tbuckley/cabot-search huggingface dataset:
Ovarian Surface Epithelium: Biology, Endocrinology, and Pathology*
Authors: Nelly Auersperg, Alice S. T. Wong, Kyung-Chul Choi, Sung Keun Kang, Peter C. K. Leung
Journal: Endocrine Reviews (2001)

Abstract The epithelial ovarian carcinomas, which make up more than 85% of human ovarian cancer, arise in the ovarian surface epithelium (OSE). The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies because there are no appropriate animal models, and because methods to culture OSE have become available only recently. The objective of this article is to review the cellular and molecular mechanisms that underlie the control of normal and neoplastic OSE cell growth, differentiation, and expression of indicators of neoplastic progression. We begin with a brief discussion of the development of OSE, from embryonic to the adult. The pathological and genetic changes of OSE during neoplastic progression are next summarized. The histological characteristics of OSE cells in culture are also described. Finally, the potential involvement of hormones, growth factors, and cytokines is discussed in terms of their contribution to our understanding of the physiology of normal OSE and ovarian cancer development.
Phase I and Pharmacokinetic Study of Tasidotin Hydrochloride (ILX651), a Third-Generation Dolastatin-15 Analogue, Administered Weekly for 3 Weeks Every 28 Days in Patients with Advanced Solid Tumors
Authors: Alain C. Mita, Lisa A. Hammond, Peter L. Bonate, Geoffrey Weiss, Heather McCreery, Samira Syed, Mitchell Garrison, Quincy S.C. Chu, Johann S. DeBono, Christopher B. Jones, Steve Weitman, Eric K. Rowinsky
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To determine the safety, tolerability, and pharmacokinetics and to seek preliminary evidence of anticancer activity of tasidotin (ILX651), a novel dolastatin analogue, when administered as a 30-minute i.v. infusion weekly for 3 weeks every 4 weeks. Experimental Design: Thirty patients with advanced solid malignancies were treated with 82 courses at six dose levels ranging from 7.8 to 62.2 mg/m2 weekly, initially according to an accelerated dose-escalation scheme, which evolved into a Fibonacci scheme as a relevant degree of toxicity was observed. Plasma and urine were sampled to characterize the pharmacokinetic behavior of tasidotin. Results: A high incidence of neutropenia complicated by fever (one patient), or precluding treatment on day 15 (three patients), was the principal toxicity of tasidotin, at doses above 46.8 mg/m2. At all dose levels, nonhematologic toxicities were generally mild to moderate and manageable. Grade 3 toxicities included diarrhea and vomiting (one patient each). Drug-induced neurosensory symptoms were mild and there was no evidence of cardiovascular toxicity, which has been previously associated with other dolastatins. Tasidotin pharmacokinetics were mildly nonlinear, whereas metabolite kinetics were linear. A patient with non–small cell lung carcinoma experienced a minor response, and a patient with hepatocellular carcinoma had stable disease lasting 11 months. Conclusions: The recommended dose for phase II studies of tasidotin administered on this schedule is 46.8 mg/m2. The mild myelosuppression and manageable nonhematologic toxicities at the recommended dose, the evidence of antitumor activity, and the unique mechanistic aspects of tasidotin warrant further disease-directed evaluations on this and alternative schedules.
B-cell precursors specific to sheep erythrocytes. Estimation of frequency in a specific helper assay.
Authors: M H Schreier
Journal: The Journal of Experimental Medicine (1978)

A sensitive, specific, and reproducible in vitro helper assay is described which is suited to limiting dilution analysis of murine B cells. 1 in about 3,000 syngeneic splenic B cells can be induced to form plaque-forming cells (PFC) to sheep erythrocytes in this system. The induction of PFC is absolutely dependent on antigen and specific helper T cells.
Chemotherapy without irradiation--a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study.
Authors: C Balmaceda, G Heller, M Rosenblum, B Diez, J G Villablanca, S Kellie, P Maher, V Vlamis, R W Walker, S Leibel, J L Finlay
Journal: Journal of Clinical Oncology (1996)

PURPOSE Radiation therapy for CNS germ cell tumors (GCT) is commonly associated with neurologic sequelae. We designed a therapeutic trial to determine whether irradiation could be avoided. PATIENTS AND METHODS Patients received four cycles of carboplatin, etoposide, and bleomycin. Those with a complete response (CR) received two further cycles; others received two cycles intensified by cyclophosphamide. RESULTS Seventy-one patients were enrolled (45 with germinoma and 26 with nongerminomatous GCT [NGGCT]). Sixty-eight were assessable for response. Thirty-nine of 68 (57%) achieved a CR within four cycles. Of 29 patients with less than a CR, 16 achieved CR with intensified chemotherapy or second surgery. Overall, 55 of 71 (78%) achieved a CR without irradiation. The CR rate was 84% for germinomas and 78% for NGGCT. With a median follow-up duration of 31 months, 28 of 71 patients were alive without relapse or progression. Thirty-five showed tumor recurrence (n = 28) or progression (n = 7) at a median of 13 months. Twenty-six of 28 patients (93%) who recurred following remission underwent successful salvage therapy. Pathology was the only variable predictive of survival. The probability of surviving 2 years was .84 for germinoma patients and .62 for NGGCT. Seven of 71 patients died of toxicity associated with study chemotherapy. CONCLUSION Forty-one percent of surviving patients and 50% of all patients were treated successfully with chemotherapy only without irradiation. Chemotherapy-only regimens for CNS GCT, although encouraging, should continue to be used only in the setting of formal clinical trials.
Effects of bowel cleansing on the intestinal microbiota
Authors: Jonna Jalanka, Anne Salonen, Jarkko Salojärvi, Jarmo Ritari, Outi Immonen, Luca Marciani, Penny Gowland, Caroline Hoad, Klara Garsed, Ching Lam, Airi Palva, Robin C Spiller, Willem M de Vos
Journal: Gut (2014)

<h3>Objective</h3> An adequate bowel cleansing is essential for a successful colonoscopy. Although purgative consumption is safe for the patient, there is little consensus on how the intestinal microbiota is affected by the procedure, especially regarding the potential long-term consequences. <h3>Design</h3> 23 healthy subjects were randomised into two study groups consuming a bowel preparation (Moviprep), either in two separate doses of 1 L or as a single 2-L dose. Participants donated faecal samples at the baseline, after bowel cleansing, 14 and 28 days after the treatment. The intestinal microbiota composition was determined with phylogenetic microarray as well as quantitative PCR analysis and correlated with the previously quantified faecal serine proteases. <h3>Results</h3> The lavage introduced an instant and substantial change to the intestinal microbiota. The total microbial load was decreased by 31-fold and 22% of the participants lost the subject-specificity of their microbiota. While the bacterial levels and community composition were essentially restored within 14 days, the rate of recovery was dose dependent: consumption of the purgative in a single dose had a more severe effect on the microbiota composition than that of a double dose, and notably increased the levels of Proteobacteria, Fusobacteria and bacteria related to <i>Dorea formicigenerans.</i> The abundance of the latter also correlated with the amount of faecal serine proteases that were increased after purging. <h3>Conclusions</h3> Our results suggest that the bowel cleansing using two separate dosages introduces fewer alterations to the intestinal microbiota than a single dose and hence may be preferred in clinical practice.
Drug therapy in undifferentiated arthritis: a systematic literature review
Authors: K V C Wevers-de Boer, L Heimans, T W J Huizinga, C F Allaart
Journal: Annals of the Rheumatic Diseases (2013)

Undifferentiated arthritis (UA) is defined as an inflammatory oligoarthritis or polyarthritis in which no definitive diagnosis can be made. We performed a literature review to assess the efficacy of various drug therapies in patients with UA. The literature search was conducted using electronic databases Pubmed, EMBASE and MEDLINE in adults with UA or early arthritis (not fulfilling the American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism (EULAR) 2010 criteria for rheumatoid arthritis). Drug therapy consisted of disease modifying antirheumatic drugs (DMARDs), biological agents and oral, intramuscular or intra-articular corticosteroids. Nine publications on eight randomised controlled trials (RCTs), two publications on two uncontrolled open-label trials and seven publications on three cohort studies were included. Temporary treatment with methotrexate (MTX), abatacept and intramuscular corticosteroids were demonstrated in RCTs with 12 months to 5 years follow-up to be more effective than placebo in suppressing disease activity or radiological progression. One study suggests that DMARD combination therapy is, at least after 4 months, superior to MTX monotherapy in patients with UA at high risk of developing persistent arthritis. The open-label uncontrolled trials and cohort studies also suggested that early treatment may provide immediate suppression of inflammation. The long-term benefit of early treatment in UA remains unclear. In conclusion, patients with UA benefit from early treatment with MTX. Combining multiple DMARDs or DMARDs with corticosteroids and biological agents may be even more beneficial. However, which treatment may provide the best results or may alter the disease course has still to be determined. More RCTs with longer follow-up time are needed.
Improved outcome in childhood acute lymphoblastic leukaemia with reinforced early treatment and rotational combination chemotherapy
Authors: G.K. Rivera, C.-H. Pui, M. Abromowitch, J. Mirro, J.S. Ochs, A.T. Look, S.B. Murphy, G.V. Dahl, D.K. Kalwinsky, J.V. Simone, W.M. Crist, S.C. Raimondi, F.G. Behm, C.-H. Pui, D.L. Williams, M.L. Hancock, W.E. Evans, L.E. Kun
Journal: The Lancet (1991)
THE INHIBITION OF ACETYLCHOLINE-INDUCED ATRIOVENTRICULAR BLOCK BY POTASSIUM*
Authors: Charles Fisch, Harvey Feigenbaum, John A. Bowers
Journal: Journal of Clinical Investigation (1963)

The exact relationship of potassium and digi- talis is still an unsettled question despite intensive study by numerous investigators.There is evi- dence to indicate that in subjects with atrial fibril- lation treated with digitalis, intravenous potas- sium results either in "improvement" of atrioven- tricular (AV) conduction, or in progression of the AV block (1-3).The possibility has been entertained that this paradoxical response to potas- sium depends on whether the digitalis-induced AV block is due to the vagal or to the direct effect of the glycoside on the conduction tissue (4).The present study was thus designed to in- vestigate the hypothesis that hyperkalemia acts by inhibiting the effect of acetylcholine on AV con- duction. METHODEleven experiments were performed in seven mongrel dogs weighing 10 to 14 kg.The animals were anesthe- tized with either 30 mg per kg body weight of pentobarbi- tal, or a combination of 2.5 mg per kg of im morphine followed by 15 mg per kg of iv pentobarbital.The dogs were then connected to a Harvard respirator, a bilateral cervical vagotomy was performed, and an arterial cath- eter was placed just above the aortic valve.Increasing amounts of acetylcholine were injected through this cathe- ter for 15 seconds until an amount was reached that consistently induced second or third degree AV block.This amount was constant for any one experiment, but varied from 0.096 to 0.955 mg in the different experiments.With an electric interval-timer, this amount of acetylcholine was then given every 2 minutes without in- terruption throughout the experiment.The control observations consisted of 4 to 8 consecu-
Memory metaphors and the real-life/laboratory controversy: Correspondence versus storehouse conceptions of memory
Authors: Asher Koriat, Morris Goldsmith
Journal: Behavioral and Brain Sciences (1996)

Abstract The study of memory is witnessing a spirited clash between proponents of traditional laboratory research and those advocating a more naturalistic approach to the study of “real-life” or “everyday” memory. The debate has generally centered on the “what” (content), “where” (context), and “how” (methods) of memory research. In this target article, we argue that the controversy discloses a further, more fundamental breach between two underlying memory metaphors, each having distinct implications for memory theory and assessment: Whereas traditional memory research has been dominated by the storehouse metaphor, leading to a focus on the number of items remaining in store and accessible to memory, the recent wave of everyday memory research has shifted toward a correspondence metaphor, focusing on the accuracy of memory in representing past events. The correspondence metaphor calls for a research approach that differs from the traditional one in important respects: in emphasizing the intentional –representational function of memory, in addressing the wholistic and graded aspects of memory correspondence, in taking an output-bound assessment perspective, and in allowing more room for the operation of subject-controlled metamemory processes and motivational factors. This analysis can help tie together soine of the what, where, and how aspects of the “real-life/laboratory” controversy. More important, however, by explicating the unique metatheoretical foundation of the accuracy-oriented approach to memory we aim to promote a more effective exploitation of the correspondence metaphor in both naturalistic and laboratory research contexts.
Clinical Phenotype and Genotype of Children with Borderline Sweat Test and Abnormal Nasal Epithelial Chloride Transport
Authors: Isabelle Sermet-Gaudelus, Emanuelle Girodon, Dorota Sands, Nathalie Stremmler, Vera Vavrova, Eric Deneuville, Philippe Reix, Stéphanie Bui, Frédéric Huet, Muriel Lebourgeois, Anne Munck, Albert Iron, Veronika Skalicka, Thierry Bienvenu, Delphine Roussel, Gérard Lenoir, Gabriel Bellon, Jacques Sarles, Milan Macek, Michel Roussey, Isabelle Fajac, Aleksander Edelman
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

The diagnosis of cystic fibrosis (CF) is based on a characteristic clinical picture in association with a sweat chloride (Cl(-)) concentration greater than 60 mmol/L or the identification of two CF-causing mutations. A challenging problem is the significant number of children for whom no definitive diagnosis is possible because they present with symptoms suggestive of CF, a sweat chloride level in the intermediate range between 30 and 60 mmol/L, and only one or no identified CF-causing mutation.To investigate the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in the airways of children with intermediate sweat tests and inconclusive genetic findings in correlation with clinical phenotype and genotype.We developed a composite nasal potential difference (NPD) diagnostic score to discriminate patients with CF from non-CF patients. We tested NPD in 50 children (age, 6 mo to 18 yr) with equivocal diagnoses and correlated the NPD diagnostic score with clinical phenotypes and genotypes.Fifteen of the 50 children had NPD scores in the CF range. Eight of the 15 carried two CFTR mutations compared with only 5 of the 35 children with normal NPD scores (P = 0.01). They were significantly younger at evaluation and had recurrent lower respiratory tract infections, chronic productive coughs, and chronic Staphylococcus aureus colonization significantly more often than the 35 children with normal NPD results.Evaluation of CFTR function in the nasal epithelium of children with inconclusive CF diagnoses can be a useful diagnostic tool and help clinicians to individualize therapeutic strategy.
HLA-A2.1–restricted Education and Cytolytic Activity of CD8+ T Lymphocytes from β2 Microglobulin (β2m) HLA-A2.1 Monochain Transgenic H-2Db β2m Double Knockout Mice
Authors: Steve Pascolo, Nathalie Bervas, Jan M. Ure, Austin G. Smith, François A. Lemonnier, Béatrice Pérarnau
Journal: The Journal of Experimental Medicine (1997)

Three different HLA-A2.1 monochains were engineered in which either the human or mouse β2-microglobulin (β2m) is covalently linked to the NH2 terminus of the heavy chain by a 15– amino acid long peptide: HHH, entirely human, HHD, with the mouse H-2Db α3, transmembrane, and cytoplasmic domains, and MHD, homologous to HHD but linked to the mouse β2mb. The cell surface expression and immunological capacities of the three monochains were compared with transfected cells, and the selected HHD construct was introduced by transgenesis in H-2Db−/− β2m−/− double knockout mice. Expression of this monochain restores a sizable peripheral CD8+ T cell repertoire essentially educated on the transgenic human molecule. Consequently, infected HHD, H-2Db−/− β2m−/− mice generate only HLA-A2.1–restricted CD8+ CTL responses against influenza A and vaccinia viruses. Interestingly, the CTL response to influenza A virus is mostly, if not exclusively, directed to the 58-66 matrix peptide which is the HLA-A2.1–restricted immunodominant epitope in humans. Such mice might constitute a versatile animal model for the study of HLA-A2.1–restricted CTL responses of vaccine interest.
Hypertrophic pulmonary osteoarthropathy in a patient with pulmonary alveolar microlithiasis
Authors: S. Emri, L. Coplu, Z T. Selcuk, A A. Sahin, Y I. Baris
Journal: Thorax (1991)

Abstract Hypertrophic pulmonary osteoarthropathy occurred in a patient with proved pulmonary alveolar microlithiasis, an association not previously reported.
Optical Action Potential Upstroke Morphology Reveals Near-Surface Transmural Propagation Direction
Authors: Christopher J. Hyatt, Sergey F. Mironov, Frederick J. Vetter, Christian W. Zemlin, Arkady M. Pertsov
Journal: Circulation Research (2005)

The analysis of surface-activation patterns and measurements of conduction velocity in ventricular myocardium is complicated by the fact that the electrical wavefront has a complex 3D shape and can approach the heart surface at various angles. Recent theoretical studies suggest that the optical upstroke is sensitive to the subsurface orientation of the wavefront. Our goal here was to (1) establish the quantitative relationship between optical upstroke morphology and subsurface wavefront orientation using computer modeling and (2) test theoretical predictions experimentally in isolated coronary-perfused swine right ventricular preparations. We show in numerical simulations that by suitable placement of linear epicardial stimulating electrodes, the angle phi of wavefronts with respect to the heart surface can be controlled. Using this method, we developed theoretical predictions of the optical upstroke shape dependence on phi. We determined that the level VF* at which the rate of rise of the optical upstroke reaches the maximum linearly depends on phi. A similar relationship was found in simulations with epicardial point stimulation. The optical mapping data were in good agreement with theory. Plane waves propagating parallel to myocardial fibers produced upstrokes with VF*<0.5, consistent with theoretical predictions for phi>0. Similarly, we obtained good agreement with theory for plane waves propagating in a direction perpendicular to fibers (VF*>0.5 when phi<0). Finally, during epicardial point stimulation, we discovered characteristic saddle-shaped VF* maps that were in excellent agreement with theoretically predicted changes in phi during wavefront expansion. Our findings should allow for improved interpretation of the results of optical mapping of intact heart preparations.
Association of Lower Plasma Fetuin-A Levels With Peripheral Arterial Disease in Type 2 Diabetes
Authors: Luis H. Eraso, Naeema Ginwala, Atif N. Qasim, Nehal N. Mehta, Rachel Dlugash, Shiv Kapoor, Stanley Schwartz, Mark Schutta, Nayyar Iqbal, Emile R. Mohler, Muredach P. Reilly
Journal: Diabetes Care (2009)

Fetuin-A is an inhibitor of vascular calcification and a mediator of insulin resistance. This study evaluated the association of plasma fetuin-A and peripheral arterial disease (PAD).A total of 738 individuals with type 2 diabetes (mean age 58.7 years, 37.1% female) without known cardiovascular or kidney disease were included in this cross-sectional analysis.Subjects with PAD had a significantly lower fetuin-A (264.3 vs. 293.4 ng/dl, P < 0.001). In multivariable analysis, a 1-SD decrease in fetuin-A increased the odds of PAD (odds ratio 1.6, P = 0.02). Subgroup analysis revealed an increased odds even in subjects with glomerular filtration rate >80 (odds ratio 1.9, P = 0.05) or high-sensitivity C-reactive protein <3 mg/dl (odds ratio 2.7, P = 0.002).Lower circulating fetuin-A is associated with PAD in type 2 diabetes beyond traditional and novel cardiovascular risk factors. Our findings suggest a potentially unique role for fetuin-A deficiency as a biomarker of PAD in patients with type 2 diabetes.
A mild variant of cystic fibrosis.
Authors: E W Alton
Journal: Thorax (1996)

Background.Cystic fibrosis is the most common lethal autosomal recessive disorder among whites.Among Dutch patients with cystic fibrosis, JF508 is the most common mutation and A455E the second most common mutation of the cystic fibrosis transmembrane conductance regulator gene on chromosome 7. A455E is associated with preserved pancreatic function and residual secretion of chloride across membranes.We investigated whether it is also associated with less severe pulmonary disease in patients with cystic fibrosis.Methods.A total of 33 patients with compound heterozygosity for the A455E mutation were matched according to age and sex with patients who were homozygous for the JF508 mutation.The pairs were analyzed with respect to the following outcome variables: age at diagnosis, pulmonary-function values, and the frequency of pseudomonas colonization, pancreatic sufficiency, and diabetes mellitus.Results.Cystic fibrosis was diagnosed at a later age in the patients with the A455E mutation than in the JF508 homozygotes (mean age at diagnosis, 15-0 vs. 3*1 years;