tbuckley/cabot-search huggingface dataset:
Comparison between polyclonal and first and second generation monoclonal radioimmunoassays in the detection of hepatitis B surface antigen in patients with hepatocellular carcinoma
Authors: Michael C. Kew, Yumiko Fujita, Hiroshi Takahashi, Ann Coppins, Jack R. Wands
Journal: Hepatology (1986)

Serum from 221 black patients with hepatocellular carcinoma was tested for HBsAg using a polyclonal radioimmunoassay, and first and second generation monoclonal radioimmunoassays designated M1-RIA and M2-RIA. These monoclonal radioimmunoassays have a lower limit of detection of about 55 and 15 pg of HBsAg-associated epitopes per ml of serum. Correlations were made with other hepatitis B virus serologic markers such as anti-HBc and anti-HBs, using polyclonal radioimmunoassays. We found 47.5% (105/221) of the patients were HBsAg positive by conventional polyclonal radioimmunoassay; all of these patients were also reactive by monoclonal radioimmunoassay. Of the 116 polyclonal radioimmunoassay-negative patients, 4 (3.4%) were reactive by M1-RIA. These four patients were all positive for anti-HBc and/or anti-HBs antibodies. There were 106 of 112 patients negative for HBsAg by polyclonal radioimmunoassay and M1-RIA available for testing by the M2-RIA; 11 (10.4%) were found to be positive only by this test. Thus, with the use of M1- and M2-RIAs, the number of hepatocellular carcinoma patients negative for HBsAg by polyclonal radioimmunoassay was reduced by 14% in this population. More importantly, of the 11 M2-RIA-positive patients, six demonstrated anti-HBc and/or anti-HBs antibodies whereas the remaining five had no serologic evidence of recent or past hepatitis B virus exposure. Finally, of the 21 patients in this series with no markers of hepatitis B virus infection using polyclonal radioimmunoassay and M1-RIA, five (24%) were reactive for HBsAg-associated epitopes by M2-RIA. Taken together, these findings may be due in part to the detection of HBsAg in immune complexes, particularly in those patients with anti-HBc and anti-HBs. However, in hepatocellular carcinoma patients with no hepatitis B virus serologic markers, the M2-RIA may have been reactive due to low levels of antigen expression co-existing with an inadequate or lack of a host immune response to HBcAg and HBsAg, variable expression of hepatitis B virus gene products or to a “hepatitis B-related virus”.
Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory
Authors: Tomohiro Kaji, Akiko Ishige, Masaki Hikida, Junko Taka, Atsushi Hijikata, Masato Kubo, Takeshi Nagashima, Yoshimasa Takahashi, Tomohiro Kurosaki, Mariko Okada, Osamu Ohara, Klaus Rajewsky, Toshitada Takemori
Journal: The Journal of Experimental Medicine (2012)

One component of memory in the antibody system is long-lived memory B cells selected for the expression of somatically mutated, high-affinity antibodies in the T cell–dependent germinal center (GC) reaction. A puzzling observation has been that the memory B cell compartment also contains cells expressing unmutated, low-affinity antibodies. Using conditional Bcl6 ablation, we demonstrate that these cells are generated through proliferative expansion early after immunization in a T cell–dependent but GC-independent manner. They soon become resting and long-lived and display a novel distinct gene expression signature which distinguishes memory B cells from other classes of B cells. GC-independent memory B cells are later joined by somatically mutated GC descendants at roughly equal proportions and these two types of memory cells efficiently generate adoptive secondary antibody responses. Deletion of T follicular helper (Tfh) cells significantly reduces the generation of mutated, but not unmutated, memory cells early on in the response. Thus, B cell memory is generated along two fundamentally distinct cellular differentiation pathways. One pathway is dedicated to the generation of high-affinity somatic antibody mutants, whereas the other preserves germ line antibody specificities and may prepare the organism for rapid responses to antigenic variants of the invading pathogen.
SERUM FERMENTS AND ANTIFERMENT DURING TRYPSIN SHOCK
Authors: James W. Jobling, William Petersen, A. A. Eggstein
Journal: The Journal of Experimental Medicine (1915)

1. The intravenous injection of trypsin in dogs results in a shock similar in many respects to anaphylactic and peptone shock. 2. The injection is followed by a marked rise of serum protease and lipase. 3. The antiferment usually shows a distinct drop in titer, with a recovery following in from four to twenty-four hours. 4. The non-coagulable nitrogen shows no constant alteration, but is never greatly changed in amount. 5. Inactivated preparations were in some respects followed by symptoms similar to those following the injection of the active preparation. 6. Subcutaneous and gastric absorption was practically without effect. 7. Intestinal absorption was followed by an increase in serum protease without evidence of intoxication, or by typical symptoms of acute poisoning. 8. The leucocyte curve bears no constant relation to the serum protease or lipase.
Population Differences in the Human Functional Olfactory Repertoire
Authors: Y. Gilad
Journal: Molecular Biology and Evolution (2003)

Olfactory receptors (OR) constitute the molecular basis for the sense of smell. They are encoded by a large multigene family that in humans includes approximately 400 functional genes and approximately 600 putative pseudogenes, distributed on all but two chromosomes. To examine the ethnogeographic variability in the functional chemosensory repertoire, we resequenced 32 OR loci reported to contain a single coding region disruption in seven Caucasians and seven Pygmies. Thirteen of the 32 OR loci were found to have an interrupted coding region in all 28 alleles sampled, seven had an intact form in all the individuals examined, and 12 were polymorphic, segregating both the intact and the null variants. Among the latter loci, the frequency of the null allele was higher in Caucasians than in Pygmies, suggesting that African populations may have a larger repertoire of functional OR genes. Interestingly, when analyzing the entire OR coding regions, we find an excess of high-frequency derived alleles at many loci in the Caucasian sample but less so in the Pygmy sample. Our observations are unlikely to be accounted for by simple demographic models but may be explained by positive selection acting on OR loci in Caucasians.
Remission and radiographic outcome in rheumatoid arthritis: application of the 2011 ACR/EULAR remission criteria in an observational cohort
Authors: Siri Lillegraven, Femke HM Prince, Nancy A Shadick, Vivian P Bykerk, Bing Lu, Michelle L Frits, Christine K Iannaccone, Tore K Kvien, Espen A Haavardsholm, Michael E Weinblatt, Daniel H Solomon
Journal: Annals of the Rheumatic Diseases (2011)

Objectives One goal of remission in rheumatoid arthritis (RA) is to halt joint damage. The authors assessed the progression of radiographic joint damage among RA patients in remission by the new ACR/EULAR criteria (Boolean approach) compared with remission thresholds for the simplified disease activity index (SDAI), clinical disease activity index (CDAI) and disease activity score based on 28 joints and C-reactive protein (DAS28-CRP) in an observational cohort, and evaluated the relationship between time in remission and radiographic joint damage. Methods 535 RA patients underwent physical examination and laboratory assessment at baseline, 1 and 2 years. Radiographs at baseline and 2 years were scored by the van der Heijde modified Sharp score (TSS). Positive likelihood ratios for a good radiographic outcome (change in TSS &lt;1 unit/year) were calculated for each of the remission criteria. Radiographic progression was compared between patients in remission at none, one, two and three visits by χ 2 goodness of fit statistics. Results 20% of patients in ACR/EULAR remission at baseline had radiographic progression, 24% in SDAI remission, 19% in CDAI remission and 30% of patients in DAS28–CRP remission. The positive likelihood ratio for good radiographic outcome was 2.6 for ACR/EULAR criteria, 2.1 for SDAI, 2.8 for CDAI and.1.5 for DAS28–CRP. Reduced radiographic progression was observed for patients with an increasing number of visits in remission (p&lt;0.003 for all criteria, χ 2 goodness of fit statistics). Conclusions Patients with RA in remission by any established criteria can experience radiographic progression. An increased number of visits in remission was associated with reduced radiographic damage.
Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a canine model
Authors: T Ohki, M Yamato, D Murakami, R Takagi, J Yang, H Namiki, T Okano, K Takasaki
Journal: Gut (2006)

With the recent development of endoscopic submucosal dissection (ESD), large oesophageal cancers can be removed with a single procedure, with few limits on the resectable range. However, after aggressive ESD, a major complication that arises is postoperative inflammation and stenosis that can considerably affect the patient's quality of life.To examine a novel treatment combining ESD and the endoscopic transplantation of tissue-engineered cell sheets created using autologous oral mucosal epithelial cells, in a clinically relevant large animal model.Oral mucosal epithelial cells, harvested from beagle dogs, were cultured under normal conditions at 37 degrees C, on temperature-responsive dishes. After ESD (5 cm in length, 180 degrees in range), cell sheets were harvested by a simple reduction in temperature to 20 degrees C, and transplanted by endoscopy.The transplanted cell sheets were able to adhere to and survive on the underlying muscle layers in the ulcer sites, providing an intact, stratified epithelium. Four weeks after surgery, complete wound healing, with no observable stenosis, was seen in the animals receiving autologous cell sheet transplantation. By contrast, noticeable fibrin mesh and host inflammation, consistent with the intermediate stages of wound healing, were observed in the control animals that received only ESD.These findings in a clinically relevant canine model show the effectiveness of a novel combined endoscopic approach for the potential treatment of oesophageal cancers that can effectively enhance wound healing and possibly prevent postoperative oesophageal stenosis.
Hodgkin's Lymphoma in Adolescents
Authors: Lynda M. Foltz, Kevin W. Song, Joseph M. Connors
Journal: Journal of Clinical Oncology (2006)

Purpose To compare the clinical presentation, response to treatment, and long-term outcome of Hodgkin's lymphoma (HL) presenting in adolescents and young adults. Patients and Methods The British Columbia Cancer Agency Lymphoid Cancer database was used to identify adolescents (16 years to 21 years) and young adults (22 years to 45 years) receiving primary treatment for HL between 1981 and 2004. All patients were treated using adult protocols. Results The study population included 259 adolescents and 890 young adults. There were no significant differences in histologic subtypes, sex, stages, or presence of B symptoms or bulky disease between adolescents and adults. Equal proportions of adolescents and adults were treated with radiation alone (38% v 35%), chemotherapy alone (13% v 15%), or combined-modality programs (49% v 50%). There was no difference in progression-free survival (PFS) or overall survival (OS) between adolescents and adults, with 10-year PFS rates of 77% versus 80% (P = .67) and 10-year OS rates of 91% versus 89% (P = .42). In limited stage disease, 10-year PFS was 89% for adolescents and 89% for adults and OS 96% and 96%, respectively. In advanced stage disease, 10-year PFS was 71% for adolescents and 75% for adults and OS 88% and 86%, respectively. Actuarial risk of second malignancy for adolescents and adults was not different (P = .68). Conclusion Adolescents and young adults with HL have similar baseline characteristics and achieve similar outcomes when treated with the same protocols. The use of adult treatment protocols is a safe and effective strategy for treating adolescents with HL.
PET-CT predictors of mediastinal dissemination in lung cancer
Authors: Mireia Serra, Carles Grimau, Luis Berna, Alberto Fernández, Rosa Cordovilla, Enrique Cases, María Guadalupe Bermudo, Concepción Montón, Miguel Gallego, Sergi Call, Manuela Iglesias, Eduard Monso
Journal: European Respiratory Journal (2014)

A multicentric study of lung cancer staged by PET-TC and EBUS-NA was performed to identify PET-TC measures with high positive predictive value (PPV) for the identification of stage III disease and to evaluate EBUS-NA sensitivity. A surgical gold standard was used when EBUS-NA was negative.  Results: 76/105 patients showed ≥1 hypermetabolic spot in mediastinum (72%). PET-TC SUVmax did not show statistically significant differences between centers. Lung SUVmax had mean of 11.4 (SD 5.3), and hypermetabolic spot in mediastinum median of 3.4 (IQR 0-6.5). EBUS-NA confirmed mediastinal metastasis in 43/54 patients (79.6%). A single hypermetabolic image in mediastinum was not a significant predictor of dissemination (OR 1.99 95%CI 0.75-5.32), but ≥2 hypermetabolic spots showed an increased risk (OR 3.64 95%CI 1.29-10.26). Lung SUVmax was not associated with mediastinal malignancy (OR 0.93 95%CI 0.86-1.01), but mediastinum SUVmax >3.4 was a significant predictor (OR 6,36 95%CI 2,71-14,91), that persists after adjustment for multilevel disease (OR 5.77 95%CI 2.37-14.06) (PPV 74.6%). Relationship between mediastinum SUV max and dissemination was stronger when SUVmax mediastinum/lung > 0.7 (OR 8.10 95%CI 2,54-25,67) and SUVmax mediastinum-lung > -11.7 cut-offs (OR 8.71 95%CI 2.98-25.44) were used (PPV 84.6% and 64.5%, respectively). Sensitivities of EBUS-NA in patients with SUVmax mediastinum/lung ratio over (86.4%) and below (75%) 0.7 did not show a statistical difference.  Conclusions: SUVmax in the mediastinum is the main PET-CT predictor of mediastinal malignancy, with higher PPV when a 0.7 SUVmax mediastinum/lung cut-off is used. EBUS-NA sensitivity for the identification of dissemination is independent of PET-CT results.
Health Care Spending and Quality in Year 1 of the Alternative Quality Contract
Authors: Zirui Song, Dana Gelb Safran, Bruce E. Landon, Yulei He, Randall P. Ellis, Robert E. Mechanic, Matthew P. Day, Michael E. Chernew
Journal: New England Journal of Medicine (2011)

In 2009, Blue Cross Blue Shield of Massachusetts (BCBS) implemented a global payment system called the Alternative Quality Contract (AQC). Provider groups in the AQC system assume accountability for spending, similar to accountable care organizations that bear financial risk. Moreover, groups are eligible to receive bonuses for quality.
A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Adenosine as an Adjunct to Reperfusion in the Treatment of Acute Myocardial Infarction (AMISTAD-II)
Authors: Allan M. Ross, Raymond J. Gibbons, Gregg W. Stone, Robert A. Kloner, R. Wayne Alexander
Journal: Journal of the American College of Cardiology (2005)
Local delivery of dexamethasone for prevention of neointimal proliferation in a rat model of balloon angioplasty.
Authors: A E Villa, L A Guzman, W Chen, G Golomb, R J Levy, E J Topol
Journal: Journal of Clinical Investigation (1994)

A periadventitial polymer system is an alternative local drug delivery technique to obtain and maintain high tissue levels of the drug at the site of vascular injury. To determine if local periadventitial delivery of dexamethasone decreases neointimal proliferation after balloon vascular injury, in three groups of Sprague-Dawley rats, 5% dexamethasone, 0.5% dexamethasone, and placebo silicone polymers were implanted around the left common carotid artery after balloon injury. In a fourth group, placebo polymers were implanted without balloon injury. Dexamethasone serum and tissue levels after polymer implantation were significantly higher in the 5% dexamethasone group compared with the 0.5% dexamethasone group. There was no neointima formation in any of the arterial segments covered with placebo polymers for 3 wk, but without balloon injury. In the arterial segments covered by the 5 and 0.5% dexamethasone polymers, there was a 76 and 75% reduction in intima/media ratios, respectively, compared with the placebo group (5% dexamethasone, 0.26 +/- 0.04; 0.5% dexamethasone, 0.27 +/- 0.03; placebo, 1.09 +/- 0.16, respectively; P < 0.0001). These results suggest that: (a) silicone polymers wrapped around the common carotid arteries for 3 wk did not, without balloon injury, stimulate neointimal proliferation in the rat model; (b) the activity of the drug-eluting polymer for suppressing intimal proliferation was chiefly, but not exclusively, site specific; and (c) transadventitial local delivery of dexamethasone at two different doses markedly inhibits neointimal proliferation after balloon vascular injury.
Contrast-Enhanced Ultrasound and Prostate Cancer; A Multicentre European Research Coordination Project
Authors: Margot Wink, Ferdinand Frauscher, David Cosgrove, Jean-Yves Chapelon, Leo Palwein, Michael Mitterberger, Chris Harvey, Olivier Rouvière, Jean de la Rosette, Hessel Wijkstra
Journal: European Urology (2008)
Relation of smoking to immunoreactive endothelin in the bronchiolar epithelial cells.
Authors: M O Shokeir, P Pare, J L Wright
Journal: Thorax (1994)

BACKGROUND--Endothelin is a potent bronchoconstrictor which appears to be important in asthma. To ascertain whether cigarette smoking is associated with any alteration in the proportion of bronchiolar epithelial cells which express endothelin immunoreactivity, the airways in the lungs of non-smokers and smokers were analysed. Since an increase in immunoreactivity has been found in the bronchial epithelial cells of asthmatic subjects, cigarette smokers with and without evidence of airway hyperresponsiveness were also selected. METHODS--A point counting method which examined the proportion of endothelin immunoreactive epithelial cells in membranous and respiratory bronchioles was used. RESULTS--Neither smoking itself nor evidence of airway hyperresponsiveness altered the percentage of endothelin immunoreactive epithelial cells in the membraneous and respiratory bronchioles. CONCLUSIONS--Cigarette smoke does not induce endothelin production in bronchiolar epithelial cells, and the airway hyperresponsiveness seen in some patients with lung disease induced by cigarette smoking is not related to exaggerated endothelin production in epithelial cells.
<i>O</i>-acetylated <i>N</i>-acetylneuraminic acid as a novel target for therapy in human pre-B acute lymphoblastic leukemia
Authors: Reshmi Parameswaran, Min Lim, Anna Arutyunyan, Hisham Abdel-Azim, Christian Hurtz, Kam Lau, Markus Müschen, Robert K. Yu, Mark von Itzstein, Nora Heisterkamp, John Groffen
Journal: The Journal of Experimental Medicine (2013)

The development of resistance to chemotherapy is a major cause of relapse in acute lymphoblastic leukemia (ALL). Though several mechanisms associated with drug resistance have been studied in detail, the role of carbohydrate modification remains unexplored. Here, we investigated the contribution of 9-O-acetylated N-acetylneuraminic acid (Neu5Ac) to survival and drug resistance development in ALL cells. A strong induction of 9-O-acetylated Neu5Ac including 9-O-acetyl GD3 was detected in ALL cells that developed resistance against vincristine or nilotinib, drugs with distinct cytotoxic mechanisms. Removal of 9-O-acetyl residues from Neu5Ac on the cell surface by an O-acetylesterase made ALL cells more vulnerable to such drugs. Moreover, removal of intracellular and cell surface–resident 9-O-acetyl Neu5Ac by lentiviral transduction of the esterase was lethal to ALL cells in vitro even in the presence of stromal protection. Interestingly, expression of the esterase in normal fibroblasts or endothelial cells had no effect on their survival. Transplanted mice induced for expression of the O-acetylesterase in the ALL cells exhibited a reduction of leukemia to minimal cell numbers and significantly increased survival. This demonstrates that Neu5Ac 9-O-acetylation is essential for survival of these cells and suggests that Neu5Ac de-O-acetylation could be used as therapy to eradicate drug-resistant ALL cells.
To live or die: a critical decision for the lung
Authors: G.R. Scott Budinger, Jacob I. Sznajder
Journal: Journal of Clinical Investigation (2005)

Every cell in the body expresses a set of proteins designed to trigger permeabilization of the mitochondria and cell death. Inactivation or inappropriate triggering of these pathways is increasingly recognized as a contributor to human disease. A study in this issue of the JCI demonstrates that IL-6 exerts its protective effect against the development of lung injury following exposure of mice to 95% O2 by increasing the expression of a Bcl-2–related protein, A1. This protein acts to prevent mitochondrial membrane permeabilization and cell death following exposure to hyperoxia. The data in this study lend support to the hypothesis that inappropriate triggering of cell-death pathways may contribute to the development of hyperoxic pulmonary edema, lung injury, and respiratory failure.
Interactions between nitric oxide and renal nerves on pressure-diuresis and natriuresis.
Authors: M I Madrid, M G Salom, J Tornel, E López, F J Fenoy
Journal: Journal of the American Society of Nephrology (1998)

The present study examined the effect of renal denervation on the impairment of the pressure-diuresis response produced by nitric oxide synthesis blockade. The experiments were performed in Inactin-anesthetized Munich-Wistar rats. The animals with innervated kidneys had lower baseline values of renal blood flow, GFR, sodium excretion (UNaV), and urine flow (V) than rats with denervated kidneys. Also, renal denervation shifted pressure-diuresis and natriuresis toward lower pressures. A low dose of N(omega)-nitro-L-arginine methyl esther (NAME, 3.7 nmol/kg per min) reduced UNaV and the fractional excretion of sodium (FENa) and blunted pressure-natriuresis only in rats with innervated kidneys, whereas it had no effects in rats with denervated kidneys. A medium dose of NAME (37 nmol/kg per min) lowered FENa only in rats with innervated kidneys. The administration of NAME (37 nmol/kg per min) blunted pressure-diuresis and natriuresis in kidneys with or without the renal nerves, but the effect was more pronounced in rats with innervated kidneys. A high dose of NAME (3.7 micromol + 185 nmol/kg per min) increased UNaV and FENa only in rats with innervated kidneys, whereas it reduced GFR, V, UnaV, and FENa in rats with denervated kidneys. However, pressure-natriuresis and diuresis were blunted by this high dose of NAME independently of the presence or absence of renal nerves. These results demonstrate that renal nerves potentiate the renal effects of low doses of NAME on renal function and pressure-diuresis and natriuresis. However, high doses of NAME abolish pressure-diuresis independently of renal nerves, and the natriuretic effect of NAME in innervated kidneys may be attributed to reflex inhibition of sympathetic tone due to the rise in arterial pressure.