tbuckley/cabot-search huggingface dataset:
Abstract P3-02-06: Correlation of BCL-2 and Apoptosis on Circulating Tumor Cells and Breast Cancer Tissue
Authors: V Maranci, DG Thomas, M Brown, TG Budd, G Doyle, DF Hayes, KA Griffith, J. Smeage
Journal: Cancer Research (2010)

Abstract Background: Circulating Tumor Cell (CTC) levels are prognostic markers in metastatic breast cancer (MBC). Further phenotypic characterization of CTC may provide an opportunity for non-invasive evaluation of predictive and prognostic markers. Apoptosis is a common form of chemotherapy-induced cell death. Monoclonal antibody (MAb) M30 recognizes a neo-epitope on fragmented cytokeratin and is a marker of apoptosis. BCL-2 is an anti-apoptotic marker and may predict for resistance to anti-neoplastic therapy. We have previously reported the results of a pilot clinical trial to estimate M30 and BCL-2 expression in CTC from patients with MBC. The current study was performed to correlate the expression of both BCL-2 and M30 in CTC with breast cancer tissue samples. Methods: Of the 85 patients in the original pilot study, 52 (61%) had evaluable tissue available (39 primary and 12 metastatic lesions; one unknown) and were included in this analysis. CTC were collected at baseline and were isolated, enumerated, and phenotypically characterized for M30 and BCL-2 using the CellSearch® System. CTC phenotype is reported as percentage of cells with positive staining. Tissue Microarrays (TMA) were constructed and immunohistochemically stained for M30 (anti-Cytodeath™ M30, Roche) and Bcl-2 (M-0887, DAKO) and scored using the Allred method. Results: Tissue staining for M30 and Bcl-2 were inversely correlated. Of the 52 patients with TMA available for investigation, 22 (42%) had &amp;gt; 5 CTC/7.5 ml whole blood. A positive, but non-significant, correlation was observed between increasing numbers of CTC levels and tissue BCL-2 Allred Score (Spearman r=0.36; p=0.1310). M30 staining was detected in ≥10% of CTC in 20 of the 22 (91%) patients with elevated CTC, while BCL-2 staining was detected in ≥10% of CTC in 19 of the 22 (86%) patients. Little if any correlation was observed between CTC M30 and tissue M30 expression, however CTC BCL-2 was positively correlated with tissue Bcl-2 expression (Spearman r=0.47; p=0.0440). Conclusions: BCL-2 and M30 can be characterized in both CTC and breast cancer tissue. The likelihood of having elevated CTC may be associated with higher BCL-2 expression, and CTC BCL-2 was associated with tissue BCL-2 expression. Although the clinical implications of these findings are unknown, they offer the opportunity for future trials to investigate whether CTC BCL-2 and M30 might be useful to identify patients with cancers that are resistant to standard therapies. Furthermore, CTC BCL-2 and M30 might be monitored in clinical trials of novel, apoptosis-inducing therapeutic agents. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-02-06.
Regulatory Functions of the Vascular Endothelium
Authors: Franklin H. Epstein, John R. Vane, Erik E. Änggård, Regina M. Botting
Journal: New England Journal of Medicine (1990)

William harvey, when studying the circulation of the blood, must have recognized that "In sound and living vessels the blood remains fluid, but it coagulates in dead ones" (Ernst Brücke, 1857). Joseph Lister (1909) provided further evidence for an active role of blood vessels in maintaining the liquidity of blood. The vascular endothelium, which envelops the circulating blood in a continuous monolayer, is mainly responsible for this function.Over the past 20 years numerous other important functions have been discovered. For instance, the outer surface of the endothelial cell contains angiotensin-converting enzyme, which catalyzes the formation of the vasoconstrictor angiotensin . . .
P371 PRIMARY SCLEROSING CHOLANGITIS-INFLAMMATORY BOWEL DISEASE IS ASSOCIATED WITH AN INCREASED FREQUENCY OF POST-TRANSPLANT COLONIC LYMPHOMA
Authors: P.J. Trivedi, T. Wright, J. Robinson, K.-K. Li, D. Burns, B.K. Gunson, D.H. Adams, J. Ferguson, G.M. Hirschfield
Journal: Journal of Hepatology (2014)
Abstract 4115: Depletion of unsaturated fatty acids by stearoyl-coA desaturase inhibition results in endoplasmic reticulum stress-mediated tumor cell death
Authors: Urvashi V. Roongta, Jonathan G. Pabalan, Cindy Wang, Rolf-Peter Ryseck, Joseph Fargnoli, Benjamin Henley, Wen-Pin Yang, Jun Zhu, Malavi Madireddi, Michael Lawrence, Tai W. Wong, Brent A. Rupnow
Journal: Cancer Research (2012)

Abstract Over the past few years, a more detailed picture of the importance of metabolic pathways to the maintenance and progression of human cancers has begun to emerge. In particular, recent studies have implicated lipid biosynthesis and desaturation as a requirement for tumor cell survival. The endoplasmic reticulum-resident Stearoyl CoA Desaturase (SCD) is the rate limiting enzyme that catalyzes conversion of saturated fatty acids to monounsaturated fatty acids, a key step in the fatty acid metabolic network. In the studies reported here, we show that inhibition of SCD1 by siRNA or a small molecule antagonist results in strong induction of apoptosis and growth inhibition when tumor cells are cultured in reduced (2%) serum conditions but has little impact on cells cultured under normal (10%) serum conditions. Consistent with the observed dependence on SCD1, levels of SCD1 protein increased in response to decreasing serum levels. Both induction of SCD1 protein and sensitivity to growth inhibition by SCD1 inhibition could be reversed by supplementing growth media with unsaturated fatty acids. Transcription profiling of cells treated with an SCD inhibitor revealed strong induction of markers of endoplasmic reticulum stress. This finding was confirmed using siRNA specifically targeting SCD1. Underscoring its importance in cancer, SCD1 protein was found to be highly expressed in a large percentage of human cancer specimens. SCD inhibition resulted in tumor growth delay in a human gastric cancer xenograft model. Altogether, these results suggest that unsaturated fatty acids are required for tumor cell survival and that SCD may represent a viable target for the development of novel agents for cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4115. doi:1538-7445.AM2012-4115
House Calls to the Elderly — A Vanishing Practice among Physicians
Authors: Gregg S. Meyer, Robert V. Gibbons
Journal: New England Journal of Medicine (1997)

Despite the growth in other home health care services, the number of house calls by physicians has declined dramatically during this century. We determined the frequency of house calls made by physicians to elderly U.S. patients in 1993 and analyzed the characteristics of the physicians and patients involved.We analyzed a 5 percent random sample of the 1993 Medicare Part B claims data for beneficiaries over the age of 65 who were not enrolled in health maintenance organizations (HMOs). With supplemental information from the Area Resource File and the American Medical Association's Physician Masterfile, we determined how many house calls were made, their cost, and a number of specific characteristics of the physicians and the patients.In our 1993 sample, 36,350 house calls were made to 11,917 of the 1,357,262 patients. When extrapolated to all Medicare beneficiaries over age 65 and not enrolled in HMOs, these figures correspond to 727,000 house calls to 238,340 patients nationwide. We estimated the cost of these house calls to be $63 million. The patients who received house calls from physicians were older than those who did not, were more likely to die within the calendar year, had higher rates of hospitalization, and were more likely to receive care from other home health providers, hospice programs, and skilled-nursing facilities. Patients residing in rural areas and those in areas with high physician-to-population ratios had an increased likelihood of receiving a house call. The physicians who made house calls were more likely than others to be generalists, osteopaths, older, male, board-certified, practicing in the Northeast, and in solo practice.A very small percentage (0.88 percent) of elderly Medicare patients, mainly those who are very sick and near the end of life, receive house calls from physicians.
Case 42-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, David A. Hafler, Raymond A. Sobel
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 41-year-old man was admitted to the hospital because of a question of meningoencephalitis.The patient was well until nine days earlier, in late May, when a severe, diffuse headache occurred, followed by anorexia, nausea, vomiting, and subsequent diarrhea. The temperature rose to 39.4°C, then fell to normal, and rose again over the next few days.Two days before admission the patient entered another hospital, where physical examination showed that the temperature was 39.1°C and the blood pressure 170/110 mm Hg. The patient was acutely ill, mildly dehydrated, and confused. A few scattered petechiae were observed over . . .
A5.7 Screening and simple counselling improved traditional cardiovascular risk factors in patients with early RA
Authors: S Wållberg-Jonsson, J Isacsson, GM Alenius, L Ångström, A Södergren
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> The risk of cardiovascular disease (CVD) is increased in RA. The chronic inflammation appears to potentiate the traditional cardiovascular (CV) risk factors in this context. In 2009, the Swedish Society of Rheumatology (SRF) approved a set of recommendations for screening and primary prevention of CVD in RA (www.svenskreumatologi.se/riktlinjer). Low aerobic capacity is a strong CV risk factor in the general population. In a pilot study, intensive spinning exercise could improve CV risk factors, including aerobic capacity, in RA. The aim of this study was to evaluate the SRF guidelines in a clinical setting and to highlight the relation between physical exercise and CV risk in RA. <h3>Materials and methods</h3> 47 patients with recent onset RA during 2012 at the department of Rheumatology, University Hospital of Umeå, were recruited. Three months after initial diagnosis of RA, patients were examined physically and blood samples were collected for traditional CV risk factors according to the SRF guidelines and CV risk (Heart-SCORE) was calculated. Furthermore, aerobic capacity was tested in a submaximal ergometer test (Åstrand). Additionally, patients received counselling regarding diet, tobacco use and exercise from a nurse and a physiotherapist. The counselling session, based upon national guidelines from The National Food Agency and The Public Health Agency respectively, was performed once per patient for approximately 45 min. A follow-up was performed nine months after the first examination. Results were adjusted for disease activity and disability. Aerobic capacity at baseline was related to SCORE. <h3>Results</h3> Among the 47 included patients, 45 could be evaluated in the follow-up. Mean diastolic blood pressure decreased significantly from 80 mmHg to 77 mmHg (P &lt; 0.05), Scholesterol decreased from 5.5 mmol/l to 5.2 mmol/l (P &lt; 0.05) and mean ApoA1/ApoB from 0.73 to 0.65 (P &lt; 0.05). In all remaining variables (waist circumference, BMI, systolic blood pressure, LDL, HDL, triglycerides, fP-glucose) numerical improvements were observed (P &gt; 0.05). CV risk, as measured by SCORE, was normal. Aerobic capacity was, however, 28 ml O2/kg/min at baseline, a level regarded as high risk for CVD in the general population. Aerobic capacity remained unchanged during follow up (P &gt; 0.05). <h3>Conclusion</h3> Several traditional risk factors of CVD were improved at the nine-month followup. This suggests that this model of screening according to the SRF guidelines and simple counselling according to national guidelines might be useful in primary prevention of CVD in patients with RA. More research is needed regarding aerobic capacity and the value of physical training for CV risk in RA.
Hepatolenticular Degeneration (Wilson's Disease) as a Form of Idiopathic Cirrhosis
Authors: Thomas C. Chalmers, Frank L. Iber, L. Lahut Uzman
Journal: New England Journal of Medicine (1957)

THE appearance of symptoms and signs of liver disease before the onset of neurologic abnormalities in hepatolenticular degeneration has been noted many times in the past,1 2 3 4 5 and there are several reported cases of siblings of patients with known Wilson's disease who died of liver failure without ever having neurologic abnormalities. These have been termed examples of "abdominalle" Wilson's disease by Kehrer6 or "les formes splanchniques" by André.7 It has been customary to refer to this group as the "formes frustes" of the disease, on the assumption that in these patients neurologic abnormalities would have developed if their lives had not . . .
SAT0563 Integrin α11β1 is Induced in Synovial Fibroblasts of Arthritic Htnftg Mice
Authors: K. Rauwolf, D. Beckmann, U. Hansen, D. Kronenberg, D. Gullberg, A. Korb-Pap, T. Pap
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Cell-matrix interactions of synovial fibroblasts (SF) with cartilage components via β1 integrins are of importance not only for cartilage degradation, but also for the persistence of synovial inflammation during rheumatoid arthritis (RA). In this context, integrin α11β1 (ITGA11) is of special interest, because it is mainly expressed in cellular adhesive structures. The loss of ITGA11 leads to disturbed cell-collagen interactions, altered metalloproteinase synthesis and reduced cell proliferation. <h3>Objectives</h3> The underlying mechanisms and the role of ITGA11 in inflammatory arthritis such as RA are of special interest, but currently unknown. <h3>Methods</h3> Hind paws of 14-week-old wild type (wt) and hTNFtg mice, an established mouse model of RA were prepared, paraffin-embedded, sectioned and stained with a specific anti-ITGA11 antibody. Furthermore, wt and hTNFtg SF were isolated and seeded on various extracellular matrix substrates, including collagen I, fibronectin and ternary collagen complexes of articular cartilage followed by an analysis of the ITGA11 expression and its subcellular location by Western blotting and immunofluorescence. The migration capacity of wt, hTNFtg as well as SF isolated from ITGA11<sup>–/–</sup> mice was investigated in a modified scratch assay and by live cell imaging. To analyse the adhesive potential, a published cartilage attachment assay was performed, using isolated IL-1β pre-treated murine femoral head cartilage followed by incubation with wt, hTNFtg and ITGA11<sup>–/–</sup> SF. <h3>Results</h3> In immunohistological stainigs and Western blot analyses, elevated ITGA11 levels were detected in hTNFtg SF as compared to wt SF. This was also confirmed by immunofluorescence, where hTNFtg SF showed an enrichment of focal adhesions with elevated and most prominent expression of ITGA11. ITGA11<sup>–/–</sup> SF showed a modified cytoskeleton and an altered cell morphology after cultivation on the different substrates. The most intriguing differences were detected when using the ternary collagen complexes of articular cartilage. Analyses of the functional assays showed an altered migration rate and adhesion capacity of ITGA11<sup>–/–</sup> SF in comparison to wt SF, as well in the modified scratch assay as in the cartilage attachment assay, even enforced by IL-1β stimulation. <h3>Conclusions</h3> Our data demonstrate that integrin α11β1 is induced under inflammatory conditions such as in hTNFtg mice and contributes to the migratory and adhesive capacity of synovial fibroblasts. Therefore, integrin α11β1<sup>–/–</sup> may be an important target for therapeutic strategies in rheumatoid arthritis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4180
Abstract 1482: Autocrine IL-1α mediates NF-κB activation by oncogenic ras in keratinocytes
Authors: Christophe Cataisson, Roselba Salcedo, Shakeeb Hakim, Andrea Barrett, Lyudmila Lyakh, Giorgio Trinchieri, Stuart H. Yuspa
Journal: Cancer Research (2010)

Abstract Inflammation is a complex process evolved to protect us against pathogens. There is increasing evidence that chronic inflammation can be a major cancer risk. Clinical and epidemiological evidence link inflammation with epithelial skin cancer. One of the best established models linking inflammation with the development of skin cancer is the classical two stage skin carcinogenesis in mice. MyD88 is a crucial intermediate in the signaling from pro-inflammatory receptors. Mice ablated for MyD88 or the IL-1R are resistant to topical skin carcinogenesis and MyD88 deficient ras -transduced keratinocytes form only small tumors in orthotopic grafts. In the skin model the clonal benign tumor defines the phenotype of the initiated cell. High proliferation, resistance to terminal differentiation and altered gene expression are hallmarks of that phenotype. Our previous studies have revealed that Ras activation is sufficient to produce this complete phenotype and fully initiate tumor formation. We recently reported that Ras induction of CXCR2 ligands was mediated by autocrine activation of EGFR and NF-κB and that activation of CXCR2 on ras transformed keratinocytes has both pro-migratory and pro-tumorigenic functions. In MyD88 deficient cells, transduction of ras activates the EGFR loop, but these keratinocytes do not upregulate CXCR2 ligands. Using both genetic and pharmacological approaches we have demonstrated that IL-1α autocrine signaling is activated downstream of EGFR in ras transformed keratinocytes. We further demonstrate that IL-1α is responsible for NF-κB mediated activation of CXCR2 ligands in those keratinocytes. Collectively, those results demonstrate that ras activation converts normal keratinocytes to a tumor phenotype through a series of feedback signals that provide therapeutic opportunities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1482.
Tc-99m Mercaptoacetyltriglycine Clearance
Authors: M Bocher, Y Shrem, A Tappiser, M Klein, D Schechter, A Taylor, R Chisin
Journal: Clinical Nuclear Medicine (2001)

To compare the accuracy of three camera-assisted methods for the measurement of Tc-99m mercaptoacetyltriglycine (MAG3) clearance.MAG3 renal scintigraphy was performed in 21 adults with different degrees of renal function. Posterior views were obtained that included the heart and the kidneys in the camera field of view. The syringe for injection was imaged before and after injection. Blood samples were drawn 24 and 43 minutes after injection and plasma radioactivity was measured. Three camera-assisted techniques to measure MAG3 clearance were tested: 1) Biexponential fitting of the left ventricular curve, normalized to plasma activity at 24 minutes; 2) calculation of clearance by relating the integral of the plasma curve (normalized to plasma activity) to the kidney activity using the Rutland-Patlak space method; and 3) a regression equation measuring clearance from the percentage of the injected dose accumulating in the kidneys during the 1- to 2.5-minute period. The camera-assisted clearances were compared with the single-sample MAG3 clearances calculated using the Russell equation. Linear regression analysis was used to measure the correlation between the camera-based methods and the single-sample techniques.Correlation with r > 0.900 was found for all three techniques. The difference in correlation coefficients between the three methods was not significant; however, the regression line of method 3 was significantly closer to the line of identity (P = 0.005).Method 3 most closely fits the line of identity and is probably the most practical because no blood sample is needed.
At a Loss
Authors: Joseph F. Merola, Paiman Peter Ghoroghchian, Martin A. Samuels, Bruce D. Levy, Joseph Loscalzo
Journal: New England Journal of Medicine (2012)

A 31-year-old woman was admitted to the hospital after being unable to eat or drink for 1 week. She had had nausea, vomiting, and abdominal discomfort, as well as episodes of crampy epigastric pain with vomiting and intermittent chills and sweats, for 8 months.
ATRIAL MYOCARDIAL INFARCTION INDUCED DURING ELECTIVE PERCUTANEOUS CORONARY INTERVENTION
Authors: Jesus Álvarez-Garcia, Miquel Vives-Borrás, Andreu Ferrero-Gregori, Montserrat Pérez-Cuellar, Dabit Arzamendi, Beatriz Vaquerizo, Jordi Ordoñez-Llanos, Antonio Serra, Juan Cinca
Journal: Journal of the American College of Cardiology (2015)
Abstract 1924: The paraproteins of patients with familial MGUS / multiple myeloma (MM) target family-specific antigens: Experience with paratarg-7 and paratarg-8
Authors: Sandra Grass, Klaus-Dieter Preuss, Aleksandra Wikowicz, Stephan Thome, Dennis D. Weisenburger, Vinetta Witt, Jane Lynch, Ulrich Mahlknecht, Michael Pfreundschuh, Henry Lynch
Journal: Cancer Research (2010)

Abstract Background: Antigenic targets of paraproteins in monoclonal gammopathy of undetermined significance (MGUS) and multiple Myeloma (MM) might play a role in the pathogenesis of these neoplasms by chronic antigenic stimulation. However, very few antigens have been identified, of which most were specific for one individual paraprotein only. In contrast, we recently described paratarg-7 (P-7), a protein of unknown function which is expressed in all human tissues as the target of 15% of IgA and IgG paraproteins in MGUS and MM (Grass et al. Lancet Oncology 2009; 10: 950-956). MGUS/MM patients with P-7 specific paraproteins all carry a hyperphosphorylated variant of P-7 (pP-7), which is inherited in a dominant fashion, explaining pP7-posistive cases of familial MGUS/MM. pP-7 is the first molecularly defined autosomal-dominant risk factor for MGUS/MM and is associated with the highest odds ratio (7.9) of all risk factors for MGUS/MM known to date. Since not all cases of familial MGUS/MM have a P-7 specific paraprotein, we set out to identify the antigenic targets of paraproteins in cases of familial MGUS/MM that are not carriers of pP-7. Methods: The sera of 28 members of a family with familial MGUS/MM (Lynch et al. N Engl J Med 2008;359:152-157) were tested for antibody reactivity against antigens represented in a fetal brain derived protein macroarray using a modified SEREX approach (Preuss et al. International J. Cancer 2009;125, 656-661). Results: Sera from 28 family members were analyzed. The sera of all 6 family members affected by MGUS (n=3) and MM (n=3) reacted with paratarg-8, which is encoded by the ATG13 gene, a member of the “autophagy regulatory complex” family of genes. The titers ranged from 1:107 to 1:108. No antibody reactivity was detected in the sera of non-affected family members nor in the paraproteins from &amp;gt;300 other patients tested. Conclusions: The paraproteins of members affected by familial MGUS/MM are directed against family-specific antigenic targets, suggesting that the genetic background shared by these patients entertains a chronic auto-immune response. Paratarg-7 and paratarg-8 are the first family-specific antigens that have been molecularly defined to date. Whether the antigen/paraprotein interaction is an epiphenomeon or invovled in the pathogenesis of familial cases of MGUS/MM can now be addressed using specific molecular tools. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1924.