tbuckley/cabot-search huggingface dataset:
Abstract 1807: Tumor-infilitrating lymphocytes derived from pancreatic adenocarcinoma exhibit an activated, pro-inflammatory phenotype
Authors: MacLean S. Hall, Barbara Centeno, Mokenge Malafa, Pamela J. Hodul, Jeffrey S. Weber, Shari Pilon-Thomas, Amod A. Sarnaik
Journal: Cancer Research (2011)

Abstract Contrary to current dogma, which maintains that pancreatic adenocarcinoma (PA) is infiltrated by predominantly inhibitory, regulatory CD4+ T cells (Treg), we demonstrate expansion of activated, pro-inflammatory tumor-infiltrating lymphocytes (TILs) from PA that could be used for adoptive cell therapy. TILs were grown in vitro in high-dose IL-2 from fragments of primary or metastatic PA. Pancreatic TILs were successfully expanded in 9 of 10 tumors and were phenotyped by flow cytometry. CD3+ TILs were predominantly CD4+ (mean frequency 76%, range 37-97%). CD4+ TILs were assessed for Treg frequency by CD25 and FoxP3 co-expression as a percent of total CD3+ TILs. Tregs were found to comprise the minority of CD3+ TILs (mean=3.1%, range=0.36-6.6%). We assessed CD4+ TIL expression of CD69, a known marker of T cell activation, and found a relatively high percentage of CD4+ TILs expressed CD69 (mean=25%, range=9-46%), which was significantly higher than the mean percent of Treg (p=0.0006). To confirm pro-inflammatory function, bulk TILs were stimulated in vitro by PMA/ionomycin, and expression of the pro-inflammatory cytokine IFNγ and the cytolytic marker CD107a was assessed. CD4+ TILs demonstrated a relatively high level of expression of IFNγ (mean=35%, range=20-47%) and CD107a (mean=19%, range=10-26%). Despite a low relative frequency, CD8+ TILs (mean=17%, range=1.8-41%) also expressed CD69 (mean=46%, range=17-83%) and exhibited a pro-inflammatory function upon stimulation as demonstrated by IFNγ (mean=43%, range=31-61%) and CD107a (mean=42%, range=22-69%) expression. After CD4 depletion, CD8-enriched TILs were effectively expanded with α-CD3 and maintained an activated, pro-inflammatory phenotype. This is the first report demonstrating that CD4+ TILs derived from PA have a predominantly pro-inflammatory phenotype. CD8+ TILs, though in the minority, also displayed an activated phenotype and preserved this phenotype throughout selective expansion. Further work is ongoing to support a phase I clinical trial involving adoptive TIL therapy in PA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1807. doi:10.1158/1538-7445.AM2011-1807
Addition of Angiotensin II Receptor Blockade to Maximal Angiotensin-Converting Enzyme Inhibition Improves Exercise Capacity in Patients With Severe Congestive Heart Failure
Authors: Glenn Hamroff, Stuart D. Katz, Donna Mancini, Ira Blaufarb, Rachel Bijou, Rajoo Patel, Guillaume Jondeau, Maria-Teresa Olivari, Sylvia Thomas, Thierry H. Le Jemtel
Journal: Circulation (1999)

Incomplete suppression of the renin-angiotensin system during long-term ACE inhibition may contribute to symptomatic deterioration in patients with severe congestive heart failure (CHF). Combined angiotensin II type I (AT1) receptor blockade and ACE inhibition more completely suppresses the activated renin-angiotensin system than either intervention alone in sodium-depleted normal individuals. Whether AT1 receptor blockade with losartan improves exercise capacity in patients with severe CHF already treated with ACE inhibitors is unknown.Thirty-three patients with severe CHF despite treatment with maximally recommended or tolerated doses of ACE inhibitors were randomized 1:1 to receive 50 mg/d losartan or placebo for 6 months in addition to standard therapy in a multicenter, double-blind trial. Peak aerobic capacity (V(O2)) during symptom-limited treadmill exercise and NYHA functional class were determined at baseline and after 3 and 6 months of double-blind therapy. Peak V(O2) at baseline and after 3 and 6 months were 13.5+/-0.6, 15.1+/-1.0, and 15.7+/-1.1 mL. kg-1. min-1, respectively, in patients receiving losartan and 14.1+/-0.6, 14.3+/-0.9, and 13.6+/-1.1 mL. kg-1. min-1, respectively, in patients receiving placebo (P<0.02 for treatment group-by-time interaction). Functional class improved by at least one NYHA class in 9 of 16 patients receiving losartan and 1 of 17 patients receiving placebo.Losartan enhances peak exercise capacity and alleviates symptoms in patients with CHF who are severely symptomatic despite treatment with maximally recommended or tolerated doses of ACE inhibitors.
How Good is Zoom Endoscopy for Assessment of Villous Atrophy in Coeliac Disease?
Authors: R. Badreldin, P. Barrett, D. A. Wooff, J. Mansfield, Y. Yiannakou
Journal: Endoscopy (2005)

Background and Study Aims: The advent of magnification endoscopy may allow the macroscopic detection of unrecognised villous atrophy in patients with unsuspected coeliac disease. In addition, it may also be possible to use this method to assess the degree of villous atrophy. The aim of this study was to determine the accuracy of zoom endoscopy for the macroscopic evaluation of villous atrophy, in comparison with histological evaluation. Patients and Methods: The zoom endoscope provided a magnification capability of × 115. A scoring system (Z score) was devised for grading the appearances of villous atrophy: “Z1” for normal mucosa, “Z2” for stunted villi, “Z3” for markedly stunted villi (with ridges and pits) and “Z4” for a flat mucosa. A total of 53 consecutive patients with treated coeliac disease were followed up over almost 2 years using the Olympus GIF-Q240Z zoom endoscope; a total of 80 procedures were carried out. Four biopsies from the second part of the duodenum were taken from each patient for histological assessment. Histological assessment of villous atrophy was made by a pathologist blinded to the Z score. The correlation between the Z score and the histological score was assessed using the weighted kappa method. Results: The kappa score for the correlation between the macroscopic assessment of villous atrophy and the histology was 0.631, indicating fair to good reproducibility. Agresti’s method revealed a very strong baseline association between the two methods (P < 0.001). Zoom endoscopy had a positive predictive value of 83 % and a negative predictive value of 77 % in detecting villous atrophy. Conclusions: Our findings suggest that zoom endoscopy may be valuable in assessing the degree of villous atrophy. However, further studies are needed to assess its efficacy in routine practice as a screening or case-finding tool.
A novel human gastric primary cell culture system for modelling<i>Helicobacter pylori</i>infection in vitro
Authors: Philipp Schlaermann, Benjamin Toelle, Hilmar Berger, Sven C Schmidt, Matthias Glanemann, Jürgen Ordemann, Sina Bartfeld, Hans J Mollenkopf, Thomas F Meyer
Journal: Gut (2014)

<h3>Background and aims</h3> <i>Helicobacter pylori</i> is the causative agent of gastric diseases and the main risk factor in the development of gastric adenocarcinoma. In vitro studies with this bacterial pathogen largely rely on the use of transformed cell lines as infection model. However, this approach is intrinsically artificial and especially inappropriate when it comes to investigating the mechanisms of cancerogenesis. Moreover, common cell lines are often defective in crucial signalling pathways relevant to infection and cancer. A long-lived primary cell system would be preferable in order to better approximate the human in vivo situation. <h3>Methods</h3> Gastric glands were isolated from healthy human stomach tissue and grown in Matrigel containing media supplemented with various growth factors, developmental regulators and apoptosis inhibitors to generate long-lasting normal epithelial cell cultures. <h3>Results</h3> Culture conditions were developed which support the formation and quasi-indefinite growth of three dimensional (3D) spheroids derived from various sites of the human stomach. Spheroids could be differentiated to gastric organoids after withdrawal of Wnt3A and R-spondin1 from the medium. The 3D cultures exhibit typical morphological features of human stomach tissue. Transfer of sheared spheroids into 2D culture led to the formation of dense planar cultures of polarised epithelial cells serving as a suitable in vitro model of <i>H. pylori</i> infection. <h3>Conclusions</h3> A robust and quasi-immortal 3D organoid model has been established, which is considered instrumental for future research aimed to understand the underlying mechanisms of infection, mucosal immunity and cancer of the human stomach.
Murine eosinophil differentiation factor. An eosinophil-specific colony-stimulating factor with activity for human cells.
Authors: A F Lopez, C G Begley, D J Williamson, D J Warren, M A Vadas, C J Sanderson
Journal: The Journal of Experimental Medicine (1986)

A purified murine lymphokine, eosinophil differentiation factor (EDF), was found to be a selective stimulus for the clonal proliferation and differentiation of murine eosinophil progenitor cells, establishing it as the murine eosinophil colony-stimulating factor (Eo-CSF). EDF was also active on human eosinophil progenitors and mature blood eosinophils, but had no effect on neutrophil or macrophage precursor cells, nor on blood neutrophils. In culture of human bone marrow cells, EDF stimulated equal numbers and equal sizes of eosinophil colonies to develop when compared with human placental conditioned medium, a source of human CSFs, suggesting that all responsive progenitor cells were stimulated. Clone transfer experiments and the linear relationship between number of bone marrow cells plated and colonies produced confirmed that the action of EDF was directly on eosinophil progenitor cells. EDF increased the capacity of human blood eosinophils, but not neutrophils, to kill antibody-coated tumor cells and to phagocytose serum-opsonized yeast cells. This functional activation was associated with the enhanced expression of functional antigens (GFA-1, GFA-2, and the receptor for C3bi) on eosinophils. The possession by EDF (Eo-CSF) of all the properties expected of a human eosinophil CSF raises the possibility that a human analog of this molecule exists, and is involved in the regulation of production and function of human eosinophils in vivo.
Communicating about Health Care: Observations from Persons Who Are Deaf or Hard of Hearing
Authors: Lisa I. Iezzoni, Bonnie L. O'Day, Mary Killeen, Heather Harker
Journal: Annals of Internal Medicine (2004)

Background: Achieving patient-centered care requires effective communication between physicians and patients. Persons who are deaf or hard of hearing face considerable barriers to communicating with physicians. Objective: To understand perceptions of health care experiences and suggestions for improving care among deaf or hard-of-hearing individuals. Design: 4 semistructured group interviews, 2 conducted in American Sign Language (for deaf individuals) and 2 using Communication Access Realtime Translation (for hard-of-hearing individuals). Men and women were interviewed separately. Tapes of interviews were transcribed verbatim for analysis. Setting: Greater Boston, Massachusetts, and Washington, DC, in 2001. Participants: 14 deaf adults (23 to 51 years of age) and 12 hard-of-hearing adults (30 to 74 years of age). Measurements: Commonly expressed themes or views organized around dimensions of communication. Results: Concerns coalesced around 6 broad themes: conflicting views between physicians and patients about being deaf or hard of hearing; different perceptions about what constitutes effective communication (such as lip reading, writing notes, and sign language interpreter); medication safety and other risks posed by inadequate communication; communication problems during physical examinations and procedures; difficulties interacting with office staff, including in waiting rooms; and problems with telephone communication, such as lengthy message menus. Participants offered extensive suggestions for improvements, starting with clinicians' asking patients about their preferred communication approach. Having patients repeat critical health information (such as medication instructions) can identify potentially dangerous miscommunication. Conclusions: As the population ages, physicians will encounter many more persons with hearing limitations. Physicians are not reimbursed for making some accommodations, such as hiring sign language interpreters. However, ensuring effective communication is essential to safe, timely, efficient, and patient-centered care.
ON THE CLASSIFICATION OF THE STREPTOTHRICES, PARTICULARLY IN THEIR RELATION TO BACTERIA
Authors: Edith J. Claypole
Journal: The Journal of Experimental Medicine (1913)

It is impossible from any point of view, morphological, biological or serological, to draw a sharp dividing line in this series. The forms change gradually from the mycelial organism to the bacillary, acid-fast organism. It is biologically a group complex and should be so considered. No doubt experiments with a larger series of species would yield results giving a possibility of closer classification and the introduction of some of the forms now in a debatable position, as Bacillus diphtheriae and Bacillus mallei, and other organisms, sometimes called, on account of their morphological irregularities, corynebacterium and mycobacterium, would help to show their real relation to both the Streptothrices and the true bacteria. The latter in many ways are acknowledged to be far from primitive; their endospores, flagella, and food habits all indicate a relatively high degree of specialization. Hence it would seem biologically more reasonable to look upon this group of Streptothrices with their variable morphology and close relationships as representing the ancestral type that gave rise to both the higher fungi and true bacteria, and not as being themselves higher bacteria. The various bacteria, other than the acid-fast forms, can readily have arisen from the non-acid-fast bacillary types, or even as non-acid-fast specializations of the mixed types. All the various forms shown at present by the bacteria,-cocci, spirilla, bacilli, etc.,-either separate or in chains and masses, are to be recognized in this group, and specializations in one or another line in the past would readily have given rise to the types we consider true bacteria. The processes of evolution have carried them far away from the parent stock and made them into this group. The recognition of this group complex and of the intermediate forms indicates clearly the past history and present relations of these interesting organisms. These relations may be represented by the following scheme. See PDF for Structure It is probable that the relation between the acid-fast organisms and the Streptothrices is a closer one than that between the Streptothrices and the bacteria, perhaps close enough to warrant a common genus for both.
Alendronate improves bone mineral density in primary biliary cirrhosis: A randomized placebo-controlled trial
Authors: Claudia O. Zein, Roberta A. Jorgensen, Bart Clarke, Doris E. Wenger, Jill C. Keach, Paul Angulo, Keith D. Lindor
Journal: Hepatology (2005)

Abstract Bone loss is a well-recognized complication of primary biliary cirrhosis (PBC). Although it has been suggested that alendronate might improve bone mineral density (BMD) in PBC, no randomized placebo-controlled trial has been conducted. The primary aim of this study was to compare the effects of alendronate versus placebo on BMD and biochemical measurements of bone turnover in patients with PBC-associated bone loss. We conducted a double-blinded, randomized, placebo-controlled trial. Patients with a PBC and BMD t score of less than −1.5 were randomized to receive 70 mg per week of alendronate or placebo over 1 year. BMD of the lumbar spine and proximal femur were measured at entry and at 1 year. Changes from baseline in BMD and biochemical measurements of bone turnover were assessed. Thirty-four patients were enrolled. Seventeen patients were randomized to each arm. After 1 year, a significantly larger improvement ( P = .005) in spine BMD was observed in the alendronate group (0.09 ± 0.03 g/cm2 SD from baseline) compared with the placebo group (−0.003 ± 0.02 g/cm2 SD from baseline). A larger improvement ( P = .046) was also observed in the femoral BMD of alendronate patients versus placebo. BMD changes were independent of concomitant estrogen therapy. The rate of adverse effects was similar in both groups. In conclusion , in patients with PBC-related bone loss, alendronate significantly improves BMD compared with placebo. Although in this study oral alendronate appears to be well tolerated in patients with PBC, larger studies are needed to formally evaluate safety. (Hepatology 2005;42:762–771.)
Can insulin-treated diabetics be given beta-adrenergic blocking drugs?
Authors: A H Barnett, D Leslie, P J Watkins
Journal: BMJ (1980)

Lack of awareness of hypoglycaemia leading to loss of consciousness is a serious problem in some insulin-treated diabetics, and beta-blocking drugs may increase this hazard. A prospective study was therefore carried out over eight months to determine the incidence of hypoglycaemic episodes in 50 insulin-treated diabetics taking beta-blockers, as compared with 100 diabetic controls matched for age, sex, and duration of diabetes. The incidence of loss of consciousness from hypoglycaemia was the same in both groups and was unrelated to the dose of beta-blocking drug used. Five patients taking beta-blockers and 10 controls had episodes of unconsciousness, but four of these patients taking beta-blockers had had similar episodes in the two years preceding treatment. It is concluded that beta-blocking drugs are generally safe in insulin-treated diabetics and that hypoglycaemic unconsciousness resulting from their use is rare.
A Relationship Between Vascular Endothelial Growth Factor, Angiogenesis, and Cardiac Repair After Muscle Stem Cell Transplantation Into Ischemic Hearts
Authors: Thomas R. Payne, Hideki Oshima, Masaho Okada, Nobuo Momoi, Kimimasa Tobita, Bradley B. Keller, Hairong Peng, Johnny Huard
Journal: Journal of the American College of Cardiology (2007)
Influence of Cl- on organic anion transport in short-term cultured rat hepatocytes and isolated perfused rat liver.
Authors: A W Wolkoff, A C Samuelson, K L Johansen, R Nakata, D M Withers, A Sosiak
Journal: Journal of Clinical Investigation (1987)

Transport of 35S-labeled sulfobromophthalein [35S]BSP was studied in short-term cultured rat hepatocytes incubated in bovine serum albumin. At 37 degrees C, initial uptake of [35S]BSP was 5-10-fold that at 4 degrees C, linear for at least 15 min, saturable, inhibited by bilirubin, and reduced by greater than 70% after ATP depletion or isosmotic substitution of sucrose for NaCl in medium. Replacement of Na+ by K+ or Li+ did not alter uptake, whereas replacement of Cl- by HCO-3 or gluconate- reduced uptake by approximately 40%. Substitution of Cl- by the more permeant NO-3 enhanced initial BSP uptake by 30%. Efflux of [35S]BSP from cells to media was inhibited by 40% after ATP depletion or sucrose substitution. To confirm these results in a more physiologic system, transport of [3H]bilirubin was studied in isolated livers perfused with control medium or medium in which Cl- was replaced by gluconate-. Perfusion data analyzed by the model of Goresky, revealed 40-50% reductions in influx and efflux with gluconate- substitution. These results are consistent with existence of a Cl-/organic anion-exchange mechanism similar to that described by others in renal tubules.
Tumor necrosis factor-alpha modifies adhesion properties of rat islet B cells.
Authors: V Cirulli, P A Halban, D G Rouiller
Journal: Journal of Clinical Investigation (1993)

The characteristic three-dimensional cell type organization of islets of Langerhans is perturbed in animal models of diabetes, suggesting that it may be important for islet function. Rat islet cells in culture are able to form aggregates with an architecture similar to native islets (pseudoislets), thus providing a good model to study the molecular basis of islet architecture and its role in islet function. Sorted islet B cells and non-B cells were permanently labeled with two different fluorescent dyes (DiO and DiI), mixed, and allowed to form aggregates during a 5-d culture in the presence or absence of TNF-alpha (100 U/ml), a cytokine suggested to be implicated in the early physiological events leading to insulin-dependent diabetes mellitus. Confocal microscopy of aggregates revealed that TNF-alpha reversibly perturbs the typical segregation between B and non-B cells. Insulin secretion, was altered in the disorganized aggregates, and returned towards normal when pseudoislets had regained their typical architecture. The homotypic adhesion properties of sorted B and non-B cells cultured for 20 h in the presence or absence of TNF-alpha were studied in a short term aggregation assay. TNF-alpha induced a significant rise in Ca(2+)-independent adhesion of B cells (from 24 +/- 1.1% to 44.3 +/- 1.2%; n = 4, P < 0.001). These findings raise the possibility that the increased expression of Ca(2+)-independent adhesion molecules on B cells leads to altered islet architecture, which might be a factor in the perturbation of islet function induced by TNF-alpha.
Catecholamine Metabolism in Experimental Hypertension in the Rat
Authors: JACQUES DE CHAMPLAIN, LAWRENCE R. KRAKOFF, JULIUS AXELROD
Journal: Circulation Research (1967)

The role of catecholamines was investigated in uninephrectomized Sprague-Dawley male rats made hypertensive by administration of desoxycorticosterone and a high salt diet. The accumulation of tritiated norepinephrine and the endogenous norepinephrine levels were measured in the various organs. The content of endogenous norepinephrine and the accumulation of 3 H-norepinephrine 1 hour after its injection were reduced in the heart, spleen, intestine, skeletal muscle, and kidney of hypertensive rats as compared to controls. Simultaneously, an increase in total 3 H-metabolites was also found in the hypertensive animals. A highly significant inverse relation was established between the level of blood pressure and the accumulation of 3 H-norepinephrine or endogenous norepinephrine levels in the heart. The abnormalities observed in the disposition of exogenously administered and endogenous norepinephrine do not appear to be secondary to a change in the distribution of cardiac output to the various organs. Since the initial uptake was normal in the hypertensive rats, the reduced capacity to accumulate norepinephrine seems to be related to a defect in the storage of norepinephrine.
Topical Anesthesia in Preendoscopic Medication: Spray Versus Lozenges
Authors: S. Heuberger, K. Weber, A. Sonnenberg, W. Mattle, R. Dolder, K. Stuby, A. Blum
Journal: Endoscopy (1979)

Patients' acceptance of upper fiberpanendoscopy was significantly (p less than 0.001) better when topical anesthesia with oxybuprocaine was performed with a spray than with a lozenge.