tbuckley/cabot-search huggingface dataset:
<i>Survivin</i>-Responsive Conditionally Replicating Adenovirus Exhibits Cancer-Specific and Efficient Viral Replication
Authors: Junichi Kamizono, Satoshi Nagano, Yoshiteru Murofushi, Setsuro Komiya, Hisayoshi Fujiwara, Toyojiro Matsuishi, Ken-ichiro Kosai
Journal: Cancer Research (2005)

Abstract Although a conditionally replicating adenovirus (CRA) exhibiting cancer-selective replication and induction of cell death is an innovative potential anticancer agent, current imperfections in cancer specificity and efficient viral replication limit the usefulness of this technique. Here, we constructed survivin-responsive CRAs (Surv.CRAs), in which expression of the wild-type or mutant adenoviral early region 1A (E1A) gene is regulated by the promoter of survivin, a new member of the inhibitor of apoptosis gene family. We explored the cancer specificity and effectiveness of viral replication of Surv.CRAs, evaluating their potential as a treatment for cancer. The survivin promoter was strongly activated in all cancers examined at levels similar to or even higher than those seen for representative strong promoters; in contrast, low activity was observed in normal cells. Surv.CRAs efficiently replicated and potently induced cell death in most types of cancer. In contrast, minimal viral replication in normal cells did not induce any detectable cytotoxicity. A single injection of Surv.CRAs into a preestablished tumor expressing survivin, even at relatively low levels, induced significant tumor death and inhibition of tumor growth. Furthermore, Surv.CRAs were superior to telomerase-dependent CRAs, one of the most effective CRAs that have been examined to date, both in terms of cancer specificity and efficiency. Thus, Surv.CRAs are an attractive potential anticancer agent that could effectively and specifically treat a variety of cancers.
Vaginal Hysterectomy for Complete Rupture of Uterus During Labour
Authors: A. H. C. Walker
Journal: BMJ (1950)

Vaginal Hysterectomy for CompleteRupture of Uterus during LabourThe following case is recorded, in spite of the fatal termination, because the operative procedure described might be of value to other obstetricians confronted with the same complication under similar working conditions.
WHO Documents Worldwide Need for Better Drug Abuse Treatment—and Access to It
Authors: Bridget M. Kuehn
Journal: JAMA (2012)

tor, increased overall survival to 18.4 months for patients taking the drug compared with 13.6 months for those taking placebo. The randomized, double-blind, placebo-controlled, multinational phase 3 study involved 1199 patients with castration-resistant prostate cancer who had received up to 2 regimens of docetaxel-based chemotherapy. Meanwhile, a 17-year study begun in 1995 comparing intermittent androgen deprivation therapy with continuous androgen deprivation therapy came up with an answer that did not sit well with some researchers and treating physicians. In this study, 1535 patients with hormone-sensitive metastatic prostate cancer were randomized to receive intermittent or continuous androgen deprivation therapy. After a median follow-up of 9.2 years, the researchers found that intermittent therapy was not proven to be noninferior to continuous therapy and may have even increased risk for shorter survival. The findings were questioned by proponents of intermittent therapy, which has become the standard of care in many communities. Roth said he was accepting of the results. “We’re not going to redo this trial or have a confirmation trial, so we’re stuck withtheresults,”Rothsaid.“Myquestion to those in favor of intermittent therapy is, ‘Whatareyougoingto tell thenextpatient you see that you offer intermittent therapy?’Areyougoingtoarguethat this isa statistical fluke?Howcanyoudefend that? The data are the data.”
Pan-European organ transplant scheme promises to cut waiting times
Authors: R. Watson
Journal: BMJ (2010)

The European Parliament overwhelmingly approved draft legislation on 19 May setting uniform quality and safety standards across the European Union that promises to reduce waiting times for organ transplants.

The measures, which cover all stages of the chain from donation to the transplantation, must now be approved by EU governments. Given that these have broad cross party support—over 640 MEPs approved them and just 16 voted against—this is now expected to be a formality.

John Dalli, the European health commissioner, described the parliamentary vote as a concrete example of how European legislation could help …
Cytokine receptors and fibroblast proliferation in interstitial pneumonia
Authors: O C Ioachimescu
Journal: Thorax (2004)

▴ Jakubzick C, Choi ES, Carpenter KJ, et al . Human pulmonary fibroblasts exhibit altered interleukin-4 and interleukin-13 receptor subunit expression in idiopathic interstitial pneumonia. Am J Pathol2004;164:1989–2001 [OpenUrl][1][PubMed][2][Web of Science][3] Fibroblasts play a pivotal role in the pathogenesis of idiopathic interstitial pneumonia (IIP). Interleukin (IL)-4 and IL-13 are Th2-type profibrotic cytokines that exert their effects on fibroblasts via multimeric receptors comprised of several shared subunits: IL-4Rα, IL-13Rα1, IL-13Rα2, and γ. This study examined the differential expression of IL-4 and IL-13 receptors … [1]: {openurl}?query=rft.jtitle%253DAmerican%2BJournal%2BOf%2BPathology%26rft.stitle%253DAm.%2BJ.%2BPathol.%26rft.issn%253D0002-9440%26rft.aulast%253DJakubzick%26rft.auinit1%253DC.%26rft.volume%253D164%26rft.issue%253D6%26rft.spage%253D1989%26rft.epage%253D2001%26rft.atitle%253DHuman%2BPulmonary%2BFibroblasts%2BExhibit%2BAltered%2BInterleukin-4%2Band%2BInterleukin-13%2BReceptor%2BSubunit%2BExpression%2Bin%2BIdiopathic%2BInterstitial%2BPneumonia%26rft_id%253Dinfo%253Apmid%252F15161635%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=15161635&link_type=MED&atom=%2Fthoraxjnl%2F59%2F9%2F760.atom [3]: /lookup/external-ref?access_num=000221601000013&link_type=ISI
A Flexible Knot to Untie
Authors: Horiana B. Grosu, Rodolfo C. Morice, Francisco A. Almeida, David Ost, Georgie A. Eapen, Carlos A. Jimenez
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

A 68-year-old woman with a right upper lobe mass and mediastinal lymphadenopathy was referred for endobronchial ultrasound with transbronchial needle aspiration and bronchoalveolar lavage (BAL).The patient was intubated using a laryngeal mask and was under general anesthesia.With a therapeutic (6.3-mm) flexible bronchoscope, the BAL was performed in the usual fashion by wedging the bronchoscope in the anterior segment of the right upper lobe bronchus (RULB).At the end of the procedure, the bronchoscope could not be removed.A second pediatric bronchoscope (3.8 mm) was introduced, and the first bronchoscope was seen looped and trapped in the trachea (Figure 1).Our hypothesis is that there was an unrecognized fissure proximal to the bending section of the bronchoscope.Wedging in the RULB in a sharp angle led to fracture of the instrument, which, combined with the usual advancing and retracting maneuvers, led to the formation of the loop (Figure 1).The bronchoscope was unlooped using a snare (Figure 2).As a consequence of the complication, mild erythema of the trachea and a small hematoma on the left vocal cord were observed.The patient was discharged the same day without any sequelae.
Expression of blood group-related antigens in the intrahepatic biliary tree and hepatocytes in normal livers and various hepatobiliary diseases
Authors: Yasuni Nakanuma, Motoko Sasaki
Journal: Hepatology (1989)

The distribution of blood group-related antigens (A, B, H, Lea and Leb) in the intrahepatic biliary tree and hepatocytes was studied by immunoperoxidase techniques. In normal livers, large and septal bile ducts expressed A and B antigens in the cases with comparable blood groups and also expressed H antigen frequently in the cases with blood group O, A or B, and infrequently in the cases with AB. Lea and Leb were found in biliary cells at any level in secretors. In hepatobiliary diseases, A, B and H were neoexpressed in the interlobular bile ducts in addition to their expression in the large and septal bile ducts. Lea and Leb were found in almost all proliferated bile ductules and in some hepatocytes, especially those adjacent to ductules, in any of the hepatobiliary diseases, and their expression seemed parallel to the disease activity. H antigen was also neoexpressed in some hepatocytes and proliferated bile ductules. Extramural peribiliary glands expressed H, Lea, Leb and, to a lesser degree, A and B antigens in normal and pathologic conditions. This study disclosed that the normal biliary tree has a specific expression of blood group antigens at different levels and that this expression is altered in pathologic conditions. Periportal hepatocytes showed neoexpression of blood group antigens in pathologic conditions, and some of these hepatocytes may undergo ductular metaplasia.
The Caning of Girls
Authors: R. L. Kitching
Journal: BMJ (1935)

<h3>Abstract</h3> COVID-19 vaccines are playing a vital role in controlling the COVID-19 pandemic. As SARS-CoV-2 variants encoding mutations in the surface glycoprotein, Spike, continue to emerge, there is increased need to identify immunogens and vaccination regimens that provide the broadest and most durable immune responses. We compared the magnitude and breadth of the neutralizing antibody response, as well as levels of Spike-reactive memory B cells, in individuals receiving a second dose of BNT126b2 at a short (3-4 week) or extended interval (8-12 weeks) and following a third vaccination approximately 6-8 months later. We show that whilst an extended interval between the first two vaccinations can greatly increase the breadth of the immune response and generate a higher proportion of Spike reactive memory B cells, a third vaccination leads to similar levels between the two groups. Furthermore, we show that the third vaccine dose enhances neutralization activity against omicron lineage members BA.1, BA.2 and BA.4/BA.5 and this is further increased following breakthrough infection during the UK omicron wave. These findings are relevant for vaccination strategies in populations where COVID-19 vaccine coverage remains low.
The nociceptin/orphanin FQ-NOP receptor antagonist effects on an animal model of sepsis
Authors: Dickson Carvalho, Fabricia Petronilho, Francieli Vuolo, Roberta Albino Machado, Larissa Constantino, Remo Guerrini, Girolamo Calo, Elaine Cristina Gavioli, Emílio Luiz Streck, Felipe Dal-Pizzol
Journal: Intensive Care Medicine (2008)
α2cDel322-325 and β1Arg389 Adrenergic Polymorphisms Are Not Associated With Reduced Left Ventricular Ejection Fraction or Increased Left Ventricular Volume
Authors: Russell M. Canham, Sandeep R. Das, David Leonard, Shuaib M. Abdullah, Sameer K. Mehta, Anne K. Chung, Jia-Ling Li, Ronald G. Victor, Richard J. Auchus, Mark H. Drazner
Journal: Journal of the American College of Cardiology (2006)
Opportunities to Reduce Childhood Hunger and Obesity
Authors: David S. Ludwig, Susan J. Blumenthal, Walter C. Willett
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Inhibiting pollen reduced nicotinamide adenine dinucleotide phosphate oxidase–induced signal by intrapulmonary administration of antioxidants blocks allergic airway inflammation
Authors: Nilesh Dharajiya, Barun K. Choudhury, Attila Bacsi, Istvan Boldogh, Rafeul Alam, Sanjiv Sur
Journal: Journal of Allergy and Clinical Immunology (2007)
S18 Activation of nociceptin orphanin FQ (N/OFQ) – N/OFQ peptide (NOP) receptor system plays a key immunomodulatory role in asthma
Authors: R Singh, N Sullo, M Matteis, G Spaziano, J McDonald, R Saunders, L Woodman, K Urbanek, A DeAngelis, R DePalma, R Berair, M Pancholi, V Mistry, P Bradding, F Rossi, R Guerrini, G Calo, B D'Agostino, C E Brightling, D G Lambert
Journal: Thorax (2013)

<h3></h3> Asthma is a complex heterogeneous disease characterised by variable airflow obstruction, bronchial hyper-responsiveness, airway inflammation and remodelling. The heptadecapeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ peptide (NOP) receptor, a non-opioid member of the opioid receptor family. The role of N/OFQ-NOP system in asthma is uncertain. We sought to evaluate N/OFQ-NOP expression in healthy and asthmatic human airway tissues and relate this to an established animal model of asthma. NOP expression in human airway cells was investigated predominantly by qRT-PCR. The functional role of N/OFQ on human airway structural and immune cells was then interrogated using a range of functional assays including proliferation,migration,collagen gel contraction and wound healing. We further investigated the functional role of N/OFQ <i>in vivo</i> using ovalbumin-sensitised mice. NOP expression was detected in human airway smooth muscle cells (HASM; mean?C? = 11 ± 0.7,n = 13), bronchial epithelial cells (HBEC;mean?C? = 10 ± 0.49,n = 12), lung mast cells (mean?C? = 7 ± 0.64,n = 5) and peripheral blood eosinophils (mean?C? = 10.4 ± 1.2,n = 16). N/OFQ inhibited chemoattractant-induced migration of mast cells and eosinophils (see Figure). N/OFQ stimulated significant HBEC wound closure with 49.62 ± 3.58% (p &lt; 0.001, n = 8) of the wound area healed relative to the control (30.88 ± 4.13%, n = 8)18 h post-wound. Similarly N/OFQ significantly promoted HASM wound closure (p &lt; 0.01). Our findings showed that SCF-stimulated IL-8 release (4.43 ± 0.69 fold over control, p &lt; 0.01,n = 7) was significantly inhibited by N/OFQ (3.32 ± 0.56 fold over control, p &lt; 0.01, n = 7). <i><i>Ex vivo</i></i> human studies demonstrate significantly (p &lt; 0.01) increased endogenous N/OFQ in asthmatic airways relative (sputum N/OFQ:59.02 ± 2.57 pg/ml,n = 26) to healthy airways (sputum N/OFQ:44.69 ± 0.43,n = 10) and identifies eosinophils as a potential source for these. Pre-treatment with N/OFQ was shown to significantly reduce agonist-induced bronchial hyper-responsiveness using <i><i>in vitro</i></i> (p &lt; 0.01) and <i><i>in vivo</i></i> models (p &lt; 0.001). <i><i>Ex vivo</i></i> animal studies show that N/OFQ significantly inhibits release of inflammatory mediators including IL4, IL5, IL12, IL13 and inflammatory cell recruitment including mast cells and eosinophils within the airways. Further mucus hyper-secretion was also reduced following N/OFQ pre-treatment in these models. This is the first study to perform a comprehensive and complementary <i>in vivo</i> and <i>in vitro</i> study of the expression and actions of the N/OFQ-NOP system in the airways and provide evidence for a role of NOP activation in the management of asthma.
General practitioner prescribing of erythropoietin.
Authors: S P Gibson, J B Hawkins, E S Nyholm
Journal: BMJ (1991)

after causing neuropathy.9In contrast, patients with leprosy are not being warned about the dangers and sensory electrophysiological testing is not being done, precluding early detection and possible recovery after withdrawal of the drug.It is inexplicable why leprologists cannot carry out a simple clinical examination of the nervous system before administering thalidomide.It is a mistake to assume that nerve damage is already present in erythema nodosum leprosum: in 10 out of 14 patients whom I managed no signs of a polyneuropathy were present, according with the natural course of the disease.'Drug toxicity to the nervous system cannot be excluded now that it is admitted that neuropathy in lepromatous leprosy may mask the effects of thalidomide neuropathy and means also that thalidomide cannot now be claimed to prevent nerve damage.The ulnar mononeuritis sometimes accompanying erythema nodosum leprosum may fail to respond to thalido- mide.9High dose corticosteroids can be avoided in the management of erytheina nodosum leprosum, a condition that is not serious.As amyloidosis occurs in untreated lepromatous leprosy the lack of progression could also have occurred in treated patients without erythema nodosum and cannot be attributable to thalidomide.'°C
Environmental Causes of Birth Defects: The Hexachlorophene Issue
Authors: Dwight T. Janerich
Journal: JAMA (1979)

The use of epidemiologic methods to study chronic diseases has brought an increased awareness of the importance of environmental factors in the causes of those diseases. Epidemiologic evidence, usually of an indirect nature, suggests that many common cancers and birth defects have an important environmental component to their cause. The studies of congenital rubella and the thalidomide syndrome were milestones in our understanding of the environmental causes of birth defects, providing clear evidence that exposure of a pregnant woman to a teratogen can cause one or more birth defects in her offspring.  Since thalidomide and rubella, the concept of teratogenesis has broadened. Minor as well as major malformations are now called birth defects, and diseases with childhood and adolescent onset are now known to be caused by prenatal maternal exposure to environmental agents. Diethylstilbestrol is a case in point. The first evidence that diethylstilbestrol could harm the fetus (reported in
Norepinephrine–Induced Cholestasis in the Isolated Perfused Rat Liver Is Secondary to Its Hemodynamic Effects
Authors: Romana Lenzen, Andreas Funk, Viktoria Kolb-Bachofen, Georg Strohmeyer
Journal: Hepatology (1990)

In this study we examined the effect of pharmacological doses of various alpha-adrenergic agents on hepatic portal perfusion, organic anion uptake and bile secretion using the isolated perfused rat liver. Addition of norepinephrine at portal perfusate concentrations ranging from 0.01 to 100 mumol/L induced a dose-related increase in portal pressure with a twofold increment at the highest concentration. This was accompanied by an inhibition of hepatocellular uptake of taurocholate by 16.8% +/- 1.8% and of sulfobromophthalein (BSP) by 32.9% +/- 3.0% compared with controls. Moreover, a 22.5% +/- 3% decrease in bile flow rate and a 22.8% +/- 4% inhibition of biliary excretion of taurocholate were observed. Addition of other alpha-adrenergic agonist (epinephrine, dopamine and phenylephrine) at similar concentrations produced the same hepatic effects as observed with norepinephrine. During infusion of these alpha-adrenergic agents, trypan blue infusion revealed a patchy perfusion pattern of the liver surface compared with the homogeneously stained organs in controls. The hemodynamic alterations could be confirmed by electron microscopy examination that demonstrated that increased portal pressure produced by norepinephrine was associated with sinusoidal shunting. All hemodynamic, metabolic and biliary changes induced by norepinephrine could be entirely prevented by concomitant infusion of the alpha-antagonist phentolamine, thus indicating that norepinephrine-induced hepatic effects were mediated by alpha-receptors. In contrast, simultaneous addition of papaverine, an unspecific vasodilator, prevented the hemodynamic and the biliary changes of norepinephrine, but failed to modify the metabolic effects of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
The receptor for advanced glycation end products (RAGE) is a central mediator of the interaction of AGE-beta2microglobulin with human mononuclear phagocytes via an oxidant-sensitive pathway. Implications for the pathogenesis of dialysis-related amyloidosis.
Authors: T Miyata, O Hori, J Zhang, S D Yan, L Ferran, Y Iida, A M Schmidt
Journal: Journal of Clinical Investigation (1996)

An important component of amyloid fibrils in dialysis-related amyloidosis is a form of beta2microglobulin modified with advanced glycation end products (AGEs) of the Maillard reaction, known as AGE-beta2M. We demonstrate here that the interaction of AGE-beta2M with mononuclear phagocytes (MPs), cells important in the pathogenesis of the inflammatory arthropathy of dialysis-related amyloidosis, is mediated by the receptor for AGEs, or RAGE. 125I-AGE-beta2M bound to immobilized RAGE or to MPs in a specific, dose-dependent manner (Kd approximately 53.5 and approximately 81.6 nM, respectively), a process inhibited in the presence of RAGE blockade. AGE-beta2M-mediated monocyte chemotaxis was prevented by excess sRAGE or anti-RAGE IgG. Induction of tumor necrosis factor-alpha (TNF) expression by MPs exposed to AGE-beta2M resulted from engagement of RAGE, as appearances of TNF transcripts and TNF antigen release into culture supernatants were prevented by addition of sRAGE, a process mediated, at least in part, by oxidant stress. AGE-beta2M reduced cytochrome c and the elaboration of TNF by MPs was inhibited by N-acetylcysteine. Consistent with these data, immunohistochemical studies of AGE-laden amyloid deposits of a long-term hemodialysis patient revealed positive staining for RAGE in the MPs infiltrating these lesions. These data indicate that RAGE is a central binding site for AGEs formed in vivo and suggest that AGE-beta2M-MP-RAGE interaction likely contributes to the initiation of an inflammatory response in amyloid deposits of long-term hemodialysis patients, a process which may ultimately lead to bone and joint destruction.