tbuckley/cabot-search huggingface dataset:
Gene Expression Signatures Predict Outcome in Non–Muscle-Invasive Bladder Carcinoma: A Multicenter Validation Study
Authors: Lars Dyrskjøt, Karsten Zieger, Francisco X. Real, Núria Malats, Alfredo Carrato, Carolyn Hurst, Sanjeev Kotwal, Margaret Knowles, Per-Uno Malmström, Manuel de la Torre, Kenneth Wester, Yves Allory, Dimitri Vordos, Aurélie Caillault, François Radvanyi, Anne-Mette K. Hein, Jens L. Jensen, Klaus M.E. Jensen, Niels Marcussen, Torben F. Ørntoft
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non–muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for molecular diagnosis of disease stage and carcinoma in situ (CIS) and for predicting disease recurrence and progression. Experimental Design: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic diagnosis and clinical outcome. Results: Classification of disease stage using a 52-gene classifier was found to be highly significantly correlated with pathologic stage (P &amp;lt; 0.001). Furthermore, the classifier added information regarding disease progression of Ta or T1 tumors (P &amp;lt; 0.001). The molecular 88-gene progression classifier was highly significantly correlated with progression-free survival (P &amp;lt; 0.001) and cancer-specific survival (P = 0.001). Multivariate Cox regression analysis showed the progression classifier to be an independently significant variable associated with disease progression after adjustment for age, sex, stage, grade, and treatment (hazard ratio, 2.3; P = 0.007). The diagnosis of CIS using a 68-gene classifier showed a highly significant correlation with histopathologic CIS diagnosis (odds ratio, 5.8; P &amp;lt; 0.001) in multivariate logistic regression analysis. Conclusion: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non–muscle-invasive bladder cancer. This information may be useful to better guide patient treatment.
FAILURE TO NEUTRALIZE THE POLIOMYELITIS VIRUS WITH SERA OF ADULT MACACUS RHESUS AND OF YOUNG FEMALE RHESUS TREATED WITH ANTERIOR PITUITARY EXTRACTS
Authors: N. Paul Hudson, Edwin H. Lennette, Ernest Q. King
Journal: The Journal of Experimental Medicine (1934)

1. Twelve specimens of serum from nine adult male monkeys failed to neutralize the virus of poliomyelitis. 2. Ten samples of serum obtained from three adult female monkeys at various phases of the menstrual cycle likewise proved incapable of neutralizing the virus. An eleventh serum, drawn from a fourth female 32 days postpartum, gave irregular results. It neutralized once and failed to do so on second test. This is the only suggestion in our experiments that a physiological factor may play a part in poliomyelitis immunity. 3. Fourteen sera from ten immature monkeys caused to menstruate by treatment with anterior pituitary extract were devoid of virucidal property. This treatment failed also to induce a systemic resistance to intracerebral injections of virus in the nine monkeys of the same group available for test. 4. We were unable to demonstrate in our monkeys a correlation between virucidal capacity of the serum and maturity or physiological variations as exemplified by menstruation.
Mechanism of Block and Identification of the Verapamil Binding Domain to HERG Potassium Channels
Authors: Shetuan Zhang, Zhengfeng Zhou, Qiuming Gong, Jonathan C. Makielski, Craig T. January
Journal: Circulation Research (1999)

Calcium channel antagonists have diverse effects on cardiac electrophysiology. We studied the effects of verapamil, diltiazem, and nifedipine on HERG K+ channels that encode IKr in native heart cells. In our experiments, verapamil caused high-affinity block of HERG current (IC50=143.0 nmol/L), a value close to those reported for verapamil block of L-type Ca2+ channels, whereas diltiazem weakly blocked HERG current (IC50=17.3 micromol/L), and nifedipine did not block HERG current. Verapamil block of HERG channels was use and frequency dependent, and verapamil unbound from HERG channels at voltages near the normal cardiac cell resting potential or with drug washout. Block of HERG current by verapamil was reduced by lowering pHO, which decreases the proportion of drug in the membrane-permeable neutral form. N-methyl-verapamil, a membrane-impermeable, permanently charged verapamil analogue, blocked HERG channels only when applied intracellularly. Verapamil antagonized dofetilide block of HERG channels, which suggests that they may share a common binding site. The C-type inactivation-deficient mutations, Ser620Thr and Ser631Ala, reduced verapamil block, which is consistent with a role for C-type inactivation in high-affinity drug block, although the Ser620Thr mutation decreased verapamil block 20-fold more than the Ser631Ala mutation. Our findings suggest that verapamil enters the cell membrane in the neutral form to act at a site within the pore accessible from the intracellular side of the cell membrane, possibly involving the serine at position 620. Thus, verapamil shares high-affinity HERG channel blocking properties with other class III antiarrhythmic drugs, and this may contribute to its antiarrhythmic mechanism.
Origin and specificity of autoreactive T cells in antigen-induced populations.
Authors: D A Faherty, D R Johnson, M Zauderer
Journal: The Journal of Experimental Medicine (1985)

We have characterized the major histocompatibility complex (MHC) specificity of autoreactive T cell clones arising from diverse donors after immunization with different antigens. The MHC fine specificity of autoreactive T cells for unique F1 hybrid determinants of BALB.K X BALB.B F1, and for the mutant I-Ab determinants of the B6.C-H-2bm12 (bm 12) strain is similar to that previously described for antigen-specific T cells. We find, furthermore, that the MHC specificity of autoreactive T cell clones selected from primed populations grown in the absence of Con A-stimulated supernatant factors reflects the predominant MHC restriction specificity of T cells specific for the immunogen. Thus, I-E subregion-specific autoreactive T cells are detected at a much higher frequency after immunization with the I-E-restricted antigen, GL (terpolymer of glutamic acid, lysine, and phenylalanine), than with the predominantly I-A-restricted antigen, keyhole limpet hemocyanin (KLH). These experiments strongly suggest that some autoreactive T cells are derived from antigen-stimulated precursors. This result contrasts with that obtained when autoreactive T cells are selected in bulk cultures, or in the presence of exogenous T cell factors. We conclude that, under optimal conditions, most autoreactive T cells are recruited from a relatively stable pool of predominantly I-A-specific precursors. Autoreactive precursors in this pool might themselves derive from previous antigenic stimulation, or be of independent origin.
Sports injury registration: the Fysion Blesreg system.
Authors: J V de Bruijn, S Keizers
Journal: British Journal of Sports Medicine (1991)

Fysion Blesreg is a new system on which sports assistants (trainers, masseurs, physiotherapists and physicians) can rely for quick and straightforward registration and retrieval of personalized injury data. Registration of injury data can provide a clear picture of the injury mechanism, which in turn can lead to effective preventive measures and a decline in sports injuries. The two components of the Fysion Blesreg system are registration forms and computer software. Registration forms are filled out when the competition starts (zero form), and when injuries occur (team cards and players' cards). Data are collected for the individual (zero form), the sports activity (team card), and the cause, nature and treatment of the injury (player's card). All data are entered into the computer with an MS-DOS based computer program, and can in various ways be reported or graphically reproduced.
An epigastric swelling
Authors: S. Rajagopalan, D A Robinson, R. Hargest
Journal: Journal of the Royal Society of Medicine (2004)

In the typical case of infective endocarditis the offending organism is bacterial and affects valves on the left side (mitral or aortic) previously abnormal because of rheumatic disease or congenital defects. 1 Fungal endocarditis, by contrast, is usually right-sided and causes larger vegetations with a greater likelihood of embolization.The ultrasound features of candida endocarditis have been described by Donal and co-workers. 2 Reviewing 270 published cases of fungal endocarditis (C.albicans 24%, non-albicans Candida spp.24%, Aspergillus spp.24%) Ellis et al. 3 found that the major risk factors were non-cardiac surgery, vascular lines, immunocompromise and injection drug abuse.The second two may well have contributed in our patient.][6]
CYCLOSPORIN INCREASES THE RATE AND LENGTH OF REMISSIONS IN INSULIN-DEPENDENT DIABETES OF RECENT ONSET
Authors: G Feutren, R Assan, G Karsenty, H Du Rostu, J Sirmai, L Papoz, B Vialettes, P Vexiau, M Rodier, A Lallemand, J.-F Bach
Journal: The Lancet (1986)
DEGRADATION OF CELL PROTEINS AND THE GENERATION OF MHC CLASS I-PRESENTED PEPTIDES
Authors: Kenneth L. Rock, Alfred L. Goldberg
Journal: Annual Review of Immunology (1999)

Major histocompatibility complex (MHC) class I molecules display on the cell surface 8- to 10-residue peptides derived from the spectrum of proteins expressed in the cells. By screening for non-self MHC-bound peptides, the immune system identifies and then can eliminate cells that are producing viral or mutant proteins. These antigenic peptides are generated as side products in the continual turnover of intracellular proteins, which occurs primarily by the ubiquitin-proteasome pathway. Most of the oligopeptides generated by the proteasome are further degraded by distinct endopeptidases and aminopeptidases into amino acids, which are used for new protein synthesis or energy production. However, a fraction of these peptides escape complete destruction and after transport into the endoplasmic reticulum are bound by MHC class I molecules and delivered to the cell surface. Herein we review recent discoveries about the proteolytic systems that degrade cell proteins, how the ubiquitin-proteasome pathway generates the peptides presented on MHC-class I molecules, and how this process is stimulated by immune modifiers to enhance antigen presentation.
An Analysis of Coronary Flow and Related Factors Following Vagotomy, Atropine, and Sympathectomy
Authors: J. C. SCOTT, T. A. BALOURDAS
Journal: Circulation Research (1959)

Coronary blood flow in the dog has been measured by the nitrous oxide desaturation method before and after acute bilateral cervical vagotomy, intravenous injection of atropine, and chronie sympathectomy. Vagotomy and atropine markedly increased coronary flow, myocardial oxygen consumption, and heart rate, but decreased left ventricular efficiency. Chronic sympathectomy resulted in the following smaller but statistically significant changes: a decrease in coronary flow, myocardial oxygen consumption, and heart rate, but an increase in left ventricular efficiency. Increasing the oxygen content of the arterial blood decreased the coronary flow. A comparison of diallylbarbiturate acid and urethane with morphine and chloralose anesthesia gave similar flow values, but cardiac efficiency was increased in the latter case. An analysis of the relationships between coronary flow, left ventricular oxygen consumption, and the arteriovenous oxygen difference is presented.
Chordal Cutting Does Not Adversely Affect Left Ventricle Contractile Function
Authors: Emmanuel Messas, Chaim Yosefy, Miguel Chaput, J. Luis Guerrero, Suzanne Sullivan, Philippe Menasché, Alain Carpentier, Michel Desnos, Albert A. Hagege, Gus J. Vlahakes, Robert A. Levine
Journal: Circulation (2006)

Severing a limited number of second-order chordae to the anterior leaflet can improve ischemic mitral regurgitation (MR). Some concerns have been raised regarding possible influence on regional and global left ventricle (LV) function. We evaluated changes in cardiac function in 5 normal sheep with cutting of pre-instrumented chords in the beating heart to maintain constant load.Under cardiopulmonary bypass, wires were placed around the 2 central basal chordae and brought outside the heart, which was restarted. Hemodynamic and imaging data were collected before and after chordal cutting by radiofrequency ablation using those wires. Segmental contractility was assessed invasively using sonomicrometers and noninvasively using Doppler tissue velocity and strain rate (with strain rate viewed as less load-dependent than ejection fraction) at 6 sites: base, mid-ventricle, and apex along the anteroseptal and posterolateral walls. We found no changes from before to after chordal cutting in LV end-diastolic volume (47.2+/-3.3 after cutting versus 48.4+/-4.6 mL before cutting, P=0.66), end-systolic volume (21.5+/-1.2 versus 22.3+/-2.8 mL, P=0.68), ejection fraction (54.2+/-1.8 versus 54.2+/-2.7%, P=0.96), systolic ventricular elastance (7.28+/-1.68 versus 7.66+/-2.11 mm Hg/mL, P=0.64), preload-recruitable stroke work (46.6+/-7.7 versus 50.2+/-10.7 mm Hg, P=0.76), and LVdP/dt (1480+/-238 versus 1392+/-250 mm Hg/s, P=0.45). Doppler tissue velocities and longitudinal strain rates surrounding the papillary muscles were unchanged, as were sonomicrometer longitudinal and mediolateral absolute strains. No wall motion abnormalities were visible around the papillary muscles, and no MR developed.We find no evidence for acutely decreased global or segmental LV contractility with chordal cutting. This absence of adverse effects is consistent with long-term clinical experience with cutting these chords in valve repair.
Broadly Neutralizing Antiviral Antibodies
Authors: Davide Corti, Antonio Lanzavecchia
Journal: Annual Review of Immunology (2013)

A fascinating aspect of viral evolution relates to the ability of viruses to escape the adaptive immune response. The widely held view has been that the great variability of viral glycoproteins would be an absolute obstacle to the development of antibody-based therapies or vaccines that could confer broad and long-lasting protection. In the past five years, new approaches have been developed to interrogate human memory B cells and plasma cells with high efficiency and to isolate several broadly neutralizing antiviral antibodies against highly variable pathogens such as HIV-1 and influenza virus. These antibodies not only provide new tools for prophylaxis and therapy for viral diseases but also identify conserved epitopes that may be used to design new vaccines capable of conferring broader protection.
Germline variable region gene segment derivation of human monoclonal anti-Rh(D) antibodies. Evidence for affinity maturation by somatic hypermutation and repertoire shift.
Authors: J M Bye, C Carter, Y Cui, B D Gorick, S Songsivilai, G Winter, N C Hughes-Jones, J D Marks
Journal: Journal of Clinical Investigation (1992)

To date, there has been no systematic study of the process of affinity maturation of human antibodies. We therefore sequenced the variable region genes (V genes) of 14 human monoclonal antibodies specific for the erythrocyte Rh(D) alloantigen and determined the germline gene segments of origin and extent of somatic hypermutation. These data were correlated with determinations of antibody affinity. The four IgM antibodies (low affinity) appear to be derived from two germline heavy chain variable region gene segments and one or two germline light chain variable region gene segments and were not extensively mutated. The 10 IgG antibodies (higher affinity) appear to be derived from somatic hypermutation of these V gene segments and by use of new V gene segments or V gene segment combinations (repertoire shift). Affinity generally increased with increasing somatic hypermutation; on average, there were 8.9 point mutations in the V gene segments of the four IgM antibodies (Ka = 1-4 x 10(7)/M-1) compared with 19 point mutations in the V gene segments of the 10 IgG antibodies. The four highest affinity antibodies (Ka = 0.9-3 x 10(9)/M-1) averaged 25.5 point mutations. The use of repertoire shift and somatic hypermutation in affinity maturation of human alloantibodies is similar to data obtained in inbred mice immunized with haptens.
Completed Suicide After a Suicide Attempt: A 37-Year Follow-Up Study
Authors: Kirsi Suominen, Erkki Isometsä, Jaana Suokas, Jari Haukka, Kalle Achte, Jouko Lönnqvist
Journal: American Journal of Psychiatry (2004)

Attempted suicide is the strongest known predictor of completed suicide. However, suicide risk declines over time after an attempt, and it is unclear how long the risk persists. Risk estimates are almost exclusively based on studies of less than 10 years of follow-up.The authors followed a cohort of 100 consecutive self-poisoned patients in Helsinki in 1963, for whom forensically classified causes of death during the following 37 years were investigated.They found that suicides continued to accumulate almost four decades after the index suicide attempt.A history of a suicide attempt by self-poisoning indicates suicide risk over the entire adult lifetime.
Ultrastructural analysis of plasma cells in coeliac patients.
Authors: M Guix, J M Skinner, R Whitehead
Journal: Gut (1979)

By accurate morphometry the length of the rough endoplasmic reticulum (RER) was estimated in electron micrographs of a population of jejunal plasma cells in biopsies obtained from normal volunteers, untreated coeliac disease patients, and coeliac disease patients treated for one year on a gluten free diet. Increase in length or hypertrophy of the endoplasmic reticulum is an indication of increased protein synthesis of the cell (Ghadially, 1977). An increase compared with normal length was demonstrated in the mean length of the plasma cell rough endoplasmic reticulum in plasma cells obtained from both groups of coeliac patients. This estimate of increased protein production--in this case immunoglobulin--indicates an increase in the immunological activity of plasma cells even after treatment and suggests not only a reaction to dietary gluten but probably to other antigens also.
Increased peak expiratory flow variation in asthma: severe persistent increase but not nocturnal worsening of airway inflammation
Authors: NH ten Hacken, W Timens, M Smith, G Drok, J Kraan, DS Postma
Journal: European Respiratory Journal (1998)

Asthma at night is characterized by a nocturnal increase in airway obstruction. It has been hypothesized that nocturnal asthma results from an increase in airway wall inflammation at night. However, studies on inflammatory cells in bronchoalveolar lavage (BAL) fluid and bronchial biopsies have produced conflicting data. This study assessed inflammatory cell numbers at 16:00 h and 04:00 h in bronchial biopsies of 13 healthy controls, 15 asthmatic patients with peak expiratory flow (PEF) variation &lt; or =15% and 10 asthmatic patients with PEF variation &gt;15%. There was no significant increase at night in the number of CD3, CD4, CD8, CD25, AAI (tryptase) and EG2-immunopositive cells in the submucosa in both groups. Numbers of EG2-positive cells in the two asthmatic groups were significantly higher than in healthy controls, both at 16:00 h (p&lt;0.05) and 04:00 h (p&lt;0.01). The number of EG2, CD4 and CD25-positive cells at 04:00 and 16:00 h tended to be higher in asthmatics with a PEF variation &gt;15% than in asthmatics with PEF variation &lt; or =15%. At 04:00 h the median numbers of EG2-positive cells (per mm basement membrane) in subjects with PEF variation &gt;15% and &lt; or =15% were 6 and 3 cells, respectively, and at 16:00 h 4 and 25 cells respectively. Increased nocturnal airway obstruction is not associated with increased numbers of inflammatory cells in the bronchial submucosa at night. Apparently, asthmatic patients with a peak expiratory flow variation &gt;15% suffer from a higher overall severity of bronchial inflammation at night and during the day.
Tiotropium improves lung function in patients with severe uncontrolled asthma: A randomized controlled trial
Authors: Huib A.M. Kerstjens, Bernd Disse, Winfried Schröder-Babo, Theo A. Bantje, Martina Gahlemann, Ralf Sigmund, Michael Engel, Jan A. van Noord
Journal: Journal of Allergy and Clinical Immunology (2011)
Mature T-lineage leukemia with growth factor-induced multilineage differentiation.
Authors: F Griesinger, D C Arthur, R Brunning, J L Parkin, A C Ochoa, W J Miller, C W Wilkowski, J M Greenberg, C Hurvitz, J H Kersey
Journal: The Journal of Experimental Medicine (1989)

We report an acute T-lymphoblastic leukemia with a predominantly mature CD3+ CD7+ WT31+ phenotype that was induced to differentiate into different cell lineages by various recombinant human growth factors. In the presence of IL-3 or GM-CSF, the leukemic cells gave rise to myeloid and monocytic cells including terminally differentiated, partially functional, segmented neutrophilic granulocytes as assessed by morphologic, cytochemical, immunophenotypic, and functional criteria. In the presence of IL-2, leukemic granulated lymphoid cells exhibiting MHC-unrestricted cytotoxicity and expressing a CD2+ CD3+ CD5+ CD7+ CD8+ CD33+ WT31+ Leu19+ phenotype arose. Leukemic cell cultures initiated with IL-3 yielded growth factor-independent cells with a mixed lineage phenotype and morphologic and cytochemical evidence of immature blasts. These were T lymphocyte and myeloid surface antigen (CD2,CD3,CD5,CD7,CD13,CD33,WT31) positive. Identical rearrangements of the constant region of the TCR-delta gene and of the joining regions of the TCR-beta, -gamma, and -delta genes were observed in the fresh and all cultured leukemic cells, indicating that they were derived from the same malignant clone. Consistent with the molecular genetic data, the cytogenetic analyses of the GM-CSF-, IL-3-cultured and the growth factor-independent leukemic cells showed the presence of multiple, closely related abnormal clones, all of which had an interstitial deletion of part of the long arm of chromosome 6 and a complex 1;10;12 translocation. In conclusion, these data demonstrate the involvement of a multipotent leukemic precursor cell in this predominantly mature CD2+ CD3+ CD5+ CD7+ WT31+ T-ALL. This multipotent leukemic precursor may be susceptible to various growth factors and respond with ordered differentiation and maturation.