tbuckley/cabot-search huggingface dataset:
Cyanidin-3-Glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2
Authors: Mei Xu, Kimberly A Bower, Siying Wang, Jacqueline A Frank, Gang Chen, Min Ding, Shiow Wang, Xianglin Shi, Zunji Ke, Jia Luo
Journal: Molecular Cancer (2010)

Abstract Background Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This study evaluated the effect of C3G on ethanol-induced breast cancer cell migration/invasion. Results C3G attenuated ethanol-induced migration/invasion of breast cancer cells expressing high levels of ErbB2 (BT474, MDA-MB231 and MCF7 ErbB2 ) in a concentration dependent manner. C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion. It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130 Cas , as well as interactions among these proteins. C3G abolished ethanol-mediated p130 Cas /JNK interaction. Conclusions C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway which is necessary for cell migration/invasion. C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis.
Diet, absorption, and hormone studies in relation to body weight in obstructive airways disease.
Authors: P d'A Semple, W S Watson, G H Beastall, M I Bethel, J K Grant, R Hume
Journal: Thorax (1979)

Sixteen male patients with stable chronic obstructive airways disease were separated into two groups of eight according to arterial carbon dioxide tensions. Hypercapnia was associated with lower arterial oxygen tensions, higher red cell volume, and increased weight, while normocapnic subjects were decidedly thin. The considerable difference in body weight between the two groups could not be explained by variation in caloric intake, and malabsorption was excluded as a cause of weight loss in the underweight subjects. Serum tri-iodothyronine, thyroxine, cortisol, and oestradiol concentrations were similar and normal in each group, but both groups had significantly low testosterone values as compared with controls, values in the hypercapnic being appreciably lower than in the normocapnic group. The adrenal androgen dehydroepiandrosterone was significantly high in the normocapnic group and low in the hypercapnic group compared with controls. Serum pituitary luteinising and follicle stimulating hormones were normal, but three hypercapnic individuals had high serum prolactin values. Early morning urinary aldosterone values were significantly higher in the hypercapnic than in the normocapnic group. Such hormone comparisons have not previously been made in subjects with chronic obstructive airways disease grouped according to arterial blood gas values, and it is concluded that major alterations in adrenal and testicular function may occur, possibly due to pituitary suppression from hypoxia. Such hormonal changes might in part account for the contrasting alterations in body habitus found in this condition.
Delay in onset of awareness of acute hypoglycemia and of restoration of cognitive performance during recovery.
Authors: M L Evans, A Pernet, J Lomas, J Jones, S A Amiel
Journal: Diabetes Care (2000)

To examine the time course for the onset of, and recovery from, acute hypoglycemia in healthy subjects.Eight healthy male volunteers were studied on 2 occasions in random order using a hyperinsulinemic (1.5 mU x kg(-1) x min(-1)) glucose clamp technique. During control studies, euglycemia (5.01 +/- 0.02 mmol/l) was maintained for 225 +/- 3 min. On the other occasion, after a euglycemic baseline period, arterialized plasma glucose was allowed to fall rapidly to 2.65 +/- 0.02 mmol/l, then maintained at this nadir for 90 min before euglycemia was rapidly restored.Cognitive function assessed by a battery of sensitive tests (4-choice reaction time, Stroop word, and color-word test) became impaired immediately at onset of hypoglycemia (P < 0.05 for all in the hypoglycemic study vs. those in the euglycemic study). Counterregulatory hormone responses (epinephrine, norepinephrine, glucagon, cortisol, and growth hormone) and symptomatic awareness of hypoglycemia (assessed by a questionnaire) were relatively delayed, being detected 20 min after the onset of hypoglycemia. There was no diminution (adaptation) of any responses, cognitive, humoral, or symptomatic, during sustained hypoglycemia. During recovery, the 4-choice reaction time continued to be abnormal even after resolution of symptomatic awareness (P = 0.025).During hypoglycemia, cognitive performance may become impaired before symptomatic awareness. During recovery from hypoglycemia, recovery of cognitive function lags behind the restoration of glucose levels and resolution of symptoms. Our findings have implications for the design of studies examining experimental hypoglycemia and need to be investigated in people with diabetes.
Neurotrophins Are Increased in Bronchoalveolar Lavage Fluid after Segmental Allergen Provocation
Authors: JOHANN CHRISTIAN VIRCHOW, PETER JULIUS, MAREK LOMMATZSCH, WERNER LUTTMANN, HARALD RENZ, ARMIN BRAUN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The mechanisms linking inflammation and airway hyperresponsiveness in allergic bronchial asthma are still not completely defined. Since neurotrophic factors increase nerve excitability and neurotransmitter synthesis and are produced by immunocompetent cells, they are likely candidates as mediators of inflammation and hyperresponsiveness. We tested the hypothesis that neurotrophin concentrations will increase in the bronchoalveolar lavage (BAL) fluid from patients with asthma after segmental allergen provocation. For this purpose an individually standardized dose of allergen or saline was instilled into different segments during bronchoscopy in eight subjects with mild allergic bronchial asthma. Segments were then lavaged 10 min and 18 h after allergen challenge or saline instillation. There was a significant increase in the neurotrophins nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 in BAL fluids 18 h after allergen but not saline challenge. We conclude that neurotrophins are produced endobronchially following allergen provocation, suggesting a contribution to the pathogenesis of asthma.
Common germline variation at the <i>TERT</i> locus contributes to familial clustering of myeloproliferative neoplasms
Authors: Roland Jäger, Ashot S. Harutyunyan, Elisa Rumi, Daniela Pietra, Tiina Berg, Damla Olcaydu, Richard S. Houlston, Mario Cazzola, Robert Kralovics
Journal: American Journal of Hematology (2014)

The C allele of the rs2736100 single nucleotide polymorphism located in the second intron of the TERT gene has recently been identified as a susceptibility factor for myeloproliferative neoplasms (MPN) in the Icelandic population. Here, we evaluate the role of TERT rs2736100_C in sporadic and familial MPN in the context of the previously identified JAK2 GGCC predisposition haplotype. We have confirmed the TERT rs2736100_C association in a large cohort of Italian sporadic MPN patients. The risk conferred by TERT rs2736100_C is present in all molecular and diagnostic MPN subtypes. TERT rs2736100_C and JAK2 GGCC are independently predisposing to MPN and have an additive effect on disease risk, together explaining a large fraction of the population attributable fraction (PAF = 73.06%). We found TERT rs2736100_C significantly enriched (P = 0.0090) in familial MPN compared to sporadic MPN, suggesting that low-penetrance variants may be responsible for a substantial part of familial clustering in MPN.
Should Supplemental Antioxidant Administration Be Avoided During Chemotherapy and Radiation Therapy?
Authors: B. D. Lawenda, K. M. Kelly, E. J. Ladas, S. M. Sagar, A. Vickers, J. B. Blumberg
Journal: JNCI Journal of the National Cancer Institute (2008)

Despite nearly two decades of research investigating the use of dietary antioxidant supplementation during conventional chemotherapy and radiation therapy, controversy remains about the efficacy and safety of this complementary treatment. Several randomized clinical trials have demonstrated that the concurrent administration of antioxidants with chemotherapy or radiation therapy reduces treatment-related side effects. Some data indicate that antioxidants may protect tumor cells as well as healthy cells from oxidative damage generated by radiation therapy and some chemotherapeutic agents. However, other data suggest that antioxidants can protect normal tissues from chemotherapy- or radiation-induced damage without decreasing tumor control. We review some of the data regarding the putative benefits and potential risks of antioxidant supplementation concurrent with cytotoxic therapy. On the basis of our review of the published randomized clinical trials, we conclude that the use of supplemental antioxidants during chemotherapy and radiation therapy should be discouraged because of the possibility of tumor protection and reduced survival.
A Dimeric Peptide That Binds Selectively to Prostate-Specific Membrane Antigen and Inhibits its Enzymatic Activity
Authors: Saurabh Aggarwal, Pratap Singh, Ozlem Topaloglu, John T. Isaacs, Samuel R. Denmeade
Journal: Cancer Research (2006)

Abstract Prostate-specific membrane antigen (PSMA) is highly expressed by both normal and malignant prostate epithelial cells and by the neovasculature of many tumor types; however, it is not expressed by normal endothelial cells or other normal tissues. PSMA, therefore, represents an attractive candidate for selectively targeted therapies for prostate and/or other solid tumors. As an alternative approach to antibody-based anti-PSMA therapies, small peptides that bind selectively to PSMA-producing cells can be used to deliver cytotoxic drugs, protein toxins, and viruses selectively to malignant sites while minimizing systemic toxicity to normal tissues. Small peptides are relatively inexpensive to produce, not immunogenic, and easily coupled to cytotoxic agents. In the present study, a random phage library consisting of linear 12 amino acid peptides was used to identify peptides that bound selectively to PSMA. From a series of monomeric peptides, one with the sequence WQPDTAHHWATL was used to show binding of soluble peptide to PSMA. A dimeric version of this peptide showed markedly enhanced binding to soluble PSMA and an IC50 of 2.2 μmol/L for inhibition of PSMA enzymatic activity. Fluorescently labeled dimeric peptide bound selectively to PSMA-producing prostate cancer cells in vitro with no significant binding to non–PSMA-producing cells. Molecular modeling of the dimeric peptide revealed that histidine residues in close vicinity can efficiently coordinate a divalent ion and hold the peptide in a favorable configuration for binding and subsequent inhibition. These dimeric peptides, therefore, represent putative PSMA-selective targeting agents that are currently being evaluated for selective binding in vivo. (Cancer Res 2006; 66(18): 9171-7)
Decline in work disability caused by early rheumatoid arthritis: results from a nationwide Finnish register, 2000–8
Authors: Vappu Marianna Rantalaiho, Hannu Kautiainen, Salme Järvenpää, Lauri Virta, Timo Pohjolainen, Markku Korpela, Timo Möttönen, Kari Puolakka
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To study whether the work disability (WD) rates in early rheumatoid arthritis (RA) have changed in Finland, where the treatment of RA has long been active but has intensified further since 2000. <h3>Methods</h3> All incident non-retired patients with RA of working age (18–64 years) in a nationwide register maintained by the Finnish Social Insurance Institution from 1 January 2000 to 31 December 2007 were identified. Patient cohorts were analysed in 2-year time periods (2000–1, 2002–3, 2004–5, 2006–7) and initial disease-modifying antirheumatic drugs (DMARDs) were elucidated from the drug purchase register. The incidence of continuous WD in the RA cohorts as well as in the entire Finnish population up to 31 December 2008 was analysed. <h3>Results</h3> A total of 7831 patients were identified (71% women, 61% rheumatoid factor-positive). Throughout the follow-up period the use of methotrexate and combination DMARDs as the initial treatment of early RA increased. During the first 2 years the incidence of RA-related continuous WD was 8.9%, 9.4%, 7.2% and 4.8% in the year cohorts, respectively (p&lt;0.001 for linearity). Compared with the entire Finnish population, the age- and sex-stratified standardised incidence ratio of a WD pension due to any cause was 3.69, 3.34, 2.77 and 2.80 in the year cohorts, respectively (p&lt;0.001 for linearity). <h3>Conclusions</h3> Since 2000 the frequency of continuous WD in early RA has declined in Finland. The present data allow no explanatory analysis but, at the same time, increasingly active treatment strategies have been introduced.
Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis
Authors: H. Ishigami, J. Kitayama, S. Kaisaki, A. Hidemura, M. Kato, K. Otani, T. Kamei, D. Soma, H. Miyato, H. Yamashita, H. Nagawa
Journal: Annals of Oncology (2009)
Kaposi's Sarcoma–Associated Herpesvirus Viral IFN Regulatory Factor 1 Inhibits Transforming Growth Factor-β Signaling
Authors: Taegun Seo, Junsoo Park, Joonho Choe
Journal: Cancer Research (2005)

Abstract Kaposi's sarcoma–associated herpesvirus, also called human herpesvirus 8, has been implicated in the pathogenesis of Kaposi's sarcoma, body cavity–based primary effusion lymphoma, and some forms of multicentric Castleman's disease. The Kaposi's sarcoma–associated herpesvirus open reading frame K9 encodes viral IFN regulatory factor 1 (vIRF1), which functions as a repressor of IFN-mediated signal transduction. vIRF1 expression in NIH 3T3 cells leads to transformation and consequently induces malignant fibrosarcoma in nude mice, suggesting that vIRF1 is a strong oncoprotein. Here, we show that vIRF1 inhibited transforming growth factor-β (TGF-β) signaling via its targeting of Smad proteins. vIRF1 suppressed TGF-β-mediated transcription and growth arrest. vIRF1 directly interacted with both Smad3 and Smad4, resulting in inhibition of their transactivation activity. Studies using vIRF1 deletion mutants showed that the central region of vIRF1 was required for vIRF1 association with Smad3 and Smad4 and that this region was also important for inhibition of TGF-β signaling. In addition, we found that vIRF1 interfered with Smad3-Smad4 complex formation and inhibited Smad3/Smad4 complexes from binding to DNA. These results indicate that vIRF1 inhibits TGF-β signaling via interaction with Smads. In addition, the data indicate the TGF-β pathway is an important target for viral oncoproteins.
The burden of atopy and asthma in children
Authors: E. J. O'Connell
Journal: Allergy (2004)

Background: There has been a world‐wide increase in the prevalence of atopic diseases. These atopic diseases, including asthma, allergic rhinoconjunctivitis and atopic eczema/dermatitis, are common in childhood and create a challenge of management for physicians and parents. Methods: MEDLINE was searched for articles related to atopy, allergy asthma, allergic rhinoconjunctivitis and atopic eczema/dermatitis. Results and conclusions: The conditions of asthma, allergic rhinoconjunctivitis and atopic eczema/dermatitis cause very significant burdens regarding the discomfort to the affected individual, management problems for the parent and physician and the economic cost to the family and the nation.
A Picture of Health
Authors: Theo Chalmers
Journal: Journal of the Royal Society of Medicine (2006)

A Picture of Health is made up of 16 enigmatic images that can perhaps best be described as ‘epic portrait-scapes’. Fullerton-Batten's use of complex yet subtle set lighting makes this collection truly fit for the big screen. And as well it might, for each sitter has contributed more to the positive advancement of healthcare than many that have received far grander pictorial homage.

Fullerton-Batten's work reveals the photographer as a true artist. Her genius here lies in her ability to project a strange suspense around her subject whilst actually doing little more than dishing out the facts. Huge attention to the most fitting environment has been given to each well-researched sitter, suspended in flawless cinematic lighting. In fact you would be forgiven for wondering if these images were in some way digital montages, as the exceptional clarity produces deep layers of colour and light within each print. The breathing space allowed in each image pays homage to the professional field that has supported the sitter in their individual work. This of course only adds to the attractive surrealness of this collection and amplifies still further the viewer's intrigue toward each sitter.

Sir Derek Wanless, Professor Lord Robert Winston, Professor Sir Brian Jarman, Claire Rayner, Professor Sir Ian Kennedy, Sir Iain Chalmers, Professor Sir Cyril Chantler, Nick Partridge, Christine Hancock,... the list of notables goes on into the night... Warmly frozen in time, this collection is a significant anthropological record of contemporary medical excellence.

We see Ray Shannon, Chief Executive of South Yorkshire Ambulance Service NHS Trust, photographed behind the sliding glass window of what appears to be an A&E check in desk. He holds a phone poised and away from his face with respectful intent. A ponderous glint in his eyes inadvertently invites the viewer to speculate on the huge task of effectively modernising the ambulance service.

Sheila Kitzinger is compassionately framed by the rich continental colours of the drapes and quilts of her four poster bed, where she often works. Fullerton-batten aims high and hits the mark when trying to summarise Sheila's massive contribution to midwifery by the use of this caring, vibrant and most fertile of locations.

Another image shows Nola Ismael OBE—standing tall and calm, highlighted with strong positive light amongst the relative uncertainty of the randomly positioned desks surrounding her. A book is placed confidently to her right suggesting assurance in her responsibility for ethnic minority health issues and ethnic staff development in the NHS.

The NPG and Fullerton-Batten have confidently delivered a most important and enjoyable body of work that rewards and educates the viewer whilst showing deep gratitude to each sitter's contribution to healthcare.
Chromogranin A: Is It a Useful Marker of Neuroendocrine Tumors?
Authors: Davide Campana, Francesca Nori, Lidya Piscitelli, Antonio Maria Morselli-Labate, Raffaele Pezzilli, Roberto Corinaldesi, Paola Tomassetti
Journal: Journal of Clinical Oncology (2007)

We evaluated the pattern of chromogranin A (CgA) plasma levels in a large number of patients with neuroendocrine tumors (NETs), in a series of patients with chronic atrophic gastritis (CAG) with and without enterochromaffin-like (ECL) cell hyperplasia, and in healthy participants (HPs).Two hundred thirty-eight patients with NETs, 42 patients with CAG with or without ECL cell hyperplasia, and 48 HPs were studied. All patients underwent a baseline visit, biochemical routine check-up, imaging techniques, endoscopy, and histologic determination.CgA plasma levels were higher in patients with NETs compared with CAG patients or HPs (P < .001). In the NET group, we observed higher CgA levels in patients with diffuse disease compared with patients with local or hepatic disease (P < .001). CgA plasma levels were significantly higher in patients with Zollinger-Ellison syndrome compared with other types of endocrine tumors (P < .001). We found the best cutoff range between HPs and NET patients to be 18 to 19 U/L (sensitivity, 85.3%; specificity, 95.8%). Comparing all participants without neoplasia (HPs, CAG patients, and disease-free patients) and patients with endocrine tumors, the best cutoff range was 31 to 32 U/L (sensitivity, 75.3%; specificity, 84.2%). Setting the specificity at 95%, the cutoff range was 84 to 87 U/L (sensitivity, 55%).Our study confirms the high specificity and sensitivity of CgA in diagnosing an endocrine tumor. It is necessary to use a cutoff range of 84 to 87 U/L to obtain a high specificity in diagnosing NETs, with the aim of excluding patients in whom the CgA was elevated as a result of other non-neoplastic diseases.
Isolation of variants in phagocytosis of a macrophage-like continuous cell line.
Authors: R J Muschel, N Rosen, B R Bloom
Journal: The Journal of Experimental Medicine (1977)

We have isolated cloned variants in phagocytosis from a cloned continuous murine macrophage-like cell line, J 774.2. A selection procedure against Fc receptor-mediated phagocytosis was devised using IgG-coated SRBC containing a toxic drug, tubercidin, as the lethal agent. A series of variant clones deficient in Fc receptor-mediated phagocytosis were isolated. Such variants occurred at low frequency (approximately 6 X 10(-5)), were stable, and appeared to possess Fc receptors. The degree to which they were defective in phagocytosis of IgG-coated SRBC varied from clone to clone, yet all clones, were able to phagocytize latex particles. The phagocytic defect in some variants could be corrected by the addition of 8 Br-cAMP, in others, the drug was without effect. It is likely, therefore, that different variants are defective in several distinct steps critical to Fc receptor-mediated phagocytosis.
A prospective national study of acute fatty liver of pregnancy in the UK
Authors: M Knight, C Nelson-Piercy, J J Kurinczuk, P Spark, P Brocklehurst
Journal: Gut (2008)

<h3>Objectives:</h3> To identify a national, population-based cohort of women with acute fatty liver of pregnancy (AFLP), to evaluate proposed diagnostic criteria and to document accurately the incidence, management and outcomes of the condition. <h3>Subjects and methods:</h3> This was a population-based descriptive study using the UK Obstetric Surveillance System, carried out in all 229 hospitals with consultant-led maternity units in the UK. The participants comprised 57 women in the UK diagnosed with AFLP between February 2005 and August 2006 in an estimated cohort of 1 132 964 maternities (women delivering). <h3>Results:</h3> The estimated incidence of AFLP was 5.0 cases per 100 000 maternities (95% CI 3.8 to 6.5 per 100 000). Fifty-five cases (90%) were confirmed by diagnostic criteria and clinical assessment, two (3%) by clinical assessment alone, representing 97% agreement (kappa statistic = 0.78). 18% of women had twin pregnancies and 20% were underweight (body mass index (BMI) &lt;20). 60% of women were admitted to intensive care and 15% to a specialist liver unit. One woman received a liver transplant. One woman died (case fatality rate 1.8%, 95% CI 0% to 9.4%). There were seven deaths among 67 infants (perinatal mortality rate 104 per 1000 births, 95% CI 43 to 203). <h3>Conclusions:</h3> The largest population-based cohort of women with AFLP to date has been identified. Diagnostic criteria previously proposed agree substantially with clinical diagnosis. The incidence estimate from this study is lower than documented by earlier hospital-based studies, but maternal and neonatal outcomes are better than previously reported, possibly related to improved ascertainment. Women with twin pregnancies appear to be at higher risk, but further studies are needed to investigate the risk associated with low BMI.