tbuckley/cabot-search huggingface dataset:
Gemcitabine Alone Versus Gemcitabine Plus Radiotherapy in Patients With Locally Advanced Pancreatic Cancer: An Eastern Cooperative Oncology Group Trial
Authors: Patrick J. Loehrer, Yang Feng, Higinia Cardenes, Lynne Wagner, Joanna M. Brell, David Cella, Patrick Flynn, Ramesh K. Ramanathan, Christopher H. Crane, Steven R. Alberts, Al B. Benson
Journal: Journal of Clinical Oncology (2011)

The purpose of this trial was to evaluate the role of radiation therapy with concurrent gemcitabine (GEM) compared with GEM alone in patients with localized unresectable pancreatic cancer.Patients with localized unresectable adenocarcinoma of the pancreas were randomly assigned to receive GEM alone (at 1,000 mg/m(2)/wk for weeks 1 to 6, followed by 1 week rest, then for 3 of 4 weeks) or GEM (600 mg/m(2)/wk for weeks 1 to 5, then 4 weeks later 1,000 mg/m(2) for 3 of 4 weeks) plus radiotherapy (starting on day 1, 1.8 Gy/Fx for total of 50.4 Gy). Measurement of quality of life using the Functional Assessment of Cancer Therapy-Hepatobiliary questionnaire was also performed.Of 74 patients entered on trial and randomly assigned to receive GEM alone (arm A; n = 37) or GEM plus radiation (arm B; n = 34), patients in arm B had greater incidence of grades 4 and 5 toxicities (41% v 9%), but grades 3 and 4 toxicities combined were similar (77% in A v 79% in B). No statistical differences were seen in quality of life measurements at 6, 15 to 16, and 36 weeks. The primary end point was survival, which was 9.2 months (95% CI, 7.9 to 11.4 months) and 11.1 months (95% CI, 7.6 to 15.5 months) for arms A and B, respectively (one-sided P = .017 by stratified log-rank test).This trial demonstrates improved overall survival with the addition of radiation therapy to GEM in patients with localized unresectable pancreatic cancer, with acceptable toxicity.
Reproducibility of histological assessments of disease activity in UC
Authors: Mahmoud H Mosli, Brian G Feagan, Guangyong Zou, William J Sandborn, Geert D'Haens, Reena Khanna, Cynthia Behling, Keith Kaplan, David K Driman, Lisa M Shackelton, Kenneth A Baker, John K MacDonald, Margaret K Vandervoort, Mark A Samaan, Karel Geboes, Mark A Valasek, Rish Pai, Cord Langner, Robert Riddell, Noam Harpaz, Maida Sewitch, Michael Peterson, Larry W Stitt, Barrett G Levesque
Journal: Gut (2014)

Histopathology is potentially an important outcome measure in UC. Multiple histological disease activity (HA) indices, including the Geboes score (GS) and modified Riley score (MRS), have been developed; however, the operating properties of these instruments are not clearly defined. We assessed the reproducibility of existing measures of HA.Five experienced pathologists with GI pathology fellowship training and expertise in IBD evaluated, on three separate occasions at least two weeks apart, 49 UC colon biopsies and scored the GS, MRS and a global rating of histological severity using a 100 mm visual analogue scale (VAS). The reproducibility of each grading system and for individual instrument items was quantified by estimates of intraclass correlation coefficients (ICCs) based on two-way random effects models. Uncertainty of estimates was quantified by 95% two-sided CIs obtained using the non-parametric cluster bootstrap method. Biopsies responsible for the greatest disagreement based on the ICC estimates were identified. A consensus process was used to determine the most common sources of measurement disagreement. Recommendations for minimising disagreement were subsequently generated.Intrarater ICCs (95% CIs) for the total GS, MRS and VAS scores were 0.82 (0.73 to 0.88), 0.71 (0.63 to 0.80) and 0.79 (0.72 to 0.85), respectively. Corresponding inter-rater ICCs were substantially lower: 0.56 (0.39 to 0.67), 0.48 (0.35 to 0.66) and 0.61 (0.47 to 0.72). Correlation between the GS and VAS was 0.62 and between the MRS and VAS was 0.61.Although 'substantial' to 'almost perfect' ICCs for intrarater agreement were found in the assessment of HA in UC, ICCs for inter-rater agreement were considerably lower. According to the consensus process results, standardisation of item definitions and modification of the existing indices is required to create an optimal UC histological instrument.
A murine C4 molecule with reduced hemolytic efficiency.
Authors: J P Atkinson, K McGinnis, L Brown, J Peterein, D Shreffler
Journal: The Journal of Experimental Medicine (1980)

C4 functional activity and antigenic levels were determined in H-2-congenic mouse strains. In strains with the H-2w7 haplotype, the C4 hemolytic activity per unit of residual Ss antigenic activity, after depletion of the nonfunctional Slp-positive molecules was 25-33% that found with other H-2 haplotypes. This reduced hemolytic efficiency was not the result of either a more labile C4 molecule or of the presence of inhibitors. Moreover, other strains with comparable antigenic concentrations of Ss (C4) and Slp has three- to fourfold higher levels of C4 hemolytic activity. Based on these data and previously reported structural differences between C4 molecules from the H-2w7 haplotype compared with other standard H-2 haplotypes, the reduced hemolytic efficiency of this molecule is probably secondary to alterations in the structure of its alpha-chain.
Diagnosis and Management of the Metabolic Syndrome
Authors: Scott M. Grundy, James I. Cleeman, Stephen R. Daniels, Karen A. Donato, Robert H. Eckel, Barry A. Franklin, David J. Gordon, Ronald M. Krauss, Peter J. Savage, Sidney C. Smith, John A. Spertus, Fernando Costa
Journal: Circulation (2005)

The metabolic syndrome has received increased attention in the past few years. This statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults.

The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors —that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).1 Patients with the metabolic syndrome also are at increased risk for developing type 2 diabetes mellitus. Another set of conditions, the underlying risk factors , give rise to the metabolic risk factors. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria to be used in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general they include a combination of both underlying and metabolic risk factors.

The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a pro-inflammatory state as well. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to which components of the syndrome are …
Cholelithiasis in Singapore: Part I A necropsy study
Authors: W. S. Hwang
Journal: Gut (1970)

The present necropsy study shows an oriental pattern of gallstone disease in Singapore, namely, a relatively low overall frequency, an equal involvement of both sexes, a high proportion of pigment stones, and the common occurrence of choledocholithiasis associated with pyogenic cholangitis. There is a close association between opium addiction and cholelithiasis in the adult male Chinese in Singapore, and the long-term abuse of opium may be an important aetiological factor in the pathogenesis of oriental cholelithiasis.
Antigen and Epitope Specificity of Anti–Glomerular Basement Membrane Antibodies in Patients with Goodpasture Disease with or without Anti-Neutrophil Cytoplasmic Antibodies
Authors: Rui Yang, Thomas Hellmark, Juan Zhao, Zhao Cui, Marten Segelmark, Ming-hui Zhao, Hai-yan Wang
Journal: Journal of the American Society of Nephrology (2007)

Goodpasture disease (GP) is defined by the presence of anti-glomerular basement membrane (anti-GBM) antibodies and rapidly progressive glomerulonephritis. Besides anti-GBM, many patients with GP produce anti-neutrophil cytoplasmic antibodies (ANCA). For elucidation of the pathophysiologic significance of ANCA in this setting, epitope and antigen specificity of the anti-GBM antibodies and antigen specificity of ANCA were studied. Bovine testis alpha(IV)NC1 (tNC1); recombinant human alpha1, alpha3, alpha4, and alpha5(IV)NC1 (ralpha1 through ralpha5); and three chimeric proteins that contain previously defined epitope regions designated E(A), E(B), and S2 were used to examine the anti-GBM antibodies by ELISA in 205 Chinese patients with GP with or without ANCA. In the 205 anti-GBM antibody-positive sera, 63 (30.7%) were also ANCA positive (61 myeloperoxidase-ANCA and six proteinase 3-ANCA, four being triple positive). All 205 sera recognized tNC1 and ralpha3(IV)NC1. In the double-positive group, 54.0, 66.7, 71.4% of the sera could recognize ralpha1, ralpha4, and ralpha5, respectively, compared with 49.3, 60.6, and 55.6% for patients with anti-GBM antibodies alone. The levels of the antibodies to ralpha3, tNC1, and the alpha3/alpha1 ratio were lower in the double-positive group than that in patients with anti-GBM antibody alone (P < 0.05). Most of the sera could recognize the epitope regions E(A), E(B), and S2, but the absorbance values to E(A), E(B), and S2 were lower in double-positive group (P < 0.05). Double-positive patients had a broader spectrum of anti-GBM antibodies and lower levels of antibodies against alpha3(IV)NC1 compared with that of patients with anti-GBM antibodies alone.
Insulin-like Growth Factor-1 Improves Survival in Sepsis via Enhanced Hepatic Bacterial Clearance
Authors: Alix Ashare, Amanda B. Nymon, Kevin C. Doerschug, John M. Morrison, Martha M. Monick, Gary W. Hunninghake
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Both insulin-like growth factor (IGF)-1 and bacterial clearance by Kupffer cells are significantly reduced in severe sepsis. Kupffer cell apoptosis is triggered by tumor necrosis factor (TNF)-alpha and activation of the PI-3 kinase pathway prevents TNF-induced Kupffer cell death.We evaluated if the marked decline in IGF-1 is related to bacterial clearance in sepsis.Sepsis was induced in C57BL/6 mice by intratracheal inoculation with Pseudomonas aeruginosa (strain PA103). Some mice received IGF-1 24 mg/kg either before infection or 12 hours after infection. In vitro studies were performed using the clonal Kupffer cell line KC13-2.Sepsis resulted in decreased levels of IGF-1. In vitro studies with KC13-2 cells demonstrated that IGF-1 protected Kupffer cells against TNF-alpha-induced apoptosis by activating the PI-3 kinase pathway and stabilizing the inhibitor of apoptosis protein, XIAP. In the animal model, pretreatment with IGF-1 decreased hepatic TNF-alpha and IL-6, improved hepatic bacterial clearance as demonstrated by real-time polymerase chain reaction with primers specific for P. aeruginosa, and improved survival in severe sepsis. Moreover, we rescued mice from severe sepsis by IGF-1 treatment 12 hours after infection.These studies show that the decline in IGF-1 levels in sepsis is related to bacterial clearance and that replacement of IGF-1 in a murine model of sepsis improves overall survival.
Antiischemic Effects of SB203580 Are Mediated Through the Inhibition of p38α Mitogen-Activated Protein Kinase
Authors: Jody L. Martin, Metin Avkiran, Roy A. Quinlan, Philip Cohen, Michael S. Marber
Journal: Circulation Research (2001)

The aim of the present study was to determine whether the attenuation of myocardial ischemic injury by SB203580 is due to the inhibition of p38 mitogen-activated protein kinase (MAPK) or to other documented nonspecific effects of the drug. We made adenoviral vectors encoding the α isoform of p38 MAPK with or without site-directed mutations to prevent SB203580 binding and inhibition. In embryonal rat heart–derived cells and adult rat cardiocytes expressing wild-type p38α MAPK, injury was reduced significantly by SB203580 present during simulated ischemia. In contrast, SB203580 did not protect cells expressing the SB203580-resistant form of p38α MAPK. These observations suggest that SB203580-mediated protection depends on the inhibition of p38α MAPK.
Type 2 Diabetes Increases the Risk for Uric Acid Stones
Authors: Michel Daudon, Olivier Traxer, Pierre Conort, Bernard Lacour, Paul Jungers
Journal: Journal of the American Society of Nephrology (2006)

An increased prevalence of nephrolithiasis has been reported in patients with diabetes. Because insulin resistance, characteristic of the metabolic syndrome and type 2 diabetes, results in lower urine pH through impaired kidney ammoniagenesis and because a low urine pH is the main factor of uric acid (UA) stone formation, it was hypothesized that type 2 diabetes should favor the formation of UA stones. Therefore, the distribution of the main stone components was analyzed in a series of 2464 calculi from 272 (11%) patients with type 2 diabetes and 2192 without type 2 diabetes. The proportion of UA stones was 35.7% in patients with type 2 diabetes and 11.3% in patients without type 2 diabetes (P < 0.0001). Reciprocally, the proportion of patients with type 2 diabetes was significantly higher among UA than among calcium stone formers (27.8 versus 6.9%; P < 0.0001). Stepwise regression analysis identified type 2 diabetes as the strongest factor that was independently associated with the risk for UA stones (odds ratio 6.9; 95% confidence interval 5.5 to 8.8). The proper influence of type 2 diabetes was the most apparent in women and in patients in the lowest age and body mass index classes. In conclusion, in view of the strong association between type 2 diabetes and UA stone formation, it is proposed that UA nephrolithiasis may be added to the conditions that potentially are associated with insulin resistance. Accordingly, it is suggested that patients with UA stones, especially if overweight, should be screened for the presence of type 2 diabetes or components of the metabolic syndrome.
Acupuncture anesthesia: pricking the balloon
Authors: R. H. De Jong
Journal: JAMA (1977)

Hopes that surgical anesthesia could be attained by nonpharmacologic means were raised when word reached us that Chinese physicians employed  for intraoperative pain relief. 1 In 1973, Bonica 2 (a member of the American medical delegation) reported personal observations of 15 operations done with analgesia provided by acupuncture; seven patients gave visual or physiologic indications that pain relief was not complete.  A study group, formed by the National Academy of Sciences, thereupon visited the People's Republic of China in May 1974 to gather firsthand scientific data about this modern application of an age-old therapeutic modality. The group's dozen members visited 16 hospitals and witnessed 48 operations performed under  analgesia. 3   Though many patients tolerated surgery with little or no discomfort when treated with acupuncture, it became evident that  does not abolish pain totally, nor does it alter consciousness—two states traditionally associated with general anesthesia. The terms acupuncture
ORTHOPNOEA AND THE EFFECT OF POSTURE UPON THE RATE OF BLOOD FLOW
Authors: H. Field, A. V. Bock
Journal: Journal of Clinical Investigation (1925)

Lindhard (1) has noted that, of seven subjects, three, all of them females, had a slower rate of blood flow in the sitting than in the recumbent posture while the four male subjects showed practically no change.As far as we know these are the only direct observations in the literature concerning the effect of posture on blood flow.We have made thirteen determinations of the circulatory rate with the subjects sitting and nine determinations with the subjects standing, each one compared with a preceding determination made while the subject was recumbent.A rest period of about an hour preceded the first determination in each experiment.Change of position was accompanied by as little exertion as possible and a further rest period of fifteen to twenty minutes preceded each determination in the new position.The method used is a gasometric one, based on the Fick principle, which we have previously described (2).The subjects were young, healthy, adult males except the last two who were females and G. R. who has a rheumatic cardiac lesion which is well compensated.None of the subjects were athletic.Our results, shown in table 1 are even more striking than those of Lindhard.In no case did we fail to observe a diminution in the rate of blood flow on changing from the recumbent to the sitting position.Only once was the reduction less than 500 cc.per minute, while another observation on the same individual showed a greater change.The slowing of the circulation was more marked in the standing than in the sitting position.The average rate of blood flow while sitting was 76 per cent and while standing it was 50 per cent of the Aided by the Tutorial Fund of the Harvard Medical School, Boston, Mass.67 6 8.66 131 70 8.42 120 89 3.90 44 A. C. ......
Membrane-bound immunoglobulins on human leukemic cells. Evidence for humoral immune responses of patients to leukemia-associated antigens.
Authors: R S Metzgar, T Mohanakumar, D S Miller
Journal: Journal of Clinical Investigation (1975)

Immunoglobulins were detected on the membranes of human leukemic cells by a microcytotoxicity technique. A significant percentage of lymphocytes from normal donors failed to react with goat antisera to human heavy chain determinants or to lambda-light chains. Lymphocytes from some normal donors, however, did react with antisera to k-light chains. A high percentage (50-90) of cells from some leukemia patients were killed by antisera to light chains and by one or more antisera to heavy chain determinants. Trypsin treatment of leukemic cells resulted in a loss of cytotoxic activity with all immunoglobulin antisera. Reactivity with the k-light chain antiserum was detectable 2 h after trypsinization of chronic myeloid leukemic (CML) cells and 8 h after treatment of acute lymphocytic leukemic (ALL) cells. Reactivity with the antisera to heavy chain determinants and lambda-light chains could not be detected 8 and 48 h after trypsinization of CML and ALL cells, respectively. The cytotoxic activity of the immunoglobulin antisera to heavy chains was abolished by absorption with the specific immunoglobulin used to define the antisera by precipitation. Eluates (pH 3.2) prepared from leukemic cells which reacted by cytotoxicity with the immunoglobulin antisera were shown to contain immunoglobulins of different heavy chain classes. In addition, some of the eluates had cytotoxic antibody activity to human leukemia cells. The specificity of the eluted antibodies is similar to the specificity previously described for cytophilic antibodies from leukemic patients and nonhuman primate antisera to human leukemia cells. The possible in vitro detection and in vivo significance of the eluted non-complement-fixing antibodies is considered.
Transgenic expression of the Ly49A natural killer cell receptor confers class I major histocompatibility complex (MHC)-specific inhibition and prevents bone marrow allograft rejection.
Authors: W Held, D Cado, D H Raulet
Journal: The Journal of Experimental Medicine (1996)

Natural killer (NK) cells and some T cells are endowed with receptors specific for class I major histocompatibility complex (MHC) molecules that can inhibit cellular effector functions. The function of the Ly49 receptor family has been studied in vitro, but no gene transfer experiments have directly established the role of these receptors in NK cell functions. We show here that transgenic expression of the H-2Dd-specific Ly49A receptor in all NK cells and T cells conferred class I-specific inhibition of NK cell-mediated target cell lysis as well as of T cell proliferation. Furthermore, transgene expression prevented NK cell-mediated rejection of allogeneic H-2d bone marrow grafts by irradiated mice. These results demonstrate the function and specificity of Ly49 receptors in vivo, and establish that their subset-specific expression is necessary for the discrimination of MHC-different cells by NK cells in unmanipulated mice.
Neurotransmitter Receptors and Phosphoinositide Turnover
Authors: D M Chuang
Journal: The Annual Review of Pharmacology and Toxicology (1989)

Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other ...Read More
CELLULAR MECHANISMS OF ANTIBACTERIAL DEFENSE IN LYMPH NODES
Authors: Ralph O. Smith, W. Barry Wood
Journal: The Journal of Experimental Medicine (1949)

Acute pneumococcic lymphadenitis produced in rats by intradermal inoculation of the foot-pad is characterized by rapid infiltration of polymorphonuclear leucocytes into the intermediary sinuses of the node, and prompt phagocytosis of pneumococci by both the macrophages of the sinuses and the recently arrived leucocytes. After 5 to 7 hours the polymorphonuclear leucocytes are found densely congregated about the hilar region, and 9 hours after inoculation most of the phagocyted organisms have been digested. At the end of the 24 hour period the popliteal node presents the picture of a subsiding inflammation with a marked macrophage reaction and regenerating lymph follicles. Phagocytosis of encapsulated pneumococci in the foot-pad and popliteal node occurs in less than 30 minutes after inoculation. It is assumed that this prompt phagocytosis is effected by the non-antibody mechanism of "surface phagocytosis." The majority of polymorphonuclear leucocytes that enter the sinuses of the inflamed node appear to come from capillaries within the node itself rather than from the primary site of inflammation in the foot-pad. The prompt inflammatory response of the nodal tissues serves as an active defense against lymph-borne infection. Macrophages invade nodal sinuses only after most of the pneumococci have been destroyed by polymorphonuclear leucocytes. It is suggested that the macrophage reaction follows removal of the primary inflammatory stimulus by the granulocytes, and thus constitutes only a late phase of recovery. Fibrin formation in the sinuses of the lymph node is rare during acute lymphadenitis. This finding may be related to the observation that within 5 minutes after entrance of bacteria into the node, heparin-containing granules from mast cells are strewn throughout the sinuses.