tbuckley/cabot-search huggingface dataset:
High Numbers of Tumor-Associated Macrophages Have an Adverse Prognostic Value That Can Be Circumvented by Rituximab in Patients With Follicular Lymphoma Enrolled Onto the GELA-GOELAMS FL-2000 Trial
Authors: Danielle Canioni, Gilles Salles, Nicolas Mounier, Nicole Brousse, Marie Keuppens, Frank Morchhauser, Thierry Lamy, Anne Sonet, Marie-Christine Rousselet, Charles Foussard, Luc Xerri
Journal: Journal of Clinical Oncology (2007)

High amounts of intratumoral macrophages have been shown to correlate with poor prognosis in patients with follicular lymphoma (FL) treated with chemotherapy without rituximab. We tried to establish whether intratumoral macrophage count (MC) definitely is able to predict the outcome of FL patients in the rituximab era.We analyzed immunohistochemical CD68 expression in 194 FL patients from the FL-2000 trial, randomly assigned to receive cyclophosphamide, doxorubicin, etoposide, prednisolone, and interferon (CHVP-I) or rituximab plus CHVP-I. Immunohistochemistry was performed on paraffin sections using anti-CD68 KP1 antibody, and stained macrophages were scored on high-power field (hpf) in either intrafollicular (IF) or extrafollicular (EF) areas.For IF MC, the best cutoff point was estimated at 10 macrophages/hpf. Low IF MC was significantly associated with a better event-free survival (EFS; P = .011). However, this effect was observed only in the CHVP-I arm (P = .012) and not in the rituximab plus CHVP-I arm. Using a cutoff of 15 IF MC, we found no significant association with EFS. For EF MC, fewer than 22 macrophages/hpf were associated with better EFS in the CHVP-I arm (P = .02) but not in the rituximab plus CHVP-I arm.These results show that MC can predict outcome of FL patients and that rituximab is able to circumvent the unfavorable outcome associated with high MC.
Contractility of isolated stratum granulosum cells
Authors: WALTER B.SHELLEY, LENNART JUHLIN
Journal: British Journal of Dermatology (1982)

Single cells isolated from the stratum granulosum and observed by phase microcopy were seen to contract upon exposure to asdenosine triphosphate (ATP) in the presence of calcium and magnesium. These cells, mechanically isolated from trypsin-treated epidermis of guinea-pig, man and cattle, had been briefly exposed to glycerol or triton X-100. The treatment with glycerol itself, but not Triton X-100 also induced a reversible contraction of the granular cell. Other keratinocytes showed no changes, nor was contraction observed in granulosum cells pretreated with cytochalasin or colchicine. These single celll experiments support the view that the stratum granulosum contains cells which are myoepithelial in nature.
Age-related changes in total protein and collagen metabolism in rat liver
Authors: Peter K. Mays, Robin McAnulty, Geoffrey J. Laurent
Journal: Hepatology (1991)

Liver collagen levels are determined by a balance between synthesis and degradation, processes known to have rapid rates in growing animals. We report age-related changes in liver collagen synthesis and degradation rates, as well as protein synthesis rates, in rats at five ages from 1 to 24 mo. Fractional collagen synthesis rates were determined after injection of [ 14 C]proline with a flooding dose of unlabeled proline and its incorporation as hydroxy-[ 14 C]proline into proteins. Fractional protein synthesis rates were based on the uptake of [ 14 C]proline into proteins. Fractional collagen degradation rates were calculated from the difference between collagen fractional synthesis and deposition rates. Fractional rates of collagen synthesis were similar between 1 mo (23.0% ± 4.6%/day) and 24 mo (19.6% ± 3.4%/day) of age. Collagen deposition into the extracellular matrix was extremely low at every age studied; therefore degradation pathways accounted for the bulk of the collagen synthesized. The mean fractional synthesis rate for the total protein pool was unaltered between 1 mo (105.0% ± 7.2%/day) and 15 mo (89.9% ± 6.0%/day) of age, after which it increased to 234.9% ± 33.0%/day (p &lt; 0.05) by 24 mo of age. These results indicate that liver collagen and total protein synthesis rates were maintained at relatively high levels during development and maturity but that protein synthesis rates were highest in senescent animals. (Hepatology 1991:14:1224-1229.)
The ABC transporter gene family of Caenorhabditis elegans has implications for the evolutionary dynamics of multidrug resistance in eukaryotes
Authors: Jonathan A Sheps, Steven Ralph, Zhongying Zhao, David L Baillie, Victor Ling
Journal: Genome biology (2004)

Many drugs of natural origin are hydrophobic and can pass through cell membranes. Hydrophobic molecules must be susceptible to active efflux systems if they are to be maintained at lower concentrations in cells than in their environment. Multi-drug resistance (MDR), often mediated by intrinsic membrane proteins that couple energy to drug efflux, provides this function. All eukaryotic genomes encode several gene families capable of encoding MDR functions, among which the ABC transporters are the largest. The number of candidate MDR genes means that study of the drug-resistance properties of an organism cannot be effectively carried out without taking a genomic perspective.We have annotated sequences for all 60 ABC transporters from the Caenorhabditis elegans genome, and performed a phylogenetic analysis of these along with the 49 human, 30 yeast, and 57 fly ABC transporters currently available in GenBank. Classification according to a unified nomenclature is presented. Comparison between genomes reveals much gene duplication and loss, and surprisingly little orthology among analogous genes. Proteins capable of conferring MDR are found in several distinct subfamilies and are likely to have arisen independently multiple times.ABC transporter evolution fits a pattern expected from a process termed 'dynamic-coherence'. This is an unusual result for such a highly conserved gene family as this one, present in all domains of cellular life. Mechanistically, this may result from the broad substrate specificity of some ABC proteins, which both reduces selection against gene loss, and leads to the facile sorting of functions among paralogs following gene duplication.
Streptococcal cysteine proteinase releases kinins: a virulence mechanism.
Authors: H Herwald, M Collin, W Müller-Esterl, L Björck
Journal: The Journal of Experimental Medicine (1996)

Previous work has indicated a crucial role for the extracellular cysteine proteinase of Streptococcus pyogenes in the pathogenicity and virulence of this important human pathogen. Here we find that the purified streptococcal cysteine proteinase releases biologically active kinins from their purified precursor protein, H-kininogen, in vitro, and from kininogens present in the human plasma, ex vivo. Kinin liberation in the plasma is due to the direct action of the streptococcal proteinase on the kininogens, and does not involve the previous activation of plasma prekallikrein, the physiological plasma kininogenase. Judged from the amount of released plasma kinins the bacterial proteinase is highly efficient in its action. This is also the case in vivo. Injection of the purified cysteine proteinase into the peritoneal cavity of mice resulted in a progressive cleavage of plasma kininogens and the concomitant release of kinins over a period of 5 h. No kininogen degradation was seen in mice when the cysteine proteinase was inactivated by the specific inhibitor, Z-Leu-Val-Gly-CHN2, before administration. Intraperitoneal administration into mice of living S. pyogenes bacteria producing the cysteine proteinase induced a rapid breakdown of endogenous plasma kininogens and release of kinins. Kinins are hypotensive, they increase vascular permeability, contract smooth muscle, and induce fever and pain. The release of kinins by the cysteine proteinase of S. pyogenes could therefore represent an important and previously unknown virulence mechanism in S. pyogenes infections.
Clinicians’ Guide to Inflammatory Bowel Disease
Authors: S TRAVIS
Journal: Gut (1998)

Clinicians’ Guide to Inflammatory Bowel Disease. Forbes A. (Pp 257; illustrated; £39.50.) London: Chapman and Hall, 1997. ISBN 0-412-7885000-0.

An “intellectual feat by one person achieves a global view of the topic with continuity and balance,” writes John Lennard-Jones in the foreword, and one has to agree. This is a monograph at its best which challenges the Goliath of multi-authored texts. Current literature is thoughtfully interpreted and coherently presented in a way that edited …
In vivo study of lactoferrin and murine rebound myelopoiesis
Authors: Athena Poppas, Michael R. Faith, Howard R. Bierman
Journal: American Journal of Hematology (1986)

Abstract Lactoferrin has been reported to inhibit the production of colony‐stimulating factor (CSF); thus we sought to study its possible effects on myelopoiesis in vivo. The characteristics of rebound myelopoiesis in C57BL mice injected with a sublethal dose of cyclophosphamide (CY) were used to test lactoferrin for any granulopoietic activity. An experimental group received daily injections of 50 μg of human lactoferrin beginning 24 hr after CY injections. By measuring the total nucleated cellularity of the femoral marrow, the peripheral blood count, and the incorporation of tritiated thymidine by the marrow in six replicate experiments, no statistically significant difference was noted between the lactoferrin injected groups and the control groups. Neither the route of lactoferrin administration (i.v. or i.p.) nor the sex of the animal altered the myelopoietic recovery. Lactoferrin had no stimulatory or inhibitory effect on murine rebound myelopoiesis in vivo contrary to the reported in vitro results.
Recording and surveillance systems for periodontal diseases
Authors: Eugenio D. Beltrán‐Aguilar, Paul I. Eke, Gina Thornton‐Evans, Poul E. Petersen
Journal: Periodontology 2000 (2012)

Abstract This paper describes tools used to measure periodontal diseases and the integration of these tools into surveillance systems. Tools to measure periodontal diseases at the surveillance level have focussed on current manifestations of disease (e.g. gingival inflammation) or disease sequelae (e.g. periodontal pocket depth or loss of attachment). All tools reviewed in this paper were developed based on the state of the science of the pathophysiology of periodontal disease at the time of their design and the need to provide valid and reliable measurements of the presence and severity of periodontal diseases. Therefore, some of these tools are no longer valid. Others, such as loss of periodontal attachment, are the current de‐facto tools but demand many resources to undertake periodical assessment of the periodontal health of populations. Less complex tools such as the Community Periodontal Index, have been used extensively to report periodontal status. Laboratory tests for detecting putative microorganisms or inflammatory agents present in periodontal diseases have been used at the clinical level, and at least one has been tested at the population level. Other approaches, such as self‐report measures, are currently under validation. In this paper, we do not review indices designed to measure plaque or residual accumulation around the tooth, indices focussed only on gingival inflammation or radiographic approaches with limited applicability in surveillance systems. Finally, we review current case‐definitions proposed for surveillance of periodontal disease severity.
Prognostic Factors for Survival in Human Immunodeficiency Virus–associated Pulmonary Arterial Hypertension
Authors: Hilario Nunes, Marc Humbert, Olivier Sitbon, Jane H. Morse, Zemin Deng, James A. Knowles, Catherine Le Gall, Florence Parent, Gilles Garcia, Philippe Hervé, Robyn J. Barst, Gérald Simonneau
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

We report a large monocentric case series of 82 patients with human immunodeficiency virus-associated pulmonary arterial hypertension (PAH). No germline mutations of the PPH1 gene (bone morphogenetic protein receptor-II) were found in any of the 19 patients tested. PAH was the direct cause of death in 72% of cases. Survival rates of the overall population at 1, 2, and 3 years were 73, 60, and 47%, respectively. Survival was significantly poorer in patients in New York Heart Association functional class III-IV at the time of diagnosis, as compared with those in functional class I-II with respective rates of 60, 45, and 28% versus 100, 90, 84% at 1, 2, and 3 years (p < 0.0001). Subsequently, we analyzed prognostic factors in patients in functional class III-IV. Univariate analysis indicated that CD4 lymphocyte count of more than 212 cells mm(-3), the use of combination antiretroviral therapy (CART), and epoprostenol infusion were related with a better survival. On multivariate analysis only CD4 lymphocyte count was an independent predictor of survival, presumably because CART and epoprostenol infusion were strongly linked in our patient population. These results suggest that patients with severe human immunodeficiency virus-associated PAH should be considered for long-term epoprostenol infusion in association with CART.
YKL-40 and Matrix Metalloproteinase-9 as Potential Serum Biomarkers for Patients with High-Grade Gliomas
Authors: Adília Hormigo, Bin Gu, Sasan Karimi, Elyn Riedel, Katherine S. Panageas, Mark A. Edgar, Meena K. Tanwar, Jasti S. Rao, Martin Fleisher, Lisa M. DeAngelis, Eric C. Holland
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Biomarkers can facilitate diagnosis, monitor treatment response, and assess prognosis in some patients with cancer. YKL-40 and matrix metalloproteinase-9 (MMP-9) are two proteins highly differentially expressed by malignant gliomas. We obtained prospective longitudinal serum samples from patients with gliomas to determine whether YKL-40 or MMP-9 could be used as serum markers. Experimental Design: Serum samples were obtained concurrently with magnetic resonance imaging scans. YKL-40 and MMP-9 were determined by ELISA and the values correlated with the patient's radiographic status and survival. Results: High-grade glioma patients who underwent a surgical resection of their tumor had transient increase of both YKL-40 and MMP-9 serum levels in the postoperative period. Glioblastoma multiforme (GBM) patients with no radiographic evidence of disease (n = 10 patients, 50 samples) had a significantly lower level of YKL-40 and MMP-9 than patients with active tumor (n = 66 patients, 209 samples; P = 0.0003 and 0.0002, respectively). Anaplastic glioma patients with no radiographic evidence of disease (n = 32 patients, 107 samples) also had a significantly lower level of YKL-40 compared with those patients with active tumor (n = 48 patients, 199 samples; P = 0.04). There was a significant inverse association between YKL-40 and survival in GBM, hazard ratio (hazard ratio, 1.4; P = 0.02), and anaplastic astrocytoma patients (hazard ratio, 2.2; P = 0.05). Conclusions: YKL-40 and MMP-9 can be monitored in patients' serum and help confirm the absence of active disease in GBM and YKL-40 in anaplastic glioma patients. YKL-40 can be used as predictor of survival in patients with high-grade glioma. Longitudinal studies with a larger patient population are needed to confirm these findings.
Tumour necrosis factor (TNF ) as a novel therapeutic target in symptomatic corticosteroid dependent asthma
Authors: P H Howarth
Journal: Thorax (2005)

Tumour necrosis factor alpha (TNFalpha) is a major therapeutic target in a range of chronic inflammatory disorders characterised by a Th1 type immune response in which TNFalpha is generated in excess. By contrast, asthma is regarded as a Th2 type disorder, especially when associated with atopy. However, as asthma becomes more severe and chronic, it adopts additional characteristics including corticosteroid refractoriness and involvement of neutrophils suggestive of an altered inflammatory profile towards a Th1 type response, incriminating cytokines such as TNFalpha.TNFalpha levels in bronchoalveolar lavage (BAL) fluid of 26 healthy controls, 42 subjects with mild asthma and 20 with severe asthma were measured by immunoassay, and TNFalpha gene expression was determined in endobronchial biopsy specimens from 14 patients with mild asthma and 14 with severe asthma. The cellular localisation of TNFalpha was assessed by immunohistochemistry. An open label uncontrolled clinical study was then undertaken in 17 subjects with severe asthma to evaluate the effect of 12 weeks of treatment with the soluble TNFalpha receptor-IgG1Fc fusion protein, etanercept.TNFalpha levels in BAL fluid, TNFalpha gene expression and TNFalpha immunoreative cells were increased in subjects with severe corticosteroid dependent asthma. Etanercept treatment was associated with improvement in asthma symptoms, lung function, and bronchial hyperresponsiveness.These findings may be of clinical significance in identifying TNFalpha as a new therapeutic target in subjects with severe asthma. The effects of anti-TNF treatment now require confirmation in placebo controlled studies.
Influence of L-Norepinephrine Upon Cardiac Output in Anesthetized Dogs
Authors: MATTHEW N. LEVY, SHIRLEY H. BRIND
Journal: Circulation Research (1957)

It was the purpose of this investigation to test again the general conclusion that norepinephrine augments cardiac output during experimental hemorrhagic hypotension but has no such effect on normal animals or man. Results are presented which fail to support this differential action in normal and hypotensive dogs and an explanation is offered for failure of the drug to increase cardiac output in human subjects.
Coronary Artery Calcification and Changes in Atheroma Burden in Response to Established Medical Therapies
Authors: Stephen J. Nicholls, E. Murat Tuzcu, Kathy Wolski, Ilke Sipahi, Paul Schoenhagen, Timothy Crowe, Samir R. Kapadia, Stanley L. Hazen, Steven E. Nissen
Journal: Journal of the American College of Cardiology (2006)
Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: A case-control study in Italy
Authors: F Donato, A Tagger, R Chiesa, M L Ribero, V Tomasoni, M Fasola, U Gelatti, G Portera, P Boffetta, G Nardi
Journal: Hepatology (1997)

We performed a case-control study to assess the association of hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol drinking. We recruited as cases 172 subjects with an initial diagnosis of HCC, who were admitted to the two major hospitals in the province of Brescia, northern Italy, and 332 subjects, sex-, age-, and hospital-matched, who were admitted to the Departments of Ophthalmology, Dermatology, Urology, Cardiology, and Internal Medicine, as controls. Of the HCC cases, 23.8% were positive for HBsAg and 37.8% for HCV RNA; among the controls, 5.4% were positive for HBsAg and 4.8% for HCV RNA. History of heavy alcohol intake (&gt;80 g of ethanol per day for at least 5 years) was found among 58.1% of the cases and among 36.4% of the controls. The relative risks (RRs) for HBsAg, HCV RNA positivity, and heavy alcohol intake were, respectively: 11.4 (95% confidence interval: 5.7-22.8), 23.2 (95% confidence interval: 11.8-45.7), and 4.6 (95% confidence interval: 2.7- 7.8). Positive interactions (synergisms) between both HBsAg positivity and HCV RNA positivity and heavy alcohol intake were found, suggesting more than additive effects of viral infections and alcohol drinking on the risk of HCC. Infection with HCV genotype 1b showed a higher risk than type 2 (RR = 2.9; 95% confidence interval: 0.9-10), suggesting a major role for the former type in causing HCC. On the basis of population attributable risks (AR), heavy alcohol intake seems to be the single most relevant cause of HCC in this area (AR: 45%), followed by HCV (AR: 36%), and HBV (AR: 22%) infection.
Effect of ipratropium bromide on mucociliary clearance and pulmonary function in reversible airways obstruction.
Authors: D Pavia, J R Bateman, N F Sheahan, S W Clarke
Journal: Thorax (1979)

The effects of (a) regular use for one week and (b) a single dose of a synthetic anticholinergic (ipratropium bromide) on lung mucociliary clearance and as a bronchodilator was ascertained in a controlled, double-blind, cross-over study in 12 patients with reversible airways obstruction (mean increase in FEV after isoprenaline: 17% range 10-50%). Two puffs from a metered dose inhaler of either placebo (propellants only) or drug (40 microgram) were administered four times a day for one week (regular use), and mucociliary clearance was measured, by radioaerosol tracer, at the end of each treatment period and after a control period in which no treatment was given. On the mornings of the measurements after the placebo and drug periods one final dose (single dose) of ipratropium (40 microgram) or placebo was given 2.5 hours before the start of the test. There was no statistically significant difference between the three mean mucociliary clearance curves (control, placebo, and drug) for the group; however, there was a significantly greater penetration towards the periphery of the lung of the tracer in the test after drug administration compared with the other two. This increased penetration was attributed to bronchodilatation caused by the drug. Ipratropium bromide does not appear to impair mucociliary clearance, and it acts an effective bronchodilator.
2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: Executive Summary
Authors: Stephan D. Fihn, Julius M. Gardin, Jonathan Abrams, Kathleen Berra, James C. Blankenship, Apostolos P. Dallas, Pamela S. Douglas, JoAnne M. Foody, Thomas C. Gerber, Alan L. Hinderliter, Spencer B. King, Paul D. Kligfield, Harlan M. Krumholz, Raymond Y.K. Kwong, Michael J. Lim, Jane A. Linderbaum, Michael J. Mack, Mark A. Munger, Richard L. Prager, Joseph F. Sabik, Leslee J. Shaw, Joanna D. Sikkema, Craig R. Smith, Sidney C. Smith, John A. Spertus, Sankey V. Williams
Journal: Circulation (2012)
Liver Transplants from Living Related Donors
Authors: Benjamin Samstein, Jean Emond
Journal: Annual Review of Medicine (2001)

▪ Abstract Liver transplantation from living related donors was unthinkable until recently, when the safety of modern hepatic surgery became widely appreciated. The first step was the successful demonstration that parts of livers could be transplanted. This technique, termed reduced-size liver transplantation, evolved into reliable procedures to allow parents to donate small parts of their livers to small children. More recently, right hepatectomy, in which up to 70% of the liver is resected for donation, has been performed in adults. As the demand for liver transplantation continues to increase, the development of ethically sound, medically and surgically optimal programs for routine use of living donors has become essential. This chapter provides a broad overview of the evolution and current state of liver transplantation with living donors.