tbuckley/cabot-search huggingface dataset:
Concordant and Discordant Bone Marrow Involvement in Diffuse Large B-Cell Lymphoma: Are They Understudied Phenomena?
Authors: Luciano Wannesson, Ekaterina Chigrinova
Journal: Journal of Clinical Oncology (2011)

TO THE EDITOR: The article by Sehn et al analyzed the prognostic significance of the concordant versus discordant bone marrow involvement (BMI) in a cohort of 795 patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. On the basis of this large series, the authors found that both types of BMI produced a negative impact in terms of progression-free survival, whereas only the concordant involvement was a negative prognostic factor for overall survival that was also independent of the International Prognostic Index score at multivariate analysis. With this report, the first step toward the understanding of this topic seemed to be completed, and it is time to look further. Nevertheless, other important clues could have been retrieved from this representative series with relatively small additional effort. For example, among the group of patients with concordant BMI, a subset analysis of outcomes according to the cell of origin (COO) (ie, the germinal center B-cell v non–germinal center B-cell categories) could potentially further discriminate variables with prognostic relevance. Because categorization according to the COO could be performed retrospectively by means of the algorithm of Hans et al or other similar algorithms that are based on conventional immunohistochemistry, it still could be explored in a follow-up report of this series. Ideally, gene-expression profiling should also be analyzed in future prospective or retrospective studies to determine whether the different COO signatures are associated with different risk of BMI or different outcomes within the category of concordant BMI, but thus far, this has been limited by the availability of frozen tissue. Concerning the group of patients with discordant BMI, it still remains to be determined whether those low-grade infiltrates that are clonally related with the diffuse large B-cell lymphoma (which define a possible transformation from a low-grade to a higher-grade histology) lead to similar biologic effects in terms of progression-free survival and overall survival compared with clonally unrelated cases (which define the presence of two different lymphomas in the same patient). This delineation could be also explored in a retrospective series by determining B-cell receptor rearrangements by polymerase chain reaction– based methods applied on paraffin-embedded tissue samples. As a result of the difficulties in gathering sufficiently large series of patients with BMI and adequate tissue availability, it would be of major interest for the clinical community to maximize the analysis of all variables that could bear a potential predictive or prognostic impact and are assessable by widely available techniques or tools.
Linking Estrogen-Induced Apoptosis With Decreases in Mortality Following Long-term Adjuvant Tamoxifen Therapy
Authors: V. C. Jordan
Journal: JNCI Journal of the National Cancer Institute (2014)

The impressive first results of the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) and the adjuvant Tamoxifen To offer more (aTTom) trials both demonstrate that 10 years of tamoxifen is superior to five years of treatment. Tamoxifen is a nonsteroidal antiestrogen that blocks estrogen-stimulated tumor growth. Paradoxically, mortality decreases dramatically only in the decade after long-term tamoxifen is stopped. It is proposed that the evolution and clonal selection of micrometastases that acquire tamoxifen resistance now become increasingly vulnerable to endogenous estrogen-induced apoptosis. Laboratory and clinical studies confirm the concept, and supporting clinical evidence from the estrogen-alone trial in the Women's Health Initiative (WHI), demonstrate that long-term estrogen-deprived women given exogenous physiologic estrogen have a decreased incidence of breast cancer and decreased mortality. It is proposed that a natural process of apoptosis is recruited to execute the long-term survival benefit of stopping ten years of adjuvant tamoxifen, but only after clonal selection of vulnerable breast cancer cells in an estrogen-deprived environment.
The British Association of Sport and Medicine.
Authors: H. E. Robson
Journal: British Journal of Sports Medicine (1978)

The British Association of Sport and Medicine has now been in existence for just over twenty five years, its first full business meeting taking place in 1953, though a steering committee had been formed a year before, as detailed in the Foreword by the President, the Rt.Hon.Lord Porritt.To celebrate our Silver Jubilee, the Editorial Board decided to bring out a special jubilee number of the journal, and that all members of the board should contribute.The wide variety of topics that follow; philosophical, physiological, clinical, descriptive, political, -all reflect the variety of interests and special attributes of the members of the board, and we appreciate the time and care these members have donated, in addition to their help with the refereeing of articles submitted for publication, and the most helpful advice they give, to be transmitted to the authors.Their efforts have been one of the principal factors in any improvements in the standards of papers and their presentation during recent years.Another factor that has helped with the journal is useful advertising revenue, which we have been used for administration of the journal and the Association, and which will be used in the future for commissioning review articles and other major papers from invited experts.We still, however, will continue to use the journal as a publication outlet for good papers from our members and from other contributors, and for publishing the relevant proceedings of our own meetings, and sometimes of meetings run by organisations relative to our inter-disciplinary association.
Protection of the ischaemic myocardium by L-propionylcarnitine: effects on the recovery of cardiac output after ischaemia and reperfusion, carnitine transport, and fatty acid oxidation
Authors: D. J PAULSON, J. TRAXLER, M. SCHMIDT, J. NOONAN, A. L SHUG
Journal: Cardiovascular Research (1986)

The effects of L-propionylcarnitine on the recovery of cardiac contractile performance after global ischaemia and reperfusion were studied in isolated perfused rat hearts. The addition of either 5.5 or 11 mmol·litre−1 L-propionylcarnitine significantly improved the recovery of cardiac output, left ventricular pressure, and dP/dt after 90 min of ischaemia and 15 min of reperfusion. Myocardial adenosine triphosphate and creatine phosphate concentrations were significantly higher in the L-propionylcarnitine treated hearts than in controls, but the concentrations of long chain acyl carnitine and coenzyme A were unaffected. The protecting effects of L-propionylcarnitine were compared with those of L-carnitine and L-acetylcarnitine. A 11 mmol·litre−1 dose of L-propionylcarnitine and L-acetylcarnitine significantly improved the recovery of cardiac output after 90 min of ischaemia and 15 min of reperfusion, but L-carnitine did not. L-Propionylcarnitine was the most protective agent. The effects of these derivatives on L-3H-carnitine transport and l4C-palmitate oxidation were also measured. All of these derivatives competitively inhibited L-3H-carnitine transport in isolated cardiac myocytes, but L-propionylcarnitine was the most potent. Carnitine and L-propionylcarnitine stimulated palmitate oxidation in the homogenate, whereas L-acetylcarnitine inhibited it. In myocytes only L-propionylcarnitine affected palmitate oxidation. These data show that L-propionylcarnitine protects the ischaemic myocardium. Its protection is greater than that for L-carnitine or L-acetylcarnitine, and the difference in effectiveness may relate to the rate of transport into the cells and the effects on fatty acid utilisation.
Use of Positron Emission Tomography to Study AT1 Receptor Regulation In Vivo
Authors: ZSOLT SZABO, ROBERT C. SPETH, P. RANDY BROWN, LEVENTE KERENYI, PAN FU KAO, WILLIAM B. MATHEWS, HAYDEN T. RAVERT, JOHN HILTON, PAIGE RAUSEO, ROBERT F. DANNALS, WEI ZHENG, SUNGHOU LEE, KATHRYN SANDBERG
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Increased sodium intake and enhanced sodium sensitivity are implicated in the pathogenesis of hypertension and in the control of a major regulator of BP, the type 1 angiotensin receptor (AT 1 receptor). An in vivo technique to study changes of renal AT 1 receptors by dietary sodium was developed that uses positron emission tomography (PET). PET revealed that renal cortical AT 1 receptor binding was increased in sodium-loaded compared with sodium-deprived dogs, which correlated with ex vivo estimations of AT 1 receptor numbers. Plasma renin activity, angiotensin II, and aldosterone were inversely related to changes in AT 1 receptor binding. These results demonstrate, for the first time in vivo , that the renal AT 1 receptor is inversely related to the activity of the renin angiotensin system, which may provide a compensatory mechanism to prevent inappropriate fluctuations in arterial BP. The ability to measure AT 1 receptor binding in vivo has potential significance for clinical studies of AT 1 receptors, because PET is a noninvasive imaging technique that is readily applicable in humans.
In vivo and in vitro effects of salbutamol on alveolar epithelial repair in acute lung injury
Authors: G D Perkins, F Gao, D R Thickett
Journal: Thorax (2007)

Acute lung injury is an important cause of respiratory failure in the critically ill patient. It is caused by damage to the alveolar barrier with subsequent alveolar flooding leading to the development of refractory hypoxaemia. beta Agonists stimulate alveolar fluid clearance in animal models of lung injury. In a clinical trial (BALTI-1), intravenous beta agonists reduced extravascular lung water, an effect that took 72 h in contrast with what animal studies suggest. One possible explanation for the delay in change in extravascular lung water is the time required for salbutamol to stimulate alveolar epithelial repair.To investigate whether salbutamol can stimulate alveolar epithelial repair in vivo and in vitro.Intravenous salbutamol reduced measures of alveolar-capillary permeability in patients with acute respiratory distress syndrome (ARDS). In vitro, salbutamol stimulated both wound repair, and spreading and proliferation of A549 cells and distal lung epithelial cells. Lung lavage fluid from patients treated with salbutamol enhanced wound repair responses compared with placebo treated patients in vitro by an interleukin 1beta dependent mechanism.Our in vivo and in vitro work suggests that salbutamol may stimulate epithelial repair--potentially a pharmacological first in ARDS. Clearly establishing the mechanisms and pathways responsible for this is important for the future, and may allow identification of novel therapeutic targets to promote alveolar epithelial repair in humans with ARDS.
Evidence for Galα(1–3)Gal expression on primary porcine hepatocytes: implications for bioartificial liver systems
Authors: Maarten-Paul van de Kerkhove, Menno R. Germans, Tanja Deurholt, Ruurdtje Hoekstra, David H. Joziasse, Albert C.W.A. van Wijk, Thomas M. van Gulik, Robert A.F.M. Chamuleau, Anja Roos
Journal: Journal of Hepatology (2005)
Vitellogenin induction and reduced serum testosterone concentrations in feral male carp (Cyprinus carpio) captured near a major metropolitan sewage treatment plant.
Authors: L C Folmar, N D Denslow, V Rao, M Chow, D A Crain, J Enblom, J Marcino, L J Guillette
Journal: Environmental Health Perspectives (1996)

Endocrine disrupting chemicals can potentially alter the reproductive physiology of fishes. To test this hypothesis, serum was collected from common carp (Cyprinus carpio) at five riverine locations in Minnesota. Male fish collected from an effluent channel below the St. Paul metropolitan sewage treatment plant had significantly elevated serum egg protein (vitellogenin) concentrations and significantly decreased serum testosterone concentrations compared to male carp collected from the St. Croix River, classified as a National Wild and Scenic River. Carp collected from the Minnesota River, which receives significant agricultural runoff, also exhibited depressed serum testosterone concentrations, but no serum vitellogenin was apparent. These data suggest that North American rivers are receiving estrogenic chemicals that are biologically active, as has been reported in Great Britain.
Illness trajectories and palliative care
Authors: Scott A Murray, Marilyn Kendall, Kirsty Boyd, Aziz Sheikh
Journal: BMJ (2005)

When people with life threatening illnesses and their carers ask about prognosis (“How long have I got?”), they are often doing more than simply inquiring about life expectancy. Within this question is another, often unspoken, question about likely patterns of decline (“What will happen?”). One aid to answering both questions may be through the use of typical illness trajectories. Thinking in terms of these trajectories provides a broad timeframe and patterns of probable needs and interactions with health and social services that can, conceptually at least, be mapped out towards death.

Such frameworks may help clinicians plan and deliver appropriate care that integrates active and palliative management. If patients and their carers gain a better understanding by considering illness trajectories this may help them feel in greater control of their situation and empower them to cope with its demands. An important implication for service planners is that different models of care will be appropriate for people with different illness trajectories. We review the main currently described illness trajectories at the end of life and draw out key clinical implications.

We searched our own database of papers, conducted a Medline search, and approached experts for additional published references (further details available from SAM). We also re-examined primary data relating to illness trajectories from our previous studies investigating the palliative care needs of people with advanced lung cancer and heart failure.1

### Different trajectories for different diseases

A century ago, death was typically quite sudden, and the leading causes were infections, accidents, and childbirth. Today sudden death is less common, particularly in Western, economically developed, societies. Towards the end of life, most people acquire a serious progressive illness—cardiovascular disease, cancer, and respiratory disorders are the three leading causes—that increasingly interferes with their usual activities until death.

Three distinct illness trajectories have been described so far for people …
Hereditary Nonpolyposis Colorectal Cancer: the Syndrome, the Genes, and Historical Perspectives
Authors: G. Marra, C. R. Boland
Journal: JNCI Journal of the National Cancer Institute (1995)

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by the occurrence within a family of multiple cases of colorectal cancer in the absence of gastrointestinal polyposis. The prevalence of this syndrome is not yet clear, but it may account for 1%–5% of all colorectal cancers. Prior to the identification of the genetic basis of this syndrome, the disease was recognized by the familial aggregation of colorectal cancers that had an early age of onset, an excess of proximally located, and often multiple, primary tumors, and an excess occurrence of cancers in certain other organs. The recent description of an abnormality called "microsatellite instability, " present in almost all cancers from HNPCC patients and in about 12%–15% of sporadic cases, led to a series of discoveries that linked this type of genomic instability to a defect in the DNA mismatch repair (MMR) system. Independent investigators have identified four HNPCC genes: hMSH2 (a homologue of the prokaryotic DNA MMR gene MutS) and hMLHl, hPMSl, and hPMS2 (all homologues of the prokaryotic DNA MMR gene MutL). Mutations in each of the four genes have been found in the germline cells of HNPCC families. A major target for research in this area is the development of clinically practical screening tests for the genetic carrier state of HNPCC. [J Natl Cancer Inst 87:1114–1125, 1995]
Conceptual discontinuity involves recycling old processes in new domains
Authors: David Landy, Colin Allen, Michael L. Anderson
Journal: Behavioral and Brain Sciences (2011)

Abstract We dispute Carey's assumption that distinct core cognitive processes employ domain-specific input analyzers to construct proprietary representations. We give reasons to believe that conceptual systems co-opt core components for new domains. Domain boundaries, as well as boundaries between perceptual–motor and conceptual cognitive resources may be useful abstractions, but do not appear to reflect constraints respected by brains and cognitive systems.
Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis
Authors: Aleeza J. Roth, Joshua D. Ooi, Jacob J. Hess, Mirjan M. van Timmeren, Elisabeth A. Berg, Caroline E. Poulton, JulieAnne McGregor, Madelyn Burkart, Susan L. Hogan, Yichun Hu, Witold Winnik, Patrick H. Nachman, Coen A. Stegeman, John Niles, Peter Heeringa, A. Richard Kitching, Stephen Holdsworth, J. Charles Jennette, Gloria A. Preston, Ronald J. Falk
Journal: Journal of Clinical Investigation (2013)

Anti-neutrophil cytoplasmic antibody–associated (ANCA-associated) small vessel necrotizing vasculitis is caused by immune-mediated inflammation of the vessel wall and is diagnosed in some cases by the presence of myeloperoxidase-specific antibodies (MPO-ANCA). This multicenter study sought to determine whether differences in ANCA epitope specificity explain why, in some cases, conventional serologic assays do not correlate with disease activity, why naturally occurring anti-MPO autoantibodies can exist in disease-free individuals, and why ANCA are undetected in patients with ANCA-negative disease. Autoantibodies from human and murine samples were epitope mapped using a highly sensitive epitope excision/mass spectrometry approach. Data indicated that MPO autoantibodies from healthy individuals had epitope specificities different from those present in ANCA disease. Importantly, this methodology led to the discovery of MPO-ANCA in ANCA-negative disease that reacted against a sole linear sequence. Autoantibodies against this epitope had pathogenic properties, as demonstrated by their capacity to activate neutrophils in vitro and to induce nephritis in mice. The confounder for serological detection of these autoantibodies was the presence of a fragment of ceruloplasmin in serum, which was eliminated in purified IgG, allowing detection. These findings implicate immunodominant epitopes in the pathology of ANCA-associated vasculitis and suggest that autoantibody diversity may be common to other autoimmune diseases.
Differential effects of MS-551 and E-4031 on action potentials and the delayed rectifier K+ current in rabbit ventricular myocytes
Authors: J. Cheng, K. Kamiya, I. Kodama, J. Toyama
Journal: Cardiovascular Research (1996)

The frequency-dependent effects of MS-551 on the action potential duration (APD) and the underlying ionic mechanisms were investigated in comparison with those of E-4031.Whole-cell clamp techniques were used to study action potentials and ionic currents in enzymatically isolated rabbit ventricular myocytes.The frequency-response obtained within the range of 0.1 to 3.3 Hz was different for MS-551 and E-4031. The APD prolongation by MS-551 (10 microM) was significant at 0.5-3.3 Hz, whereas that by E-4031 (1 microM) was significant at 0.1-1.0 Hz. The prolongation by MS-551 (10 microM) of APD of a test action potential, which was preceded by a train of 1.0 Hz stimulation, decreased progressively as the rest duration increased, whereas that by E-4031 (1 microM) remained at the same level. Both MS-551 (10 microM) and E-4031 (1 microM) significantly decreased IK, but showed no effects on the transient outward current (Ito) and the inward rectifier K+ current (IKl). The development of the block on IK and the recovery from the block by MS-551 were voltage dependent. At a holding potential of -50 mV, MS-551 reduced the tail current to a similar extent (21-34%, n = 6) across all the tested durations of the depolarizing pulses to +10 mV, whereas at -75 mV, the intensity of the block progressively increased as the durations of depolarizing pulses were prolonged. The recovery from the block by MS-551 was absent at -50 mV, but occurred at -75 mV with a time constant of 577 +/- 179 ms (n = 6). The development of the block on IK by E-4031 was voltage and time independent. No recovery from the block was observed for E-4031 at either -50 or -75 mV.These findings suggest that MS-551 produces frequency-dependent class III action, presumably due to the voltage-dependent binding and unbinding to the IK channels. The reverse frequency dependence of class III action by E-4031 cannot be explained by the effects on IK.
GEOMETRIC DIFFERENCES OF MITRAL APPARATUS BETWEEN INFERIOR AND ANTERIOR MYOCARDIAL INFARCTION WITH SIGNIFICANT ISCHEMIC MITRAL REGURGITATION: THREE-DIMENSIONAL ANALYSIS WITH MULTISLICE COMPUTED TOMOGRAPHY
Authors: Yoshimori An, Shuichiro Kaji, Kitae Kim, Atsushi Yamamuro, Makoto Kinoshita, Natsuhiko Ehara, Atsushi Kobori, Atsushi Kobori, Takeshi Kitai, Tomoko Tani, Toru Kita, Yutaka Furukawa
Journal: Journal of the American College of Cardiology (2010)
Lack of Efficacy of an Inhibitor of PDE4 in Phase 1 and 2 Trials of Patients With Nonalcoholic Steatohepatitis
Authors: Vlad Ratziu, Pierre Bedossa, Sven M. Francque, Dominique Larrey, Guruprasad P. Aithal, Lawrence Serfaty, Mihai Voiculescu, Liliana Preotescu, Frederik Nevens, Victor De Lédinghen, Gabriele I. Kirchner, Pavel Trunecka, Stephen D. Ryder, Christopher P. Day, Jun Takeda, Klaudia Traudtner
Journal: Clinical Gastroenterology and Hepatology (2014)
<i>Leishmania major</i> LACK Antigen Is Required for Efficient Vertebrate Parasitization
Authors: Ben L. Kelly, Daniel B. Stetson, Richard M. Locksley
Journal: The Journal of Experimental Medicine (2003)

The Leishmania major LACK antigen is a key target of the immune response in susceptible BALB/c mice and remains a viable vaccine candidate for human leishmaniasis. We describe the genomic organization of the four lack genes in the L. major diploid genome together with results of selected lack gene targeting. Parasites containing a single lack gene in either the upstream or downstream locus grew comparably to wild-type promastigotes in vitro, but failed to parasitize BALB/c mice efficiently, even in a T cell–deficient environment. The replication of single copy lack mutants as amastigotes was attenuated in macrophages in vitro, and parasites failed to increase in numbers in immunodeficient mice, despite their persistence over months. Complementation with an additional lack copy was sufficient to induce robust lesion development, which also occurred using parasites with two lack genes. Conversely, attempts to generate lack-null parasites failed, suggesting that LACK is required for parasite viability. These data suggest that LACK is critical for effective mammalian parasitization and thus represents a potential drug target for leishmaniasis.
Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia
Authors: Sima Jeha, Varsha Gandhi, Ka Wah Chan, Lisa McDonald, Irma Ramirez, Renee Madden, Michael Rytting, Mark Brandt, Michael Keating, William Plunkett, Hagop Kantarjian
Journal: Blood (2003)
The activity of cyclic guanosine monphosphate specific phosphodiesterase (cGMP-PDE) in the renal tissue and the blunted renal responsiveness to endogenous natriuretic peptides (ENP) in cirrhotic rats with ascites
Authors: R. Veggian, P. Angeli, S. Fasolato, A. Sticca, R. Craighero, V. Dalla Libera, S. Garbisa, A. Gatta
Journal: Journal of Hepatology (1998)