverse consequences including psychological distress, unassisted delivery and neonaticide. It is difficult to predict which women will develop denial of pregnancy. There are a number of forms of denial of pregnancy, including psychotic and non-psychotic variants. Denial of pregnancy is a ‘red flag’ that should trigger referral for psychiatric assessment. A national registry may help to provide more information about this condition and implement appropriate care. This condition poses challenging legal and ethical issues including assessment of maternal capacity, evaluation of maternal (and possibly fetal) best interests and the possibility of detention in hospital.
Survey of French prison found that injecting drug use and tattooing occurred
Authors: M Rotily, C Delorme, Y Obadia, N Escaffre, A Galinier-Pujol
Journal: BMJ (1998)

<b>Objective:</b> Clinical and genetic characterization of a neurologic disorder resembling Refsum disease in a Norwegian consanguineous family. <b>Methods:</b> The affected individuals comprise a brother and sister and their third cousin. The family comes from a small island community and genealogic studies showed that both sets of parents are descendants of a man born in 1585. Based on the hypothesis that this is an autosomal recessive disease and that the patients were homozygous for the same mutation (identical by descent), we used homozygosity mapping to define the genetic locus of this disorder. <b>Results:</b> This slowly progressive disorder starts in childhood with signs of peripheral neuropathy (pes cavus, tendoachilles contracture). Hearing loss and cataract become evident in the third decade. Subsequently, patients develop a disorder of gait due to the combination of ataxia and spasticity, and a pigment retinopathy. While the clinical picture is reminiscent of Refsum disease, affected individuals have normal phytanic and pristanic acid levels in plasma, as well as normal enzymatic activity for α-oxidation. We mapped the disease to a 15.96 Mb region on chromosome 20 (20p11.21-q12), containing approximately 200 genes (maximum lod score = 6.3). Sequencing of 23 candidate genes failed to demonstrate detrimental sequence variants. <b>Conclusions:</b> Our findings show that the clinical syndromes that include Refsum disease are more heterogeneous than previously recognized. We have chosen to report the clinical features and mapping of this novel disorder in the hope that this will permit identification of other families and thus proper genetic characterization.
Alkalinization of Urine
Authors: Donald F. McDonald
Journal: JAMA (1975)

To the Editor.—  Dr. Berman's article suggests the use of the carbonic anhydrase inhibitor acetazolamide (Diamox) to improve the effectiveness of orally given sodium bicarbonate in alkalinization of the urine for prevention of uric acid and cystine calculi. Acetazolamide reduces citrate excretion, thereby increasing the risk of calcium-containing stone formation. A safer alternative is one of the thiazide natriuretic drugs such as chlorothiazide or hydrochlorothiazide. These drugs, in addition to increasing sodium excretion, thereby alkalinizing the urine, decrease urinary calcium excretion, thus preventing the formation of a calcium stone. It seems of little benefit to prevent a uric acid stone only to foster growth of a calcium-containing stone.
High-level erythroid-specific gene expression in primary human and murine hematopoietic cells with self-inactivating lentiviral vectors
Authors: Francois Moreau-Gaudry, Ping Xia, Gang Jiang, Natalya P. Perelman, Gerhard Bauer, James Ellis, Katherine H. Surinya, Fulvio Mavilio, Che-Kun Shen, Punam Malik
Journal: Blood (2001)
Elevated Blood Lead Levels of Children in Guiyu, an Electronic Waste Recycling Town in China
Authors: Xia Huo, Lin Peng, Xijin Xu, Liangkai Zheng, Bo Qiu, Zongli Qi, Bao Zhang, Dai Han, Zhongxian Piao
Journal: Environmental Health Perspectives (2007)

BackgroundElectronic waste (e-waste) recycling has remained primitive in Guiyu, China, and thus may contribute to the elevation of blood lead levels (BLLs) in children living in the local environment.ObjectivesWe compared the BLLs in children living in the e-waste recycling town of Guiyu with those living in the neighboring town of Chendian.MethodsWe observed the processing of e-waste recycling in Guiyu and studied BLLs in a cluster sample of 226 children &lt; 6 years of age who lived in Guiyu and Chendian. BLLs were determined with atomic absorption spectrophotometry. Hemoglobin (Hgb) and physical indexes (height and weight, head and chest circumferences) were also measured.ResultsBLLs in 165 children of Guiyu ranged from 4.40 to 32.67 μg/dL with a mean of 15.3 μg/dL, whereas BLLs in 61 children of Chendian were from 4.09 to 23.10 μg/dL with a mean of 9.94 μg/dL. Statistical analyses showed that children living in Guiyu had significantly higher BLLs compared with those living in Chendian (p &lt; 0.01). Of children in Guiyu, 81.8% (135 of 165) had BLLs &gt; 10 μg/dL, compared with 37.7% of children (23 of 61) in Chendian (p &lt; 0.01). In addition, we observed a significant increasing trend in BLLs with increasing age in Guiyu (p &lt; 0.01). It appeared that there was correlation between the BLLs in children and numbers of e-waste workshops. However, no significant difference in Hgb level or physical indexes was found between the two towns.ConclusionsThe primitive e-waste recycling activities may contribute to the elevated BLLs in children living in Guiyu.
COMPARISON OF FIVE-YEAR OUTCOMES OF STENTING VS. BYPASS SURGERY FOR OSTIAL AND SHAFT UNPROTECTED LEFT MAIN CORONARY ARTERY DISEASE; DATA FROM A MULTI-CENTER REGISTRY
Authors: Jung-Min Ahn, Duk-Woo Park, Ki Bae Seung, Young-Hak Kim, Hae Geun Song, Jong-Young Lee, Won-Jang Kim, Soo-Jin Kang, Seung-Whan Lee, Cheol Whan Lee, Seong-Wook Park, Sung-Cheol Yun, Hyeon-Cheol Gwon, Myung-Ho Jeong, Yangsoo Jang, Hyo-Soo Kim, Pum Joon Kim, In-Whan Seong, Hun Sik Park, Taehoon Ahn, In-Ho Chae, Seung-Jea Tahk, Wook-Sung Chung, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2011)
A CORRELATIVE STUDY BY ELECTRON AND LIGHT MICROSCOPY OF THE DEVELOPMENT OF TYPE 5 ADENOVIRUS
Authors: Councilman Morgan, Gabriel C. Godman, Peter M. Breitenfeld, Harry M. Rose
Journal: The Journal of Experimental Medicine (1960)

Stages in the nuclear changes consequent to infection with type 5 adenovirus are shown and described. Viral development seems to be confined to the nucleus where characteristic particles are found. The shape of the intracellular virus depends upon the method of preservation employed, appearing spherical after osmium tetroxide or freezing-substitution, occasionally exhibiting angulated faces after formalin and often assuming an hexagonal profile after potassium permanganate. The non-viral crystals are encountered in zones of low density, and it is suggested that crystallization results from the accumulation of protein in these areas. An hypothesis is presented to explain why these crystals, in contrast to the insect polyhedra, contain few viral particles.
The sickening of medical research: multiple diagnoses and two remedies
Authors: R. Smith
Journal: BMJ (1988)

The sickening of medical research: multiple diagnoses and two remedies Britain's research effort in science and medicine is ailing.Sir George Porter, president of the Royal Society, lectured passionately on the subject last Sunday evening on prime time television when delivering the Richard Dimbleby lecture.Objective measures-for example, numbers of published papers and their impact, of Nobel prize winners, and of patents-show the decline,'`3 and the subjective impression of most researchers is that these measures underestimate it.But why this failure?Is it underfunding, as Save British Science tends to argue?Or is it a deeper problem to do with cultural attitudes to science, the organisation and management of the research effort, and unwillingness to change, as the government argues?The House of Lords Select Committee on Science and Technology delivered its judgment on medical research earlier this week (its recommendations are summarised on p 1109),4 and I feel licensed to give my views after researching and writing a series of articles on research policy.My diagnosis is that underfunding is by no means the only problem.The decline in British medical research, and particularly in clinical research, does, as the government argues, have much to do with attitudes and with how the enterprise is organised.The lack of enthusiasm for research begins, however, with governments having shown little sign that they care for or value research, but the government's scientific philistinism grows out of a people who support research enough to put pennies into collecting boxes but who often are too poorly educated to understand the process or the results.
Victims of violence flood Rio's hospitals
Authors: J. Rocha
Journal: BMJ (1994)

A 13 year old schoolgirl has become the 40th child with bullet wounds to be treated at Rio de Janeiro's Souza Aguiar hospital since September, and the fourth to die. The girl had been hit in the head by a stray bullet during a police chase of a stolen car. Doctors in Rio say that they are now treating so many victims of gunshot wounds it is as …
CLINICAL AND BIOLOGICAL INTERRELATIONS BETWEEN SCHIZOPHRENIA AND EPILEPSY
Authors: PAUL H. HOCH
Journal: American Journal of Psychiatry (1943)

1. In the majority of cases showing an association of epileptic and schizophrenic symptoms, we may deal either with symptomatic epilepsy in schizophrenia, or, what is more common, with a symptomatic schizophrenia in epilepsy. 2. The number of cases showing a mixed symptomatology is very small compared with the vast number of schizophrenics and epileptics where a combination of the two disorders is not present. 3. The clinical, genetic and EEG evidence up to date does not permit the conclusion that epilepsy and schizophrenia are related disorders. 4. The group of schizophrenics showing abnormal EEG findings suggestive of epilepsy has to be split off from the schozophrenias and treated as a separate entity, similar to other organic psychoses with schizophrenic-like symptoms.
FDA regulations make it harder to sue drug companies
Authors: David Spurgeon
Journal: BMJ (2006)

The US Food and Drug Administration has added a preamble to its new regulations that will make it difficult for anyone to bring legal action against a drug manufacturer for harm caused by one of its products, says an article in this week's edition of the New England Journal of Medicine (2006; 354: 2409-11). The new regulations, which have attracted little publicity, come into effect on 30 June.

Along with modest alterations to drug labelling to be phased in over the next …
Quantitative assessment of left ventricular myocardial viability during low dose dobutamine stress echocardiography in combination with color tissue doppler imaging
Authors: Hideji Tanaka, Tomotsugu Tabata, Eriko Kimura, Kenji Harada, Tetsuzo Wakatsuki, Takashi Yamamoto, Akihiro Saito, Kozo Uehara, Norihito Kageyama, Takashi Oki
Journal: Journal of the American College of Cardiology (2003)
Endoscopic Injection of Botulinum Toxin for Biliary Sphincter of Oddi Dysfunction
Authors: T. Wehrmann, H. Seifert, M. Seipp, B. Lembcke, W. F. Caspary
Journal: Endoscopy (1998)

Background and Study Aims: Endoscopic sphincterotomy is not without risks, and is also ineffective in about half of patients with type III sphincter of Oddi dysfunction (SOD), i.e. those without clinical evidence of biliary obstruction (normal liver tests, normal bile duct diameter, and regular drainage time at endoscopic retrograde cholangiography). The present study therefore investigated the efficacy and safety of endoscopic botulinum toxin (BTX) injection into the papilla of Vater, and analyzed whether the symptomatic response to BTX injection might be a predictor of outcome for endoscopic sphincterotomy.
565. A Ready-to-Use Process for Large-Scale Plasmid DNA Manufacturing
Authors: Astrid Breul, Wayne Tvrdik, Markus Müller, Joachim Schorr
Journal: Molecular Therapy (2005)

Bringing a gene therapy or genetic vaccination drug candidate from the lab bench to the clinic requires considerable investment, not only in the organization of clinical trials but also in drug production. Usually, biotechnology companies and researchers rely on contract manufacturing organizations for GMP-compliant production of the therapeutic drug; however, in order to reduce cost, an increasing number of companies and research centers are now investigating in-house GMP production. Numerous small multipurpose GMP facilities have already been established at major international research centers, and many more are being planned.
The Treatment of AIDS-Related Lymphoma-Reply
Authors: Alexandra M. Levine
Journal: JAMA (1992)

In Reply.  —Unfortunately, Tirelli et al are incorrect in their first assumption that  with poor prognosis, ie, those with low performance status and presence of OIs, were not eligible for entry into this study. This is not true. Several retrospective and prospective series have confirmed those factors that are considered to be of poor prognostic impact in the patient with AIDS lymphoma. 1,2 These include history of prior AIDS, CD4 cell counts less than 200 × 10 6 /L as a continuous variable, Karnofsky performance status of 70% or less, and stage IV disease, especially with bone marrow involvement. None of these factors served to exclude patients from our study, which allowed patients with Kaposi's sarcoma as low as 50% (defined as the patient who is unable to work, and requires considerable assistance and frequent medical care), any CD4 cell count, any history of AIDS or 01, and
α-1-Antitrypsin Ameliorates Cigarette Smoke–induced Emphysema in the Mouse
Authors: Andrew Churg, Rong D. Wang, Changshi Xie, Joanne L. Wright
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Serine elastase inhibitors have been proposed as a treatment for cigarette smoke-induced emphysema, but little is known about whether such agents actually are effective. We recently reported that a synthetic serine elastase inhibitor, ZD0892, provided some protection against emphysema in a guinea pig model. For these experiments, we used transgenic mice that expressed extremely low levels of human alpha-1-antitrypsin (A1AT) but were tolerant of exogenous human A1AT. Mice were exposed to daily cigarette smoke for up to 6 months; some animals received 20 mg of human A1AT (Prolastin) every 48 hours. Treatment with A1AT produced an approximate twofold increase in serum A1AT levels and elastase inhibitory capacity and abolished smoke-induced elevations in lavage neutrophils and matrix breakdown products (desmosine and hydroxyproline) measured from 2 to 30 days of smoke exposure. A1AT oxidized to remove antiproteolytic activity did not increase serum elastase inhibitory capacity but did prevent neutrophil influx. Treatment with A1AT for 6 months provided 63% protection against increased airspace size (emphysema) and abolished smoke-mediated increases in plasma tumor necrosis factor-alpha. We conclude that A1AT therapy ameliorates smoke-induced inflammation and matrix breakdown, possibly via an antiinflammatory mechanism related to tumor necrosis factor-alpha suppression, and provides partial protection against emphysema.
Influenzal Vaccine Response in Systemic Lupus Erythematosus
Authors: RICHARD BRODMAN
Journal: Annals of Internal Medicine (1978)

The response of patients with systemic lupus erythematosus and normal subjects to systemic immunization and boosting with influenza A vaccines was studied. Symptoms after vaccination were somewhat more frequent in the patients than in the normal subjects; however, all symptoms were minor and no major flare of illness occurred. No significant induction or increase of pre-existing autoantibodies among the patients was detected after vaccination. The immunogenecity of the vaccinations, as assessed by antibody titers, was similar in the patient and control groups. No correlation between serologic response to influenzal antigens and HLA was found. Thus, in this group of patients with systemic lupus erythematosus, who were either in remission or had mild-to-moderate disease activity, killed influenzal vaccination caused no apparent worsening of disease activity.
Treatment of multiple sclerosis with T–cell receptor peptides: Results of a double–blind pilot trial
Authors: Arthur A. Vandenbark, Yuan K. Chou, Ruth Whitham, Michele Mass, Abigail Buenafe, Diane Liefeld, Daniel Kavanagh, Shelley Cooper, George A. Hashim, Halina Offner, Dennis N. Bourdette
Journal: Nature Medicine (1996)