tbuckley/cabot-search huggingface dataset:
Relationship of proctitis and rectal capacity in Crohn's disease.
Authors: P Buchmann, G A Mogg, J Alexander-Williams, R N Allan, M R Keighley
Journal: Gut (1980)

In patients with Crohn9s disease involving the rectum (n=25), there was an inverse relationship between rectal capacity and the degree of proctitis. However, in patients with Crohn9s disease not involving the rectum (n=22) the rectal capacity was similar to that of normal controls (n=20). The frequency of defaecation was not related to the degree of proctitis or to the pressure of a colectomy and ileorectal anastomosis. Control subjects had a significantly lower frequency of defaecation than patients with Crohn9s disease irrespective of involvement of the rectum.
Ultrastructure and Transport Across Epithelial Membranes
Authors: C. ADRIAN M. HOGBEN
Journal: Circulation (1962)

For epithelia, all too frequently this or that ultrastructure is spoken of as "absorptive" or "(secretory." Correlation between structure and function must relate to phenomena, such as the apparent active transport of weak electrolytes or water, that are unique for the epithelium. The macroscopic tubule of the gastric mucosa cannot sequester the active transport of hydrochloric acid from the solution bathing the mucosa. In the absence of both intracellular canaliculi and a microvillous border from the amphibian parietal cell, by exclusion, the endoplasmic reticulum or the plasma membrane proper must be considered as possible structures responsible for the sequestration.
Phase I and Pharmacokinetic Study of the Polyamine Synthesis Inhibitor SAM486A in Combination with 5-Fluorouracil/ Leucovorin in Metastatic Colorectal Cancer
Authors: Lia van Zuylen, John Bridgewater, Alex Sparreboom, Ferry A. L. M. Eskens, Peter de Bruijn, Ivo Sklenar, Andre S. T. Planting, Les Choi, Douglas Bootle, Christian Mueller, Jonathan A. Ledermann, Jaap Verweij
Journal: Clinical Cancer Research (2004)

The purpose of our study was to determine the maximum-tolerated dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the polyamine synthesis inhibitor SAM486A given in combination with 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients.Patients with advanced colorectal cancer were treated with 5-FU [bolus (400 mg/m(2)) followed by a 22-h infusion (600 mg/m(2))] and LV (200 mg/m(2)) and escalating doses of SAM486A, 1-3-h infusion daily for 3 days. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of the combinationTwenty-seven patients with metastatic colorectal cancer and 1 with pseudomyxoma peritonei were treated. Twenty-six patients received SAM486A in the combination at doses ranging from 25 to 150 mg/m(2)/day. Dose-limiting toxicity consisting of fatigue grade 3 was seen at 150 mg/m(2)/day. Other adverse events included neutropenia, hand and foot syndrome, nausea, vomiting, diarrhea, and constipation. Fifteen of 26 patients evaluable for best response according to the Southwest Oncology Group criteria achieved a partial response [8 (30%) of 26] or stable disease [9 (35%) of 26]. SAM486A did not influence the pharmacokinetics of 5-FU, and SAM486A clearance was similar to that when used as a single agent.The novel molecular agent SAM486A is tolerable and safe in combination with a standard 5-FU regimen in patients with advanced colorectal cancer. The dose of SAM486A recommended for additional studies with this combination is 125 mg/m(2)/day. A disease-directed evaluation of SAM486A using this regimen is warranted.
Cardiovascular Complications of Cancer Therapy
Authors: Edward T.H. Yeh, Ann T. Tong, Daniel J. Lenihan, S. Wamique Yusuf, Joseph Swafford, Christopher Champion, Jean-Bernard Durand, Harry Gibbs, Alireza Atef Zafarmand, Michael S. Ewer
Journal: Circulation (2004)

The cardiotoxicity of anticancer agents can lead to significant complications that can affect patients being treated for various malignancies. The severity of such toxicity depends on many factors such as the molecular site of action, the immediate and cumulative dose, the method of administration, the presence of any underlying cardiac condition, and the demographics of the patient. Moreover, toxicity can be affected by current or previous treatment with other antineoplastic agents. Cardiotoxic effects can occur immediately during administration of the drug, or they may not manifest themselves until months or years after the patient has been treated. In this article we review commonly used chemotherapy agents, including several recently approved medications, for their propensity to cause cardiotoxicity. Further research will be required to more accurately predict which patients are at risk for developing cardiotoxicity. In addition, management plans, as well as strategies to reduce cardiotoxicity, need to be developed.
Selective accumulation of virus-specific CD8+ T cells with unique homing phenotype within the human bone marrow
Authors: Umaimainthan Palendira, Rosanna Chinn, Wajid Raza, Karen Piper, Guy Pratt, Lee Machado, Andrew Bell, Naeem Khan, Andrew D. Hislop, Richard Steyn, Alan B. Rickinson, Christopher D. Buckley, Paul Moss
Journal: Blood (2008)
Initial Clinical Sensitivity and Acquired Resistance to MET Inhibition in <i>MET</i>-Mutated Papillary Renal Cell Carcinoma
Authors: Jennifer R. Diamond, Ravi Salgia, Marileila Varella-Garcia, Rajani Kanteti, Patricia M. LoRusso, Jeffrey W. Clark, Ling-Guo Xu, Keith Wilner, S. Gail Eckhardt, Keith A. Ching, Maruja E. Lira, Eric F.P.M. Schoenmakers, James G. Christensen, D. Ross Camidge
Journal: Journal of Clinical Oncology (2013)
Validation of a Brief Observation Period for Patients with Cocaine-Associated Chest Pain
Authors: Jim Edward Weber, Frances S. Shofer, G. Luke Larkin, Amit S. Kalaria, Judd E. Hollander
Journal: New England Journal of Medicine (2003)

Retrospective studies of patients with cocaine-associated chest pain suggest that a strategy of discharging patients from the emergency department after a 12-hour observation period if they do not have evidence of ischemia should be associated with a very low rate of complications.We prospectively evaluated the safety of a 9-to-12-hour observation period in patients with cocaine-associated chest pain who were at low-to-intermediate risk of cardiovascular events. Consecutive patients who reported or tested positive for cocaine use and who received protocol-driven care in a chest-pain observation unit were included. Patients who had normal levels of troponin I, without new ischemic changes on electrocardiography, and who had no cardiovascular complications (dysrhythmias, acute myocardial infarction, or recurrent symptoms) during the 9-to-12-hour observation period were discharged from the unit. The main outcome was death from cardiovascular causes at 30 days.Three hundred forty-four patients with cocaine-associated chest pain were evaluated. Forty-two of these patients (12 percent) were directly admitted to the hospital. The study cohort comprised the remaining 302 patients. During the 30-day follow-up period, none of the patients died of a cardiovascular event (0 percent; 95 percent confidence interval, 0 to 0.99), and only 4 of the 256 patients for whom detailed follow-up data were available had a nonfatal myocardial infarction (1.6 percent; 95 percent confidence interval, 0.1 to 3.1). All four nonfatal myocardial infarctions occurred in patients who continued to use cocaine.Patients with cocaine-associated chest pain who do not have evidence of ischemia or cardiovascular complications over a 9-to-12-hour period in a chest-pain observation unit have a very low risk of death or myocardial infarction during the 30 days after discharge.
Assessment of Therapeutic Misconception in Older Schizophrenia Patients With a Brief Instrument
Authors: Laura B. Dunn, Barton W. Palmer, Monique Keehan, Dilip V. Jeste, Paul S. Appelbaum
Journal: American Journal of Psychiatry (2006)

"Therapeutic misconception," or conflation of goals and procedures of clinical research with those of usual clinical care, is an important topic in research ethics because it may impede informed consent. How best to assess therapeutic misconception is unclear. Also unclear is to what degree patients with severe mental illnesses, such as schizophrenia, may manifest these beliefs.With a hypothetical, double-blind, placebo-controlled trial as a stimulus, the authors examined the frequency of a key aspect of therapeutic misconception with a true/false scale in 87 middle-age and older patients with schizophrenia or schizoaffective disorder. They also analyzed the demographic, clinical, neurocognitive, and decision-making correlates of therapeutic misconception and examined the psychometric properties of a scale designed to measure therapeutic misconception.Subjects showed variable performance on the therapeutic misconception measure. Nearly one-third answered all questions correctly; two-thirds answered four or more of the six items correctly. Patients with less education or worse cognitive functioning manifested higher levels of therapeutic misconception. Degree of therapeutic misconception was inversely associated with understanding, appreciation, and reasoning scores on the MacArthur Competence Assessment Tool for Clinical Research but was not associated with severity of psychopathology. The scale showed fair internal consistency.As in studies of other patient populations, patients with schizophrenia show a substantial incidence of beliefs associated with therapeutic misconception. Further work should focus on refining measures of therapeutic misconception, identifying participants or protocols (e.g., higher-risk studies) in which it may warrant greater concern, and developing educational interventions to mitigate it.
Does Delay in Starting Treatment Affect the Outcomes of Radiotherapy? A Systematic Review
Authors: Jenny Huang, Lisa Barbera, Melissa Brouwers, George Browman, William J. Mackillop
Journal: Journal of Clinical Oncology (2003)

Purpose: The objective of this study was to synthesize what is known about the relationship between delay in radiotherapy (RT) and the outcomes of RT. Methods: A systematic review of the world literature was conducted to identify studies that described the association between delay in RT and the probability of local control, metastasis, and/or survival. Studies were classified by clinical and methodologic criteria and their results were combined using a random-effects model. Results: A total of 46 relevant studies involving 15,782 patients met our minimum methodologic criteria of validity; most (42) were retrospective observational studies. Thirty-nine studies described rates of local recurrence, 21 studies described rates of distant metastasis, and 19 studies described survival. The relationship between delay and the outcomes of RT had been studied in diverse situations, but most frequently in breast cancer (21 studies) and head and neck cancer (12 studies). Combined analysis showed that the 5-year local recurrence rate (LRR) was significantly higher in patients treated with adjuvant RT for breast cancer more than 8 weeks after surgery than in those treated within 8 weeks of surgery (odds ratio [OR] = 1.62, 95% confidence interval [CI], 1.21 to 2.16). Combined analysis also showed that the LRR was significantly higher among patients who received postoperative RT for head and neck cancer more than 6 weeks after surgery than among those treated within 6 weeks of surgery (OR = 2.89; 95% CI, 1.60 to 5.21). There was little evidence about the impact of delay in RT on the risk of metastases or the probability of long-term survival in any situation. Conclusion: Delay in the initiation of RT is associated with a decrease in LRR in breast cancer and head and neck cancer. Delays in starting RT should be as short as reasonably achievable.
The Surgical Learning Curve for One-stage Anterior Urethroplasty: A Prospective Single-surgeon Study
Authors: Nicola Fossati, Guido Barbagli, Alessandro Larcher, Paolo Dell’Oglio, Salvatore Sansalone, Giovanni Lughezzani, Giorgio Guazzoni, Francesco Montorsi, Massimo Lazzeri
Journal: European Urology (2015)
Corticosteroid Inhibition of ACTH Secretion*
Authors: MAUREEN E. KELLER-WOOD, MARY F. DALLMAN
Journal: Endocrine Reviews (1984)

THE LEVEL of activity within the adrenocortical system is determined by endogenous (circadian) and exogenous (stress) excitatory inputs, by inhibitory neural modulation and also by corticosteroid negative feedback control. Although corticosteroid feedback on (CRF and) ACTH secretion is easily demonstrated by treatment of mammals with exogenous glucocorticoids and subsequent measurement of either basal or stimulated activity in the system, the physiological role of this negative feedback is not so easily discerned. It is likely that most disagreement about feedback regulation of ACTH secretion has arisen because of three characteristics of the system. First, it now appears that there are at least three distinct time domains in which negative feedback by glucocorticoids on ACTH secretion are exerted. These can be distinguished at the level of the corticotrope in vitro by the different cellular effects of glucocorticoid action. Thus, interpretation of results of in vivo experiments is critically dependent on the timing of the experiment relative to the glucocorticoid signal.
MicroRNAs in colorectal cancer: translation of molecular biology into clinical application
Authors: Ondrej Slaby, Marek Svoboda, Jaroslav Michalek, Rostislav Vyzula
Journal: Molecular Cancer (2009)

MicroRNAs (miRNAs) are small non-coding RNAs 18-25 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Changes in the expression profiles of miRNAs have been observed in a variety of human tumors, including colorectal cancer (CRC). Functional studies indicate that miRNAs act as tumor suppressors and oncogenes. These findings significantly extend Vogelstein's model of CRC pathogenesis and have shown great potential for miRNAs as a novel class of therapeutic targets. Several investigations have also described the ability of miRNA expression profiles to predict prognosis and response to selected treatments in CRC patients, and support diagnosis of CRC among cancer of unknown primary site. miRNAs' occurrence has been repeatedly observed also in serum and plasma, and miRNAs as novel minimally invasive biomarkers have indicated reasonable sensitivity for CRC detection and compare favorably with the fecal occult blood test. In this review, we summarize the knowledge regarding miRNAs' functioning in CRC while emphasizing their significance in pathogenetic signaling pathways and their potential to serve as disease biomarkers and novel therapeutic targets.
Evidence for GC-biased gene conversion as a driver of between-lineage differences in avian base composition
Authors: Claudia C Weber, Bastien Boussau, Jonathan Romiguier, Erich D Jarvis, Hans Ellegren
Journal: Genome biology (2014)

While effective population size (Ne) and life history traits such as generation time are known to impact substitution rates, their potential effects on base composition evolution are less well understood. GC content increases with decreasing body mass in mammals, consistent with recombination-associated GC biased gene conversion (gBGC) more strongly impacting these lineages. However, shifts in chromosomal architecture and recombination landscapes between species may complicate the interpretation of these results. In birds, interchromosomal rearrangements are rare and the recombination landscape is conserved, suggesting that this group is well suited to assess the impact of life history on base composition.
Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates
Authors: A NEWBY
Journal: Cardiovascular Research (2005)

Intimal thickening occurs in blood vessels in response to injury or atherosclerosis. The balance of migration and proliferation of vascular smooth muscle cells (VSMC) over death by apoptosis has an important impact on the final size of intimal thickening and may also affect atherosclerotic plaque stability. All aspects of VSMC behaviour are under coordinated control by growth factors, cell–matrix and cell–cell interactions. We review the evidence that matrix-degrading metalloproteinases (MMPs) regulate migration, proliferation and survival of VSMC. Moreover, we discuss critically the underlying mechanisms, which include changing growth factor availability and remodelling cell–matrix and cell–cell contacts. We conclude that MMPs influence VSMC behaviour by cleaving both matrix and non-matrix substrates.
The Major Podocyte Protein Nephrin Is Transcriptionally Activated by the Wilms’ Tumor Suppressor WT1
Authors: Nicole Wagner, Kay-Dietrich Wagner, Yiming Xing, Holger Scholz, Andreas Schedl
Journal: Journal of the American Society of Nephrology (2004)

NPHS1 encodes the structural protein nephrin, which has a crucial role in the filtration barrier of the glomerular podocyte. Mutations or deregulation of NPHS1 are associated with a variety of renal diseases, including the Finnish type congenital nephrotic syndrome. This study analyzed a potential regulation of nephrin by the Wilms’ tumor protein, Wt1. Using an inducible U2OS osteosarcoma cell line, it is shown that upon Wt1 induction, endogenous nephrin mRNA becomes highly upregulated. Co-transfection studies demonstrate that Wt1 can activate the nephrin promoter >10-fold. DNase footprinting and mutation analysis identify a Wt1 responsive element in the nephrin promoter, which is required for the binding of Wt1 protein. Mutations or deletion of this Wt1 responsive element completely abolished transactivation of the nephrin promoter by Wt1. Moreover, transgenic analysis demonstrates the requirement of the identified binding site to direct podocyte-specific expression of a reporter gene in transgenic mice, thus confirming the importance of this site for the regulation of nephrin in vivo. Finally, it is shown that nephrin expression is lowest in kidneys of mice that lack specifically the Wt1(−KTS) splice variant, but in comparison with wild-type littermates, it is also reduced in animals with disruption of the Wt1(+KTS) splice variant. Taken together, these data identify nephrin as a direct transcriptional target for Wt1 and underline the importance of Wt1 as a key regulator in podocyte function.
Molecular evolution of the fungi: human pathogens.
Authors: B H Bowman, J W Taylor, T J White
Journal: Molecular Biology and Evolution (1992)

The morphological, ecological, and clinical diversity among ascomycete fungi that are pathogenic to humans suggest that the potential for pathogenicity may have arisen multiple times within these higher fungi. We have obtained 18S ribosomal DNA sequences from a diverse group of human pathogenic fungi in order to determine their evolutionary origins. The fungi studied include a skin pathogen that is confined to humans (Trichophyton rubrum) and three systemic, facultative parasites that cause histoplasmosis (Histoplasma capsulatum), blastomycosis (Blastomyces dermatitidis) and coccidioidomycosis (Coccidioides immitis) in humans and other higher animals. Also included in our analysis are representatives of non-pathogenic fungi, as well as two opportunistic pathogens, Pneumocystis carinii and Candida albicans, that cause severe disease in immunocompromised individuals, especially those with AIDS. Two of the fungi we sequenced, T. rubrum and C. immitis, are limited to asexual modes of reproduction and therefore lack the sexual structures that are most useful for evolutionary comparison as well as being essential for classification among the higher fungi. Coccidioides immitis is particularly problematic owing to its contradictory and confusing asexual morphologies, which have caused it to be placed in three fungal classes and the protista. Our analysis shows that the specialized, superficial parasite and the systemic, facultative parasites, including C. immitis, are closely related ascomycetes, which clearly demonstrates the power of molecular characters to compensate for missing or confusing reproductive morphology. Analysis also shows that the opportunistic pathogens are more distantly related, with the likely explanation that pathogenicity has arisen more than once within the Ascomycetes.
Different perceptions of disease severity and self care between patients with cystic fibrosis, their close companions, and physician.
Authors: J Abbott, M Dodd, A K Webb
Journal: Thorax (1995)

BACKGROUND--An investigation was carried out to determine whether patients with cystic fibrosis, their close companions, and physician perceived the severity of the disease and the level of patient self care similarly. METHODS--Sixty adults with cystic fibrosis (16-44 years), their close companion, and physician independently completed scales measuring their perceptions of disease severity and patient self care on three occasions over a two year period. Percentage predicted forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), Shwachman score, and weight for height were recorded following each assessment. RESULTS--Patients and close companions considered the disease to be less severe than their physician. Fifty patients (83%) rated their health as "above/well above average", and 49 (82%) close companions rated the patient9s health in the same way, but only 21 (35%) patients were considered by their physician to have mild disease. Differences also emerged in the estimation of patient self care; 48 close companions (80%) rated patients as "very good" or "excellent" in their self care, compared with 26 (44%) of the patients themselves. Only nine patients (15%) were considered to achieve this level of self care by their physician. Over the two year period the physician9s ratings of severity increased in accordance with the decline in lung function. Patients9 perceptions remained unchanged. CONCLUSIONS--From the physician9s view-point, patients and close companions underestimate the severity of cystic fibrosis and overestimate patient self care. Patients9 perceptions remain constant over time even when their health is clinically deteriorating.