tbuckley/cabot-search huggingface dataset:
Increased sialylation of surface glycopeptides of human trophoblast compared with fetal cells from the same conceptus.
Authors: A Whyte, Y W Loke
Journal: The Journal of Experimental Medicine (1978)

The surface glycopeptides of human trophoblastic cells have been compared with those of fetal cells from the same embryos using double-labeling methods with isotopes of L-fucose and D-glucosamine. A faster eluting, neuraminidase-sensitive, fraction was observed on Sephadex chromatography of the trophoblast spectra when D-glucosamine was used as precursor. Labeling with fucose did not appear to result in any differences, thus suggesting that the glycopeptides characertistic of trophoblast contained glucosamine-derived metabolic products, including sialic acid, but excluding fucose. This increased sialylation is similar to, but not identical with, modifications observed in neoplastic cells, and on this basis it is postulated that two species of glycopeptides may be involved in atypical cellular behavior. The first contains sialic acid and other sugars excluding fucose, and is associated with localized cellular growth and invasion. The second contains both sialic acid and fucose and is characteristic of neoplastic cells.
A prospective study of PET/CT in initial staging of small-cell lung cancer: comparison with CT, bone scintigraphy and bone marrow analysis
Authors: B.M. Fischer, J. Mortensen, S.W. Langer, A. Loft, A.K. Berthelsen, B.L. Petersen, G. Daugaard, U. Lassen, H.H. Hansen
Journal: Annals of Oncology (2006)
Clinical Outcomes and Prognostic Factors in Patients With Richter's Syndrome Treated With Chemotherapy or Chemoimmunotherapy With or Without Stem-Cell Transplantation
Authors: Apostolia-Maria Tsimberidou, Susan O'Brien, Issa Khouri, Francis J. Giles, Hagop M. Kantarjian, Richard Champlin, Sijin Wen, Kim-Anh Do, Susan C. Smith, Susan Lerner, Emil J. Freireich, Michael J. Keating.
Journal: Journal of Clinical Oncology (2006)

The purpose of this study was to assess the incidence, presenting characteristics, and treatment outcomes of Richter's syndrome (RS) and factors predicting response and survival.An electronic database search of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who presented at The University of Texas M.D. Anderson Cancer Center (Houston, TX) between January 1975 and June 2005 was performed, and patient medical records were reviewed.Of the 3,986 patients with CLL/SLL, 204 patients (5.1%) had possible RS, and 148 patients (3.7%) had biopsy- or fine-needle aspiration-proven RS. Treatment included chemotherapy alone and chemoimmunotherapy with rituximab. The overall response rate for the 130 assessable patients was 39% (chemotherapy, 34%; chemoimmunotherapy, 47%; P = .2). In multivariate analysis, factors predicting prolonged survival were Zubrod performance status 0-1 (P = .006), lactate dehydrogenase < or = 1.5x the upper limit of normal (P = .003), platelet count > or = 100,000 (P = .01), tumor size < or = 5 cm (P = .02), and fewer than two prior therapies (P = .02). The five adverse factors predicting shorter survival were used to design a model to predict an individual patient's risk of death: the RS score. A total of 20 patients underwent stem-cell transplantation (SCT). Patients who underwent allogeneic SCT as postremission therapy had longer survival than patients who achieved remission and received no additional therapy or patients who underwent allogeneic or autologous SCT as salvage therapy (P = .019).A score to predict an individual patient's risk of death is proposed. Chemotherapy and rituximab combinations are effective in RS. Patients with available donors may be considered for allogeneic SCT as postremission therapy.
Immunoglobulin-containing cells in the coeliac syndrome
Authors: K. W. Pettingale
Journal: Gut (1971)

Immunofluorescent studies were performed upon the small intestinal mucosa obtained by jejunal biopsy of seven patients suffering from the coeliac syndrome and six control subjects. Seven patients had normal villous morphology and six had subtotal villous strophy. In the group whose jejunal biopsies were normal using routine histological examination, the predominant type of immunoglobulin-containing cell was IgA followed by IgM, then IgG, with the approximate ratio of 3:2:1 respectively. The cell densities were found to be much higher than in other published series and the predominance of IgA was not so marked. These findings may be in part due to differences in technique, but probably are also due to differences in the patients studied. In the group with villous atrophy the density of IgA cells was significantly lower than in the group with normal histology and three of the six patients showed a reversal in the normal ratio between IgA-and IgM-containing cells. A positive correlation was observed between serum IgM levels and the density of corresponding immunoglobulin-containing cells.
AMP-Activated Protein Kinase Regulation and Biological Actions in the Heart
Authors: Vlad G. Zaha, Lawrence H. Young
Journal: Circulation Research (2012)

AMP-activated protein kinase (AMPK) is a stress-activated kinase that functions as a cellular fuel gauge and master metabolic regulator. Recent investigation has elucidated novel molecular mechanisms of AMPK regulation and important biological actions of the AMPK pathway that are highly relevant to cardiovascular disease. Activation of the intrinsic AMPK pathway plays an important role in the myocardial response to ischemia, pressure overload, and heart failure. Pharmacological activation of AMPK shows promise as a therapeutic strategy in the treatment of heart disease. The purpose of this review is to assess how recent discoveries have extended and in some cases challenged existing paradigms, providing new insights into the regulation of AMPK, its diverse biological actions, and therapeutic potential in the heart.
Cytokine production of RSV/PHA-stimulated tonsillar mononuclear cells: influences of age and atopy
Authors: S. Ichinohe, I.R. Hussain, S.L. Johnston
Journal: European Respiratory Journal (2003)

Links between immune responses to respiratory syncytial virus (RSV), age and atopic sensitisation are poorly understood. This study investigated the induction of target organ type‐1, type‐2 and pro-inflammatory cytokine responses to RSV and/or phytohaemagglutinin (PHA) in tonsillar mononuclear cells from children, in relation to age and atopic status. In comparison with the control medium, RSV induced production of the type‐1 cytokines interferon (IFN)‐γ and interleukin (IL)‐18, the pro-inflammatory cytokines IL‐6, ‐8 and RANTES (regulated on activation, normal T‐cell expressed and secreted), but not any of the type‐2 cytokines IL‐4, ‐5, ‐10 and ‐13. Induction of IL‐6, ‐8 and RANTES, but not IFN‐γ or IL‐18, were shown to be dependent on virus replication. PHA induced all except IL‐12, ‐13, and ‐15. Induction of IFN‐γ, IL‐6, ‐8, and RANTES was significantly increased in atopic children. Induction of both IFN‐γ andIL‐4 increased in parallel in relation to age, with no change in the IFN‐γ:IL‐4 ratio. These data are compatible with the hypothesis that immature type‐1 immunity during early childhood plays a role in both respiratory syncytial virus bronchiolitis and in its relationship with atopy.
Targeting small airways in asthma: the new challenge of inhaled corticosteroid treatment
Authors: S. Lahzami, G. G. King
Journal: European Respiratory Journal (2008)

The small airways have long been considered to be important in asthma. The presence of inflammation in small airways has been well established in studies of post mortem tissue 1. Inflammation even extends to peribronchial tissues seen in transbronchial biopsy studies 2. In this issue of the European Respiratory Journal , the study by Cohen et al. 3 underscores the increasing interest in targeting treatment to the small airways with currently available fine-particle aerosols with median diameters of ∼1 μm. The study also highlights the as yet unproven potential of aerosol treatment in targeting the small airways and the complexities of such research. Cohen et al. 3 found that 5 weeks of ciclesonide treatment, a small-particle inhaled corticosteroid, improved alveolar exhaled nitric oxide, airway hyperresponsiveness and spirometry but not closing volume. They also found that the expiratory lung volume measured using high-resolution computed tomography (HRCT), after methacholine challenge, was smaller in the ciclesonide-treated group compared with the placebo group. However, the question as to whether ciclesonide is better than larger-particle aerosols for treating small airways in asthma remains unanswered.

Establishing the clinical significance of small airways disease is a priority if advances in asthma management are to occur; however, this has been difficult because of the challenges in measurement. Assessment of small airways continues to be a complex undertaking and includes techniques such as transbronchial biopsy, gas washout tests 4, 5, frequency dependence of compliance, intrabronchial pressure measurements 6, forced oscillation technique (FOT) …
Capecitabine Plus Paclitaxel As Front-Line Combination Therapy for Metastatic Breast Cancer: A Multicenter Phase II Study
Authors: William J. Gradishar, Luis A. Meza, Bipinkumar Amin, Dvorit Samid, Todd Hill, Yin-Miao Chen, Elyse E. Lower, P. Kelly Marcom
Journal: Journal of Clinical Oncology (2004)

Purpose The goal of this multicenter, open-label phase II study was the clinical evaluation of combination therapy with the oral fluoropyrimidine capecitabine and the taxane paclitaxel in patients with metastatic breast cancer (MBC). Patients and Methods Forty-seven patients with MBC received oral capecitabine at 1,650 mg/m 2 /d (825 mg/m 2 twice daily) on days 1 through 14, and intravenous infusion of paclitaxel at 175 mg/m 2 on day 1 of each 21-day treatment cycle. Treatment continued until disease progression, intolerable toxicity, or patient's decision to discontinue. Patients (35 to 76 years old) had a median Karnofsky performance status of 90%. Forty-four patients (94%) received study treatment as first-line therapy for metastatic disease. Results Objective responses occurred in 24 (51%) patients; seven (15%) complete responses and 17 (36%) partial responses. Stable disease lasting 180 days or more was observed in nine (19%); the clinical response rate was 70%. Median duration of response was 12.6 months, median time to disease progression was 10.6 months, and median overall survival time was 29.9 months. The most common treatment-related adverse events, regardless of severity, were alopecia, hand-foot syndrome, nausea, and fatigue. Neutropenia (15%), alopecia (13%), and hand-foot syndrome (11%) were the only grade 3 or 4 treatment-related adverse events that occurred in more than 10% of patients. Conclusion The combination of capecitabine plus paclitaxel is a highly active and generally well-tolerated regimen for first-line treatment of MBC.
Comparison of Annual and Biannual Mass Antibiotic Administration for Elimination of Infectious Trachoma
Authors: Muluken Melese
Journal: JAMA (2008)

Treatment recommendations assume that repeated mass antibiotic distributions can control, but not eradicate or even locally eliminate, the ocular strains of chlamydia that cause trachoma. Elimination may be an important end point because of concern that infection will return to communities that have lost immunity to chlamydia after antibiotics are discontinued.To determine whether biannual treatment can eliminate ocular chlamydial infection from preschool children and to compare results with the World Health Organization-recommended annual treatment.A cluster-randomized clinical trial of biannual vs annual mass azithromycin administrations to all residents of 16 rural villages in the Gurage Zone, Ethiopia, from March 2003 to April 2005.At scheduled treatments, all individuals aged 1 year or older were offered a single dose of oral azithromycin either annually or biannually.Village prevalence of ocular chlamydial infection and presence of elimination at 24 months in preschool children determined by polymerase chain reaction, correcting for baseline prevalence. Antibiotic treatments were performed after sample collections.Overall, 14,897 of 16,403 eligible individuals (90.8%) received their scheduled treatment. In the villages in which residents were treated annually, the prevalence of infection in preschool children was reduced from a mean of 42.6% (range, 14.7%-56.4%) to 6.8% (range, 0.0%-22.0%) at 24 months. In the villages in which residents were treated biannually, infection was reduced from 31.6% pretreatment (range, 6.1%-48.6%) to 0.9% (range, 0.0%-4.8%) at 24 months. Biannual treatment was associated with a lower prevalence at 24 months (P = .03, adjusting for baseline prevalence). At 24 months, no infection could be identified in 6 of 8 of those treated biannually and in 1 of 8 of those treated annually (P = .049, adjusting for baseline prevalence).Local elimination of ocular chlamydial infection appears feasible even in the most severely affected areas, although it may require biannual mass antibiotic distributions at a high coverage level.clinicaltrials.gov Identifier: NCT00221364.
Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN)
Authors: Joachim Sieper, Jürgen Braun, Jonathan Kay, Salvatore Badalamenti, Allen R Radin, Lixia Jiao, Stefano Fiore, Tanya Momtahen, George D Yancopoulos, Neil Stahl, Robert D Inman
Journal: Annals of the Rheumatic Diseases (2014)

The ALIGN study (NCT01061723) evaluated the efficacy and safety of sarilumab, the first fully human monoclonal antibody against interleukin-6 receptor-α (IL-6Rα), in patients with ankylosing spondylitis (AS).Patients with active AS despite conventional treatment were randomised to placebo, or one of five subcutaneous dose regimens of sarilumab (100, 150 or 200 mg every other week, or 100 or 150 mg every week), for 12 weeks. The primary efficacy end point was the percentage of patients achieving the Axial SpondyloArthritis international Society (ASAS) 20 response criteria at week 12. Secondary endpoints included ASAS40 response, ASAS partial remission, AS Disease Activity Score, high-sensitivity C-reactive protein (hs-CRP) value, and safety.Baseline demographic and disease characteristics of the 301 patients enrolled were similar across treatment groups. At week 12, there was no statistically significant difference in ASAS20 response rate between placebo (ASAS20 = 24.0%) and any sarilumab dose group. A significantly greater reduction in hs-CRP value was achieved with the higher sarilumab doses versus placebo. No other statistically significant differences were evident for secondary efficacy endpoints. The most common treatment-emergent adverse events reported for sarilumab included infections (non-serious), neutropenia, and increase in alanine aminotransferase. No cases of tuberculosis, opportunistic, or fungal infections, or bowel perforations were reported. Seven patients experienced a treatment-emergent serious adverse event (all in sarilumab treatment groups). No deaths occurred.The ALIGN study shows that IL-6Rα blockade with sarilumab was not an effective treatment for AS. Sarilumab was generally well tolerated with a manageable safety profile.
Long-Term Exposure to Ambient Air Pollution and Risk of Hospitalization with Community-acquired Pneumonia in Older Adults
Authors: Binod Neupane, Michael Jerrett, Richard T. Burnett, Thomas Marrie, Altaf Arain, Mark Loeb
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Little is known about the long-term effects of air pollution on pneumonia hospitalization in the elderly.To assess the effect of long-term exposure to ambient nitrogen dioxide, sulfur dioxide, and fine particulate matter with diameter equal to or smaller than 2.5 microm (PM(2.5)) on hospitalization for community-acquired pneumonia in older adults.We used a population-based case-control study in Hamilton, Ontario, Canada. We enrolled 345 hospitalized patients aged 65 years or more for community-acquired pneumonia and 494 control participants, aged 65 years and more, randomly selected from the same community as cases from July 2003 to April 2005. Health data were collected by personal interview. Annual average levels of nitrogen dioxide, sulfur dioxide, and PM(2.5) before the study period were estimated at the residential addresses of participants by inverse distance weighting, bicubic splined and land use regression methods and merged with participants' health data.Long-term exposure to higher levels of nitrogen dioxide and PM(2.5) was significantly associated with hospitalization for community-acquired pneumonia (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.25 to 4.21; P = 0.007 and OR, 2.26; 95% CI, 1.20 to 4.24; P = 0.012, respectively, over the 5th-95th percentile range increase of exposure). Sulfur dioxide did not appear to have any association (OR, 0.97; 95% CI, 0.59 to 1.61; P = 0.918). Results were somewhat sensitive to the choice of methods used to estimate air pollutant levels at residential addresses, although all risks from nitrogen dioxide and PM(2.5) exposure were positive and generally significant.In older adults, exposure to ambient nitrogen dioxide and PM(2.5) was associated with hospitalization for community-acquired pneumonia.
Olfactory Maps in the Brain
Authors: Venkatesh N. Murthy
Journal: Annual Review of Neuroscience (2011)

The responses of neural elements in many sensory areas of the brain vary systematically with their physical position, leading to a topographic representation of the outside world. Sensory representation in the olfactory system has been harder to decipher, in part because it is difficult to find appropriate metrics to characterize odor space and to sample this space densely. Recent experiments have shown that the arrangement of glomeruli, the elementary units of processing, is relatively invariant across individuals in a species, yet it is flexible enough to accommodate new sensors that might be added. Evidence supports the existence of coarse spatial domains carved out on a genetic or functional basis, but a systematic organization of odor responses or neural circuits on a local scale is not evident. Experiments and theory that relate the properties of odorant receptors to the detailed wiring diagram of the downstream olfactory circuits and to behaviors they trigger may reveal the design principles that have emerged during evolution.
Clinical Outcomes of Poor Prognosis Germ Cell Tumors (Gct): an Analysis of a Series from a Single Referral Center
Authors: E. Farè, S. Lo Vullo, P. Giannatempo, N. Nicolai, D. Raggi, L. Piva, D. Biasoni, M. Catanzaro, T. Torelli, M. Marongiu, S. Stagni, M. Maffezzini, L. Mariani, A.M. Gianni, R. Salvioni, A. Necchi
Journal: Annals of Oncology (2014)
Androgen and Estrogen Response to Adrenal and Gonadal Stimulation in Idiopathic Hemochromatosis: Evidence for Decreased Estrogen Formation
Authors: Hans K. Kley, Wolfgang Stremmel, Claus Niederau, Rainer Hehrmann, Omar Shams, Georg Strohmeyer, Hans L. Krüskemper
Journal: Hepatology (1985)

Gonadal function in idiopathic hemochromatosis (IHC) was evaluated by comparing clinical features and levels of sex hormones in 10 male patients with IHC (cirrhosis, 4; fibrosis, 6), 6 male patients with alcoholic cirrhosis (AC) and 10 healthy, age-matched controls. Impotence was present in 9 IHC and all AC patients and was associated with decreased plasma testosterone levels. However, gynecomastia, a feature in all patients with AC, was not present in IHC, and plasma sex hormone binding globulin was normal. Patients with IHC showed significantly lower basal estradiol levels (17.7 +/- 6.3 pg per ml) than did controls (28.5 +/- 8.5 pg per ml), and low LH levels (p less than 0.01), which were insufficiently stimulated by luteinizing hormone releasing hormone (n = 8) as well as a decrease in prolactin concentration (2.9 +/- 1.4 vs. 5.9 +/- 1.9 ng per ml in the controls) suggesting pituitary failure. Synthesizing capacity of sex hormones was determined by adrenocorticotropic hormone and human chorionic gonadotropin administration. Basal and stimulated levels of androstenedione and cortisol indicated normal function of the adrenals in IHC. However after adrenocorticotropic hormone, estrone levels increased to only 16.2 +/- 8.4 pg per ml (controls, 27.3 +/- 4.7 pg per ml; p less than 0.01). Increments of estrone (12.5 +/- 9.2 pg per ml) and estradiol (17.9 +/- 11.6 pg per ml) were also lower in IHC following human chorionic gonadotropin administration than in controls (26.0 +/- 7.2 and 37.5 +/- 11.4 pg per ml, respectively). In contrast, plasma human chorionic gonadotropin raised testosterone levels 3.3-fold in IHC and 2.2-fold in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Long-Term Antithrombotic Protection by in Vivo Depletion of Platelet Glycoprotein VI in Mice
Authors: Bernhard Nieswandt, Valerie Schulte, Wolfgang Bergmeier, Rabée Mokhtari-Nejad, Kirsten Rackebrandt, Jean-Pierre Cazenave, Philippe Ohlmann, Christian Gachet, Hubert Zirngibl
Journal: The Journal of Experimental Medicine (2001)

Coronary artery thrombosis is often initiated by abrupt disruption of the atherosclerotic plaque and activation of platelets on the subendothelial layers in the disrupted plaque. The extracellular matrix protein collagen is the most thrombogenic constituent of the subendothelial layer; therefore, a selective inhibition of the collagen activation pathway in platelets may provide strong antithrombotic protection while preserving other platelet functions. Here we demonstrate that treatment of mice with a monoclonal antibody against the activating platelet collagen receptor glycoprotein VI (GPVI; JAQ1) results in specific depletion of the receptor from circulating platelets and abolished responses of these cells to collagen and collagen-related peptides (CRPs). JAQ1-treated mice were completely protected for at least 2 wk against lethal thromboembolism induced by infusion of a mixture of collagen (0.8 mg/kg) and epinephrine (60 μg/ml). The tail bleeding times in JAQ1-treated mice were only moderately increased compared with control mice probably because the treatment did not affect platelet activation by other agonists such as adenosine diphosphate or phorbol myristate acetate. These results suggest that GPVI might become a target for long-term prophylaxis of ischemic cardiovascular diseases and provide the first evidence that it is possible to specifically deplete an activating glycoprotein receptor from circulating platelets in vivo.