tbuckley/cabot-search huggingface dataset:
Diffuse oesophageal spasm: diagnosis by ambulatory 24 hour manometry
Authors: C P Barham, D C Gotley, A Fowler, A Mills, D Alderson
Journal: Gut (1997)

Background —Diffuse oesophageal spasm (DOS) is a potential cause of intermittent chest pain and/or dysphagia. In the past, the diagnosis of DOS has relied on criteria obtained from standard oesophageal manometry (more than one simultaneous contraction in a series of 10 wet swallows with the rest being peristaltic). As symptoms are intermittent, however, 24 hour manometry may well be more suited to its investigation. Aims —To determine the ability of 24 hour manometry to detect the symptomatic contractions of DOS and to compare standard, laboratory based manometry with 24 hour manometry in its diagnosis. Patients —Three hundred and ninety consecutive patients referred with suspected oesophageal disorders. Methods —Standard laboratory based manometry and 24 hour outpatient manometry. Results —Sixteen patients were classified by 24 hour manometry as having DOS on the basis of painful contractions (spasms) of excessive duration and increased amplitude. Laboratory based manometry failed to detect the majority of these patients with DOS (14/16), and 53/55 were incorrectly labelled as having DOS on the basis of asymptomatic manometric findings. Conclusion —The detection of symptomatic DOS requires 24 hour manometry.
Selenium and Cabbage and Colon Carcinogenesis in Mice
Authors: N J Temple, T K Basu
Journal: JNCI Journal of the National Cancer Institute (1987)

The influence of dietary selenium and cabbage on the formation of colon tumors in female Swiss mice treated with 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8] was reported. Mice received a control diet (laboratory chow), the control diet plus selenium in the drinking water (1 mg/liter), or the control diet with added cabbage (12.8 g/100 g diet). They also received 8 weekly sc injections of DMH. The experiment was divided into two time periods: a) from 5 weeks before the first injection until 3 days after the last one (initiation period), and b) the subsequent 19.5 weeks until sacrifice of the mice (promotion period). Selenium had a strong protective effect when given during the initiation period; adenomas were reduced to a much greater extent than adenocarcinomas. The only effect of selenium supplementation in the promotion period was a small decrease in adenomas. Cabbage apparently had two opposing actions. It increased tumor incidence, particularly adenocarcinomas, if given in the initiation period, but it reduced adenoma formation considerably when given in the promotion period.
The structure, operation, and functionality of intracerebral grafts
Authors: Jean-Christophe Cassel, Bruno Will
Journal: Behavioral and Brain Sciences (1995)

Abstract The concept of structure, operation, and functionality, as they may be understood by clinicians or researchers using neural transplantation techniques, are briefly defined. Following Stein &amp; Glasier, we emphasize that the question of whether an intracerebral graft is really functional should be addressed not only in terms of what such a graft does in a given brain structure, but also in terms of what it does at the level of the organism.
A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial
Authors: A. Keith Stewart, Suzanne Trudel, Nizar J. Bahlis, Darrell White, Waleed Sabry, Andrew Belch, Tony Reiman, Jean Roy, Chaim Shustik, Michael J. Kovacs, Morel Rubinger, Guy Cantin, Kevin Song, Kirsty A. Tompkins, Deb C. Marcellus, Martha Q. Lacy, Jonathan Sussman, Donna Reece, Michael Brundage, Erica L. Harnett, Lois Shepherd, Judy-Anne W. Chapman, Ralph M. Meyer
Journal: Blood (2013)
Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial
Authors: Istvan Lang, Thomas Brodowicz, Larisa Ryvo, Zsuzsanna Kahan, Richard Greil, Semir Beslija, Salomon M Stemmer, Bella Kaufman, Zanete Zvirbule, Günther G Steger, Bohuslav Melichar, Tadeusz Pienkowski, Daniela Sirbu, Diethelm Messinger, Christoph Zielinski
Journal: The Lancet Oncology (2013)
Signal Pathway of Hypoxia-Inducible Factor-1α Phosphorylation and its Interaction with von Hippel-Lindau Tumor Suppressor Protein During Ischemia in MiaPaCa-2 Pancreatic Cancer Cells
Authors: Seok J. Kwon, Jae J. Song, Yong J. Lee
Journal: Clinical Cancer Research (2005)

Abstract Purpose and Experimental Design: Previously, we observed that the activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK1) is mediated through the activation of apoptosis signal–regulating kinase 1 (ASK1) as a result of the reactive oxygen species–mediated dissociation of glutaredoxin and thioredoxin from ASK1. In this study, we examined whether p38 MAPK and JNK1 are involved in the accumulation of hypoxia-inducible factor-1α (HIF-1α) during ischemia. Human pancreatic cancer MiaPaCa-2 cells were exposed to low glucose (0.1 mmol/L) with hypoxia (0.1% O2). Results and Conclusions: During ischemia, p38 MAPK and JNK1 were activated in MiaPaCa-2 pancreatic cancer cells. The activated p38 MAPK, but not JNK1, phosphorylated HIF-1α. Data from in vivo binding assay of von Hippel-Lindau tumor suppressor protein with HIF-1α suggests that the p38-mediated phosphorylation of HIF-1α contributed to the inhibition of HIF-1α and von Hippel-Lindau tumor suppressor protein interaction during ischemia. SB203580, a specific inhibitor of p38 MAPK, inhibited HIF-1α accumulation during ischemia, probably resulting from the ubiquitination and degradation of HIF-1α.
Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance
Authors: Dharminder Chauhan, Guilan Li, Teru Hideshima, Klaus Podar, Constantine Mitsiades, Nicholas Mitsiades, Laurence Catley, Yu Tzu Tai, Toshiaki Hayashi, Reshma Shringarpure, Renate Burger, Nikhil Munshi, Yasuyuki Ohtake, Satya Saxena, Kenneth C. Anderson
Journal: Blood (2003)
Glycemic Control Over 5 Years in 4,900 People With Type 2 Diabetes
Authors: James D. Best, Paul L. Drury, Timothy M.E. Davis, Marja-Riitta Taskinen, Y. Antero Kesäniemi, Russell Scott, Christopher Pardy, Merryn Voysey, Anthony C. Keech
Journal: Diabetes Care (2012)

Glycemic control in type 2 diabetes generally worsens over time, requiring intensification of therapy. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial provided the opportunity to observe glycemic control in a real-world setting. We assessed the adequacy of metformin, sulfonylureas, and insulin to maintain glycemic control and their effects on weight.Diabetes control was measured at baseline and yearly for a median of 5 years in the 4,900 patients from the nonintervention arm of this study allocated to placebo.Median HbA(1c) was 6.9% at baseline and increased by an average of 0.22% over 5 years (P < 0.001). Median weight was 86.3 kg at baseline and decreased by 0.4 kg over 5 years (P = 0.002). Baseline therapy was lifestyle measures only in 27%, oral agents without insulin in 59%, and insulin in 14% (7% also taking oral agents). Over 5 years, insulin use increased to 32% (21% also taking oral agents). Use of oral agents remained similar at 56%. Only 2% of patients at baseline and 4% after 5 years were taking oral agents other than metformin or sulfonylureas. Initiation of insulin therapy in 855 patients produced a sustained reduction of HbA(1c) from a median of 8.2 to 7.7%, with a weight gain of 4.6 kg over 5 years.With intensification of traditional therapies, glycemic control deteriorated very little over 5 years in a large cohort of type 2 diabetes. However, the requirement for insulin therapy doubled, at the expense of significant weight gain and risk of hypoglycemia.
Development of an assay for in vivo human neutrophil elastase activity. Increased elastase activity in patients with alpha 1-proteinase inhibitor deficiency.
Authors: J I Weitz, S L Landman, K A Crowley, S Birken, F J Morgan
Journal: Journal of Clinical Investigation (1986)

Leukocyte extracts contain enzymes that digest fibrinogen and release a fibrinopeptide A-containing fragment. This study was undertaken to identify the responsible proteinase and to characterize the fibrinopeptide A-containing fragment so that it could be used as an index of enzyme activity. Both the fibrinogenolytic activity and the release of the fibrinopeptide A-containing fragment mediated by the leukocyte extracts were shown to be due to human neutrophil elastase (HNE) by the following criteria: activity was completely blocked by a specific HNE inhibitor or by adsorbing HNE from the extracts with a monospecific antibody and reconstitution with purified HNE restored the ability to release the fibrinopeptide A-containing fragment. This fragment was not released by a variety of other proteinases or by HNE-inhibitor complexes indicating that, at least with respect to the enzymes tested, it is a specific product of HNE and its release requires the free enzyme. By separating the products of HNE digestion of fibrinogen using high performance liquid chromatography, identifying the immunoreactive fractions and subjecting them to amino acid analysis, the fragment was identified as A alpha 1-21, indicating an HNE cleavage site at the Val(A alpha 21)-Glu(A alpha 22) bond. The mean plasma A alpha 1-21 level was markedly higher in patients with alpha 1-proteinase inhibitor deficiency as compared to healthy controls (0.2 nM vs. 7.9 nM; P less than 0.0001), consistent with increased in vivo HNE activity in these individuals.
Cranial nerve involvement in children with leukemia and lymphoma.
Authors: S B Paryani, S S Donaldson, M D Amylon, M P Link
Journal: Journal of Clinical Oncology (1983)

Between 1965 and 1982, 52 children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma were found to have central nervous system involvement of their disease. Of this group, 20 developed clinically apparent cranial nerve paresis or palsy. The cranial nerve most frequently affected was No. VII. With therapy, 16 of the patients had objective control of their central nervous system disease. Among these 16 patients, cranial nerve palsies resolved completely in 14, and only two children were left with residual cranial nerve dysfunction. Seven patients received intrathecal chemotherapy before radiation therapy was instituted in an attempt to control their cranial nerve palsies. Cranial nerve palsy resolved in only two of these seven patients. However, the addition of whole-brain irradiation in the remaining five patients reversed cranial nerve dysfunction in four of them. The combination of intrathecal chemotherapy and central nervous system irradiation was successful in reversing cranial nerve dysfunction in 11 of 13 patients in whom central nervous system disease was ultimately controlled. As cranial nerve dysfunction is associated with distressing signs and symptoms, the combination of central nervous system irradiation and intrathecal chemotherapy is important palliative therapy to initiate promptly. Intrathecal therapy alone appears to be inadequate therapy for prompt and durable reversal of symptoms in this group of patients.
Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II
Authors: Zhonghua Qi, Chuan-Ming Hao, Robert I. Langenbach, Richard M. Breyer, Reyadh Redha, Jason D. Morrow, Matthew D. Breyer
Journal: Journal of Clinical Investigation (2002)

Therapeutic use of cyclooxygenase-inhibiting (COX-inhibiting) nonsteroidal antiinflammatory drugs (NSAIDs) is often complicated by renal side effects including hypertension and edema. The present studies were undertaken to elucidate the roles of COX1 and COX2 in regulating blood pressure and renal function. COX2 inhibitors or gene knockout dramatically augment the pressor effect of angiotensin II (Ang II). Unexpectedly, after a brief increase, the pressor effect of Ang II was abolished by COX1 deficiency (either inhibitor or knockout). Ang II infusion also reduced medullary blood flow in COX2-deficient but not in control or COX1-deficient animals, suggesting synthesis of COX2-dependent vasodilators in the renal medulla. Consistent with this, Ang II failed to stimulate renal medullary prostaglandin E2 and prostaglandin I2 production in COX2-deficient animals. Ang II infusion normally promotes natriuresis and diuresis, but COX2 deficiency blocked this effect. Thus, COX1 and COX2 exert opposite effects on systemic blood pressure and renal function. COX2 inhibitors reduce renal medullary blood flow, decrease urine flow, and enhance the pressor effect of Ang II. In contrast, the pressor effect of Ang II is blunted by COX1 inhibition. These results suggest that, rather than having similar cardiovascular effects, the activities of COX1 and COX2 are functionally antagonistic.
MicroRNA 802 Stimulates ROMK Channels by Suppressing Caveolin-1
Authors: Dao-Hong Lin, Peng Yue, Chunyang Pan, Peng Sun, Wen-Hui Wang
Journal: Journal of the American Society of Nephrology (2011)

Dietary potassium stimulates the surface expression of ROMK channels in the aldosterone-sensitive distal nephron, but the mechanism by which this occurs is incompletely understood. Here, a high-potassium diet increased the transcription of microRNA (miR) 802 in the cortical collecting duct in mice. In addition, high-potassium intake decreased the expression of caveolin-1, whose 3′ untranslated region contains the seed sequence of miR-802. In vitro, expression of miR-802 suppressed the expression of caveolin-1, and conversely, downregulation of endogenous miR-802 increased the expression of caveolin-1. Sucrose-gradient centrifugation suggested that caveolin-1 closely associated with ROMK channels, and immunoprecipitation showed that caveolin-1 interacted with the N terminus of ROMK. Expression of caveolin-1 varied inversely with the expression of ROMK1 in the plasma membrane, and caveolin-1 inhibited ROMK1 channel activity. Removal of the clathrin-dependent endocytosis motif from ROMK1 failed to abolish the effect of caveolin-1 on ROMK1 channel activity. Last, expression of miR-802 increased ROMK1 channel activity, an effect blocked by coexpression of caveolin-1. Taken together, miR-802 mediates the stimulatory effect of a high-potassium diet on ROMK channel activity by suppressing caveolin-1 expression, which leads to increased surface expression of ROMK channels in the distal nephron.
The futility of genomic counseling: essential role of electronic health records
Authors: John Belmont, Amy L McGuire
Journal: Genome Medicine (2009)

Technological advances over the past several years have dramatically reduced the cost of whole-genome sequencing. At the same time, understanding of the functional significance of genetic variation has advanced considerably. The routine generation of whole-genome sequence data for individual patients will soon be sufficiently cost-effective for widespread clinical integration. Yet, the clinical utility of whole-genome data is currently limited by an inability to effectively process, store, interpret and update genomic data, while at the same time protecting patient privacy. Enter the electronic health record. We propose that without the integration of a dynamic uniform electronic health record, counseling patients on the basis of genome-wide data will be futile.
Ethnic Differences in the Relationship Between Adiponectin and Insulin Sensitivity in South Asian and Caucasian Women
Authors: Marlene Martin, Latha P. Palaniappan, Andrea C. Kwan, Gerald M. Reaven, Peter D. Reaven
Journal: Diabetes Care (2008)

To assess whether lower adiponectin concentrations in South Asian Indians may be responsible for their greater degree of insulin resistance.Insulin-mediated glucose uptake and plasma total and high molecular weight (HMW) adiponectin concentrations were quantified in 52 women of South Asian (SA) and Caucasian (CAU) ancestry and compared.Mean +/- SD total (2,965 +/- 1,278 vs. 4,235 +/- 160 ng/ml) and HMW (1,001 +/- 352 vs. 1,591 +/- 854 ng/ml) adiponectin were lower in SAs than CAUs (P < 0.005). Insulin-resistant CAUs (CAU-IR) had lower total (2,665 +/- 1,040 vs. 5,133 +/- 1,086 ng/ml) and HMW (987 +/- 479 vs. 1,935 +/- 838 ng/ml) adiponectin than insulin-sensitive CAUs (CAU-IS) (P < 0.01), but there were no significant differences between insulin-resistant (SA-IR) and insulin-sensitive (SA-IS) SAs. HMW adiponectin did not differ between SA-IR and CAU-IR, but SA-IS had significantly lower adiponectin concentrations than CAU-IS.Insulin resistance status is not associated with significantly lower levels of adiponectin in these SA women, in contrast to the CAU women.
Large bowel myoelectrical activity in man.
Authors: I Taylor, H L Duthie, R Smallwood, D Linkens
Journal: Gut (1975)

The myoelectrical activity of human colon and rectum has been studied by three types of electrode in man--intraluminal (suction), serosal and cutaneous. The patterns obtained indicate a high degree of consistency between the methods and the value of surface electrodes is emphasized. Gradient along the large bowel of both frequency and percentage electrical activity have been observed and possible physiological roles are postulated for them. By correlating the features of regular electrical and corresponding regular motor waves an alteration in the myoelectrical pattern is observed in the region of the rectosigmoid junction.
Psychosocial Intervention Improves Depression, Quality of Life, and Fluid Adherence in Hemodialysis
Authors: Daniel Cukor, Nisha Ver Halen, Deborah Rosenthal Asher, Jeremy D. Coplan, Jeremy Weedon, Katarzyna E. Wyka, Subodh J. Saggi, Paul L. Kimmel
Journal: Journal of the American Society of Nephrology (2013)

Patients with ESRD have high rates of depression, which is associated with diminished quality of life and survival. We determined whether individual cognitive behavioral therapy (CBT) reduces depression in hemodialysis patients with elevated depressive affect in a randomized crossover trial. Of 65 participants enrolled from two dialysis centers in New York, 59 completed the study and were assigned to the treatment-first group (n=33) or the wait-list control group (n=26). In the intervention phase, CBT was administered chairside during dialysis treatments for 3 months; participants were assessed 3 and 6 months after randomization. Compared with the wait-list group, the treatment-first group achieved significantly larger reductions in Beck Depression Inventory II (self-reported, P=0.03) and Hamilton Depression Rating Scale (clinician-reported, P<0.001) scores after intervention. Mean scores for the treatment-first group did not change significantly at the 3-month follow-up. Among participants with depression diagnosed at baseline, 89% in the treatment-first group were not depressed at the end of treatment compared with 38% in the wait-list group (Fisher's exact test, P=0.01). Furthermore, the treatment-first group experienced greater improvements in quality of life, assessed with the Kidney Disease Quality of Life Short Form (P=0.04), and interdialytic weight gain (P=0.002) than the wait-list group, although no effect on compliance was evident at follow-up. In summary, CBT led to significant improvements in depression, quality of life, and prescription compliance in this trial, and studies should be undertaken to assess the long-term effects of CBT on morbidity and mortality in patients with ESRD.
Peptides containing a dominant T-cell epitope from red cell band 3 have in vivo immunomodulatory properties in NZB mice with autoimmune hemolytic anemia
Authors: Chia-Rui Shen, Abdel-Rahman Youssef, Anne Devine, Laura Bowie, Andrew M. Hall, David C. Wraith, Christopher J. Elson, Robert N. Barker
Journal: Blood (2003)
Endogenous inhibitors of angiogenesis in malignant gliomas: Nature's antiangiogenic therapy
Authors: Tanya A. Rege, Constance Y. Fears, Candece L. Gladson
Journal: Neuro-Oncology (2005)

Angiogenesis is necessary for tumor growth beyond a volume of approximately 2 mm3. This observation, along with the accessibility of tumor vessels to therapeutic targeting, has resulted in a research focus on inhibitors of angiogenesis. A number of endogenous inhibitors of angiogenesis are found in the body. Some of these are synthesized by specific cells in different organs, and others are created by extracellular proteolytic cleavage of plasma-derived or extracellular matrix-localized proteins. In this review, we focus on angiostatin, endostatin, PEX, pigment epithelial-derived factor, and thrombospondin (TSP)-1 and -2, either because these molecules are expressed in malignant glioma biopsies or because animal studies in malignant glioma models have suggested that their therapeutic administration could be efficacious. We review the known mechanisms of action, potential receptors, expression in glioma biopsy samples, and studies testing their potential therapeutic efficacy in animal models of malignant glioma. Two conclusions can be made regarding the mechanisms of action of these inhibitors: (1) Several of these inhibitors appear to mediate their antiangiogenic effect through multiple protein-protein interactions that inhibit the function of proangiogenic molecules rather than through a specific receptor-mediated signaling event, and (2) TSP-1 and TSP-2 appear to mediate their antiangiogenic effect, at least in part, through a specific receptor, CD36, which initiates the antiangiogenic signal. Although not proven in gliomas, evidence suggests that expression of specific endogenous inhibitors of angiogenesis in certain organs may be part of a host antitumor response. The studies reviewed here suggest that new antiangiogenic therapies for malignant gliomas offer exciting promise as nontoxic, growth-inhibitory agents.
The development of features in object concepts
Authors: Philippe G. Schyns, Robert L. Goldstone, Jean-Pierre Thibaut
Journal: Behavioral and Brain Sciences (1998)

According to one productive and influential approach to cognition, categorization, object recognition, and higher level cognitive processes operate on a set of fixed features, which are the output of lower level perceptual processes. In many situations, however, it is the higher level cognitive process being executed that influences the lower level features that are created. Rather than viewing the repertoire of features as being fixed by low-level processes, we present a theory in which people create features to subserve the representation and categorization of objects. Two types of category learning should be distinguished. Fixed space category learning occurs when new categorizations are representable with the available feature set. Flexible space category learning occurs when new categorizations cannot be represented with the features available. Whether fixed or flexible, learning depends on the featural contrasts and similarities between the new category to be represented and the individual's existing concepts. Fixed feature approaches face one of two problems with tasks that call for new features: If the fixed features are fairly high level and directly useful for categorization, then they will not be flexible enough to represent all objects that might be relevant for a new task. If the fixed features are small, subsymbolic fragments (such as pixels), then regularities at the level of the functional features required to accomplish categorizations will not be captured by these primitives. We present evidence of flexible perceptual changes arising from category learning and theoretical arguments for the importance of this flexibility. We describe conditions that promote feature creation and argue against interpreting them in terms of fixed features. Finally, we discuss the implications of functional features for object categorization, conceptual development, chunking, constructive induction, and formal models of dimensionality reduction.