tbuckley/cabot-search huggingface dataset:
Staging for Cutaneous Squamous Cell Carcinoma as a Predictor of Sentinel Lymph Node Biopsy Results
Authors: Adam R. Schmitt, Jerry D. Brewer, Jeremy S. Bordeaux, Christian L. Baum
Journal: JAMA Dermatology (2013)

The appropriate clinical setting for the application of sentinel lymph node biopsy (SLNB) in the management of cutaneous squamous cell carcinoma (cSCC) is not well characterized. Numerous case reports and case series examine SLNB findings in patients who were considered to have high-risk cSCC, but no randomized clinical trials have been performed.To analyze which stages in the American Joint Committee on Cancer (AJCC) criteria and a recently proposed alternative staging system are most closely associated with positive SLNB findings in nonanogenital cSCC.Medical literature review and case data extraction from private and institutional practices to identify patients with nonanogenital cSCC who underwent SLNB. Patients were eligible if sufficient tumor characteristics were available to classify tumors according to AJCC staging criteria and a proposed alternative staging system. One hundred thirty patients had sufficient data for AJCC staging, whereas 117 had sufficient data for the alternative system.Nonanogenital cSCC and SLNB.Positive SLNB findings by cSCC stage, quantified as the number and percentage of positive nodes.A positive SLN was identified in 12.3% of all patients. All cSCCs with positive SLNs were greater than 2 cm in diameter. The AJCC criteria identifed positive SLNB findings in 0 of 9 T1 lesions (0%), 13 of 116 T2 lesions (11.2%), and 3 of 5 T4 lesions (60.0%). No T3 lesions were identified. The alternative staging system identified positive SNLB findings in 0 of 9 T1 lesions (0%), 6 of 85 T2a lesions (7.1%), 5 of 17 T2b lesions (29.4%), and 3 of 6 T3 lesions (50.0%). Rates of positive SLNB findings in patients with T2b lesions were statistically higher than those with T2a lesions (P = .02, Fisher exact test) in the alternative staging system.Our findings suggest that most cSCCs associated with positive SLNB findings occur in T2 lesions (in both staging systems) that are greater than 2 cm in diameter. The alternative staging system appears to more precisely delineate high-risk lesions in the T2b category that may warrant consideration of SLNB. Future prospective studies are necessary to validate the relationship between tumor stage and positive SLNB findings and to identify the optimal staging system.
Pharmacological therapy can increase capillary density in post-infarction remodeled rat hearts
Authors: R Van Kerckhoven
Journal: Cardiovascular Research (2003)

Postinfarction hypertrophied hearts have been shown to display a lower capillary density and reduced mechanical efficiency amplified by tachycardia. We investigated whether pharmacological reduction of postinfarction tachycardia would induce capillary growth by treating myocardial infarcted (MI) rats with aspirin, methylprednisolone, moxonidine or captopril, during the first 3 weeks after infarction.Effects on in vivo heart rate were measured in conscious unrestrained rats, while in vitro heart rate effects were evaluated in isolated perfused hearts. Compared to sham-rats, MI-rats manifested a significant in vivo as well as in vitro tachycardia (increase 9% and 20% vs. sham, respectively). Whereas aspirin, methylprednisolone and moxonidine significantly reduced postinfarction in vivo tachycardia, captopril rather increased in vivo heart rate. In vitro tachycardia of MI-hearts was reduced to sham-values with aspirin and methylprednisolone (P<0.05), but not with moxonidine and captopril. Capillary density defined as the number of Lectin stained capillaries per tissue area, which significantly decreased in MI-hearts (decrease 42% vs. sham), was restored by all treatments (P<0.05). Concentric left ventricular hypertrophy after MI, defined as increased cross-sectional area of transversally cut Gomori stained myocytes, was indicated by almost double myocyte size (P<0.05), while capillary to myocyte ratio remained unchanged. Methylprednisolone, moxonidine and captopril, but not aspirin, prevented hypertrophy (P<0.05). However, treatment with aspirin and methylprednisolone, but not moxonidine and captopril, increased capillary to myocyte ratio (P<0.05) up to twice the values of non-treated MI hearts, indicating newly formed capillaries.The above findings confirm that post-MI pharmacological treatment can increase capillary density in the remodeled left ventricle. Whereas prevention of left ventricular hypertrophy normalizes capillary density without actually affecting capillary number, increased capillary to myocyte ratio (at preserved hypertrophic response) indicates actual capillary growth.
Eotaxin induces a sustained reduction in the functional adhesive state of very late antigen 4 for the connecting segment 1 region of fibronectin
Authors: K.-L.Paul Sung, Li Yang, John Kim, Derek Ko, Gregory Stachnick, Diego Castaneda, Jyothi Nayar, David H. Broide
Journal: Journal of Allergy and Clinical Immunology (2000)
Computer Game Delusions
Authors: S A Spence
Journal: Journal of the Royal Society of Medicine (2001)

Dr Forsyth and colleagues describe a patient with delusional involvement in a computer game scenario (April 2001 JRSM, pp. 184-185). Such cases may be understood within a broader context—the content of psychotic phenomenology incorporating elements of the patient's psychosocial environment, while the form of a psychotic symptom (e.g. ‘delusion’) represents an underlying biological ‘signal’1,2. In 1993 we reported a patient with paranoid schizophrenia whose auditory hallucinations derived from a computer game. These hallucinations underwent delusional interpretation, the patient believing that they ‘meant’ she was homeless3. In that report we predicted that ‘similar cases will arise as video games become more widely accessible’3.
Increasing prostate-specific antigen profile following definitive radiation therapy for localized prostate cancer: clinical observations.
Authors: W R Lee, G E Hanks, A Hanlon
Journal: Journal of Clinical Oncology (1997)

To examine the natural history of patients who have received definitive radiation therapy alone for clinically localized prostate cancer and have an increasing prostate-specific antigen (PSA) profile.One hundred fifty-one men with an increasing PSA profile after definitive radiotherapy were identified. The subsequent natural history of these men, including local recurrence, distant metastasis, and survival, was examined. In 119 men, posttreatment PSA doubling times (PSADT) were calculated using linear regression. Cox regression models were used to examine the effect of clinical and treatment variables on clinical failure and survival.Patients with high pretreatment PSA values, high Gleason scores, and T3 tumors were more likely to develop a PSA elevation. The median calculated post-treatment PSADT was 13 months, and 95% of patients had posttreatment PSADT of less than 3 years. PSADT was correlated with tumor stage and Gleason score. Five years after PSA elevation, the estimated rate of clinical local recurrence is 26% and the estimated rate of distant metastases is 47%. Rapid PSADT (< 12 months) and a short interval from the end of treatment to PSA elevation (< 12 months) were significant independent predictors of distant metastases. The estimated rates of overall and cause-specific survival 5 years after PSA elevation are 65% and 76%, respectively. Gleason grade is the only significant independent predictor of overall and cause-specific survival after PSA elevation.The natural history of men who have an increasing PSA profile following definitive radiotherapy is heterogeneous. In the absence of salvage therapy, at least three quarters of men will have clinical evidence of recurrent disease 5 years after a PSA elevation is detected. Men with a rapid posttreatment PSADT and a short interval from the end of treatment to an increasing PSA profile are at a very high risk of developing distant metastasis within 5 years of PSA elevation.
Results of a Nationwide Screening for Anderson-Fabry Disease among Dialysis Patients
Authors: Peter Kotanko, Reinhard Kramar, Danijela Devrnja, Eduard Paschke, Till Voigtla[Combining Diaeresis]nder, Martin Auinger, Klaus Demmelbauer, Matthias Lorenz, Anna-Christine Hauser, Hans-Jo[Combining Diaeresis]rg Kofler, Karl Lhotta, Ulrich Neyer, Wolfgang Pronai, Manfred Wallner, Clemens Wieser, Martin Wiesholzer, Herbert Zodl, Manuela Fo[Combining Diaeresis]dinger, Gere Sunder-Plassmann
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Anderson-Fabry disease is possibly underdiagnosed in patients with end-stage renal disease. Nationwide screening was therefore undertaken for Anderson-Fabry disease among dialysis patients in Austria. Screening for α-galactosidase A (AGAL) deficiency was performed by a blood spot test. In patients with a positive screening test, AGAL activity in leukocytes was determined. Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the <i>GLA</i> gene. Fifty (90.9%) of 55 Austrian hemodialysis centers participated in this study; 2480 dialysis patients (80.1% of the Austrian dialysis population) were screened. In 85 patients, the screening test was positive (85 of 2480, 3.42%; women, 3.32%; men, 3.50%). Among these 85 patients, 4 men (in 3 of whom Anderson-Fabry disease was already known before screening) had a severely decreased and 11 subjects had a borderline low AGAL activity. Genetic testing revealed mutations associated with Fabry disease in all four men with severely decreased AGAL activity resulting in a prevalence of 0.161% for the entire study population. A nationwide screening of dialysis patients permitted detection of a hitherto unknown man with Anderson-Fabry disease. The overall prevalence among dialysis patients was at least ten times higher as compared with recent registry data. Screening programs among patients with end-stage renal disease, especially men, should be put in place to identify families with Anderson-Fabry disease who probably may benefit from specific clinical care, and perhaps from enzyme replacement therapy. In dialysis patients, however, there is no evidence to support enzyme replacement therapy at present.
Catheter Ablation to Maintain Sinus Rhythm
Authors: Hugh Calkins
Journal: Circulation (2012)

O ver the past 12 years, catheter ablation of atrial fibrilla- tion (AF) has emerged from being a novel, largely unproven procedure to its role today as a very commonly performed procedure for treatment of patients with symptomatic AF. [1][2][3][4] In fact, catheter ablation of AF has become one of the most commonly performed catheter ablation procedures at most large medical centers throughout the world.The objective of the present report is to provide a state-of-the-art review of the techniques, outcomes, and complications of catheter ablation of AF.Three main topic areas will be discussed.First, I will review the current approaches for and outcomes of AF ablation.Second, I will identify and briefly review areas in the field of AF ablation about which less is known and that remain active areas for research.Third, I will briefly review the current status of a number of emerging technologies, approaches, and tools that are being developed with the aim of improving the outcomes of AF ablation.Finally, I will conclude by sharing with you my perspective on the indications for AF ablation.
Overexpression of p8 Is Inversely Correlated with Apoptosis in Pancreatic Cancer
Authors: Shi-Bing Su, Yoshiharu Motoo, Juan Lucio Iovanna, Patrice Berthézène, Min-Jue Xie, Hisatsugu Mouri, Koushiro Ohtsubo, Fujitsugu Matsubara, Norio Sawabu
Journal: Clinical Cancer Research (2001)

A recently identified gene, p8, has cell growth-promoting activity and is strongly induced in acute pancreatitis. In this study, we detected p8 and single-stranded DNA (ssDNA) for apoptosis by immunohistochemistry in human pancreatic cancer. The p8 was overexpressed (>30% per 1000 cancer cells) in 26 of 44 (59%) pancreatic cancers, and apoptosis (ssDNA-positive cells >10% per 1000 cancer cells) was recognized in 18 of 44 (41%) pancreatic cancers. There was a significant inverse correlation between the p8 overexpression and apoptosis (P < 0.05). Moreover, the expression pattern of high p8 and low ssDNA was seen significantly more often in lower age (<65 years), in moderately or poorly differentiated cancers, and in node-positive cases (P < 0.05). The p8 expression and apoptosis were not significantly correlated with survival. These results suggest that p8 overexpression is involved in antiapoptotic activity and the biological characteristics of pancreatic cancer.
Inhibition by aurintricarboxylic acid of von Willebrand factor binding to platelet GPIb, platelet retention, and thrombus formation in vivo
Authors: T. Kawasaki, S. Kaku, T. Kohinata, Y. Sakai, Y. Taniuchi, K. Kawamura, S. Yano, T. Takenaka, Y. Fujimura
Journal: American Journal of Hematology (1994)

Commercial aurintricarboxylic acid (ATA) was separated into molecular-weight (MW) fractions of < 210 to > 25,000, using gel permeation chromatography. Fractions with MW > 1,300 effectively inhibited both botrocetin-induced vWF and bovine vWF binding to fixed human platelets. These activities decreased with a MW > 17,000. Platelet retention for a human in vitro was reduced by ATA at 150 microM, as was that for rats ex vivo at 3 mg/kg. ATA prolonged tail transection bleeding time in rats but had only a weak effect on buccal mucosal bleeding time in dogs. ATA had no effect on platelet count but markedly prolonged PTT. ATA at 10 mg/kg exhibited antithrombotic activity and caused a marked improvement in patency status following successful thrombolysis by t-PA in electrically and copper coil-induced thrombosis models. These results suggest that specific inhibitors of the vWF-GPIb interaction such as ATA may prove useful as antithrombotic agents.
The Lyt-2 molecule recognizes residues in the class I alpha 3 domain in allogeneic cytotoxic T cell responses.
Authors: J M Connolly, T A Potter, E M Wormstall, T H Hansen
Journal: The Journal of Experimental Medicine (1988)

The involvement of the different domains of the MHC class I molecule in CTL recognition was investigated. mAbs specific for the alpha 1/alpha 2 domains of H-2Ld interfered with both the primary and secondary generation and effector function of in vitro Ld-specific CTL. mAbs specific for the alpha 3 domain of H-2Ld interfered with the generation and function of primary in vitro Ld-specific CTL; however, there was no effect on the in vitro generation of secondary CTL and only partial inhibition of their function. In vivo treatment with graft-specific antibodies to both the alpha 3 domain and the alpha 1/alpha 2 domains together resulted in a dramatic enhancement of Ld- or Dd-disparate skin grafts, whereas the individual mAbs showed minimal effects. This suggested that the class I alpha 3 domain is recognized by alloreactive CTL. Several approaches were undertaken to examine whether recognition of the alpha 3 domain determinants is mediated by the Lyt-2 molecule. When mAbs specific for the alpha 3 domain of either H-2Ld or H-2Dd were used in vivo and in vitro, the resulting CTL population was not inhibited by antibody to the alpha 3 domain and was only partially inhibited by antibody to Lyt-2. We therefore observed a correlation between the effects of antibody to the class I alpha 3 domain of the target molecule and antibody to the Lyt-2 molecule on the CTL. To further test the relationship between CTL recognition of the alpha 3 domain and the involvement of Lyt-2, we used a cell expressing a mutation in the alpha 3 domain of the Dd molecule. The mutation resulted in a single amino acid substitution of glu to lys at residue 227 of the alpha 3 domain. Consistent with an earlier report, cells expressing the mutant Dd lys molecule were not lysed by CTL from a primary stimulation against the wild-type Dd glu molecule. However, this same cell line was killed by the Lyt-2-independent secondary Dd-specific CTL generated in the presence of antibody to the alpha 3 domain in vivo and in vitro. Furthermore, cells expressing the mutant Dd lys molecule failed to stimulate a primary response. In conclusion, several independent lines of evidence indicate that residues in the alpha 3 domain of the class I molecule are involved in recognition by the Lyt-2 molecule, and that Lyt-2-mediated recognition can be specifically blocked using mAb to determinants in the alpha 3 domain.
Current pharmacologic treatment of elevated serum cholesterol.
Authors: M J Tikkanen, E A Nikkilä
Journal: Circulation (1987)

A basic difference between dietary and drug therapy of hypercholesterolemia is that dietary therapy can be used as part of a population strategy, whereas the decision to use drugs is always made on an individual basis. In each case, the decision to treat must be based on the assumption that more good than harm is caused to the patient. This is a difficult situation for the physician. As long as there is no easy way of assessing the state and rate of progression of coronary lesions, the physician must treat the patient on statistical grounds only, i.e., rely on the results of studies showing that lowering serum cholesterol significantly decreases the risk of coronary events. Such evidence has recently been strengthened, which increases motivation for both physician and patients. The current general opinion is that drug therapy must be generally confined to those at high risk, i.e., patients with severe hypercholesterolemia. For individuals with moderately elevated serum cholesterol levels, dietary advice and correction of other risk factors should be adequate.
P168 The effect of fluticasone propionate/formoterol fumarate combination therapy on quality of life scores in asthma patients
Authors: T McIver, S Dissanayake
Journal: Thorax (2013)

<h3>Introduction</h3> The Asthma Quality of Life Questionnaire (AQLQ) is a validated questionnaire which measures the effect of asthma on patient’s lives. AQLQ data from four phase III studies were pooled to assess how AQLQ scores are affected by treatment with fluticasone propionate (FP)/formoterol fumarate (FORM) in a single MDI (FP/FORM; <b><i>flutiform</i></b>) compared with other combination treatments. <h3>Method</h3> AQLQ data from a pooled analysis of two phase III open-label studies in patients with mild-moderate/severe asthma [pool 1; FP/FORM 50/5 or 125/5 (n = 206) vs. FP 50 + FORM 12 given together in separate inhalers and FP/salmeterol 50/25 or 125/25 (n = 206)], and a pooled analysis of two phase III double-blind studies in patients with moderate/severe asthma [pool 2; FP/FORM 250/10 (n = 294) vs. FP 250 + FORM 12 given together in separate inhalers and budesonide/FORM 200/6 (n = 295)] were analysed. AQLQ scores range from 1–7; a low score indicates the most severe impairment. Change in AQLQ from baseline to end of study was analysed using an ANCOVA. The proportion of subjects achieving a clinically relevant change of = 0.5 units was analysed using a logistic regression model. <h3>Results</h3> In pool 1, both groups had a similar increase in overall AQLQ score from baseline to end of study (0.635 in the FP/FORM group and 0.771 in the combination group) and the percentage of patients with a clinically relevant change in overall AQLQ score was 56% and 59%, respectively. In pool 2, the mean increase in overall AQLQ score from baseline to end of study was 0.837 in the FP/FORM group and 0.756 in the combination group, with 58% and 56% of patients experiencing a clinically relevant change in overall AQLQ score, respectively. The difference between the groups in each analysis was not statistically significant. <h3>Conclusion</h3> FP/FORM has a similar effect on the quality of life of asthma patients as other combination treatments, with a similar improvement shown in each treatment group for both pools. Over 50% of patients in both treatment groups showed a clinically relevant change in AQLQ from baseline to end of study. <h3>References</h3> Juniper EF, <i>et al. Am J Respir Med</i> 2002;1(6):435–40.
A Prospective Study of Muscular Strength and All-Cause Mortality in Men With Hypertension
Authors: Enrique G. Artero, Duck-chul Lee, Jonatan R. Ruiz, Xuemei Sui, Francisco B. Ortega, Timothy S. Church, Carl J. Lavie, Manuel J. Castillo, Steven N. Blair
Journal: Journal of the American College of Cardiology (2011)
Competition between concanavalin A-induced stimulatory and inhibitory effects in the in vitro immune response to antigen.
Authors: J Scavulli, R W Dutton
Journal: The Journal of Experimental Medicine (1975)

The humoral response of nude spleen cells (b cells) to sheep erythrocytes was measured in the presence of varying numbers of concanavalin A (ConA)-acvated stimulatory spleen T cells (helper) and Con A-activated inhibitory spleen T cells (suppressor) from BDF1 mice. It was found that suppressive effects could be reversed by the presence of additional numbers of stimulatory cells. These results seem incompatible with the hypothesis that suppression is mediated by supraoptimal numbers of stimulatory cells and provides additional evidence that separate populations of T cells mediate stimulation and suppression.
Coamplification and Cooperation: Toward Identifying Biologically Relevant Oncogenes
Authors: Guochang Huang, Bhuvanesh Singh
Journal: Clinical Cancer Research (2013)

Identification of biologically relevant genes from genomic assays is limited by the complexity of changes present in most solid tumors. Assessing for coactivation of functionally related genes resulted in the identification of SENP2, DCUN1D1, and DVL3--consensus candidates that drive selection for 3q amplification in lung squamous cell carcinomas.
Function and dysfunction of presenilin in Alzheimer’s disease
Authors: Jie Shen
Journal: Molecular Neurodegeneration (2013)

Presenilins are the major genes responsible for familial Alzheimer's disease (FAD).To elucidate the pathogenic mechanisms underlying FAD mutations, we employ advanced genetic approaches to investigate the normal function of presenilin in the brain and the dysfunction caused by disease causing mutations.Through development and multidisciplinary analysis of a number of cell type specific conditional mutant mice, we defined essential roles of presenilins in processes that are highly relevant to AD pathogenesis, such as memory, synaptic function and age-related neuronal survival.Our detailed analysis further elucidated the mechanisms by which presenilins regulate these processes, and whether presenilins regulate these processes via Notch receptors and in a γ-secretase-dependent manner.We also investigated the effects of various missense mutations in presenilin-1 associated with either FAD or frontotemporal dementia using both culture systems and knockin mice, and discovered their distinct molecular mechanisms.While FAD mutations cause partial to complete loss of γ-secretase activity in cis, mutant proteins further interfere the function of wild-type proteins in trans.The implications of our in vivo studies to disease mechanisms will be discussed.