tbuckley/cabot-search huggingface dataset:
<i>N</i>-Acetylglucosaminyltransferase V and β1-6 Branching <i>N</i>-Linked Oligosaccharides Are Associated with Good Prognosis of Patients with Bladder Cancer
Authors: Hirofumi Ishimura, Toshiko Takahashi, Hiroaki Nakagawa, Shin-Ichiro Nishimura, Yoichi Arai, Yohei Horikawa, Tomonori Habuchi, Eiji Miyoshi, Atsushi Kyan, Shigeru Hagisawa, Chikara Ohyama
Journal: Clinical Cancer Research (2006)

Abstract Purpose: N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins. We examined the relationship between GnT-V expression and clinicopathologic features of the patients with bladder cancer. Experimental Design: We immunohistochemically examined GnT-V expression in paraffin-embedded bladder cancer specimen using anti-GnT-V monoclonal antibody. We compared GnT-V expression with cause-specific survival of the patients with bladder cancer treated by radical cystectomy. Kaplan-Meier survival curves were generated to show the cause-specific survival. Univariate and multivariate analyses were carried out to compare GnT-V expression with other clinical and pathologic variables. We also evaluated mRNA expression of GnT-V and N-linked oligosaccharide structure in bladder cancer specimens. Results: Immunohistochemistry revealed that GnT-V expression inversely correlated with tumor grade and stage. The incidence of positive GnT-V expression in bladder cancer was significantly higher in low-grade/superficial cancer than in high-grade/invasive cancer. The patients whose tumor was positive for GnT-V survived significantly longer than those whose tumor was negative for GnT-V. Univariate and multivariate analyses revealed that GnT-V expression was an independent predictor of prognosis of the patient. The expression of GnT-V mRNA determined by reverse transcription-PCR was consistent with the results with immunohistochemistry for tumor samples. Carbohydrate structural analysis revealed that superficial bladder cancer is rich in branched N-linked oligosaccharides, for which biosynthesis GnT-V is responsible. Conclusions: GnT-V and its resultant β1-6 branching N-linked oligosaccharides are closely related to low malignant potential and good prognosis of the patients with bladder cancer.
URINARY SUBSTANCES PROVOKING ALLERGIC REACTIONS*
Authors: HENRI THIERS
Journal: British Journal of Dermatology (1961)

Journal Article URINARY SUBSTANCES PROVOKING ALLERGIC REACTIONS Get access HENRI THIERS HENRI THIERS Dermatological Clinic, Hôpital Ed. Herriot, Place d'Arsonval, Lyon Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 8-9, 1 August 1961, Pages 310–312, https://doi.org/10.1111/j.1365-2133.1961.tb14453.x Published: 01 August 1961
Unexpected Late Relapses Seen in Testicular Cancer
Authors: J. McCann
Journal: JNCI Journal of the National Cancer Institute (1998)

Unexpected Late Relapses Seen in Testicular CancerA disturbing -although still quite small -number of very late relapses in testicular cancer are being seen, and specialists are now warning that men treated for this disease may need to be followed indefinitely.An estimated 2% of men with testicular cancers are experiencing relapses 5 to 15 years following treatment -even those treated for early disease."We used to think that after 2 years, if there were no problem, you could quit following them," said Larry Einhorn, M.D.
Impaired clearance of apoptotic cardiocytes is linked to anti-SSA/Ro and -SSB/La antibodies in the pathogenesis of congenital heart block
Authors: R. M. Clancy
Journal: Journal of Clinical Investigation (2006)

The role of cardiocytes in physiologic removal of apoptotic cells and the subsequent effect of surface binding by anti-SSA/Ro and -SSB/La antibodies was addressed. Initial experiments evaluated induction of apoptosis by extrinsic and intrinsic pathways. Nuclear injury and the translocation of SSA/Ro and SSB/La antigens to the fetal cardiocyte plasma membrane were common downstream events of Fas and TNF receptor ligation, requiring caspase activation. As assessed by phase-contrast and confirmed by confocal microscopy, coculturing of healthy cardiocytes with cardiocytes rendered apoptotic via extrinsic pathways revealed a clearance mechanism that to our knowledge has not previously been described. Cultured fetal cardiocytes expressed phosphatidylserine receptors (PSRs), as did cardiac tissue from a fetus with congenital heart block (CHB) and an age-matched control. Phagocytic uptake was blocked by anti-PSR antibodies and was significantly inhibited following preincubation of apoptotic cardiocytes with chicken and murine anti-SSA/Ro and -SSB/La antibodies, with IgG from an anti-SSA/Ro– and -SSB/La–positive mother of a CHB child, but not with anti–HLA class I antibody. In a murine model, anti-Ro60 bound and inhibited uptake of apoptotic cardiocytes from wild-type but not Ro60-knockout mice. Our results suggest that resident cardiocytes participate in physiologic clearance of apoptotic cardiocytes but that clearance is inhibited by opsonization via maternal autoantibodies, resulting in accumulation of apoptotic cells, promoting inflammation and subsequent scarring.
Diabetics Need Not Apply
Authors: Joseph N Fisher
Journal: Diabetes Care (1989)

As the end of the twentieth century draws near, we can look back with some satisfaction at the progress that has been made in combating discrimination on many fronts and applaud the laws—national, state and local— that have attempted to ensure fair employment practices. For example, it is worth remembering that before 1941, no one with diabetes was eligible for any federal employment, and until 1985, if you took &amp;gt;25 U insulin/ day, you were ineligible for any hazardous federal job, regardless of how well controlled your diabetes might be. Although such blatant and irrational discrimination against people with diabetes has been eliminated, more subtle societal barriers to employment still exist.
Mortality rates are a blunt tool, says health minister
Authors: A. O'Dowd
Journal: BMJ (2008)

The health minister Ara Darzi has admitted that mortality rates are a “blunt tool” to measure the quality of medical care in the NHS in England.

Lord Darzi was giving evidence to MPs on the parliamentary health select committee on Thursday 17 July as part of its inquiry into the government’s next stage review, published last month.

He said that alternative measures were needed to rate the safety, effectiveness, and patients’ experience of health care because death rates were “irrelevant” for many procedures in modern medicine.

Although the government recently published survival data for surgery patients for the first time and suggested that …
A Polymorphism in the Complement Component<i>C1qA</i>Correlates with Prolonged Response Following Rituximab Therapy of Follicular Lymphoma
Authors: Emilian Racila, Brian K. Link, Wen-Kai Weng, Thomas E. Witzig, Stephen Ansell, Matthew J. Maurer, Jian Huang, Christopher Dahle, Ahmad Halwani, Ronald Levy, George J. Weiner
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Complement may play a role in the clinical response to rituximab and other monoclonal antibody–based therapies of cancer. The purpose of this study was to explore the relationship between the C1qA[276] polymorphism and the clinical response to rituximab in patients with follicular lymphoma. Experimental Design: Genotyping for C1qA[276A/G] was done in 133 subjects with follicular lymphoma treated with single-agent rituximab, and correlation with clinical response was done using Cox regression analysis. Results: Prolonged remission was observed among subjects that responded clinically to rituximab therapy and were carriers of the A allele compared with homozygous G subjects. Homozygous G subjects had a time to progression of 282 days, whereas A-allele carriers had a time to progression of 708 days [hazard ratio, (HR), 2.5; 95% confidence interval (95% CI), 2.0-3.1; P = 0.02]. Among subjects who achieved complete remission, homozygous G subjects had a time to progression of 250 days, whereas A-allele carriers had a time to progression of 1,118 days (HR, 4.5; 95% CI, 4.1-4.8, P = 0.04). The difference persisted after controlling for CD32 and CD16 polymorphisms. In patients who responded to rituximab used as first-line agent, a linear trend was observed among the C1qA[276] genotypes, with homozygous A subjects achieving complete response at a higher rate compared with heterozygous or homozygous G subjects. Conclusions: Our findings indicate that polymorphisms in the C1qA gene may affect the clinical response and duration of response to rituximab therapy of follicular lymphoma. These results could have direct implications on designing antibodies with improved efficiency and enhance our understanding of the role of complement in monoclonal antibody therapy.
Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type
Authors: R. Suzuki, J. Suzumiya, M. Yamaguchi, S. Nakamura, J. Kameoka, H. Kojima, M. Abe, T. Kinoshita, T. Yoshino, K. Iwatsuki, Y. Kagami, T. Tsuzuki, M. Kurokawa, K. Ito, K. Kawa, K. Oshimi
Journal: Annals of Oncology (2009)
Human homolog of Drosophila Hairy and enhancer of split 1, Hes1, negatively regulates δ-catenin (CTNND2) expression in cooperation with E2F1 in prostate cancer
Authors: Jian-Ping Lu, Jiao Zhang, Kwonseop Kim, Thomas C Case, Robert J Matusik, Yan-hua Chen, Michael Wolfe, Jongdee Nopparat, Qun Lu
Journal: Molecular Cancer (2010)

Neuronal synaptic junction protein δ-catenin (CTNND2) is often overexpressed in prostatic adenocarcinomas but the mechanisms of its activation are unknown. To address this question, we studied the hypothesis that Hes1, human homolog of Drosophila H airy and e nhancer of s plit (Hes) 1, is a transcriptional repressor of δ-catenin expression and plays an important role in molecular carcinogenesis. We identified that, using a δ-catenin promoter reporter assay, Hes1, but not its inactive mutant, significantly repressed the upregulation of δ-catenin-luciferase activities induced by E2F1. Hes1 binds directly to the E-boxes on δ-catenin promoter and can reduce the expression of δ-catenin in prostate cancer cells. In prostate cancer CWR22-Rv1 and PC3 cell lines, which showed distinct δ-catenin overexpression, E2F1 and Hes1 expression pattern was altered. The suppression of Hes1 expression, either by γ-secretase inhibitors or by siRNA against Hes1, increased δ-catenin expression. γ-Secretase inhibition delayed S/G2-phase transition during cell cycle progression and induced cell shape changes to extend cellular processes in prostate cancer cells. In neuroendocrine prostate cancer mouse model derived allograft NE-10 tumors, δ-catenin showed an increased expression while Hes1 expression was diminished. Furthermore, E2F1 transcription was very high in subgroup of NE-10 tumors in which Hes1 still displayed residual expression, while its expression was only moderately increased in NE-10 tumors where Hes1 expression was completely suppressed. These studies support coordinated regulation of δ-catenin expression by both the activating transcription factor E2F1 and repressive transcription factor Hes1 in prostate cancer progression.
Utility of Doppler Echocardiography and Tissue Doppler Imaging in the Estimation of Diastolic Function in Heart Failure With Normal Ejection Fraction
Authors: Mario Kasner, Dirk Westermann, Paul Steendijk, Regina Gaub, Ursula Wilkenshoff, Kerstin Weitmann, Wolfgang Hoffmann, Wolfgang Poller, Heinz-Peter Schultheiss, Matthias Pauschinger, Carsten Tschöpe
Journal: Circulation (2007)

Various conventional and tissue Doppler echocardiographic indexes were compared with pressure-volume loop analysis to assess their accuracy in detecting left ventricular (LV) diastolic dysfunction in patients with heart failure with normal ejection fraction (HFNEF).Diastolic dysfunction was confirmed by pressure-volume loop analysis obtained by conductance catheter in 43 patients (19 men) with HFNEF. Their Doppler indexes were compared with those of 12 control patients without heart failure symptoms and with normal ejection fraction. Invasively measured indexes for diastolic relaxation (tau, dP/dt(min)), LV end-diastolic pressure, and LV end-diastolic pressure-volume relationship (stiffness, b [dP/dV], and stiffness constant, beta) were correlated with several conventional mitral flow and tissue Doppler imaging indexes. Conventional Doppler indexes correlated moderately with the degree of LV relaxation index, tau (E/A: r=-0.36, P=0.013; isovolumic relaxation time: r=0.31, P=0.040) and b (deceleration time: r=0.39, P=0.012) but not with beta, in contrast to the tissue Doppler imaging indexes E'/A'(lateral) (r=-0.37, P=0.008) and E/E'(lateral) (r=0.53, P<0.001). Diastolic dysfunction was detected in 70% of the HFNEF patients by mitral flow Doppler but in 81% and 86% by E'/A'(lateral), and E/E'(lateral), respectively.Of all echocardiographic parameters investigated, the LV filling index E/E'(lateral) was identified as the best index to detect diastolic dysfunction in HFNEF in which the diagnosis of diastolic dysfunction was confirmed by conductance catheter analysis. We recommend its use as an essential tool for noninvasive diagnostics of diastolic function in patients with HFNEF.
The pro and anti-inflammatory activities of immunoglobulin G
Authors: A Lux, S Aschermann, M Biburger, F Nimmerjahn
Journal: Annals of the Rheumatic Diseases (2009)

Immunoglobulin G (IgG) molecules are a family of glycoproteins essential for defending the body against invading pathogens. The antibody constant domain is very potent in initiating proinflammatory pathways such as the activation of innate immune effector cells via cellular receptors specific for the antibody constant region (Fc receptors) and the activation of the complement pathway. During autoimmune disease the normally protective antimicrobial function of these molecules is targeted to healthy tissues often with disastrous consequences. Interestingly, one successful anti-inflammatory therapy for many autoimmune diseases is the infusion of high doses of IgG molecules, the so-called intravenous IgG therapy. How one class of molecules can have such opposing functions will be the major focus of this review.
A lymphokine that activates the cytolytic program of both cytotoxic T lymphocyte and natural killer clones.
Authors: C Milanese, R F Siliciano, R E Schmidt, J Ritz, N E Richardson, E L Reinherz
Journal: The Journal of Experimental Medicine (1986)

A 10-12 kD lymphokine, herein termed TCAF, was recently shown to be secreted from Th after crosslinking of their antigen/MHC (T3-Ti) receptors. TCAF stimulates resting T lymphocyte proliferation via binding to surface components of the T11 pathway. To determine whether TCAF could induce antigen-independent activation of the lytic machinery of cytotoxic cells, the present studies were conducted. In the presence of TCAF, both T8+ class I MHC-specific and T4+ class II MHC-specific cytotoxic T cell clones were induced to kill targets, including those lacking the appropriate MHC molecules. This effect was unique to TCAF, since IL-1, IL-2, IFN-gamma could not stimulate lytic activity. Furthermore, both T3+T11+ and T3-T11+ NK clones were triggered to lyse NK-resistant target cells. These findings suggest that TCAF can function in an antigen-independent fashion to amplify cytotoxic effector responses.
Improvements in Survival After Follicular Lymphoma by Race/Ethnicity and Socioeconomic Status: A Population-Based Study
Authors: Theresa H.M. Keegan, Laura A. McClure, James M. Foran, Christina A. Clarke
Journal: Journal of Clinical Oncology (2009)

A recent report suggested improvements in survival after follicular lymphoma (FL), but not for all racial/ethnic groups. To better understand the reasons for these FL survival differences, we examined the joint influences of diagnostic period, race/ethnicity, and neighborhood socioeconomic status (SES) on survival in a large population-based case series.
Superantigens: Mechanism of T-Cell Stimulation and Role in Immune Responses
Authors: A Herman, J W Kappler, P Marrack, A M Pullen
Journal: Annual Review of Immunology (1991)

Superantigens combine with MHC class-II molecules to form the ligands that stimulate T cells via the V β element of the T-cell receptor. Two groups of superantigens have been described so far: first, endogenous murine products that include the MIs determinants, and second, bacterial products such as the Staphylococcal enterotoxins. Here, we review studies that address the interactions between the foreign superantigens and MHC class-II molecules, the mechanism of T-cell stimulation, and the role that tolerance to self -superantigens plays in shaping the T-cell repertoire. We speculate on the possible evolutionary significance of superantigens.
THE POOR LAW COMMISSION
Authors: F. L. Dodd
Journal: BMJ (1909)

<h3>Abstract</h3> Capsid-integrity quantitative PCR (qPCR), a molecular detection method for infectious viruses combining azo-dye pretreatment with qPCR, has been widely used in recent years; however, variations in pretreatment conditions for various virus types can limit the efficacy of specific protocols. By identifying and critically synthesizing forty-two recent peer-reviewed studies employing capsid-integrity qPCR for viruses in the last decade (2009 to 2019) in the fields of food safety and environmental virology, we aimed to establish recommendations for the detection of infectious viruses. Intercalating dyes are effective measures of viability in PCR assays provided the viral capsid is damaged; viruses that have been inactivated by other causes, such as loss of attachment or genomic damage, are less well detected using this approach. Although optimizing specific protocols for each virus is recommended, we identify a framework for general assay conditions. These include concentrations of ethidium monoazide, propidium monoazide or its derivates between 10 and 200 µM; incubation on ice or at room temperature (20 - 25°C) for 5 to 120 min; and dye activation using LED or high light (500 – 800 Watts) exposure for periods ranging from 5 to 20 min. These simple steps can benefit the investigation of infectious virus transmission in routine (water) monitoring settings and during viral outbreaks such as the current COVID-19 pandemic or endemic diseases like dengue fever. <h3>Graphical abstract</h3>
Direct Current Make and Break Thresholds for Pacemaker Electrodes on the Canine Ventricle
Authors: EGBART DEKKER
Journal: Circulation Research (1970)

Thresholds to anodal make, anodal break, cathodal make and cathodal break have been studied throughout the cardiac cycle in 13 dogs under pentobarbital anesthesia. Unipolar direct current pulses were applied through epicardial pacemaker electrodes to the left ventricle. Make and break responses were separated by letting the break and make occur in the refractory periods of the following and preceding cycle, respectively. Four distinct threshold interval curves were obtained from each of 17 electrodes. The anodal break and cathodal break curves showed an early diastolic dip. Dips were deepest in the anodal break curves. These also had the shortest effective refractory period. Thresholds for cathodal make and anodal make first dipped steeply, then gradually sloped down towards end-diastolic levels. The magnitude of end-diastolic mean threshold values increased in the following order: cathodal make, anodal make, cathodal break, anodal break. Comparison of threshold interval curves for make and break responses with those for shorter rectangular anodal and cathodal curves throughout the cardiac cycle supports the hypothesis that the threshold behavior to a short rectangular pulse is determined by whichever of two thresholdsis lowest: make or break at that particular cycle interval.
Auranofin Induces Lethal Oxidative and Endoplasmic Reticulum Stress and Exerts Potent Preclinical Activity against Chronic Lymphocytic Leukemia
Authors: Warren Fiskus, Nakhle Saba, Min Shen, Mondana Ghias, Jinyun Liu, Soumyasri Das Gupta, Lata Chauhan, Rekha Rao, Sumedha Gunewardena, Kevin Schorno, Christopher P. Austin, Kami Maddocks, John Byrd, Ari Melnick, Peng Huang, Adrian Wiestner, Kapil N. Bhalla
Journal: Cancer Research (2014)

Chronic lymphocytic leukemia (CLL) exhibits high remission rates after initial chemoimmunotherapy, but with relapses with treatment, refractory disease is the most common outcome, especially in CLL with the deletion of chromosome 11q or 17p. In addressing the need of treatments for relapsed disease, we report the identification of an existing U.S. Food and Drug Administration-approved small-molecule drug to repurpose for CLL treatment. Auranofin (Ridaura) is approved for use in treating rheumatoid arthritis, but it exhibited preclinical efficacy in CLL cells. By inhibiting thioredoxin reductase activity and increasing intracellular reactive oxygen species levels, auranofin induced a lethal endoplasmic reticulum stress response in cultured and primary CLL cells. In addition, auranofin displayed synergistic lethality with heme oxygenase-1 and glutamate-cysteine ligase inhibitors against CLL cells. Auranofin overcame apoptosis resistance mediated by protective stromal cells, and it also killed primary CLL cells with deletion of chromosome 11q or 17p. In TCL-1 transgenic mice, an in vivo model of CLL, auranofin treatment markedly reduced tumor cell burden and improved mouse survival. Our results provide a rationale to reposition the approved drug auranofin for clinical evaluation in the therapy of CLL.
An economic analysis of the INTEREST trial, a randomized trial of docetaxel versus gefitinib as second-/third-line therapy in advanced non-small-cell lung cancer
Authors: A.M. Horgan, P.A. Bradbury, E. Amir, R. Ng, J.Y. Douillard, E.S. Kim, F.A. Shepherd, N.B. Leighl
Journal: Annals of Oncology (2011)