tbuckley/cabot-search huggingface dataset:
Cytokines Regulate Proteolysis in Major Histocompatibility Complex Class II–Dependent Antigen Presentation by Dendritic Cells
Authors: Edda Fiebiger, Paul Meraner, Ekkehard Weber, I-Fei Fang, Georg Stingl, Hidde Ploegh, Dieter Maurer
Journal: The Journal of Experimental Medicine (2001)

Endo/lysosomal proteases control two key events in antigen (Ag) presentation: the degradation of protein Ag and the generation of peptide-receptive major histocompatibility complex (MHC) class II molecules. Here we show that the proinflammatory cytokines tumor necrosis factor α and interleukin (IL)-1β rapidly increase the activity of cathepsin (cat) S and catB in human dendritic cells (DCs). As a consequence, a wave of MHC class II sodium dodecyl sulfate stable dimer formation ensues in a catS-dependent fashion. In contrast, the antiinflammatory cytokine IL-10 renders DCs incapable of upregulating catS and catB activity and in fact, attenuates the level of both enzymes. Suppressed catS and catB activity delays MHC class II sodium dodecyl sulfate stable dimer formation and impairs Ag degradation. In DCs exposed to tetanus toxoid, IL-10 accordingly reduces the number of MHC class II–peptide complexes accessible to tetanus toxoid–specific T cell receptors, as analyzed by measuring T cell receptor downregulation in Ag-specific T cell clones. Thus, the control of protease activity by pro- and antiinflammatory cytokines is an essential feature of the Ag presentation properties of DCs.
THE ROLE OF HUMORAL ANTIBODIES IN REJECTION OF SKIN HOMOGRAFTS IN RABBITS
Authors: Roberto R. Kretschmer, Ruy Peréz-Tamayo
Journal: The Journal of Experimental Medicine (1961)

Gross and microscopic observations of skin homograft rejection carried out in cortisone-conditioned and non-conditioned rabbits seem to indicate that humoral antibodies play an important role in the phenomenon. Thus, local administration of isoimmune serum to animals bearing skin homografts resulted in a significantly earlier rejection of that particular test graft without modifying the course of a neighboring control-skin graft. This result appears to support the idea that homograft rejection is not only due to cellular antibodies but to a combination of both humoral and cellular immune responses, which should not be regarded as completely unrelated.
Early diagnosis of lentivirus-induced infiltrative lung disease in sheep by high resolution computed tomography
Authors: JL Cadore, P Loubeyre, S Vuillermoz, I Court-Fortune, D Revel, JF Mornex
Journal: European Respiratory Journal (1997)

The visna-maedi lentivirus can induce an interstitial pneumonitis in sheep, and provides a convenient example to study natural or experimental lentiviral pathology. We wanted to determine whether high resolution computed tomography (HRCT) is able to detect early morphological changes following lentiviral infection in the lungs. Spontaneously infected adult sheep (n=3) and experimentally infected lambs (n=5) were compared to uninfected controls (n=4). The HRCT scans generally showed abnormal features in infected animals, including: increased parenchymal density; alveolar oedema; thickened interlobular septa; and increased density in peribronchiolar areas. HRCT was more sensitive than chest radiography for the early diagnosis of interstitial pneumonitis, although one sheep with advanced disease and radiographic and histopathological abnormalities had a paradoxically normal scan. One control animal showed minor abnormalities on scanning, which were probably due to the procedure used for anaesthesia. The HRCT observations were confirmed by postmortem histological examination of the lungs. In conclusion, high resolution computed tomography provides a noninvasive means of following the development of lung pathology in a natural ovine model of lentiviral disease.
RAG<scp>s and</scp>R<scp>egulation of</scp>A<scp>utoantibodies</scp>
Authors: Mila Jankovic, Rafael Casellas, Nikos Yannoutsos, Hedda Wardemann, Michel C. Nussenzweig
Journal: Annual Review of Immunology (2004)

Autoreactive antibodies are etiologic agents in a number of autoimmune diseases. Like all other antibodies these antibodies are produced in developing B cells by V(D)J recombination in the bone marrow. Three mechanisms regulate autoreactive B cells: deletion, receptor editing, and anergy. Here we review the prevalence of autoantibodies in the initial antibody repertoire, their regulation by receptor editing, and the role of the recombinase proteins (RAG1 and RAG2) in this process.
Regional Myocardial Sympathetic Denervation Predicts the Risk of Sudden Cardiac Arrest in Ischemic Cardiomyopathy
Authors: James A. Fallavollita, Brendan M. Heavey, Andrew J. Luisi, Suzanne M. Michalek, Sunil Baldwa, Terry L. Mashtare, Alan D. Hutson, Robert A. deKemp, Michael S. Haka, Munawwar Sajjad, Thomas R. Cimato, Anne B. Curtis, Michael E. Cain, John M. Canty
Journal: Journal of the American College of Cardiology (2013)
Usefulness of peritoneal fluid amylase levels in the differential diagnosis of peritonitis in peritoneal dialysis patients.
Authors: J Burkart, S Haigler, R Caruana, B Hylander
Journal: Journal of the American Society of Nephrology (1991)

Peritonitis continues to be a major cause of morbidity in peritoneal dialysis patients despite recent technological advances (Y systems) that have reduced peritonitis rates to much more acceptable levels. Most of the time when a peritoneal dialysis patient presents with peritonitis, it is infectious in origin. However, these patients occasionally develop other intra-abdominal pathology that requires more intensive medical care or, at times, surgical intervention. To help in the early differential diagnosis of the cause of peritonitis in these patients, peritoneal fluid amylase levels were prospectively obtained from 50 patients presenting to the hospital with peritonitis. Thirty-nine of them had typical infectious peritonitis, and their mean peritoneal fluid amylase level was 11.1 (range, 0 to 90). Six patients had pancreatitis and a mean peritoneal fluid amylase level of 550 U/L (range, 100 to 1,140 U/L). Five patients were found to have other intra-abdominal pathology, and their mean peritoneal fluid amylase level was 816 U/L (range, 142 to 1,746 U/L). In patients who did not respond to initial therapy, sequential peritoneal fluid amylase levels did not increase in patients with typical infectious peritonitis whereas it did increase in patients with other intra-abdominal pathology. In conclusion, it was found that peritoneal fluid amylase levels were helpful in the differential diagnosis of peritonitis in these patients. An elevated level (greater than 100 U/L) differentiated those patients with other intra-abdominal causes of peritonitis from those with typical infectious peritonitis.
Dependence of human respiratory thermal washout on extrathoracic airway conditions
Authors: JW Kaufman
Journal: European Respiratory Journal (1997)

Thermal washout curves have been proposed as noninvasive tools for analysing lower airway dimensions and pulmonary blood flow, but how upper airway heat transfer affects these washout curves is unclear. The present study was designed to compare extrathoracic and tracheobronchial contributions to thermal washout curves. Respiratory frequency, air ambient temperature, and body core temperature (tc) were varied in six male subjects before and after immersion in cold (1.1 degrees C) water for up to 2 h under three conditions: 1) control: ambient temperature (tamb) = 25 degrees C, rectal temperature change (delta tre) = 0 degrees C; 2) pre-immersion: tamb = 4 degrees C, delta tre = 0 degrees C; and 3) post-immersion: tamb = 25 degrees C, delta tre = -0.7 degrees C. Both peak expiratory nasal (tpn) and oral (tpo) airstream temperatures were measured. Each subject was tested twice. Expiratory tpo was generally higher than tpn in all conditions. Increasing breathing rates lowered tpn and tpo in the control and cold air environments. Orifice temperatures, which are presumed to reflect upper airway blood temperatures, correlated with both tpn and tpo. Lowering tc had no effect on washout curves during quiet breathing and affected only tpn during rapid breathing. The results suggest that while tracheobronchial conditions may contribute to thermal washout curves, extrathoracic conditions predominate. Strong correlations between orifice temperatures, peak expiratory nasal temperatures and peak expiratory oral temperature demonstrate the dominant role of upper airway heat exchange in determining thermal washout curves.
Metagenomic biomarker discovery and explanation
Authors: Nicola Segata, Jacques Izard, Levi Waldron, Dirk Gevers, Larisa Miropolsky, Wendy S Garrett, Curtis Huttenhower
Journal: Genome biology (2011)

Abstract This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/ .
Use of Video to Facilitate End-of-Life Discussions With Patients With Cancer: A Randomized Controlled Trial
Authors: Areej El-Jawahri, Lisa M. Podgurski, April F. Eichler, Scott R. Plotkin, Jennifer S. Temel, Susan L. Mitchell, Yuchiao Chang, Michael J. Barry, Angelo E. Volandes
Journal: Journal of Clinical Oncology (2009)

To determine whether the use of a goals-of-care video to supplement a verbal description can improve end-of-life decision making for patients with cancer.Fifty participants with malignant glioma were randomly assigned to either a verbal narrative of goals-of-care options at the end of life (control), or a video after the same verbal narrative (intervention) in this randomized controlled trial. The video depicts three levels of medical care: life-prolonging care (cardiopulmonary resuscitation [CPR], ventilation), basic care (hospitalization, no CPR), and comfort care (symptom relief). The primary study outcome was participants' preferences for end-of-life care. The secondary outcome was participants' uncertainty regarding decision making (score range, 3 to 15; higher score indicating less uncertainty). Participants' comfort level with the video was also measured.Fifty participants were randomly assigned to either the verbal narrative (n = 27) or video (n = 23). After the verbal description, 25.9% of participants preferred life-prolonging care, 51.9% basic care, and 22.2% comfort care. In the video arm, no participants preferred life-prolonging care, 4.4% preferred basic care, 91.3% preferred comfort care, and 4.4% were uncertain (P < .0001). The mean uncertainty score was higher in the video group than in the verbal group (13.7 v 11.5, respectively; P < .002). In the intervention arm, 82.6% of participants reported being very comfortable watching the video.Compared with participants who only heard a verbal description, participants who viewed a goals-of-care video were more likely to prefer comfort care and avoid CPR, and were more certain of their end-of-life decision making. Participants reported feeling comfortable watching the video.
Partitioning of Alveolar and Conducting Airway Nitric Oxide in Scleroderma Lung Disease
Authors: Reda E. Girgis, Manish K. Gugnani, Judith Abrams, Maureen D. Mayes
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

We partitioned exhaled nitric oxide (NO) into alveolar concentration (Ca) and conducting airway flux (Jnoair,max) in scleroderma (SSc) lung disease and hypothesized that Ca would be elevated. Twenty patients with SSc, 15 with interstitial lung disease (SSc–ILD) alone, and 5 with pulmonary hypertension (SSc–PH) were compared with 20 control subjects. Ca and Jnoair,max were derived from the slope and y intercept, respectively, of the NO output versus expiratory flow rate (V·exh) relationship obtained by measuring exhaled NO (FeNO) at multiple V·exh values of 50–200 ml/second. There were no significant differences in FeNO at any V·exh between the SSc group and control subjects. Jnoair,max was reduced (0.6 ± 0.1 versus 1.2 ± 0.2 nl of NO per second; p = 0.01), whereas Ca was increased (4.7 ± 0.5 versus 1.8 ± 0.2 ppb; p < 0.001) in the SSc group compared with control subjects. No differences were noted between SSc–ILD and SSc–PH. There was a negative correlation between Ca and DlCO among the patients with SSc (R = −0.66, p = 0.002). We conclude that Ca is increased whereas Jnoair,max is decreased in SSc–ILD and SSc–PH. A reduced diffusing capacity of NO from the alveolar space into the blood could explain the observed increase in Ca.
Brain and leptomeningeal metastases from cutaneous melanoma: Survival outcomes based on clinical features
Authors: Jeffrey J. Raizer, Wen-Jen Hwu, Katherine S. Panageas, Andrew Wilton, Drew E. Baldwin, Elizabeth Bailey, Caroline von Althann, Lynne A. Lamb, Gladys Alvarado, Mark H. Bilsky, Philip H. Gutin
Journal: Neuro-Oncology (2008)

Brain metastases (BM) are among the most devastating and debilitating complications of melanoma. This retrospective study was conducted to gain a better understanding of patient and disease characteristics that have the greatest impact on overall survival in melanoma patients with BM; therapeutic interventions were also assessed. The records of all patients diagnosed with cutaneous melanoma and BM who were seen at Memorial Sloan-Kettering Cancer Center between 1991 and 2001 were retrospectively reviewed. A variety of factors, including age at diagnosis of stage IV disease, gender, race, disease stage at diagnosis, presence of BM at diagnosis of stage IV disease, neurologic symptoms, radiographic findings, number of BM, status and site(s) of extracranial metastasis, and treatment modalities, were analyzed for correlation with overall survival using univariate and multivariate Cox regression models. The records of 355 patients with BM were included in the analysis. On univariate analysis, seven patient and disease characteristics were significantly associated with poorer survival: age > 65 years, extracranial metastases, BM at stage IV diagnosis, neurologic symptoms, four or more BM, hydrocephalus, and leptomeningeal metastases. Of these, age, extracranial metastasis, neurologic symptoms, and number of BM were significantly associated with poorer survival in a multivariate analysis. Multivariate analysis of treatment modalities suggested that patients who had surgery, radiosurgery, or chemotherapy with temozolomide had improved survival outcomes, although this analysis has limitations. The prognostic factors identified in this retrospective study should be considered when making treatment decisions for patients with BM and used as stratification factors in future clinical trials.
Antiproliferative Effect of Lapatinib in HER2-Positive and HER2-Negative/HER3-High Breast Cancer: Results of the Presurgical Randomized MAPLE Trial (CRUK E/06/039)
Authors: Alexandra Leary, Abigail Evans, Stephen R.D. Johnston, Roger A'Hern, Judith M. Bliss, Rashmita Sahoo, Simone Detre, Benjamin P. Haynes, Margaret Hills, Catherine Harper-Wynne, Nigel Bundred, Gill Coombes, Ian Smith, Mitch Dowsett
Journal: Clinical Cancer Research (2014)

Not all breast cancers respond to lapatinib. A change in Ki67 after short-term exposure may elucidate a biomarker profile for responsive versus nonresponsive tumors.
Accuracy of electronic digital calipers compared with quantitative angiography in measuring coronary arterial diameter.
Authors: A Uehata, T Matsuguchi, J A Bittl, J Orav, I T Meredith, T J Anderson, A P Selwyn, P Ganz, A C Yeung
Journal: Circulation (1993)

BACKGROUND Quantitative angiography is the accepted method for measuring coronary luminal diameter. Electronic digital calipers have been used to assess arterial diameters in vasomotor function studies and after interventional procedures. However, careful validation of calipers against quantitative angiography has not been described. METHODS AND RESULTS We used digital calipers and quantitative angiography to measure 517 arterial diameters (88 nonstenotic segments) in 24 transplant patients undergoing vasomotor function studies with acetylcholine and nitroglycerin, 20 stenoses in 14 patients with coronary artery disease, and 15 stenoses in 15 patients before and after excimer laser-facilitated coronary angioplasty and at 6 months' follow-up. In nonstenotic arterial segments ranging in size from 0.6 to 3.5 mm, calipers overestimated diameters measured by quantitative angiography by 0.29 +/- 0.21 mm (mean +/- SD) (limits of agreement, -0.13 to 0.71 mm). However, when the vasomotor responses were expressed as percent diameter change, the two methods did not differ significantly (-1 +/- 10%; limits of agreement, -21% to 19%). In the 35 stenoses measured before intervention and 30 stenoses measured after intervention, calipers and quantitative angiography differed by 3 +/- 9% (limits of agreement, -15% to 21%) across a range of stenosis severity (11% to 80%). Repeat caliper measurements by the same observer of the percent diameter change in the transplant patients and the percent stenosis in the coronary artery disease patients led to standard deviations of the differences of 9.3% and 7.6%, respectively. Two different observers recorded percent diameter change and percent stenosis that differed with standard deviations of 9.6% and 7.8%, respectively. CONCLUSIONS Quantitative angiography and electronic digital calipers produce similar relative changes in arterial diameters and percent stenosis in a broad range of severities. Digital calipers thus are a rapid and convenient alternative to computerized quantitative angiography in certain research studies and clinical practice of assessing stenosis severity.
Computer-Based Analysis of Preoperative and Postoperative Prognostic Factors in 100 Patients with Combined Aortic and Mitral Valve Replacement
Authors: DAVID B. MELVIN, PAUL L. TECKLENBERG, JEFFERSON F. HOLLINGSWORTH, FREDERICK H. LEVINE, D. LUKE GLANCY, STEPHEN E. EPSTEIN, ANDREW G. MORROW
Journal: Circulation (1973)

From 1963 to 1971, aortic and mitral valves were replaced in 100 patients; 22 died in hospital. Follow-up in survivors is 100%. Catheterization was performed preoperatively in 99 patients and postoperatively in 85% of survivors. The influence of 19 preoperative potential risk factors on hospital mortality, postoperative symptomatic improvement, and long-term survival (assessed by monthly cohort-adjusted survival tables) was determined. Long-term survival was also assessed by comparing average values of the various risk factors in patients surviving 1, 2, and 3 years with values in patients who died during these intervals. In addition, changes induced by operation were studied 6 months postoperatively and their value in predicting subsequent longevity assessed. Significant ( P &lt; 0.05) findings were: a higher hospital mortality in patients with left atrial pressures ≥30 mm Hg or with fabric-covered valves; less postoperative symptomatic improvement in older patients; lower long-term survival rate in men and in patients with high left atrial, right atrial, pulmonary arterial, or right ventricular end-diastolic pressures. A decrease in radiographic heart size or a New York Heart Association class I or II status 6 months postoperatively was associated with a favorable subsequent prognosis. Postoperative hemodynamic values did not predict subsequent survival.
Post-Treatment Change in Serum Estrone Predicts Mammographic Percent Density Changes in Women Who Received Combination Estrogen and Progestin in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial
Authors: Giske Ursin, Shana L. Palla, Beth A. Reboussin, Stacey Slone, Carol Wasilauskas, Malcolm C. Pike, Gail A. Greendale
Journal: Journal of Clinical Oncology (2004)

Postmenopausal estrogen and progestin therapy (EPT) increases mammographic percent density and breast cancer risk substantially more than does estrogen therapy alone. We determined whether increases in serum estrone as a function of treatment predict increases in mammographic percent density.We measured mammographic percent density and serum estrone levels in participants in the Postmenopausal Estrogen/Progestin Interventions Trial who were randomly assigned to receive conjugated equine estrogens (CEE) 0.625 mg/d; CEE and medroxyprogesterone acetate (MPA) 10 mg on days 1 to 12 per 28-day cycle; CEE and MPA 2.5 mg/d; or CEE and micronized progesterone (MP) 200 mg on days 1 to 12 per 28-day cycle. We used linear regression to determine whether serum estrone changes predicted mammographic percent density changes from baseline to 1 year.Mammographic percent density increased with increasing change in estrone level in the EPT groups, but not in the CEE group. Combined, the mammographic percent density in the three EPT groups demonstrated an absolute increase of 2.95% per 100 pg/mL increase in serum estrone level (P =.0003). The absolute increases were 4.09% (P =.0018) in the CEE + MPA continuous group, 2.79% (P =.0292) in the CEE + MPA cyclical group, and 1.40% (P =.36) in the CEE + MP group, but the differences among the EPT groups were not statistically significant.Greater increase in serum estrone level as a function of treatment is a significant predictor of increase in mammographic percent density in women randomly assigned to the combination of estrogen and progestin.
Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function
Authors: James A. Thomas, Caroline Pope, Davina Wojtacha, Andrew J. Robson, Timothy T. Gordon-Walker, Stephen Hartland, Prakash Ramachandran, Marielle Van Deemter, David A. Hume, John P. Iredale, Stuart J. Forbes
Journal: Hepatology (2011)

Clinical studies of bone marrow (BM) cell therapy for liver cirrhosis are under way but the mechanisms of benefit remain undefined. Cells of the monocyte-macrophage lineage have key roles in the development and resolution of liver fibrosis. Therefore, we tested the therapeutic effects of these cells on murine liver fibrosis. Advanced liver fibrosis was induced in female mice by chronic administration of carbon tetrachloride. Unmanipulated, syngeneic macrophages, their specific BM precursors, or unfractionated BM cells were delivered during liver injury. Mediators of inflammation, fibrosis, and regeneration were measured. Donor cells were tracked by sex-mismatch and green fluorescent protein expression. BM-derived macrophage (BMM) delivery resulted in early chemokine up-regulation with hepatic recruitment of endogenous macrophages and neutrophils. These cells delivered matrix metalloproteinases-13 and -9, respectively, into the hepatic scar. The effector cell infiltrate was accompanied by increased levels of the antiinflammatory cytokine interleukin 10. A reduction in hepatic myofibroblasts was followed by reduced fibrosis detected 4 weeks after macrophage infusion. Serum albumin levels were elevated at this time. Up- regulation of the liver progenitor cell mitogen tumor necrosis factor-like weak inducer of apoptosis (TWEAK) preceded expansion of the progenitor cell compartment. Increased expression of colony stimulating factor-1, insulin-like growth factor-1, and vascular endothelial growth factor also followed BMM delivery. In contrast to the effects of differentiated macrophages, liver fibrosis was not significantly altered by the application of macrophage precursors and was exacerbated by whole BM. Conclusion: Macrophage cell therapy improves clinically relevant parameters in experimental chronic liver injury. Paracrine signaling to endogenous cells amplifies the effect. The benefits from this single, defined cell type suggest clinical potential. (HEPATOLOGY 2011;)