tbuckley/cabot-search huggingface dataset:
Colon Cancer Growth and Dissemination Relies upon Thrombin, Stromal PAR-1, and Fibrinogen
Authors: Gregory N. Adams, Leah Rosenfeldt, Malinda Frederick, Whitney Miller, Dusty Waltz, Keith Kombrinck, Kathryn E. McElhinney, Matthew J. Flick, Brett P. Monia, Alexey S. Revenko, Joseph S. Palumbo
Journal: Cancer Research (2015)

Thrombin-mediated proteolysis is a major determinant of metastasis, but is not universally important for primary tumor growth. Here, we report that colorectal adenocarcinoma represents one important exception whereby thrombin-mediated functions support both primary tumor growth and metastasis. In contrast with studies of multiple nongastrointestinal cancers, we found that the growth of primary tumors formed by murine and human colon cancer cells was reduced in mice by genetic or pharmacologic reduction of circulating prothrombin. Reduced prothrombin expression was associated with lower mitotic indices and invasion of surrounding tissue. Mechanistic investigations revealed that thrombin-driven colonic adenocarcinoma growth relied upon at least two targets of thrombin-mediated proteolysis, protease-activated receptor-1 (PAR-1) expressed by stromal cells and the extracellular matrix protein, fibrinogen. Colonic adenocarcinoma growth was reduced in PAR-1-deficient mice, implicating stromal cell-associated PAR-1 as one thrombin target important for tumor outgrowth. Furthermore, tumor growth was dramatically impeded in fibrinogen-deficient mice, offering the first direct evidence of a critical functional role for fibrinogen in malignant tumor growth. Tumors harvested from fibrinogen-deficient mice displayed a relative reduction in cell proliferative indices, as well as increased tumor necrosis and decreased tumor vascular density. Collectively, our findings established a functional role for thrombin and its targets PAR-1 and fibrinogen in the pathogenesis of colonic adenocarcinoma, supporting tumor growth as well as local invasion and metastasis.
IGKC and Prognosis in Breast Cancer–Response
Authors: Theresa L. Whiteside, Soldano Ferrone
Journal: Clinical Cancer Research (2012)

We are appreciative of the comments made by Schmidt and colleagues in a letter responding to our CCR Translations article ([1][1]), in which we discussed their data recently published in Clinical Cancer Research ([2][2]). The purpose of our CCR Translations was to emphasize the importance of the
Re: Incidence of Adenocarcinoma of the Esophagus Among White Americans by Sex, Stage, and Age
Authors: Chun-Ru Chien, Chen-Yuan Lin, Chih-Yi Chen
Journal: JNCI Journal of the National Cancer Institute (2009)

We read the excellent study by Brown et al. ( 1 ) in your great Journal. This study provides consistent evidence that the incidence of adenocarcinoma of the esophagus has been increasing substantially in the Western world for the past 20 years ( 1 , 2 ). We would like to provide some complementary data from the point of view of the Far East that indicate that this trend may not be universal. Shibata et al. ( 3 ), in their populationbased study, reported no dramatic increase in the incidence of adenocarcinoma of the esophagus in Japan from 1993 to 2001. Similar results have also been reported in Hong Kong ( 4 ) and Korea ( 5 ). Using methodology similar to that of Shibata et al. ( 3 ) and up-to-date data from the Cancer Registry of Taiwan, we found a similar trend in Taiwan. The age-standardized incidence rate for adenocarcinoma of the esophagus in Taiwan remained relatively stable from 1996 to 2005 among both men and women, with the Taiwan population in year 2005 as the reference population. The proportion of adenocarcinoma among all patients with esophageal cancer was also persistently low in these regions ( Table 1 ). Obesity is a common problem in the Western counties . It may lead to increasing intra-abdominal pressure with subsequent gastroesophageal reflux disease and Barrett’s esophagus ( 1 , 3 ). These conditions have been assumed to be one of the main reasons for the increasing incidence of adenocarcinoma of the esophagus in Western countries ( 1 , 2 ). The decreasing frequency of Helicobacter pylori infection with subsequent gastric atrophy may also partly explain this trend in incidence ( 1 , 2 ). However, although the lifestyle in regions of the Far East is becoming westernized and possible similar trends in these risk factors were noted in these regions ( 3 , 4 , 6 , 7 ), no dramatic increase in the incidence of adenocarcinoma of the esophagus has been observed in these regions ( Table 1 ). Whether this observation is associated with some unobserved regional and/or ethnic etiology warrants further study.
CEREBRAL ABSCESS FOLLOWING ACUTE TONSILLITIS
Authors: E. G. Housden
Journal: BMJ (1929)

THE sequence inidicated in the above title is suifficiently rare to make the following ease wortlh recording.No reference could be found in the literiature of the suibject to a case of cerebral abscess secondary to throa-t coniditions, although foci of sepsis in the lunigs, cardiac valves, liver, and bones are menitionied as posLsible causes.Otlher remiiark- able featur es of this case were the patienit's apparent complete reeovery after a-n illnless of six weeks' duration, in which lie had for a period of a moutlh shown unmistak- able signs of ani in-itracraniial abscess, anid theni his comllparatively sudden death.A plunmber, a healthy, well-built lad of 18, witlh nio hiistory of previous illniess or ear trouble, was first seenl Onl Janiuary 11tlh.
What's in a goal? The role of motivational relevance in cognition and action
Authors: Baruch Eitam, E. Tory Higgins
Journal: Behavioral and Brain Sciences (2014)

Abstract We argue that it is possible to go beyond the “selfish goal” metaphor and make an even stronger case for the role of unconscious motivation in cognition and action. Through the relevance of a representation (ROAR) framework, we describe how not only value motivation, which relates to “selfish goals,” but also truth motivation and control motivation impact cognition and action.
Independent insertion of Alu elements in the human ribosomal spacer and their concerted evolution.
Authors: I L Gonzalez, R Petersen, J E Sylvester
Journal: Molecular Biology and Evolution (1989)

A 2,700-bp segment of human ribosomal DNA (rDNA) spacer upstream of the rRNA promoter contains a set of four Alu elements, two in the direction of rRNA transcription and two in the opposite orientation. We report and compare the sequences of these Alu elements found in three rDNA clones and seek to determine the origin of the cluster, either from a single insertion followed by duplications or from multiple simultaneous or independent insertions. The high (20%-27%) divergence among members of a set and the lack of similarity/complementarity of sequences flanking different members of the set demonstrate the independent insertion of each of the four Alu elements into A-rich sequences on the appropriate strand of the rDNA. We also demonstrate that the Alu sets found in different rDNA repeats are subject to concerted evolution, yielding divergences of only 0.4%-3% between Alu elements in equivalent positions. However, the pairs of adjacent similarly oriented Alu elements do not show reduced divergence, indicating that there is no recombination or gene conversion between similarly oriented but not equivalently positioned Alu elements. Finally, crossing-over must occur in the rDNA junction region between Alu element 3 and the nonribosomal sequences at the telomere end of the acrocentric chromosome, so that the Alu elements of the terminal rDNA repeats and the terminal repeats themselves evolve in concert with the rDNA repeats located internally in the tandem array.
Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis
Authors: H Yamada, Y Nakashima, K Okazaki, T Mawatari, J-I Fukushi, N Kaibara, A Hori, Y Iwamoto, Y Yoshikai
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> Recent animal studies have revealed critical roles of interleukin (IL)17, which is produced by a newly identified subset of helper T cells, Th17 cells, in the development of autoimmune diseases including arthritis. However, in human rheumatoid arthritis (RA), detailed characteristics and the prevalence of Th17 cells are unclear. <h3>Methods:</h3> Peripheral blood mononuclear cells (PBMC) were obtained from 123 patients with RA and 28 healthy controls. Mononuclear cells were also prepared from synovial membrane or synovial fluid of 12 patients with RA. IL17 (IL17A) positive T cells were identified by a flow cytometer after ex vivo stimulation with phorbol myristate acetate and ionomycin. Disease activity was assessed with the 28-joint Disease Activity Score (DAS28). <h3>Results:</h3> IL17 positive cells were detected in CD45RO+ CD4 T cells. Most IL17 positive T cells produced neither interferon (IFN)γ nor IL4, but tumour necrosis factor (TNF)α similar to murine Th17 cells. The frequency of Th17 cells was neither increased in RA nor correlated with DAS28. Unexpectedly, the frequency of Th17 cells was significantly decreased in the joints compared with PBMC of the same patients with RA, whereas Th1 cells were more abundant in the joints than in PBMC. <h3>Conclusions:</h3> We could not obtain evidence that positively supports predominance of Th17 cells in RA. Further careful investigation is necessary before clinical application of IL17-targeting therapy.
Poor Glucose Control in the Year Before Admission as a Powerful Predictor of Amputation in Hospitalized Patients With Diabetic Foot Ulceration
Authors: Giuseppe Lepore, Maria L. Maglio, Carlo Cuni, Alessandro R. Dodesini, Italo Nosari, Bruno Minetti, Roberto Trevisan
Journal: Diabetes Care (2006)

Although there is a strong association between lower-extremity amputation (LEA) and HbA1c (A1C) in diabetic patients (1,2), little information is available on glucose control in the period preceding and following LEA (3). Our objective was to evaluate the predictors of LEA and to examine the role of blood glucose control during the year before and the year after admission. A total of 122 diabetic patients (82 men and 40 women aged 69.7 ± 10.9 years, disease duration 19.7 ± 10.4 years) consecutively admitted for diabetic foot ulcers to the Medicine Department of United Hospitals of Bergamo between January 2003 and December 2004 were enrolled in our observational study and assigned to one …
Elastosis in diverticular disease of the sigmoid colon.
Authors: J Whiteway, B C Morson
Journal: Gut (1985)

Diverticular disease of the sigmoid colon is an increasingly common clinical problem in the ageing population of western industrialised countries but the mechanism by which the disease develops remains unknown. The muscular abnormality is the most striking and consistent feature and this has been studied by light and electron microscopy in 25 surgical specimens of uncomplicated diverticular disease and in 25 controls. This is the first ultrastructural study of human colonic muscle to be published and shows that the muscle cells in diverticular disease are normal; neither hypertrophy nor hyperplasia is present. There is, however, an increase in the elastin content of the taeniae coli by greater than 200% compared with controls: elastin is laid down between the muscle cells and the normal fascicular pattern of the taeniae coli is distorted. There is no alteration in the elastin content of the circular muscle. As elastin is laid down in a contracted form, this elastosis may be responsible for the shortening or 9contracture9 of the taeniae which in turn leads to the characteristic concertina-like corrugation of the circular muscle. Such a structural change could explain the altered behaviour of the colon wall in diverticular disease and its failure to change on treatment with bran.
Creation of a Biological Pacemaker by Cell Fusion
Authors: Hee Cheol Cho, Yuji Kashiwakura, Eduardo Marbán
Journal: Circulation Research (2007)

As an alternative to electronic pacemakers, we explored the feasibility of converting ventricular myocytes into pacemakers by somatic cell fusion. The idea is to create chemically induced fusion between myocytes and syngeneic fibroblasts engineered to express HCN1 pacemaker channels (HCN1-fibroblasts). HCN1-fibroblasts were fused with freshly isolated guinea pig ventricular myocytes using polyethylene-glycol 1500. In vivo fused myocyte-HCN1-fibroblast cells exhibited spontaneously oscillating action potentials; the firing frequency increased with beta-adrenergic stimulation. The heterokaryons created ectopic ventricular pacemaker activity in vivo at the site of cell injection. Coculture of nonfused HCN1-fibroblasts and myocytes without polyethylene-glycol 1500 revealed no evidence of dye transfer, demonstrating that the I(f)-mediated pacemaker activity arises from heterokaryons rather than electrotonic coupling. This nonviral, non-stem cell approach enables autologous, adult somatic cell therapy to create biopacemakers.
Long-term use of thiazolidinediones and the associated risk of pneumonia or lower respiratory tract infection: systematic review and meta-analysis
Authors: S. Singh, Y. K. Loke, C. D. Furberg
Journal: Thorax (2011)

<h3>Introduction</h3> The peroxisome proliferator-activated receptor-γ agonists rosiglitazone and pioglitazone activate glucocorticoid receptors and have an immunomodulatory effect. The authors aimed to systematically determine the risk of pneumonia or lower respiratory tract infections associated with thiazolidinediones. <h3>Methods</h3> Systematic searches of MEDLINE, EMBASE, regulatory documents and trial registries were carried out for randomised controlled trials of thiazolidinediones with no date restrictions through March 2010. The authors selected long-term (≥1 year) randomised controlled trials of thiazolidinediones versus a placebo, metformin or sulfonylurea control for prevention or treatment of type 2 diabetes that reported on pneumonia or lower respiratory tract infection adverse events or serious adverse events (hospitalisation, disability or death). Relative risks (RRs) were estimated using a fixed-effects meta-analysis, and statistical heterogeneity was assessed using the I<sup>2</sup> statistic. <h3>Results</h3> Thirteen trials (n=17 627, including 8163 patients receiving thiazolidinediones and 9464 patients receiving control therapy) with a duration of follow-up of 1–5.5 years were included after a detailed screening of 58 studies. Thiazolidinediones were associated with a statistically significantly increased risk for any pneumonia or lower respiratory tract infection (n=130/8163 vs 100/9464; RR 1.40; 95% CI 1.08 to 1.82; p=0.01; I<sup>2</sup>=0%) and serious pneumonia or lower respiratory tract infection (n=111/7391 vs 87/8692; RR 1.39; 95% CI 1.05 to 1.83; p=0.02; I<sup>2</sup>=0%). <h3>Interpretation</h3> Long-term thiazolidinedione use is associated with a modestly increased risk of any pneumonia or lower respiratory tract infection and serious pneumonia or lower respiratory tract infection in patients with type 2 diabetes.
Reproducibility of Chronic Infarct Size Measurement by Contrast-Enhanced Magnetic Resonance Imaging
Authors: Heiko Mahrholdt, Anja Wagner, Thomas A. Holly, Michael D. Elliott, Robert O. Bonow, Raymond J. Kim, Robert M. Judd
Journal: Circulation (2002)

The reproducibility of contrast-enhanced MRI has not been established. We compared MRI reproducibility for infarct size determination with that of (99m)Tc-sestamibi (MIBI) single photon emission computed tomography (SPECT).Patients with chronic myocardial infarction defined by enzymes (peak creatine kinase-MB 173+/-119 U/L) were scanned twice by MRI (MRI I and MRI II, n=20) and twice by SPECT (SPECT I and SPECT II, n=15) on the same day. The MRI contrast agent was injected during MRI I but not MRI II to test the effect of imaging time after contrast. Resting Tc-MIBI SPECT images were acquired and infarct size was determined with commercial software. Infarct size in patients scanned by MRI and SPECT was 14+/-6% of left ventricular mass (%LV) by MRI (range 4%LV to 27%LV) and 14+/-7%LV by SPECT (range 4%LV to 26%LV). MRI I and II scans were performed 10+/-2 and 27+/-3 minutes after contrast, respectively. For MRI, the difference in infarct size between scans I and II (bias) was -0.1%LV, and the coefficient of repeatability was +/-2.4%LV. For SPECT, bias was -1.3%LV, and the coefficient of repeatability was +/-4.0%LV. Within individual patients, no systematic differences in infarct size were detected when the 2 MRI scans were compared, the 2 SPECT scans were compared, or MRI was compared to SPECT.The size of healed infarcts measured by contrast-enhanced MRI does not change between 10 and 30 minutes after contrast. The clinical reproducibility of contrast-enhanced MRI for infarct size determination compares favorably with that of routine clinical SPECT.
Priming of CD4+ T cells by liver sinusoidal endothelial cells induces CD25low forkhead box protein 3− regulatory T cells suppressing autoimmune hepatitis
Authors: Nils Kruse, Katrin Neumann, Arnhild Schrage, Katja Derkow, Eckart Schott, Ulrike Erben, Anja Kühl, Christoph Loddenkemper, Martin Zeitz, Alf Hamann, Katja Klugewitz
Journal: Hepatology (2009)

Elucidating cellular mechanisms that maintain the intrahepatic immune balance is crucial to our understanding of viral or autoimmune liver diseases and allograft acceptance. Liver sinusoidal endothelial cells (LSECs) play an important role in modifying local immune responses to tolerance in major histocompatibility complex (MHC) I–restricted models, whereas their contribution in the MHCII context is still controversial. In an MHCII chimeric mouse model that excludes MHCII-mediated antigen presentation by professional antigen-presenting cells, we demonstrated that LSECs prime CD4+ T cells to a CD45RBlow memory phenotype lacking marker cytokine production for effector cells that was stable in vivo following immunogenic antigen re-encounter. Although these cells, which we term TLSEC, had the capacity to enter lymph nodes and the liver, they did not function as effector cells either in a delayed-type hypersensitivity reaction or in a hepatitis model. TLSEC inhibited the proliferation of naïve CD4+ T cells in vitro although being CD25low and lacking expression of forkhead box protein (FoxP)3. Furthermore, these cells suppressed hepatic inflammation as monitored by alanine aminotransferase levels and cellular infiltrates in a T cell-mediated autoimmune hepatitis model in vivo. Conclusion: TLSEC first described here might belong to the expanding group of FoxP3− regulatory T cells. Our findings strengthen the previously discussed assumption that CD4+ T cell priming by nonprofessional antigen-presenting cells induces anti-inflammatory rather than proinflammatory phenotypes. Because recruitment of CD4+ T cells is increased upon hepatic inflammation, TLSEC might contribute to shifting antigen-dependent immune responses to tolerance toward exogenous antigens or toward endogenous self-antigens, especially under inflammatory conditions. (HEPATOLOGY 2009.)
In Vitro Studies on the Enhancement of Rauscher Virus-Induced Erythroblastosis by Complete Freund's Adjuvant in BALB/c Mice2
Authors: Kees Nooter, Peter Bentvelzen
Journal: JNCI Journal of the National Cancer Institute (1976)

Inoculation of complete Freund's adjuvant (CFA) into BALB/c mice either before or after infection with Rauscher murine leukemia virus (MuLV-R) led to an acceleration of the disease as determined by spleen weight. Treatment with CFA also induced a higher number of spleen erythroblast foci and, in the bone marrow, erythropoietin-independent cells that produced erythroid colonies in vitro. CFA induced in the bone marrow not only an increase in myeloid progenitor cells that can produce colonies in agar, but an ever larger increase in the number of erythroid colony-forming cells. Virus-induced erythroblastosis was probably enhanced by CFA due to the production of many target cells. The more primitive burst-forming cell, which produced large colonies of erythroid cells after 10 days in culture, was also physiologically transformed in MuLV-R-infected mice; bursts could be formed by cells of such animals in the absence of erythropoietin.
Comparison of Iodine-123 Metaiodobenzylguanidine (MIBG) Scan and [<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography to Evaluate Response After Iodine-131 MIBG Therapy for Relapsed Neuroblastoma
Authors: Denah R. Taggart, Myo M. Han, Alekist Quach, Susan Groshen, Wei Ye, Judith G. Villablanca, Hollie A. Jackson, Carina Mari Aparici, David Carlson, John Maris, Randall Hawkins, Katherine K. Matthay
Journal: Journal of Clinical Oncology (2009)

Children with relapsed neuroblastoma have poor survival. It is crucial to have a reliable method for evaluating functional response to new therapies. In this study, we compared two functional imaging modalities for neuroblastoma: metaiodobenzylguanidine (MIBG) scan for uptake by the norepinephrine transporter and [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) uptake for glucose metabolic activity.Patients enrolled onto a phase I study of sequential infusion of iodine-131 ((131)I) MIBG (NANT-2000-01) were eligible for inclusion if they had concomitant FDG-PET and MIBG scans. (131)I-MIBG therapy was administered on days 0 and 14. For each patient, we compared all lesions identified on concomitant FDG-PET and MIBG scans and gave scans a semiquantitative score.The overall concordance of positive lesions on concomitant MIBG and FDG-PET scans was 39.6% when examining the 139 unique anatomic lesions. MIBG imaging was significantly more sensitive than FDG-PET overall and for the detection of bone lesions (P < .001). There was a trend for increased sensitivity of FDG-PET for detection of soft tissue lesions. Both modalities showed similar improvement in number of lesions identified from day 0 to day 56 scan and in semiquantitative scores that correlated with overall response. FDG-PET scans became completely negative more often than MIBG scans after treatment.MIBG scan is significantly more sensitive for individual lesion detection in relapsed neuroblastoma than FDG-PET, though FDG-PET can sometimes play a complementary role, particularly in soft tissue lesions. Complete response by FDG-PET metabolic evaluation did not always correlate with complete response by MIBG uptake.