tbuckley/cabot-search huggingface dataset:
Plasma Markers for Identifying Patients with Metastatic Melanoma
Authors: Harriet M. Kluger, Kathleen Hoyt, Antonella Bacchiocchi, Tina Mayer, Jonathan Kirsch, Yuval Kluger, Mario Sznol, Stephan Ariyan, Annette Molinaro, Ruth Halaban
Journal: Clinical Cancer Research (2011)

With the rising incidence of melanoma, more patients are undergoing surveillance for disease recurrence. Our purpose was to study levels of proteins that might be secreted in the blood of patients with metastatic melanoma that can be used for monitoring these individuals.Genome-wide gene expression data were used to identify abundantly expressed genes in melanoma cells that encode for proteins likely to be present in the blood of cancer patients, based on high expression levels in tumors. ELISA assays were employed to measure proteins in plasma of 216 individuals; 108 metastatic melanoma patients and 108 age- and gender-matched patients with resected stage I/II disease split into equal-sized training and test cohorts.Levels of seven markers, CEACAM (carcinoembryonic antigen-related cell adhesion molecule), ICAM-1 (intercellular adhesion molecule 1), osteopontin, MIA (melanoma inhibitory activity), GDF-15 (growth differentiation factor 15), TIMP-1 (tissue inhibitor of metalloproteinase 1), and S100B, were higher in patients with unresected stage IV disease than in patients with resected stage I/II disease. About 81% of the stage I/II patients in the training set had no marker elevation, whereas 69% of the stage IV patients had elevation of at least one marker (P < 0.0001). Receiver operating characteristic curves for the markers in combination in these two patient populations had an area under curve (AUC) of 0.79 in the training set and 0.8 in the test set. A CART (Classification and Regression Trees) model developed in the training set further improved the AUC in the test set to 0.898.Plasma markers, particularly when assessed in combination, can be used to monitor patients for disease recurrence and can compliment currently used lactate dehydrogenase and imaging studies; prospective validation is warranted.
Management of Carotid Stenosis in Women
Authors: SreyRam Kuy, Gary R. Seabrook, Peter J. Rossi, Brian D. Lewis, Anahita Dua, Kellie R. Brown
Journal: JAMA Surgery (2013)

The management of carotid stenosis in women remains a topic of controversy. In this review article, we aimed to define carotid disease burden in women, review outcomes of carotid endarterectomy and carotid artery stenting in women, discuss differences in practice patterns based on sex, and provide guidelines for management of women with carotid stenosis. Symptomatic women with high-grade stenosis derive benefit from carotid endarterectomy, although they have different risk profiles than men and are often not taking appropriate medical therapy. Women with asymptomatic carotid artery stenosis have less stroke risk reduction with CEA than their male counterparts; therefore, they should be screened for other treatable risk factors for stroke, with the institution of lifestyle changes and the appropriate medical therapy. After medical optimization, the decision to proceed with CEA in asymptomatic women must be made by carefully assessing that the benefits of stroke risk reduction outweigh perioperative risks.
Myocardial Ischemia in Coronary Disease
Authors: Andrew P. Selwyn, Peter Ganz
Journal: New England Journal of Medicine (1988)

In this issue of the Journal, Rozanski and colleagues offer evidence that different forms of mental stress can provoke transient myocardial ischemia in patients with coronary artery disease.1 The performance of mathematical calculations and formal psychological testing (the Stroop color–word test) both produced moderate increases in heart rate and blood pressure and resulted in myocardial ischemia as assessed by the development of wall-motion abnormalities, ST-segment changes, or angina pectoris. Giving a speech to an audience about personal matters produced more substantial increases in double product (heart rate times systolic blood pressure) and evidence of even more extensive ischemia. Finally, . . .
Serum High-Sensitivity C-Reactive Protein Levels Are Associated With High Risk of Development, Not Progression, of Diabetic Nephropathy Among Japanese Type 2 Diabetic Patients: A Prospective Cohort Study (Diabetes Distress and Care Registry at Tenri [DDCRT7])
Authors: Yasuaki Hayashino, Tsuyoshi Mashitani, Satoru Tsujii, Hitoshi Ishii
Journal: Diabetes Care (2014)

To assess the prospective association between baseline serum hs-CRP concentration and the subsequent risk of development or progression of diabetic nephropathy.Longitudinal data were obtained from 2,518 patients with type 2 diabetes registered in a Japanese diabetes registry. To assess the independent correlations between serum baseline hs-CRP and either the development or progression of diabetic nephropathy 1 year later, the Cox proportional hazards model was used and adjusted for potential confounders.The mean patient age, BMI, and HbA1c level were 66.1 years, 24.6 kg/m2, and 7.5% (57.6 mmol/mol), respectively. Baseline serum hs-CRP levels were significantly associated with the urinary albumin-to-creatinine ratio at baseline (P < 0.001). Multivariable adjusted hazard ratio for the development from normoalbuminuria to microalbuminuria was 1.31 (95% CI 0.80-2.17; P = 0.286), 1.55 (1.16-2.08; P = 0.003), and 1.57 (1.22-2.03; P = 0.001), respectively, for the second, third, and fourth quartiles of serum hs-CRP levels, showing a statistically significant linear trend across categories (P < 0.001). We did not observe a significant association between hs-CRP levels and the subsequent risk of diabetic nephropathy progression (P for trend = 0.575).Serum hs-CRP levels, independent of possible confounders, were associated with a subsequent risk of developing, not progressing, diabetic nephropathy in type 2 diabetic patients. Serum hs-CRP may be useful for predicting the future risk of developing diabetic nephropathy.
Unscheduled DNA synthesis in normal human skin after single and combined doses of V-A, UV-B and UV-A with methoxsalen (PUVA)
Authors: HERBERT HONIGSMANN, KURT F. JAENICKE, WILHELM BRENNER, WALTRAUT RAUSCHMEIER, JOHN A. PARRISH
Journal: British Journal of Dermatology (1981)

The aim of this study was to measure unscheduled DNA synthesis (UDS) by autoradiography in normal human skin (I) after high dose UV-A, (2) after low dose UV-A applied before or after erythemogenic doses of UV-B, (3) after high dose PUVA and (4) after therapeutic doses of PUVA applied before and after erythemogenic doses of UV-B. Single high dose UV-A exposure induced roughly 60% of the amount of UDS induced by equally erythemogenic doses of UV-B. Single low dose UV-A exposure did not induce UDS, nor did it significantly alter the amount of UV-B induced UDS when combined with UV-B exposure. Single high dose PUVA did not lead to UDS and had no influence on UV-B induced UDS when combined with UV-B exposure. Our findings indicate: (I) erythemogenic doses of UV-A induce a considerable DNA excision repair; (2) low dose UV-A neither augments UV-B induced DNA repair nor does it inhibit the repair process; (3) no UDS was shown to occur after eight high or therapeutic doses of PUVA. This was unexpected since psoralen-DNA monoadducts have been shown to be repairable by a mechanism similar to excision repair of pyrimidine dimers. It is therefore assumed that PUVA as performed for therapeutic purposes either preferentially induced interstrand crosslinks not repairable via the classical repair mechanism or the repair of monoadducts was below resolution in this study; (4) therapeutic PUVA doses apparently do not interfere with excision repair of UV-B induced DNA lesions.
Family Consent to Orders Not to Resuscitate-Reply
Authors: J. Chris Hackler
Journal: JAMA (1991)

<h3>In Reply.—</h3> We thank Drs Steffen and Paradis for their letters supporting our recent article on hospital resuscitation policies. Dr Paradis agrees that policies requiring family agreement to DNR orders sometimes create serious problems for patients and families. He then goes beyond our arguments to considerations of equity or justice toward other patients. We believe that these concerns augment our case and are worthy of further discussion, but we also think that considerations of patient best interests and of the proper role of surrogates are sufficient to justify our proposal. We agree with Dr Steffen that a decision that CPR would be futile should not be based solely on the diagnosis but rather on a case-by-case review of all the medical evidence. Dr Doukas disagrees with our other proposal, that hospital policy not require that futile CPR always be discussed with patients or families. He points, as do Youngner<sup>1</sup>
Enhanced antigen immunogenicity induced by bispecific antibodies.
Authors: D P Snider, A Kaubisch, D M Segal
Journal: The Journal of Experimental Medicine (1990)

The binding of protein antigens to APC with heterocrosslinked bispecific antibodies (HBAs) enhances their processing and presentation to Th cells in vitro. Here we have asked whether HBAs could also increase immune responses in vivo. We immunized mice with hen egg lysozyme (HEL) in the presence or absence of HBA, and followed antibody production after the primary challenge and after a secondary boost. We found that HBAs that bind antigen to MHC class I or II molecules, to Fc gamma R, but not to surface IgD, enhance the immunogenicity of HEL. HBAs that bound HEL to MHC class II molecules, for examples, decreased the amount of antigen required to elicit a primary anti-HEL antibody response in mice by 300-fold, and the amount required to prime for a secondary response by 10(3)- to 10(4)-fold. In fact, HBAs were as effective as IFA in generating antibody responses. Since adjuvants cannot be used in humans, HBAs could prove useful for immunizing people, especially in cases where, due to scarcity or toxicity, minute doses of antigen must be used.
Implications of the incidence of influenza-like illness in nursing homes for influenza chemoprophylaxis: descriptive study
Authors: Richard Harling, Andrew Hayward, John M Watson
Journal: BMJ (2004)

Influenza causes substantial morbidity and mortality among nursing home residents. In September 2003, the National Institute for Clinical Excellence (NICE) issued guidelines for the use of neuraminidase inhibitors for flu prophylaxis.1 These state that oseltamivir should be given to all residents in nursing and residential homes each time a single case of influenza-like illness (ILI) is recognised in a resident or staff member and when flu is known to be circulating in the community. Oseltamivir is effective for flu prophylaxis in young healthy people, but there is little evidence of its effectiveness in elderly nursing home residents.2 Estimates of its cost effectiveness vary widely. Last winter, from 3 November 2003 to 25 January 2004, we conducted surveillance for ILI in a chain of nursing homes across England. The data allow an analysis of the implications of implementing the NICE guidelines.

Nurses in 48 nursing homes recorded data daily about ILI in residents on …
US and International Standards for Resuscitators
Authors: John Hedley-Whyte
Journal: JAMA (1989)

<h3>To the Editor. —</h3> Representatives of the US Department of Defense have informed us that there are incompatibilities in the requirements for manually triggered oxygen-powered resuscitators in the Standards and Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care,<sup>1(p2905)</sup>American Society for Testing and Materials US Standard F 920,<sup>2</sup>and the recently published International Standard 8382.<sup>3</sup>At a meeting of American Society for Testing and Materials Committee F-29.03.03 held in Boston, Mass, on January 26, 1989, and attended by representatives of the Department of Defense and of the Emergency Cardiac Care Committee of the American Heart Association, it was unanimously decided that until Standard F 920 can be brought into accord with International Standard 8382<sup>3</sup>and the American Heart Association's Standards and Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care,<sup>1</sup>the International Standard 8382 should be used as the specific reference for manually triggered gas-powered resuscitators. All
Clinical resolution of vemurafenib-induced squamous cell carcinoma with topical 5-fluorouracil
Authors: R. Sinha, J. Larkin, L. Fearfield
Journal: British Journal of Dermatology (2014)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Vemurafenib was the first BRAF inhibitor to be licensed for the treatment of metastatic melanoma. It is associated with a spectrum of cutaneous toxicities including benign and malignant squamous proliferations.1 2 Treatment of these lesions can be challenging as the lesions may be eruptive and frequent. Effective skin‐preserving therapeutic measures would therefore be favourable. A 67‐year‐old woman with a background of breast adenocarcinoma presented with a left groin mass in January 2012. Macroscopic histological examination showed a large metastatic deposit within the lymph node comprised of nests of highly pleomorphic, atypical epithelioid discohesive cells, with areas of necrosis. Immunohistochemistry showed the tumour cells to be diffusely positive for S100 and MelanA, and negative for CD45. The histological appearance together with the immunoprofile was consistent with metastasis. No primary lesion was found. Subsequent inguinal lymph node dissection was performed, with five of nine nodes involved. Recurrent nodal disease was identified and the patient was found to harbour the BRAF V600E mutation (cobas® 4800 BRAF V600 mutation kit; Roche Diagnostics Limited, Burgess Hill, U.K.).
Antibody to phosphatidylethanolamine in a patient with lupus anticoagulant and thrombosis.
Authors: H L Staub, E N Harris, M A Khamashta, G Savidge, W H Chahade, G R Hughes
Journal: Annals of the Rheumatic Diseases (1989)

Most patients with lupus anticoagulant (LA) activity have coincident antibodies to a group of negatively charged phospholipids, and its is suggested that LA and anticardiolipin tests detect antibodies with overlapping specificities. Some discordance between the two assays has been described, however. One patient presenting with severe thrombotic disease (recurrent deep vein thrombosis, pulmonary embolism, inferior venocaval obstruction, myocardial infarction, and digital gangrene) showed strong LA activity in February 1987. An enzyme linked immunosorbent assay (ELISA) showed no binding to the negatively charged phospholipids cardiolipin, phosphatidylserine, and phosphatidic acid, but binding to zwitterionic phosphatidylethanolamine (PE) was demonstrated. Inhibition studies and affinity purification confirmed this finding. Interestingly, the serum did not bind to the kaolin cephalin clotting time reagent when used as antigen in an ELISA. The pathogenic significance of anti-PE antibodies and their relation to LA remains to be clarified. Further studies of the occurrence of anti-PE antibodies in patients with LA activity who have negative anticardiolipin tests are suggested.
Abstract SY09-01: Control of class III PI 3-kinase in autophagy and cancers
Authors: Marta Lipinski, Tsuyoshi Furuya, Minsu Kim, Greg Hoffman, Aylwin Ng, John Blenis, Ramnik Xavior, Junying Yuan
Journal: Cancer Research (2011)

Abstract Autophagy, a lysosome-dependent catabolic process involved in the turnover of cellular components, mediates normal homeostasis during development and protects multicellular eukaryotes from neurodegeneration, cancer and other diseases. However, the mechanisms regulating autophagy under normal nutritional conditions most frequently encountered by cells in organisms under physiological conditions remain unknown. Our recent studies highlight an important role of class III PI 3-kinase in regulating autophagy. First, we show that phosphorylation of Vps34 by Cdk1 and Cdk5 negatively regulate type III PI 3-kinase and production of PI3P in mitotic cells and in neurodegeneration. Second, we show that multiple growth factors negatively regulate the activity of type III PI 3-kinase. In an image-based genome-wide human siRNA screen, we show that upregulation of autophagy by only 14 (6.4%) of the identified hit genes was accompanied by downregulation of activity of mTORC1, an essential regulator of starvation-induced autophagy. On the other hand, we found that 110 (50.2%) of the hit genes, including a group of growth factors and cytokines, regulate autophagy by targeting the type III PI 3-kinase. These cytokines inhibit the type III PI 3-kinase through multiple pathways. Third, we show that ROS may have a general signaling function in autophagy. We uncovered a large group of genes (117, or 54% of all genes tested) whose knockdown led to vesicular translocation of LC3-GFP in the absence but not the presence of antioxidant, suggesting that ROS are required for the induction of autophagy. Finally, using a small-molecule inhibitor that promotes the degradation of class III PI 3-kinase, we show that successful targeting this pathway can lead to selective cancer cell death. Our study suggests that the type III PI 3-kinase integrates diverse signals to regulate cellular levels of autophagy. Thus, autophagy and cell proliferation may represent two alternative cell fates that are regulated in a mutually exclusive manner, implicating autophagy as a common tumor suppression mechanism downstream of multiple signaling pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY09-01. doi:10.1158/1538-7445.AM2011-SY09-01
MULTI-MODALITY IMAGING-VISIBLE REPORTER GENE LABELED HUMAN MESENCHYMAL STEM CELLS FOR TREATING ISCHEMIC ARTERIAL DISEASES
Authors: Yingli Fu, Dorota Kedziorek, Ronnie Mease, Ying Chen, Gary Huang, Yi Xu, Dara L. Kraitchman
Journal: Journal of the American College of Cardiology (2011)
Considerations in the design of an environmental specimen bank: experiences of the National Biomonitoring Specimen Bank Program.
Authors: S A Wise, B J Koster
Journal: Environmental Health Perspectives (1995)

Since 1979 the National Institute of Standards and Technology (NIST) has been involved in environmental specimen banking activities as part of the National Biomonitoring Specimen Bank (NBSB). These activities have focused on the development of procedures for the collection, processing, analysis, and long-term storage of a variety of environmental specimens including: human liver, mussels and oysters, fish tissue (liver and muscle), marine mammal tissues (blubber, liver, and kidney), and marine sediments. The experiences of the NBSB can provide valuable information to assist in the design of new specimen bank efforts. Based on the experiences of the NBSB, the issues that should be addressed in the design and operation of a valid specimen bank program are presented.
The value of in vivo electrophysiological measurements for monitoring functional adaptation after massive small bowel resection in the rat.
Authors: M C Wolvekamp, N M Durante, M A Meyssen, J Bijman, H R de Jonge, R L Marquet, E Heineman
Journal: Gut (1993)

The process of functional adaptation after extensive small bowel resection is complex and imprecisely understood. In vivo electrophysiological measurements for monitoring the functional adaptive process after massive small bowel resection in Brown-Norway rats were evaluated. Rats underwent either a sham operation (SH) or a 90% small bowel resection (SB). Standard rat chow was fed in unlimited quantities. At three or 10 weeks after operation, jejunal and ileal transepithelial potential differences (PD, mV) were determined. Electrogenic ion transport in the villus was measured after glucose (sodium coupled active glucose absorption; PD-glu) and in the crypt, after theophylline infusion (theophylline stimulated chloride secretion; PD-theo). Biopsies were taken simultaneously. Each experimental group consisted of three to five animals. At three weeks the PD-theo and PD-glu in SB rats were significantly lower than in SH rats in both jejunal and ileal segments. At 10 weeks PD-theo and PD-glu were significantly diminished in the jejunal segment of the SB rats compared with the SH rats. The values of PD-theo and PD-glu in the ileal segments were, however, no longer different between the two groups. Three and 10 weeks after operation the length of the villi in the SB group was increased significantly compared with the SH controls. These results indicate that in the early phase of adaptation in vivo electrophysiological variables do not correlate with histological changes in the SB rats. This might be due to cell immaturity resulting from an increased rate of cell turnover or lack of intercellular tight junctions. This hypothesis is supported by a recovery of PD responses in the ileum 10 weeks after resection.
Polypoid Lesions of the Gastrointestinal Tract
Authors: Joel W. Baker
Journal: JAMA (1965)

Here is a timely monograph which leads the clinician through the confusion created by opposing views on the significance of adenomatous polyps of the colon. The author has ably summarized, both succinctly and fairly, the opposing arguments and has in addition given an editorial statement of his own considered opinion. Presented in a well organized manner, the book is a valuable contribution which serves to clarify the clinical problem involved and which obviously represents a tremendous amount of review work. In this concise volume, the reader will gain an up-to-date and clearer understanding of the possible relationships between adenomatous polyps, papillary adenomas, and polypoid carcinoma. Equally well covered are all polypoid lesions found along the gastrointestinal tract, including multiple and familial polyposis, pseudoinflammatory polyps, carcinoid polyps of the rectum, lymphoid polyps, juvenile polyps, etc. Also of particular value, and well represented, is the<i>surgical management</i>of polypoid lesions of the
Linitis Plastica of the Rectum As a Clinical Presentation of Metastatic Lobular Carcinoma of the Breast
Authors: Filippo Venturini, Valentina Gambi, Stefano Di Lernia, Angelo Vanzulli, Manuela Bramerio, Katia Bencardino, Alessio Amatu, Tiziana Cipani, Edoardo Forti, Emiliana Tarenzi, Andrea Sartore-Bianchi, Raffaele Pugliese, Salvatore Siena
Journal: Journal of Clinical Oncology (2014)