tbuckley/cabot-search huggingface dataset:
Oxidation Status of Human OGG1-S326C Polymorphic Variant Determines Cellular DNA Repair Capacity
Authors: Anne Bravard, Monique Vacher, Eva Moritz, Laurence Vaslin, Janet Hall, Bernd Epe, J. Pablo Radicella
Journal: Cancer Research (2009)

Abstract The hOGG1 gene encodes the DNA glycosylase that removes the mutagenic lesion 7,8-dihyro-8-oxoguanine (8-oxoG) from DNA. A frequently found polymorphism resulting in a serine to cysteine substitution at position 326 of the OGG1 protein has been associated in several molecular epidemiologic studies with cancer development. To investigate whether the variant allele encodes a protein with altered OGG1 function, we compared the 8-oxoG repair activity, both in vivo and in cell extracts, of lymphoblastoid cell lines established from individuals carrying either Ser/Ser or Cys/Cys genotypes. We show that cells homozygous for the Cys variant display increased genetic instability and reduced in vivo 8-oxoG repair rates. Consistently, their extracts have an almost 2-fold lower basal 8-oxoG DNA glycosylase activity when compared with the Ser variant. Treatment with reducing agents of either the Cys variant cells directly or of protein extracts from these cells increases the repair capacity to the level of the Ser variant, whereas it does not affect the activity in cells or extracts from the latter. Furthermore, the DNA glycosylase activity of cells carrying the Cys/Cys alleles is more sensitive to inactivation by oxidizing agents when compared with that of the Ser/Ser cells. Analysis of the redox status of the OGG1 protein in the cells confirms that the lower activity of OGG1-Cys326 is associated with the oxidation of Cys326 to form a disulfide bond. Our findings support the idea that individuals homozygous for the OGG1-Cys variant could more readily accumulate mutations under conditions of oxidative stress. [Cancer Res 2009;69(8):3642–9]
Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon
Authors: P. Seksik, Lionel Rigottier Gois, G. Gramet, Marie-Madeleine Sutren, P. Pochart, Philippe Marteau, R. Jian, J. Dore
Journal: Gut (2003)

The colonic microflora is involved in the pathogenesis of Crohn's disease (CD) but less than 30% of the microflora can be cultured. We investigated potential differences in the faecal microflora between patients with colonic CD in remission (n=9), patients with active colonic CD (n=8), and healthy volunteers (n=16) using culture independent techniques.Quantitative dot blot hybridisation with six radiolabelled 16S ribosomal ribonucleic acid (rRNA) targeting oligonucleotide probes was used to measure the proportions of rRNA corresponding to each phylogenetic group. Temporal temperature gradient gel electrophoresis (TTGE) of 16S rDNA was used to evaluate dominant species diversity.Enterobacteria were significantly increased in active and quiescent CD. Probe additivity was significantly lower in patients (65 (11)% and 69 (6)% in active CD and quiescent CD) than in healthy controls (99 (7)%). TTGE profiles varied markedly between active and quiescent CD but were stable in healthy conditions.The biodiversity of the microflora remains high in patients with CD. Enterobacteria were observed significantly more frequently in CD than in health, and more than 30% of the dominant flora belonged to yet undefined phylogenetic groups.
MSF launches lifesaving mission in Mediterranean because Europe "is not willing"
Authors: S. Arie
Journal: BMJ (2015)

The charity Medecins Sans Frontieres is launching an independent mission to save lives of migrants because it says Europe is still not doing enough to rescue them as they try to cross the Mediterranean from Africa.

From early May the medical charity, working jointly with a small Maltese charity called Migrant Offshore Aid Station, will operate rescue missions across the Mediterranean and as close as possible to Libya, where most migrant boats set out. The European Union stopped doing similar missions last year out of concern that they were encouraging migration and, despite agreeing to triple spending on its rescue efforts, …
Molecular Basis for High Renal Cell Sensitivity to the Cytotoxic Effects of Shigatoxin-1
Authors: Alisa K. Hughes, Zuhal Ergonul, Peter K. Stricklett, Donald E. Kohan
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Cellular injury in post-diarrheal hemolytic-uremic syndrome (D+HUS) is related to shigatoxin (Stx) binding to globotriaosylceramide (Gb3). High renal Gb3 expression may determine renal susceptibility in D+HUS; however, the molecular mechanism(s) responsible for such relatively abundant Gb3 levels are unknown. Consequently, kidney cells expressing high Gb3 (cultured human proximal tubule cells [HPT]) were compared with non-kidney cells with low Gb3 content (cultured human brain microvascular endothelial cells [HBEC]). HPT were much more sensitive to the cytotoxic and protein synthesis inhibitory effects of Stx-1; this correlated with Gb3 content and 125I-Stx-1 binding. HPT had greater Gb3 synthase (GalT6) and lower α-galactosidase activities than HBEC, whereas lactosylceramide synthase (GalT2) activity was higher in HBEC. Ceramide glucosyltransferase (CGT) activity was similar between the two cell types. The higher HPT GalT6 activity was associated with increased GalT6 mRNA steady-state levels, but no difference in GalT6 mRNA half-life. The lower HPT α-galactosidase activity was associated with reduced α-galactosidase mRNA steady-state levels but no difference in α-galactosidase mRNA half-life. Higher HBEC GalT2 activity was associated with increased steady-state GalT2 mRNA levels. These studies suggest that high renal Gb3 expression is due to enhanced GalT6 gene transcription and reduced α-galactosidase gene transcription and occur despite relatively low GalT2 activity.
Spontaneous Urinary Bladder Tumors in DA/Han Rats: A Feasible Model of Human Bladder Cancer
Authors: F Deerberg, S Rehm, H H Jostmeyer
Journal: JNCI Journal of the National Cancer Institute (1985)

In a life-span study of virgin DA/Han inbred rats, 53.9% of the males and 14.4% of the females developed spontaneous urinary bladder tumors. A peak incidence was noted between the ages of 25 and 30 months. With the exception of 1 leiomyosarcoma, all neoplasms were of epithelial origin. After the papilloma, the majority of tumors were classified as transitional cell carcinoma of the papillary, solid, or mixed type. Less frequent were unclassified microcarcinoma, squamous cell, adenoid, and undifferentiated carcinomas. A sexual difference was found for almost every tumor type. Of the rats bearing tumors, 3.5% of the males and 64.4% of the females also were affected with urinary bladder stones. Squamous cell and glandular metaplasias of the tumors commonly were observed, and invasive growth into the bladder wall occurred frequently in less-differentiated tumors. Metastases were rare. The DA/Han rat strain is discussed as a suitable animal model for human urinary bladder cancer.
Sputum processing methods to improve the sensitivity of smear microscopy for tuberculosis: a systematic review
Authors: Karen R Steingart, Vivienne Ng, Megan Henry, Philip C Hopewell, Andrew Ramsay, Jane Cunningham, Richard Urbanczik, Mark D Perkins, Mohamed Abdel Aziz, Madhukar Pai
Journal: The Lancet Infectious Diseases (2006)
Consumer Health Plan Choice: Current Knowledge and Future Directions
Authors: Dennis P. Scanlon, Michael Chernew, Judith R. Lave
Journal: Annual Review of Public Health (1997)

▪ Abstract A keystone of the competitive strategy in health insurance markets is the assumption that “consumers” can make informed choices based on the costs and quality of competing health plans, and that selection effects are not large. However, little is known about how individuals use information other than price in the decision making process. This review summarizes the state of knowledge about how individuals make choices among health plans and outlines an agenda for future research. We find that the existing literature on health plan choice is no longer sufficient given the widespread growth and acceptance of managed care, and the increased proportion of consumers' income now going toward the purchase of health plans. Instead, today's environment of health plan choice requires better understanding of how plan attributes other than price influence plan choice, how other variables such as health status interact with plan attributes in the decision making process, and how specific populations differ from one another in terms of the sensitivity of their health plan choices to these different types of variables.
Increased hepatic platelet activating factor (PAF) and PAF receptors in carbon tetrachloride induced liver cirrhosis
Authors: Y Yang
Journal: Gut (2004)

<b>Background and aims:</b> The liver is a major site for the synthesis and actions of platelet activating factor (PAF), a potent hepatic vasoconstrictor and systemic vasodilator. As PAF is implicated in portal hypertension and hyperdynamic circulation associated with liver cirrhosis, we characterised changes in the hepatic PAF system in experimental cirrhosis. <b>Methods:</b> In rats made cirrhotic by carbon tetrachloride (CCl<sub>4</sub>) administration for eight weeks, we determined hepatic levels of PAF and its cognate receptor, and the effects of PAF and PAF antagonist (BN52021) on portal and arterial pressure. <b>Results:</b> Compared with control rats, cirrhotic rats had higher hepatic PAF levels, higher apparent hepatic efflux of PAF, and higher PAF levels in arterial blood (p&lt;0.01, p&lt;0.01, p&lt;0.05, respectively). Relative to controls, cirrhotic livers had elevated hepatic PAF receptors (by mRNA and protein levels and [<sup>3</sup>H]PAF binding), higher (p&lt;0.01) baseline hepatic portal pressure, and an augmented (p = 0.03) portal pressure response to PAF infusion (1 μg/kg). Portal infusion of BN52021 (5 mg/kg) showed that elevated endogenous PAF was responsible for 23% of the cirrhotic portal pressure increase but made no contribution to systemic hypotension. Finally, increased PAF receptor density was observed in the contractile perisinusoidal stellate cells isolated from cirrhotic livers relative to those from control livers. <b>Conclusions:</b> In cirrhosis, increased hepatic release of PAF elevates systemic PAF; in combination with upregulated hepatic PAF receptors in stellate cells, this contributes to portal hypertension.
A Novel EGFR Isoform Confers Increased Invasiveness to Cancer Cells
Authors: Min Zhou, Hai Wang, Keke Zhou, Xiaoying Luo, Xiaorong Pan, Bizhi Shi, Hua Jiang, Jiqin Zhang, Kesang Li, Hua-Mao Wang, Huiping Gao, Shun Lu, Ming Yao, Ying Mao, Hong-Yang Wang, Shengli Yang, Jianren Gu, Chuanyuan Li, Zonghai Li
Journal: Cancer Research (2013)

As a validated therapeutic target in several human cancers, the EGF receptor (EGFR) provides a focus to gain deeper insights into cancer pathophysiology. In this study, we report the identification of a naturally occurring and widely expressed EGFR isoform termed EGFRvA, which substitutes a Ser/Thr-rich peptide for part of the carboxyl-terminal regulatory domain of the receptor. Intriguingly, EGFRvA expression relates more closely to histopathologic grade and poor prognosis in patients with glioma. Ectopic expression of EGFRvA in cancer cells conferred a higher invasive capacity than EGFR in vitro and in vivo. Mechanistically, EGFRvA stimulated expression of STAT3, which upregulated heparin-binding EGF (HB-EGF). Reciprocally, HB-EGF stimulated phosphorylation of EGFRvA at Y845 along with STAT3, generating a positive feedback loop that may reinforce invasive function. The significance of EGFRvA expression was reinforced by findings that it is attenuated by miR-542-5p, a microRNA that is a known tumor suppressor. Taken together, our findings define this newfound EGFR isoform as a key theranostic molecule.
[83] TREATMENT OF BUDD CHIARI SYNDROME WITH TIPS. LONG-TERM RESULTS IN 124 PATIENTS AND EVALUATION OF PROGNOSTIC FACTORS
Authors: S. Raffa, M. Heydtmann, A. Plessier, S. Darwish Murad, F. Fabris, G. Vizzini, J.G. Abraldes, P. Bellot, A. Luca, M. Primignani, H.L.A. Janssen, D. Valla, E. Elias, J. Bosch, J.C. Garcia-Pagan
Journal: Journal of Hepatology (2007)
Regulation of myosin heavy chain expression in the hearts of hypertensive rats by testosterone.
Authors: I Morano, J Gerstner, J C Rüegg, U Ganten, D Ganten, H P Vosberg
Journal: Circulation Research (1990)

Stroke-prone spontaneously hypertensive rats were used for our investigation of the influence of prepubertal gonadectomy and testosterone substitution on blood pressure, cardiac hypertrophy, and the expression of ventricular myosin heavy chain (MHC) isoenzymes at different developmental stages. Blood pressure and the degree of cardiac hypertrophy were decreased by castration and increased by testosterone substitution. We found the same relative distributions of MHC isoforms on the protein level (investigated by pyrophosphate electrophoresis) and on the messenger RNA level (investigated by the polymerase chain reaction). Castration favored the expression of the beta-MHC form, and testosterone substitution enhanced the expression of the alpha-MHC form. These effects were more pronounced in 8-week-old than in 14-16-week-old animals. We conclude that testosterone regulates cardiac MHC expression on a pretranslational level. This regulation is independent of hemodynamic load or cardiac hypertrophy.
Differentiation between Cell Death Modes Using Measurements of Different Soluble Forms of Extracellular Cytokeratin 18
Authors: Gero Kramer, Hamdiye Erdal, Helena J. M. M. Mertens, Marius Nap, Julian Mauermann, Georg Steiner, Michael Marberger, Kenneth Bivén, Maria C. Shoshan, Stig Linder
Journal: Cancer Research (2004)

Abstract Cytokeratins are released from carcinoma cells by unclear mechanisms and are commonly used serum tumor markers (TPA, TPS, and CYFRA 21–1). We here report that soluble cytokeratin-18 (CK18) is released from human carcinoma cells during cell death. During necrosis, the cytosolic pool of soluble CK18 was released, whereas apoptosis was associated with significant release of caspase-cleaved CK18 fragments. These results suggested that assessments of different forms of CK18 in patient sera could be used to examine cell death modes. Therefore, CK18 was measured in local venous blood collected during operation of patients with endometrial tumors. In most patient sera, caspase-cleaved fragments constituted a minor fraction of total CK18, suggesting that tumor apoptosis is not the main mechanism for generation of circulating CK18. Monitoring of different CK18 forms in peripheral blood during chemotherapy of prostate cancer patients showed individual differences in the patterns of release. Importantly, several examples were observed where the increase of apoptosis-specific caspase-cleaved CK18 fragments constituted only a minor fraction of the total increase. These results suggest that cell death of epithelially derived tumors can be assessed in patient serum and suggest that tumor apoptosis may not necessarily be the dominating death mode in many tumors in vivo.
Prophylactic endoscopic sclerotherapy of oesophageal varices in liver cirrhosis. A multicentre prospective controlled randomised trial in Vienna.
Authors: R Potzi, P Bauer, W Reichel, E Kerstan, F Renner, A Gangl
Journal: Gut (1989)

The effect of prophylactic treatment of oesophageal varices by endoscopic injection sclerotherapy before the first episode of variceal haemorrhage was studied in patients with cirrhosis in a prospective, randomised and controlled multicentre trial. From February 1984 to March 1987 patients with liver cirrhosis and large varices (stage III-IV according to Paquet) were treated and followed up. The sample comprised 87 patients: 45 in the prophylactic treatment and 42 in the control group. After excluding drop outs, 41 patients were treated in each group. Twenty nine per cent of patients in the sclerotherapy group and 34% in the control group had a variceal haemorrhage during the period of observation. There was no significant difference in the distributions of the bleeding free intervals between the sclerotherapy and the control groups. During the follow up period 24% of patients in the sclerotherapy group and 46% in the control group died. The distribution of survival times indicates a tendency towards longer survival of patients with prophylactic sclerotherapy, particularly in those with alcoholic cirrhosis.
Vascular heat shock protein expression in response to stress. Endocrine and autonomic regulation of this age-dependent response.
Authors: R Udelsman, M J Blake, C A Stagg, D G Li, D J Putney, N J Holbrook
Journal: Journal of Clinical Investigation (1993)

Adaptation to stress requires coordinated interactions between the vascular and endocrine systems. Previously we demonstrated that restraint stress induces the expression of the major heat shock protein, HSP70, in the adrenal cortex of the rat. Here we demonstrate that restraint also induces expression of HSP70 in the vasculature. We further demonstrate that the adrenal and vascular responses are differentially regulated: the adrenal response is adrenocorticotropin dependent, whereas the vascular response is under adrenergic control. In addition, the adrenal response is restricted to members of the HSP70 gene family, whereas in vascular tissue the low molecular weight HSP, HSP27, is also induced by restraint. Further characterization of the vascular response revealed that HSP70 induction occurred in both the thoracic and abdominal aortas as well as in the vena cava. However, no HSP70 induction was apparent in the heart or in a wide variety of other tissues examined. In situ hybridization showed that the vascular expression was localized to the aortic smooth muscle cells with minimal expression in the endothelium. Induction of HSP70 mRNA in both the adrenal cortex and aorta was followed by an elevation in HSP70 protein. Maximum HSP70 protein levels were seen within 3-12 h after restraint, but declined thereafter. Stress induced HSP70 expression was dramatically reduced with age, which may explain, in part, the diminished tolerance to stress seen in elderly individuals.
Watchdog launches urgent inspection as 79 women are recalled over cancer test mistakes
Authors: A. O'Dowd
Journal: BMJ (2012)

The main watchdog of the NHS in England has launched an in-depth urgent inspection at a trust after 79 women were recalled for breast clinic appointments amid concerns over breast cancer biopsies carried out there.

Monitor, the independent regulator of NHS foundation trusts, has asked the NHS watchdog the Care Quality Commission (CQC) to carry out what it calls a “deep dive” inspection at Sherwood Forest Hospitals NHS Foundation Trust in Nottinghamshire.

The inspection, which began on 8 October, will look at breast cancer screening, pathology, and clinical governance at the trust.

The trust has invited 79 women to come back for breast clinic appointments to discuss test results relating to breast tissue biopsies and to …
Association of molecular subtypes with Ki-67 changes in untreated breast cancer patients undergoing pre-surgical trials
Authors: S. Gandini, A. Guerrieri-Gonzaga, G. Pruneri, D. Serrano, M. Cazzaniga, M. Lazzeroni, P. Veronesi, H. Johansson, B. Bonanni, G. Viale, A. DeCensi
Journal: Annals of Oncology (2013)
Noninvasive Detection of Target Modulation following Phosphatidylinositol 3-Kinase Inhibition Using Hyperpolarized 13C Magnetic Resonance Spectroscopy
Authors: Christopher S. Ward, Humsa S. Venkatesh, Myriam M. Chaumeil, Alissa H. Brandes, Mark VanCriekinge, Hagit Dafni, Subramaniam Sukumar, Sarah J. Nelson, Daniel B. Vigneron, John Kurhanewicz, C. David James, Daphne A. Haas-Kogan, Sabrina M. Ronen
Journal: Cancer Research (2010)

Abstract Numerous mechanism-based anticancer drugs that target the phosphatidylinositol 3-kinase (PI3K) pathway are in clinical trials. However, it remains challenging to assess responses by traditional imaging methods. Here, we show for the first time the efficacy of hyperpolarized 13C magnetic resonance spectroscopy (MRS) in detecting the effect of PI3K inhibition by monitoring hyperpolarized [1-13C]lactate levels produced from hyperpolarized [1-13C]pyruvate through lactate dehydrogenase (LDH) activity. In GS-2 glioblastoma cells, PI3K inhibition by LY294002 or everolimus caused hyperpolarized lactate to drop to 42 ± 12% and to 76 ± 5%, respectively. In MDA-MB-231 breast cancer cells, hyperpolarized lactate dropped to 71 ± 15% after treatment with LY294002. These reductions were correlated with reductions in LDH activity to 48 ± 4%, 63 ± 4%, and 69 ± 12%, respectively, and were associated with a drop in levels of LDHA mRNA and LDHA and hypoxia-inducible factor-1α proteins. Supporting these findings, tumor growth inhibition achieved by everolimus in murine GS-2 xenografts was associated with a drop in the hyperpolarized lactate-to-pyruvate ratio detected by in vivo MRS imaging, whereas an increase in this ratio occurred with tumor growth in control animals. Taken together, our findings illustrate the application of hyperpolarized 13C MRS of pyruvate to monitor alterations in LDHA activity and expression caused by PI3K pathway inhibition, showing the potential of this method for noninvasive imaging of drug target modulation. Cancer Res; 70(4); 1296–305
Sequence-Based Discovery of<i>Bradyrhizobium enterica</i>in Cord Colitis Syndrome
Authors: Ami S. Bhatt, Samuel S. Freeman, Alex F. Herrera, Chandra Sekhar Pedamallu, Dirk Gevers, Fujiko Duke, Joonil Jung, Monia Michaud, Bruce J. Walker, Sarah Young, Ashlee M. Earl, Aleksander D. Kostic, Akinyemi I. Ojesina, Robert Hasserjian, Karen K. Ballen, Yi-Bin Chen, Gabriela Hobbs, Joseph H. Antin, Robert J. Soiffer, Lindsey R. Baden, Wendy S. Garrett, Jason L. Hornick, Francisco M. Marty, Matthew Meyerson
Journal: New England Journal of Medicine (2013)

Immunosuppression is associated with a variety of idiopathic clinical syndromes that may have infectious causes. It has been hypothesized that the cord colitis syndrome, a complication of umbilical-cord hematopoietic stem-cell transplantation, is infectious in origin.
Gastric emptying following vagotomy and antrectomy and proximal gastric vagotomy.
Authors: H Kalbasi, F R Hudson, A Herring, S Moss, H I Glass, J Spencer
Journal: Gut (1975)

Gastric emptying of solid meals labelled with 129Cs was studied in patients for up to one year after vagotomy and antrectomy or after proximal gastric vagotomy. Significant delay was found one month after vagotomy and antrectomy but this had returned to normal by six months. No delay was found after proximal gastric vagotomy. The effect of posture on gastric emptying was also studied in the same subjects. No significant differences were found between gastric emptying in the supine or sitting positions after solid meals.