tbuckley/cabot-search huggingface dataset:
Expression of UDP-<b> <i>N</i> </b>-Acetyl-α-<scp>d</scp>-Galactosamine-Polypeptide <b> <i>N</i> </b>-Acetylgalactosaminyltransferase Isozyme 3 in the Subserosal Layer Correlates with Postsurgical Survival of Pathological Tumor Stage 2 Carcinoma of the Gallbladder
Authors: Naoki Miyahara, Junichi Shoda, Toru Kawamoto, Masato Furukawa, Tetsuya Ueda, Takeshi Todoroki, Naomi Tanaka, Kenichi Matsuo, Yuji Yamada, Kimitoshi Kohno, Tatsuro Irimura
Journal: Clinical Cancer Research (2004)

Abstract Purpose and Experimental Design: Little is known about the molecular events leading to the development and progression of pathological tumor stage 2 (pT2) gallbladder carcinoma. An alteration in the site of O-glycosylation may be associated with malignant behavior of carcinoma cells by modulation of the biological properties of the target mucin. The UDP-N-acetyl-α-d-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 (GalNAc-T3) has the epithelial gland-specific expression and catalyzes mucin-type O-glycosylation. In this study, immunohistochemistry was performed to determine the expression level of GalNAc-T3 in 34 cases of pT2 gallbladder carcinoma to determine the correlation of the GalNAc-T3 expression level with mode of recurrence and postsurgical survival. Results: The expression levels of GalNAc-T3 protein and mRNA were increased in gallbladder carcinomas compared with the levels in adjacent noncancerous tissues and in intact gallbladders. Immunostaining of GalNAc-T3 was recognized in the cancerous epithelia, and the subcellular localization was classified into granular and diffuse types. In the 34 cases of pT2 carcinoma, the localization of GalNAc-T3 was granular type in 50% and diffuse type in 50% of the cases at the deepest invading sites in the subserosal layer. Postsurgical recurrence was significantly more frequent in cases showing diffuse-type localization of GalNAc-T3 at the deepest invading sites (65%) than in those showing granular-type localization (23%; P &amp;lt; 0.05). Postsurgical survival was significantly poorer in cases showing diffuse-type localization than in those showing granular-type localization (P = 0.033) Conclusions: In pT2 gallbladder carcinoma, the presence of diffuse-type localization of GalNAc-T3 in the subserosal layer is correlated with aggressiveness of the disease. This phenotype may serve as a unique biological feature associated with the malignant behavior.
Defending the concept of “concepts”
Authors: Brett K. Hayes, Lauren Kearney
Journal: Behavioral and Brain Sciences (2010)

Abstract We critically review key lines of evidence and theoretical argument relevant to Machery's “heterogeneity hypothesis.” These include interactions between different kinds of concept representations, unified approaches to explaining contextual effects on concept retrieval, and a critique of empirical dissociations as evidence for concept heterogeneity. We suggest there are good grounds for retaining the concept construct in human cognition.
Tinea Faciale and Lupus Erythematosus
Authors: L. Ben McEachin
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Tinea faciale may be easily confused with certain other dermatoses, as emphasized recently in two interesting communications (<b>215</b>:2091, 1971,<b>215</b>:2106, 1971). In a patient followed up since October 1968 at the University of Virginia Hospital, the coexistence of both tinea faciale (and corporis) and systemic lupus erythematosus (SLE) was observed. <h3>Report of a Case.—</h3> This 16-year-old girl presented with a nine-month history of a sun-sensitive facial rash as well as with other changes of shorter duration which included polyarthralgia, fever, malaise, weight loss, anorexia, oral ulcers, and hair loss. Initial physical examination revealed an erythematous, scaling, crusting eruption covering the entire face; follicular plugging and telangiectasia were noted. Scalp hair was easily pulled out. The diagnosis of SLE was confirmed. Antinuclear factor was positive (4+) and LE-cell preparations were positive. The patient had been receiving prednisone for two months when, on March 4, 1969, facial
Effect of Rosiglitazone Treatment on Nontraditional Markers of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus
Authors: Steven M. Haffner, Andrew S. Greenberg, Wayde M. Weston, Hongzi Chen, Ken Williams, Martin I. Freed
Journal: Circulation (2002)

Background — Markers of systemic inflammation (eg, C-reactive protein [CRP] and interleukin-6 [IL-6]) have been proposed to be “nontraditional” risk factors for cardiovascular disease in patients with type 2 diabetes mellitus. Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of atherosclerotic plaque rupture, which raises the possibility of the use of MMP-9 levels as a marker for future myocardial infarction or unstable angina. In vitro and animal studies suggest that thiazolidinediones can reduce the expression of these markers. The purpose of this analysis was to determine whether rosiglitazone alters serum concentrations of CRP, IL-6, MMP-9, and white blood cell count (WBC) and to examine the relationship of these effects with demographic and disease variables. Methods and Results — CRP, IL-6, MMP-9, and WBC were analyzed from stored frozen serum samples obtained from patients with type 2 diabetes who completed a 26-week randomized, double-blind, placebo-controlled study. After 26 weeks of rosiglitazone treatment, the percentage reductions in mean CRP, MMP-9, and WBC levels were statistically significant compared with baseline and placebo ( P &lt;0.01). The percentage reduction in mean IL-6 was small and similar in the rosiglitazone and placebo groups. The change in each inflammatory marker from baseline to week 26 was significantly correlated ( P &lt;0.05) with each of the other markers, as well as with the homeostasis model assessment estimate of insulin resistance. Conclusions — Rosiglitazone reduces serum levels of MMP-9 and the proinflammatory marker CRP in patients with type 2 diabetes, which indicates potentially beneficial effects on overall cardiovascular risk.
Changes in Phasic Coronary Blood Flow Velocity Profile and Relative Coronary Flow Reserve in Patients With Hypertrophic Obstructive Cardiomyopathy
Authors: Michael K. Kyriakidis, John M. Dernellis, Aristides E. Androulakis, Glafkos A. Kelepeshis, John Barbetseas, Aristides N. Anastasakis, Athanasios G. Trikas, Costas A. Tentolouris, John E. Gialafos, Pavlos K. Toutouzas
Journal: Circulation (1997)

In this study, we both investigated coronary flow velocity in hypertrophic obstructive cardiomyopathy (HOCM) and tested the hypothesis of differing coronary flow reserve (CFR) of coronary arteries perfusing left ventricular regions with nonuniform myocardial hypertrophy by measuring the relative CFR.Coronary flow velocity was assessed in left anterior descending coronary (LAD) and left circumflex (LCX) arteries in 18 patients with HOCM and marked hypertrophy only in the ventricular septum, in 13 patients without obstruction (HCM), and in 9 age- and sex-matched normal subjects at rest, during rapid atrial pacing, and after dobutamine infusion (5 to 30 microg/kg per minute). Relative CFR was estimated as the ratio between absolute CFR of the LAD and absolute CFR of the LCX (LAD/LCX(CF)). At the peak of rapid atrial pacing and during dobutamine stress, LAD/LCX(CF) was reversed in HOCM patients (from 1.25+/-0.11 to 0.82+/-0.07 and 0.79+/-0.06, respectively), whereas it remained unchanged in control subjects (from 1.0+/-0.1 to 1.0+/-0.05 and 1.0+/-0.05, respectively; P<.001). In HCM patients, LAD/LCX(CF) at rest was 1.10+/-0.11, whereas during rapid atrial pacing and dobutamine stress, it was 0.92+/-0.08 and 0.90+/-0.09, respectively. Relative CFR was 0.62+/-0.05 in HOCM patients and 1.05+/-0.05 (P<.001) in normal subjects. There was an inverse correlation between relative CFR and peak systolic outflow tract gradient (r2=.74, P<.001).Regional distribution of hypertrophy in some patients with HOCM resulted in regional impairment of coronary flow. Relative CFR can be used to estimate regional disturbances of coronary flow and may help in patient selection for new interventional therapeutic techniques.
24 hour ambulatory oesophageal pH monitoring in uncomplicated Barrett's oesophagus.
Authors: C S Neumann, B T Cooper
Journal: Gut (1994)

The aim of this study was to compare acid reflux in 16 patients with uncomplicated Barrett9s oesophagus with 37 patients with reflux oesophagitis and 10 control subjects of comparable age. All patients had 24 hour ambulatory pH monitoring within one week of endoscopy. The controls differed significantly from the other groups in all indices of reflux but there was no difference between the Barrett9s oesophagus patients and the reflux oesophagitis patients in any index of reflux over the total 24 hour period. Barrett9s oesophagus patients differed significantly, however, with respect to the percentage time pH &lt; 4 and the number of reflux episodes of &gt; five minutes during the supine period when compared with patients with grade I reflux oesophagitis, but not when compared with patients with grade II and III reflux oesophagitis. Barrett9s oesophagus patients with associated grade II reflux oesophagitis had more reflux than those with no oesophagitis or grade I reflux oesophagitis. Within each disease group patients &gt; or = 50 years had more acid reflux than patients &lt; 50 years. The severity of acid reflux in patients with uncomplicated Barrett9s oesophagus was no greater than in patients with reflux oesophagitis of comparable age. It seems probable that other factors must be important in the development of Barrett9s oesophagus.
Glucocorticoids induce basophil apoptosis
Authors: Chitose Yoshimura, Misato Miyamasu, Hiroyuki Nagase, Motoyasu Iikura, Masao Yamaguchi, Oichi Kawanami, Yutaka Morita, Tsutomu Iwata, Kazuhiko Yamamoto, Koichi Hirai
Journal: Journal of Allergy and Clinical Immunology (2001)
Does This Patient Have Carpal Tunnel Syndrome?
Authors: C A D'Arcy, S McGee
Journal: JAMA (2000)

History taking and physical examination maneuvers, including Tinel and Phalen signs, are widely used for the diagnosis of carpal tunnel syndrome (CTS).To systematically review the precision and accuracy of history taking and physical examination in diagnosing CTS in adults.English-language literature was searched using MEDLINE (January 1966-February 2000) as well as bibliographies of relevant articles.Studies of patients presenting to clinicians with symptoms suggestive of CTS in which findings from clearly described physical examination maneuvers were independently compared with electrodiagnostic testing. Twelve of 42 initially identified articles met these criteria and were included in the review.Two authors independently reviewed and abstracted data from all of the articles and reached consensus about any discrepancies.In patients presenting with hand dysesthesias, the findings that best distinguish between patients with electrodiagnostic evidence of CTS and patients without it are hypalgesia in the median nerve territory (likelihood ratio [LR], 3. 1; 95% confidence interval [CI], 2.0-5.1), classic or probable Katz hand diagram results (LR, 2.4; 95% CI, 1.6-3.5), and weak thumb abduction strength (LR, 1.8; 95% CI, 1.4-2.3). Findings that argue against the diagnosis of carpal tunnel syndrome are unlikely Katz hand diagram results (LR, 0.2; 95% CI, 0.0-0.7) and normal thumb abduction strength (LR, 0.5; 95% CI, 0.4-0.7). Several traditional findings of CTS have little or no diagnostic value, including nocturnal paresthesias; Phalen and Tinel signs; thenar atrophy; and 2-point, vibratory, and monofilament sensory testing. Other less commonly used maneuvers, including the square wrist sign, flick sign, and closed fist sign, require validation by other studies before they can be recommended.Hand symptom diagrams, hypalgesia, and thumb abduction strength testing are helpful in establishing the [corrected] electrodiagnosis of CTS. The utility of these results is limited, however, by problems inherent in using nerve conduction studies as a criterion standard. JAMA. 2000.
Dissecting the Heterogeneity of Skin Gene Expression Patterns in Systemic Sclerosis
Authors: Shervin Assassi, William R. Swindell, Minghua Wu, Filemon D. Tan, Dinesh Khanna, Daniel E. Furst, Donald P. Tashkin, Richard R. Jahan‐Tigh, Maureen D. Mayes, Johann E. Gudjonsson, Jeffrey T. Chang
Journal: Arthritis & Rheumatology (2015)

To examine the heterogeneity of global transcriptome patterns in systemic sclerosis (SSc) skin in a large sample of patients with SSc and control subjects.Skin biopsy specimens obtained from 61 patients enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort and 36 unaffected control subjects with a similar demographic background were examined by Illumina HumanHT-12 bead arrays. Followup experiments using quantitative polymerase chain reaction and immunohistochemical analysis were also performed.We identified 2,754 differentially expressed transcripts in SSc patients compared with controls. Clustering analysis revealed 2 prominent transcriptomes in SSc patients: the keratin and fibroinflammatory signatures. Higher keratin transcript scores were associated with shorter disease duration and interstitial lung disease, while higher fibroinflammatory scores were associated with diffuse cutaneous involvement, a higher skin score at the biopsy site, and a higher modified Rodnan skin thickness score. A subgroup of patients with significantly longer disease duration had a normal-like transcript pattern. Analysis of cell type-specific signature scores revealed remarkable heterogeneity across patients. Significantly higher scores were calculated for fibroblasts (72% of patients), microvascular cells (61%), macrophages (54%), and dendritic cells (DCs) (49%). The majority of samples with significantly higher fibroblast scores (35 of 44 [80%]) had significantly increased macrophage and/or DC scores. Further analysis and immunohistochemical staining indicated that the keratin signature was not a general marker of keratinocyte activation but was in fact associated with an activation pattern in hair and adnexal structures.Prominent fibroinflammatory and keratin signatures are present in SSc skin. Expression profiles of SSc skin show significant heterogeneity, and this finding might be useful for stratifying patients for targeted therapies or predicting the response to immunosuppression.
NRF2 Blockade Suppresses Colon Tumor Angiogenesis by Inhibiting Hypoxia-Induced Activation of HIF-1α
Authors: Tae-Hyoung Kim, Eu-gene Hur, Su-Jin Kang, Jung-Ae Kim, Dinesh Thapa, You Mie Lee, Sae Kwang Ku, Yunjin Jung, Mi-Kyoung Kwak
Journal: Cancer Research (2011)

Abstract Transcription factor NRF2 is an important modifier of cellular responses to oxidative stress. Although its cytoprotective effects are firmly established, recent evidence suggesting important roles in cancer pathobiology has yet to be mechanistically developed. In the current study, we investigated the role of NRF2 in colon tumor angiogenesis. Stable RNAi-mediated knockdown of NRF2 in human colon cancer cells suppressed tumor growth in mouse xenograft settings with a concomitant reduction in blood vessel formation and VEGF expression. Similar antiangiogenic effects of NRF2 knockdown were documented in chick chorioallantoic membrane assays and endothelial tube formation assays. Notably, NRF2-inhibited cancer cells failed to accumulate HIF-1α protein under hypoxic conditions, limiting expression of VEGF and other HIF-1α target genes. In these cells, HIF-1α was hydroxylated but pharmacological inhibition of PHD domain-containing prolyl hydroxylases was sufficient to restore hypoxia-induced accumulation of HIF-1α. Mechanistic investigations demonstrated that reduced mitochondrial O2 consumption in NRF2-inhibited cells was probably responsible for HIF-1α degradation during hypoxia; cellular O2 consumption and ATP production were lower in NRF2 knockdown cells than in control cells. Our findings offer novel insights into how cellular responses to O2 and oxidative stress are integrated in cancer cells, and they highlight NRF2 as a candidate molecular target to control tumor angiogenesis by imposing a blockade to HIF-1α signaling. Cancer Res; 71(6); 2260–75. ©2011 AACR.
Hypoxia Inducible Factor (HIF) Alpha Subunits Modulate Eosinophil Migration, Oxidative Burst, and Degranulation
Authors: Laura E. Crotty Alexander, Shari Nicatia, Elisa McEachern, Randall Johnson, David H. Broide, Victor Nizet
Journal: Journal of Allergy and Clinical Immunology (2013)
Soft Tissue Sarcomas: Classification and Natural History
Authors: S. I. Hajdu
Journal: CA A Cancer Journal for Clinicians (1981)

Soft tissue sarcomas represent about one percent of all malignant tumors..2In the United States, their incidence is about the same as that of multiple myeloma and car cinoma of the thyroid, and twice that of liver cell carcinoma, carcinoma of the sal ivary gland, and sarcoma of bone.2Be @: L.. (
Mechanisms of alphafetoprotein transfer in the perfused human placental cotyledon from uncomplicated pregnancy.
Authors: P Brownbill, D Edwards, C Jones, D Mahendran, D Owen, C Sibley, R Johnson, P Swanson, D M Nelson
Journal: Journal of Clinical Investigation (1995)

We investigated the mechanisms of alphafetoprotein (AFP) transfer across the human placenta by correlating measurements of AFP transfer with cytochemical localization of AFP. Placental cotyledons were dually perfused in vitro with either the fetal or maternal perfusate containing umbilical cord plasma as a source of AFP. Steady state AFP clearance, corrected for release of endogenous AFP, was 0.973 +/- 0.292 microliter/min per gram in the fetal to maternal direction (n = 10), significantly higher (P < 0.02) than that in the maternal to fetal direction (n = 5; 0.022 +/- 0.013 microliter/min per gram). Clearance of a similarly sized protein, horseradish peroxidase was also asymmetric but clearance of the small tracer creatinine was not. Using a monoclonal antibody, we localized AFP to fibrinoid deposits in regions of villi with discontinuities of the syncytiotrophoblast, to cytotrophoblast cells in these deposits, to syncytiotrophoblast on some villi, and to trophoblast cells in the decidua. We conclude that AFP transfer in the placenta is asymmetric and that there are two available pathways for AFP transfer: (a) from the fetal circulation into the villous core and across fibrinoid deposits at discontinuities in the villous syncytiotrophoblast to enter the maternal circulation; and (b) AFP present in the decidua could enter vessels that traverse the basal plate.
Patient-reported outcome measures in nonmelanoma skin cancer of the face: a systematic review
Authors: A.S. Bates, C.R. Davis, A. Takwale, G.J. Knepil
Journal: British Journal of Dermatology (2013)

Nonmelanoma skin cancer (NMSC) is the most common malignancy in the western world, with an incidence of 98,000 in the U.K. Since 2009 the Department of Health (DoH) has collected patient-reported outcome measure (PROM) data following four common surgical procedures. However, a DoH PROM for NMSC does not exist. A systematic review of questionnaires published on patient concerns due to NMSC of the face was conducted. Keywords relevant to PROMs, NMSC and the facial region were comprehensively searched in medical databases. Inclusion criteria stipulated that questionnaires from relevant papers recruited patients with NMSC for both the item formulation and subsequent validation. Questionnaires were then discussed by a multispecialty skin cancer research team. Initially 2548 papers were found; after exclusion criteria were applied, 73 articles were retrieved. Four patient questionnaires for NMSC featured adequate development and validation according to the inclusion criteria. The Facial Skin Cancer Index (FSCI) was the only PROM specific to facial NMSC. Additional questionnaires identified included the Skin Cancer Quality of Life Impact Tool, Skindex, and Dermatology Life Quality Index. There is a scarcity of data relating to NMSC PROMs and appearance concerns. Only one questionnaire--the FSCI--was specific to patients with facial NMSC. We recommend nationally standardized data collection from patients with NMSC in order to create an evidence-based validated PROM for patients with facial skin cancer.
Preferential increase in subendocardial perfusion produced by endothelium-dependent vasodilators.
Authors: L R Pelc, G J Gross, D C Warltier
Journal: Circulation (1987)

The transmural distribution of myocardial blood flow across the left ventricles of anesthetized dogs was measured with radioactive microspheres during intracoronary infusion of the endothelium-dependent vasodilators acetylcholine (10 micrograms/min), adenosine triphosphate (ATP; 20 micrograms/min), and arachidonic acid (600 micrograms/min) and the endothelium-independent vasodilator nifedipine (5 micrograms/min). These compounds were administered before and after a 30 min intracoronary infusion of the phospholipase A2 inhibitor quinacrine (300 micrograms/min). Acetylcholine, ATP, and arachidonic acid produced significant (p less than .05) increases in transmural blood flow and in the ratio of subendocardial to subepicardial blood flow (endo/epi) when compared with control. Infusion of quinacrine did not affect this ratio and did not block the increase in transmural blood flow produced by each agent; however, it did block the redistribution of flow to the subendocardium. In contrast, there was no change in endo/epi during intracoronary infusion of nifedipine before and after quinacrine. These results suggest that endothelium-dependent vasodilators produce a preferential increase in subendocardial perfusion via a product of unsaturated fatty acid metabolism.
Gender-based outcomes after paclitaxel-eluting stent implantation in patients with coronary artery disease
Authors: Alexandra J. Lansky, Ricardo A. Costa, Michael Mooney, Mark G. Midei, Henry K. Lui, Warren Strickland, Roxana Mehran, Martin B. Leon, Mary E. Russell, Stephen G. Ellis, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2005)