tbuckley/cabot-search huggingface dataset:
Antitumoral Immune Response by Recruitment and Expansion of Dendritic Cells in Tumors Infected with Telomerase-Dependent Oncolytic Viruses
Authors: Edukulla Ramakrishna, Norman Woller, Bettina Mundt, Sarah Knocke, Engin Gürlevik, Michael Saborowski, Nisar Malek, Michael P. Manns, Thomas Wirth, Florian Kühnel, Stefan Kubicka
Journal: Cancer Research (2009)

Virotherapy can potentially be used to induce tumor-specific immune responses and to overcome tumor-mediated tolerance mechanisms because apoptotic tumor cells are exposed together with viral danger signals during oncolysis. However, insufficient numbers of dendritic cells (DC) present at the site of oncolysis can limit a tumor-specific immune response and the resulting therapeutic benefit. We investigated MHC class I peptide-specific immune responses against model antigens ovalbumin (OVA) and hemagglutinin (HA) in mouse tumor models that support efficient replication of the oncolytic adenovirus hTert-Ad. Virotherapy resulted in peptide-specific cytotoxic T-cell responses against intracellular tumor antigens. Triggering of DC and T-cell infiltration to the oncolytic tumors by macrophage inflammatory protein 1alpha (MIP-1alpha, CCL3) and Fms-like tyrosine kinase-3 ligand (Flt3L) enhanced both antitumoral and antiviral immune responses. Although immune-mediated clearance of the virus can restrict therapeutic efficacy of virotherapy, MIP-1alpha/FLT3L-augmented hTert-Ad virotherapy inhibited local tumor growth more effectively than virotherapy alone. In agreement with the hypothesis that immune-mediated mechanisms account for improved outcome in MIP-1alpha/FLT3L virotherapy, we observed systemic antitumoral effects by MIP-1alpha/FLT3L virotherapy on uninfected lung metastasis in immunocompetent mice but not in nude mice. Furthermore, MIP-1alpha/FLT3L virotherapy of primary tumors was strongly synergistic with tumor DC vaccination in inhibition of established lung metastasis. Combined viroimmunotherapy resulted in long-term survival of 50% of treated animals. In summary, improvement of cross-presentation of tumor antigens by triggering of DC and T-cell infiltration during virotherapy enhances antitumoral immune response that facilitates an effective viroimmunotherapy of primary tumors and established metastases.
Fishing for New Drugs
Authors: Alan Hilary Calvert
Journal: Journal of Clinical Oncology (2005)

Natural products have provided a rich source of biologically active compounds and have contributed several of our most active anticancer drugs. For example, doxorubicin is a bacterial product, while paclitaxel is extracted from the yew tree, Taxus brevifolia. Many marine organisms have been found to contain pharmacologically active novel toxic compounds and have possibly evolved these as a defense mechanism against predators. Historically, extracts from marine organisms have been used more with the intention of poisoning for political advantage than for therapeutic purposes. The following excerpt shows that the Romans were well aware of the potential of organisms found in the sea: “Domitian (81-96) was accused (probably wrongly) of poisoningwithsea-harehisbrotherTitus(whodiedunexpectedly at the age of 42, probably of malaria), and Agricola, governorofBritain(Tac.Agr.43).” 1 So far, a limited number of compounds discovered in marine organisms have undergone clinical trials with the more charitable intention of improving the treatment of cancer. Among these are dolastatins, ecteinastatins, and didemnins. A phase I trial of dehydrodidemnin-B (aplidine) is reported in this issue. 2
Ethical dilemma: Sharia punishment, treatment, and speaking out Supporting sharia or providing treatment: the International Committee of the Red Cross Learning to express dissent: Medecins Sans Frontieres
Authors: P. Perrin, H. Nolan
Journal: BMJ (1999)

# Sharia punishment, treatment, and speaking out {#article-title-2}

Humanitarian aid organisations may face situations which challenge their guiding ethics and principles. Amputations after convictions under sharia law, in countries such as Afghanistan, have posed just such a problem. Should the aid organisation continue to provide health care, including treatment to the person who had been punished, or would this make it complicit in a practice that it sees as contrary to human rights? The conclusions and the actions taken by the International Committee of the Red Cross and Medecins Sans Frontieres differ, as outlined in these two accounts. But the ethical bases of their positions are remarkably similar.

# Supporting sharia or providing treatment: the International Committee of the Red Cross {#article-title-3}

In 1997 an Afghan surgeon who was being paid by the International Committee of the Red Cross but who was working in a Ministry of Health hospital was taken by the local authorities to a marketplace. There he amputated the hand of a person who had been convicted under sharia law. Following an appeal by the international committee to the Taliban authorities, an agreement was eventually reached that ensured that neither hospitals assisted materially by the international committee nor staff paid by it would be involved in this practice.

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(Credit: IAN BARRACLOUGH)

Subsequent requests made by the authorities to the assisted hospitals to provide an ambulance or surgical instruments to perform public amputations were refused. Many of the international committee's personnel working with and training Afghan staff were health professionals from Western countries and they faced a dilemma in treating people brought to hospital after having suffered an amputation under sharia. Did treating these victims constitute offering support to a process of torture or cruel and degrading treatment, or was it treating a patient in need of urgent surgical care?

These dilemmas forced the International Committee of the Red Cross to examine its position on corporal punishment, its field operations, …

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Morphological study of myocardial capillaries in endurance trained rats.
Authors: X Qu
Journal: British Journal of Sports Medicine (1990)

In this morphological study of the effects of training on myocardial capillaries, four week old Wistar rats were selected to accept four months of treadmill training. The rats were then sacrificed for morphological study of myocardial capillaries by means of perfused Chinese ink, AKP stain and ultrathin section methods. The results showed that the number of capillaries in trained rats was increased markedly by 14.8 per cent (P less than 0.05) in the outer layer and 13.7 per cent (P less than 0.05) in the inner layer. The ratio of capillaries to myocardial fibres was increased by 17.6 per cent and 13.7 per cent (P less than 0.05) respectively. The area and girth of capillaries in the trained rats were increased by 25 per cent and 26 per cent (P less than 0.01) respectively. Collateral branches in the trained rats were also increased and were more irregular in shape or appeared locally expanding and tortuous. Unopened capillaries were often observed in the control rats, while in the trained rats, no unopened capillaries were observed. In addition, the small vacuoles in the cytoplasm of endothelial cells were also increased.
Predictors of work-related sensitisation, allergic rhinitis and asthma in early work life
Authors: Jessica Kellberger, Astrid S. Peters-Weist, Sabine Heinrich, Susanne Pfeiffer, Christian Vogelberg, Diana Roller, Jon Genuneit, Gudrun Weinmayr, Erika von Mutius, Christian Heumann, Dennis Nowak, Katja Radon
Journal: European Respiratory Journal (2014)

Although work-related asthma and allergies are a huge burden for society, investigation of occupational exposures in early work life using an unexposed reference group is rare. Thus, the present analyses aimed to assess the potential impact of occupational exposure and other risk factors on the prevalence of work-related sensitisation and incidence of allergic rhinitis/asthma using a population-based approach and taking into account an unexposed reference group. In SOLAR (Study on Occupational Allergy Risks) II, German participants of ISAAC (International Study of Asthma and Allergies in Childhood) phase II were followed from childhood (9-11 years) until early adulthood (19-24 years). Data on 1570 participants were available to fit predictive models. Occupational exposure was not statistically significantly associated with disease prevalence/incidence. Sensitisation in childhood, parental asthma, environmental tobacco smoke exposure during puberty, sex and study location were statistically significant predictors of outcome. Our results indicate that occupational exposure is of little relevance for work-related sensitisation prevalence and allergic rhinitis/asthma incidence in early work life, while other risk factors can be used to improve career guidance for adolescents. Further research on the role of a potential healthy hire effect and the impact of longer exposure duration is needed.
Bacterial Lipopolysaccharide Rapidly Inhibits Expression of C–C Chemokine Receptors in Human Monocytes
Authors: Antonio Sica, Alessandra Saccani, Alessandro Borsatti, Christine A. Power, Timothy N.C. Wells, Walter Luini, Nadia Polentarutti, Silvano Sozzani, Alberto Mantovani
Journal: The Journal of Experimental Medicine (1997)

The present study was designed to investigate the effect of bacterial lipopolysaccharide (LPS) on C-C chemokine receptors (CCR) expressed in human mononuclear phagocytes. LPS caused a rapid and drastic reduction of CCR2 mRNA levels, which binds MCP-1 and -3. CCR1 and CCR5 mRNAs were also reduced, though to a lesser extent, whereas CXCR2 was unaffected. The rate of nuclear transcription of CCR2 was not affected by LPS, whereas the mRNA half life was reduced from 1.5 h to 45 min. As expected, LPS-induced inhibition of CCR2 mRNA expression was associated with a reduction of both MCP-1 binding and chemotactic responsiveness. The capacity to inhibit CCR2 expression in monocytes was shared by other microbial agents and cytokines (inactivated Streptococci, Propionibacterium acnes, and to a lesser extent, IL-1 and TNF-alpha). In contrast, IL-2 augmented CCR2 expression and MCP-1 itself had no effect. These results suggest that, regulation of receptor expression in addition to agonist production is likely a crucial point in the regulation of the chemokine system.
Interaction of nitric oxide and cyclic guanosine 3',5'-monophosphate in erythropoietin production.
Authors: T Ohigashi, J Brookins, J W Fisher
Journal: Journal of Clinical Investigation (1993)

The present study was designed to investigate whether in vivo and in vitro erythropoietin (EPO) production is modulated by nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP). Serum levels of EPO in ex-hypoxic polycythemic mice were significantly increased after injections of 200 micrograms/kg sodium nitroprusside for 4 d. One injection of NG-nitro-L-arginine methyl ester (L-NAME) produced a significant dose-related decrease in serum levels of EPO in ex-hypoxic polycythemic mice in response to hypoxia. When EPO producing Hep3B cells were incubated in 1% O2 for 30 min, cGMP levels in the Hep3B cells were significantly elevated, compared with cells incubated in 20% O2. The elevation of cGMP by hypoxia was inhibited by L-NAME (100 microM). Sodium nitroprusside (10 and 100 microM) and NO (2 microM) also significantly increased cGMP levels in Hep3B cells. L-NAME, LY 83583 (6-Anilino-5,8-quinolinedione, a soluble guanylate cyclase inhibitor), and Rp-8-Bromo-cGMPS (Rp-8-Bromo-guanosine 3',5'-cyclic monophosphothioate, a cGMP-dependent protein kinase inhibitor) significantly inhibited the hypoxia-induced increase in medium levels of EPO in Hep3B cells. 8-Bromo-cGMPS produced a dose-dependent decrease in EPO messenger RNA levels in Hep3B cells in response to hypoxia. 8-Bromo-cGMP (10(-3) M) produced significant increases in medium levels of EPO in Hep3B cell cultures incubated under normoxic conditions, which was enhanced by the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (0.2 mM). These results suggest that NO and cGMP may interact in modulating hypoxic stimulation of EPO production.
Ethnic Density of Neighborhoods and Incidence of Psychotic Disorders Among Immigrants
Authors: Wim Veling, Ezra Susser, Jim van Os, Johan P Mackenbach, Jean-Paul Selten, Hans W Hoek
Journal: American Journal of Psychiatry (2007)

A high incidence of psychotic disorders has been reported in immigrant ethnic groups in Western Europe. Some studies suggest that ethnic density may influence the incidence of schizophrenia. The authors investigated whether this increased incidence among immigrants depends on the ethnic density of the neighborhoods in which they live.This was a prospective first-contact incidence study of psychotic disorders in The Hague, by ethnicity and neighborhood of residence. Over a 7-year period, individuals who made contact with a physician for a suspected psychotic disorder underwent diagnostic interviews and received DSM-IV diagnoses. A comprehensive municipal registration system provided the denominator for incidence rates. Data were sufficient to examine incidence rates in native Dutch and in first- and second-generation immigrants from Morocco, Suriname, and Turkey. The ethnic density of a neighborhood was computed for each immigrant group as the proportion of residents belonging to that group. Multilevel regression analyses predicted the incidence of psychotic disorders as a function of individual ethnicity and neighborhood ethnic density. Models were fitted for all immigrants together and for each immigrant group separately.A total of 226 native Dutch and 240 immigrants were diagnosed as having a psychotic disorder. Compared with native Dutch, the adjusted incidence rate ratio for immigrants was significantly increased in low-ethnic-density neighborhoods (2.36) but not in high-ethnic-density neighborhoods (1.25). There was a strong interaction between individual ethnicity and neighborhood ethnic density as predictors of incidence of illness. These findings were consistent across all immigrant groups.The incidence of psychotic disorders was elevated most significantly among immigrants living in neighborhoods where their own ethnic group comprised a small proportion of the population.
The impact of psoriasis guidelines on appropriateness of referral from primary to secondary care: a randomized controlled trial
Authors: C.E.M. Griffiths, H. Taylor, S.I. Collins, J.E. Hobson, P.A. Collier, R.J.G. Chalmers, E.J.C. Stewart, P. Dey
Journal: British Journal of Dermatology (2006)

Journal Article The impact of psoriasis guidelines on appropriateness of referral from primary to secondary care: a randomized controlled trial Get access C.E.M. Griffiths, C.E.M. Griffiths The Dermatology Centre, Hope Hospital, The University of Manchester, Salford, Manchester M6 8HD, U.K. Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K C.E.M. Griffiths. E‐mail: christopher.griffiths@manchester.ac.uk Search for other works by this author on: Oxford Academic Google Scholar H. Taylor, H. Taylor The Dermatology Centre, Hope Hospital, The University of Manchester, Salford, Manchester M6 8HD, U.K. Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K Search for other works by this author on: Oxford Academic Google Scholar S.I. Collins, S.I. Collins The Dermatology Centre, Hope Hospital, The University of Manchester, Salford, Manchester M6 8HD, U.K. Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K Search for other works by this author on: Oxford Academic Google Scholar J.E. Hobson, J.E. Hobson The Dermatology Centre, Hope Hospital, The University of Manchester, Salford, Manchester M6 8HD, U.K. Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K Search for other works by this author on: Oxford Academic Google Scholar P.A. Collier, P.A. Collier Pendleton Medical Centre, Paddington Close, Salford, Manchester M6 8HD, U.K Search for other works by this author on: Oxford Academic Google Scholar R.J.G. Chalmers, R.J.G. Chalmers The Dermatology Centre, Hope Hospital, The University of Manchester, Salford, Manchester M6 8HD, U.K. Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K Search for other works by this author on: Oxford Academic Google Scholar E.J.C. Stewart, E.J.C. Stewart The Dermatology Centre, Hope Hospital, The University of Manchester, Salford, Manchester M6 8HD, U.K. Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K Search for other works by this author on: Oxford Academic Google Scholar P. Dey P. Dey University of Central Lancashire, Preston PR1 2HE, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 2, 1 August 2006, Pages 393–400, https://doi.org/10.1111/j.1365-2133.2006.07354.x Published: 01 August 2006 Article history Accepted: 03 February 2006 Published: 01 August 2006
MRI and FDG-PET in the assessment of inflammatory aortic arch syndrome in complicated courses of giant cell arteritis
Authors: M Both, K Ahmadi-Simab, M Reuter, O Dourvos, E Fritzer, S Ullrich, W L Gross, M Heller, M Bahre
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> To evaluate the use of MRI and FDG-PET for the diagnosis and measurement of disease activity of inflammatory aortic arch syndrome in patients with complicated giant cell arteritis. <h3>Methods:</h3> MRI and FDG-PET were performed for 25 patients with giant cell arteritis who presented with a complicated disease course despite immunosuppressive therapy. Disease activity of the thoracic aorta and the supra-aortic arteries as assessed by both modalities was compared with serological (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and clinical findings (Birmingham vasculitis activity score (BVAS.2)). Additionally, the usefulness of MRI for assessment of vessel wall thickening, aneurysms and stenoses was evaluated. <h3>Results:</h3> In 17/25 patients, MRI disclosed structural vessel lesions suspicious for vasculitis. Active disease was detected by MRI, thoracic PET, and whole body PET in 22, 14 and 20 patients, respectively. While serological and clinical findings correlated significantly with each other, there was no concordance with MRI and only low, non-significant correlation of PET with CRP (<i>r</i><sub>s</sub> = −0.158, 0.136), ESR (<i>r</i><sub>s</sub> = −0.232, 0.320) and BVAS.2 (<i>r</i><sub>s</sub> = −0.064, 0.221) for disease activity. <h3>Conclusions:</h3> MRI and PET are unreliable for assessing large-vessel inflammation in patients with giant cell arteritis and pre-existing immunosuppressive therapy. MRI is valuable for its ability to detect morphological vessel lesions, such as aneurysms and stenoses.
Glomerular Filtration Rate and Albuminuria for Detection and Staging of Acute and Chronic Kidney Disease in Adults
Authors: Andrew S. Levey, Cassandra Becker, Lesley A. Inker
Journal: JAMA (2015)

Because early-stage kidney disease is asymptomatic and is associated with both morbidity and mortality, laboratory measurements are required for its detection.To summarize evidence supporting the use of laboratory tests for glomerular filtration rate (GFR) and albuminuria to detect and stage acute kidney injury, acute kidney diseases and disorders, and chronic kidney disease in adults.We reviewed recent guidelines from various professional groups identified via the National Guideline Clearing House and author knowledge, and systematically searched MEDLINE for other sources of evidence for selected topics.The KDIGO (Kidney Disease Improving Global Outcomes) guidelines define and stage acute and chronic kidney diseases by GFR and albuminuria. For initial assessment of GFR, measuring serum creatinine and reporting estimated GFR based on serum creatinine (eGFRcr) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation is recommended. If confirmation of GFR is required because of conditions that affect serum creatinine independent of GFR (eg, extremes of muscle mass or diet), or interference with the assay, cystatin C should be measured and estimated GFR should be calculated and reported using cystatin C (eGFRcys) and serum creatinine (eGFRcr-cys) or GFR should be measured directly using a clearance procedure. Initial assessment of albuminuria includes measuring urine albumin and creatinine in an untimed spot urine collection and reporting albumin-to-creatinine ratio. If confirmation of albuminuria is required because of diurnal variation or conditions affecting creatinine excretion, such as extremes of muscle mass or diet, the albumin excretion rate should be measured from a timed urine collection.Detection and staging of acute and chronic kidney diseases can be relatively simple. Because of the morbidity and mortality associated with kidney disease, early diagnosis is important and should be pursued in at-risk populations.
The "Sunshine Vitamin": Benefits Beyond Bone?
Authors: C. D. Davis, J. T. Dwyer
Journal: JNCI Journal of the National Cancer Institute (2007)

Nutritional Sciences Research Group, National Cancer Institute, National Institutes of Health, Bethesda, MD (CDD); Office of Dietary Supplements, National Institutes of Health, Bethesda, MD (JTD); School of Medicine and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (JTD) . Correspondence to: Johanna T. Dwyer, DSc, RD, NIH, Office of Dietary Supplements, 6100 Exec Blvd, MSC7517 Room 3B01, Bethesda, MD 20892 ( e-mail: Dwyerj1@od.nih.gov .) DOI: 10.1093/jnci/djm211 Published by Oxford University Press 2007.
Spontaneously Occurring Arrhythmogenic Right Ventricular Cardiomyopathy in the Domestic Cat
Authors: Philip R. Fox, Barry J. Maron, Cristina Basso, Si-Kwang Liu, Gaetano Thiene
Journal: Circulation (2000)

Background —Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary myocardial disease of incompletely resolved pathogenesis and is a largely unappreciated cause of sudden death in the young. Methods and Results —Clinical features of 12 domestic cats with ARVC (7 male; 1 to 20 years old, mean 7.3±5.2 years) were right-sided congestive heart failure (n=8), supraventricular tachyarrhythmias (n=5), ventricular tachycardia (n=3), polymorphic ventricular arrhythmias (n=6), and right bundle-branch block (n=5). ARVC was suspected in all 8 cats examined with echocardiography by marked enlargement of the right ventricle (RV) and right atrium and tricuspid regurgitation. Eight died of cardiovascular disease and 4 died of noncardiac conditions. At autopsy, hearts of ARVC cats were characterized grossly by moderate-to-severe RV cavity enlargement and wall thinning (n=12) and apical aneurysm formation (n=6). Histology demonstrated pronounced RV lesions in all 12 ARVC cats, including marked myocardial injury (myocyte death and atrophy) and repair (fibrous and/or fatty replacement). Injury and repair were also evident in the left ventricle (LV) in 10 cats, and 2 had involvement of both atria. Myocarditis was present in 10 of the 12 ARVC cats. Apoptosis was detected in 9 ARVC cats (mean apoptotic index, 28±23% RV, 21±19% LV, and 17±15% ventricular septum) but not in controls. Conclusions —In the common domestic cat, we identified a clinically relevant cardiomyopathy that closely mimics ARVC in humans. This unique feline model of human disease will be relevant to defining pathogenesis and investigating mechanisms responsible for disease progression in ARVC.