tbuckley/cabot-search huggingface dataset:
Modulation of the fecal bile acid profile by gut microbiota in cirrhosis
Authors: Genta Kakiyama, William M. Pandak, Patrick M. Gillevet, Phillip B. Hylemon, Douglas M. Heuman, Kalyani Daita, Hajime Takei, Akina Muto, Hiroshi Nittono, Jason M. Ridlon, Melanie B. White, Nicole A. Noble, Pamela Monteith, Michael Fuchs, Leroy R. Thacker, Masoumeh Sikaroodi, Jasmohan S. Bajaj
Journal: Journal of Hepatology (2013)
Epitope‐dependent synergism and antagonism between CD40 antibodies and soluble CD40 ligand for the regulation of CD23 expression and IgE synthesis in human B cells
Authors: A Challa, JD Pound, J Gordon, RJ Armitage
Journal: Allergy (1999)

Background: The induction of IgE synthesis in naïve B cells requires two T‐cell‐derived signals: one delivered through CD40 and the other via interleukin‐4 (IL‐4). The natural counterstructure to CD40 is the CD40 ligand (CD40L). We have asked about the interplay between CD40L and CD40 mAb that recognize distinct epitopes in delivering signals for regulating IL‐4‐dependent IgE synthesis and the expression of CD23, the low‐affinity IgE receptor, in resting B cells. Methods: After culture of purified human tonsillar B cells with CD40 agonists and IL‐4, surface CD23 was determined by flow cytometric analysis. CD23 levels in cell lysates and supernatants were quantified by ELISA, as were those of secreted IgE. Results: With regard to both induction of CD23 and IgE production, soluble CD40L trimer (sCD40LT) showed synergistic interaction with two mAb to CD40 which bind to epitopes located outside the ligand binding site (EA5 and 5C3), but not with a mAb (G28‐5) which effectively competes for CD40L binding to CD40. Each of the two noncompeting mAb to CD40 was able to cooperate strongly with sCD40LT in promoting high‐level induction of CD23 even in the absence of IL‐4, an effect mirrored in the promotion of strong homotypic clustering and high‐rate DNA synthesis. G28‐5, uniquely, induced a down‐regulation in IL‐4‐induced CD23 expression with time, a change that was accompanied by an increase in the amount of soluble CD23 detected. While the two noncompeting mAb consistently synergized with sCD40LT for the promotion of IL‐4‐dependent IgE synthesis, sCD40LT and G28‐5 (which, by itself, was the most potent of the CD40 mAb at inducing IL‐4‐dependent IgE production) exhibited mutual antagonism in this regard, the level of which could be quite profound. Conclusions: This study demonstrates that appropriate targeting of CD40 can modulate IgE synthesis either positively or negatively.
Life threatening haemorrhage from a mycotic renal pseudoaneurysm treated by segmental renal artery embolisation.
Authors: C L Hall, P Cumber, C M Higgs, A H Chalmers
Journal: BMJ (1987)

chest pain, with definite myocardial infarction on the second occasion, occurred one hour after he had injected amphetamine.He had taken amphetamine intravenously on other occasions without chest pain, but this may reflect the varying strength of amphetamine available on the streets or variation in the coronary vascular response to noradrenaline release induced by amphetamine.Nevertheless, the association between amphetamine and myocardial infarction in our patient is unlikely to be coincidental.
Tuberculosis Transmission in Methadone Maintenance Programs
Authors: Judith A. Hahn
Journal: JAMA (1995)

<h3>To the Editor.</h3> —We recently reported<sup>1</sup>that among homeless injection drug users in San Francisco, Calif, there was an increased risk for tuberculosis (TB) infection among those who had ever been in a methadone program. At that time we were unable to distinguish subjects who had been in methadone maintenance programs from those who had been in short-term (≤21 days) methadone detoxification only. We have now reexamined this question in a large group of 2774 homeless and unstably housed persons. A total of 632 subjects had skin test results, were negative for the human immunodeficiency virus (HIV), and had used injection drugs. One hundred of these had been in methadone treatment programs. We grouped the 632 subjects as follows: (1) those who had never been in any methadone treatment programs, (2) those who had ever been in methadone detoxification programs only, and (3) those who had ever been in
Changes in the gastric mucosa of the mouse associated with long lasting unsurmountable histamine H2 blockade.
Authors: D Poynter, S A Selway, S A Papworth, S R Riches
Journal: Gut (1986)

The oral administration of loxtidine to mice at doses of 600, 250, and 50 mg/kg/day for 746 days produced carcinoid tumours of the gastric fundus.The fundic mucosa also showed marked atypical hyperplasia with changes in foveolar cells similar to those seen in early incomplete metaplasia.These effects may be related to the prolonged achlorhydria produced by this potent unsurmountable histamine H2 receptor antagonist.Spontaneous tumours of the alimentary tract of mice are rare and most occur in the forestomach.l Occasionally hyperplastic or neoplastic lesions of the glandular stomach are observed.2-5Experimentally squamous cell carcinomas of the forestomach are produced6 7 with N-methyl-N'-nitro-N-nitro- soguanidine (MNNG) but surprisingly no tumours of the glandular stomach, such as occur in the rat,8 have been recorded.The mouse glandular stomach is susceptible, however, as whole body irradiation leads to precancerous polypoid hyperplasia and adenocarcinoma.9Loxtidine is a potent, non- competitive, unsurmountable histamine H2 antagonist.10Its administration to rodents produces unremitting achlorhydria and in rats treated for prolonged periods the late development of carcinoid tumours of the fundus."The present communica- tion describes the more extensive and different gastric changes seen in mice which were given loxtidine for 107 weeks, a major part of their normal life span. Methods ANIMALSLoxtidine was administered daily in the drinking water to mice of the C57BL/lOScSn strain from the age of 6-8 weeks onwards.Treatment continued for 107 weeks.It was calculated that mean dose levels of 50, 250, and 600 mg/kg/day were attained.Precise plasma levels of loxtidine were measured by the
Quantitative Proteomics Reveals Subset-Specific Viral Recognition in Dendritic Cells
Authors: Christian A. Luber, Jürgen Cox, Henning Lauterbach, Ben Fancke, Matthias Selbach, Jurg Tschopp, Shizuo Akira, Marian Wiegand, Hubertus Hochrein, Meredith O'Keeffe, Matthias Mann
Journal: Immunity (2010)
Theophylline Therapy During Pregnancy
Authors: James A. Pollowitz
Journal: JAMA (1980)

To the Editor.—  Several points should be emphasized regarding the use of theophylline in the pregnant patient, a subject covered in the excellent review by Weinstein et al (241:1161, 1979) recently. A study by Sutton et al1examined the pharmacokinetics of orally administered theophylline during the second and third trimester. Since the volume of distribution of the drug increased while body clearance remained constant, their data suggest that a patient's absolute requirement for theophylline will increase during the latter part of pregnancy. Because the patient's weight is also elevated, the milligrams-per-kilograms basis for this dosage might remain unchanged.  There may also be problems associated with use of theophylline during the immediate intrapartum period. McGentry and Murphy2have found that asthmatics receiving bronchodilator therapy had a longer average duration of labor than untreated patients. Another consideration is the transplacental passage of this drug to the fetus. This has recently
Autoimmune Thyroid Disease: Developments in Our Understanding
Authors: ANTHONY P. WEETMAN, ALAN M. MCGREGOR
Journal: Endocrine Reviews (1984)

THIS REVIEW of autoimmune thyroid disease will highlight the recent advances made in understanding the control of the autoimmune process particularly at pathogenetic and therapeutic levels. Many novel techniques have recently been applied to the investigation of thyroid autoimmunity although the results obtained have not always clarified the overall picture. These new methodologies are discussed and attention is also focused upon experimental thyroiditis produced in a variety of animals. We believe that these models have been neglected somewhat by clinically oriented investigators. Yet their use originally led to the foundation of autoimmune concepts, and experimental thyroiditis continues to provide major insights into the possible etiology and pathogenesis of the human counterpart. Before discussing thyroid disease in detail however, it is worth considering the current themes in autoimmunity in general.
Autoimmune mice make anti-Fc gamma receptor antibodies.
Authors: P Boros, J M Chen, C Bona, J C Unkeless
Journal: The Journal of Experimental Medicine (1990)

We demonstrate, using a recombinant truncated Fc gamma RII molecule as a probe, the presence of anti-Fc gamma R antibodies in several strains of autoimmune mice. Affinity chromatography on a truncated Fc gamma R column of pooled sera from aged NZB females resulted in isolation of 16 micrograms of IgM per ml of serum, approximately 2% of the total IgM; no anti-Fc gamma R IgM was found in sera from C58/J mice. Mice with high titers of anti-Fc gamma R IgM also had anti-Fc gamma R IgG. Affinity-purified anti-Fc gamma R IgG bound to Fc gamma R-bearing cells. A good correlation was found between the presence of anti-Fc gamma R Ig and impaired phagocytosis of immune complexes in autoimmune strains such as NZB or NZB/NZW F1. Sera with high titers of anti-Fc gamma R Ig from NZB and motheaten mice inhibited the binding of soluble immune complexes. Furthermore, BXSB, a lupus-prone mouse strain that does not produce anti-Fc gamma R Ig, shows normal macrophage binding and phagocytosis of immune complexes. A set of four IgM mAbs that bind to Fc gamma R was identified. These antibodies were polyspecific; some were directed against DNA, and others recognized a wide variety of antigens including histones, thyroglobulin, and transferrin, but all anti-Fc gamma R IgM antibodies effectively inhibited the binding of IgG1 anti-DNP/DNP20BSA complexes to J774 macrophages. The role of anti-Fc gamma R Ig in autoimmunity remains to be established. It may act to crosslink and activate Fc gamma Rs on neutrophils, macrophages, NK, and mesangial cells, or it may desensitize Fc gamma R function of Fc gamma R-bearing cells.
917-97 Decreased Resistance Against Oxidation of LDL from Patients with Homozigous Familial Hypercholesterolemia
Authors: Claudio Napoli, Alfredo Postiglione, Giuseppe Palumbo, Antonio Ruocco, Giuseppe Ambrosio, Mario Condorelli, Mario Mancini, Massimo Chiariello
Journal: Journal of the American College of Cardiology (1995)
Phase I Trial of Imexon in Patients With Advanced Malignancy
Authors: Tomislav Dragovich, Michael Gordon, David Mendelson, Lucas Wong, Manuel Modiano, H.-H. Sherry Chow, Betty Samulitis, Steven O'Day, Kathryn Grenier, Evan Hersh, Robert Dorr
Journal: Journal of Clinical Oncology (2007)

Purpose Imexon, a pro-oxidant small molecule, has antitumor activity in preclinical models. The drug induces apoptosis through accumulation of reactive oxygen species. The purpose of this trial was to define the maximum-tolerated dose (MTD), toxicities, pharmacokinetics, and pharmacodynamics of imexon in patients with advanced cancers. Patients and Methods Forty-nine patients with metastatic cancer received intravenous imexon over 30 to 45 minutes for 5 consecutive days (one course) every other week (days 1 through 5 and 15 through 19) monthly. Doses were initially escalated using an accelerated trial design and then a modified Fibonacci method. Plasma imexon levels and six different thiols were measured by high-performance liquid chromatography assays. Results There were 13 dose levels evaluated, from 20 mg/m 2 /d to 1,000 mg/m 2 /d. The MTD recommended for phase II studies was 875 mg/m 2 /d for 5 days every 2 weeks (n = 9 patients). The two dose-limiting toxicities at 1,000 mg/m 2 /d involved grade 3 abdominal pain and fatigue and grade 4 neutropenia, which occurred in one patient each. Other common toxicities included nausea and vomiting (58%) and constipation (63%); both were managed well with prophylactic medications. One partial response was obtained in a heavily pretreated patient with non-Hodgkin's lymphoma. Pharmacokinetic studies showed dose-independent clearance, with a 95-minute mean half-life. Plasma thiol studies showed a dose- and area under the curve–dependent decrease in cystine levels 8 hours after dosing at ≥ 750 mg/m 2 /d. Conclusion The phase II recommended dose of imexon is 875 mg/m 2 /d for 5 days every other week. A decrease in plasma thiols did correlate with imexon exposure.
The Mechanism of Hyponatremia in Pulmonary Tuberculosis
Authors: ROBERT J. SHALHOUB
Journal: Annals of Internal Medicine (1969)

The diuretic response to acute water loading was studied in six patients with pulmonary tuberculosis and hyponatremia. In one of these a pulmonary alveolar-cell carcinoma was also present. Five out of six patients responded abnormally (fractional excretion less than 65% ) when compared with a control group, but the response was consistently improved or corrected by ethanol. In two out of three patients, pretreatment with cortisone also resulted in improvement. For comparison, similar studies were performed on two patients with bronchogenic carcinoma and inappropriate secretion of antidiuretic hormone (ADH). Unlike the tuberculous group, these patients could not excrete dilute urine in response to water, ethanol, or cortisone. These patients also suffered from severe chronic alcoholism and malnutrition. They gained weight during the course of antituberculous therapy, and the hyponatremia gradually disappeared in four patients in whom it could be followed. We conclude that in this group an acquired disturbance of neurohypophyseal function exists resulting in unregulated ADH release. Whether this is related specifically to tuberculosis or to the associated alcoholism or malnutrition is not clear from our studies.
Cardioprotection with adenosine metabolism inhibitors in ischemic–reperfused mouse heart
Authors: Jason Nigel John Peart, Paul Matherne, Rachel Cerniway, John Patrick Headrick
Journal: Cardiovascular Research (2001)

Objectives: To characterize the ‘anti-ischemic’ effects of adenosine metabolism inhibition in ischemic–reperfused myocardium. Methods: Perfused C57/B16 mouse hearts were subjected to 20 min ischemia 40 min reperfusion in the absence or presence of adenosine deaminase inhibition (50 μM erythro-2-(2-hydroxy-3-nonyl)adenine; EHNA) adenosine kinase inhibition (10 μM iodotubercidin; IODO), or 10 μM adenosine. Hearts overexpressing A1 adenosine receptors (A1ARs) were also studied. Results: EHNA treatment reduced ischemic contracture and post-ischemic diastolic pressure (14±2 vs. 20±1 mmHg), increased recovery of developed pressure (66±3 vs. 53±2%) and reduced LDH efflux (8.9±1.6 vs. 18.0±1.7 I.U./g). IODO also improved functional recovery (to 60±2%) and reduced LDH efflux (5.3±1.7 I.U./g), as did treatment with 10 μM adenosine. Protection with EHNA was reversed by co-infusion of IODO or 50 μM 8-ρ-sulfophenyltheophylline (adenosine receptor antagonist), but unaltered by 20 μM inosine+10 μm hypoxanthine. Similarly, effects of iodotubercidin were inhibited by EHNA and 8-ρ-sulfophenyltheophylline. A1AR overexpression exerted similar effects to EHNA and EHNA or IODO alone enhanced recovery while EHNA+IODO reduced recovery in transgenic hearts. Functional recoveries and xanthine oxidase reactant levels were unrelated in the groups studied. Conclusions: Adenosine deaminase or kinase inhibition protects from ischemia–reperfusion. Cardioprotection via these enzyme inhibitors requires a functioning purine salvage pathway and involves enhanced adenosine receptor activation. Reduced formation of inosine is unimportant in EHNA-mediated protection.
Long‐term effects of non‐excitatory cardiac contractility modulation electric signals on the progression of heart failure in dogs
Authors: Hideaki Morita, George Suzuki, Walid Haddad, Yuval Mika, Elaine J. Tanhehco, Sidney Goldstein, Shlomo Ben‐Haim, Hani N. Sabbah
Journal: European Journal of Heart Failure (2004)
Gene polymorphism at the interleukin 6 -174 G&gt;C locus affects the outcome of chronic hepatitis B
Authors: Carlo Fabris, Pierluigi Toniutto, Davide Bitetto, Giovanna Fattovich, Edmondo Falleti, Elisabetta Fontanini, Annarosa Cussigh, Rosalba Minisini, Giuseppa Occhino, Mario Pirisi
Journal: Journal of Infection (2009)
The Treatment of Acute Leukaemia
Authors: R. B. Scott
Journal: BMJ (1955)

The last decade has seen the focus of haematological interest shift to the problem of acute leukaemia. This disease has been forced upon the clinicians' attention by its steadily mounting frequency; while the research workers have found it a convenient field for the study of chemotherapy in cancer, and as a result of their exertions it has become possible for the first time to influence its course. The aim of this paper is to review the methods of treatment at present available and to discuss their application and value in the light of experience gained in the past six years.
PRESENT-DAY PROBLEMS AND PROGRESS IN PREVENTION OF TYPHOID FEVER
Authors: WALTON FOREST DUTTON
Journal: JAMA (1910)

The health of a people is its most valuable asset. This truth has been recognized by most governments of the world. They have found that the virtue of national strength lies, in great part, in the conservation of national health. The United States government in its battle against malaria, yellow fever, cholera, uncinariasis, and plague, has accomplished much for the common good, but seems to have taken little interest in the prevention of typhoid fever. The first effort of any magnitude in this direction was during the Spanish-American war. The result was a signal, dismal, and disgraceful failure. The camps of Chickamauga, Tampa, Fernandino, Anniston. Mantauk Point, and those in Cuba, were enough to arouse the medical world to the inefficiency of the medical department in the prevention of typhoid fever. The national government's aid in the past twelve years, however, has materially increased, but not to the degree of
Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment
Authors: Ravi Bhatia, Melissa Holtz, Ning Niu, Rachel Gray, David S. Snyder, Charles L. Sawyers, Daniel A. Arber, Marilyn L. Slovak, Stephen J. Forman
Journal: Blood (2003)
Breathing pattern during bronchial challenge in humans
Authors: NE Meessen, CP van der Grinten, SC Luijendijk, HT Folgering
Journal: European Respiratory Journal (1997)

Increases in minute ventilation (V'E) have been observed during exacerbations of asthma and in response to administration of histamine. However, it is not yet clear how the breathing pattern is affected, and whether the increase in V'E is found in general. In the present study, the effects of inhalation of histamine on respiratory frequency (fR), tidal volume (VT), V'E, and on functional residual capacity (FRC) were evaluated in 63 humans. Forty four subjects were hyperresponsive (BHR+). In each of these subjects, the doses of histamine applied for the present study (mean 3.5 mg x mL(-1)) caused a decrease in forced expiratory volume in one second (FEV1) that was greater than 20% of the control value. The dose of histamine applied in the 19 nonhyperresponsive subjects (BHR-) was substantially larger (8.0 mg x mL(-1)) whilst for this dose the decrease in FEV1 was less than 20% of control value. After histamine, fR was significantly increased in both subgroups of subjects, BHR+ and BHR-. The increase in V'E was significant in BHR- but not significant in BHR+. In general, the changes in V'E,fR and VT were not uniform; comparable numbers of subjects responded with increases (n=33) and decreases (n=30) in V'E. For fR 40 subjects responded with an increase and 23 with a decrease, and for VT these numbers were 26 and 37, respectively. The increase in FRC after histamine was significantly larger in BHR+ subjects than in BHR-. These findings may be interpreted to indicate that different mechanisms with opposite effects may be operating simultaneously, e.g. excitation of central inspiratory activity by stimulation of rapidly-adapting pulmonary stretch receptors, which will promote increases in respiratory frequency, tidal volume and minute ventilation, and bronchoconstriction with increased airway resistance, which will promote decreases in these parameters. As a consequence, depending on the net result of these opposite contributions to, e.g. minute ventilation, administration of histamine will cause an increase in minute ventilation in one subject and a decrease in another.
The Long Shadow of Flexner: A Prolonged Polemic in Assessing Outcomes in Medical Education
Authors: Carlos J. M. Martini
Journal: JAMA (1989)

Eighty-three years after the first recorded use of outcome measures in the evaluation of medical education, the US Secretary of Education has strengthened the outcome criterion for its recognition of accrediting agencies as follows<sup>1</sup>: The secretary determines whether an accrediting agency, in making its accrediting decisions, systematically obtains and considers substantial and accurate information on educational effectiveness... by determining that institutions or programs document the educational achievement of their students,... in verifiable and consistent ways, such as... graduate or professional school placements, job placement rates, licensing examination results, employer evaluations, and other recognized measures. At least one of these applications of outcome evaluation, the use of licensing examination results, would not have been accepted by Abraham Flexner in his time, although Dr Nathan P. Colwell, a former secretary of the American Medical Association (AMA) Council on Medical Education, surely would have felt vindicated. <h3>Colwell vs Flexner</h3> In 1906, the
Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion
Authors: Bernd Jahrsdörfer, Angelika Vollmer, Sue E. Blackwell, Julia Maier, Kai Sontheimer, Thamara Beyer, Birgit Mandel, Oleg Lunov, Kyrylo Tron, G. Ulrich Nienhaus, Thomas Simmet, Klaus-Michael Debatin, George J. Weiner, Dorit Fabricius
Journal: Blood (2009)
Surgery outperforms other treatment options for obesity, finds analysis
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Obese patients who undergo bariatric surgery lose more weight and are more likely to achieve remission from type 2 diabetes than those who try to lose weight by other means, a meta-analysis has found.

The authors said that their analysis showed that surgery was more efficient than dieting, exercise, lifestyle change, and drug treatment for obesity for up to two years of follow-up, although further research was needed to look at differences beyond that time.

They conducted the systematic review and meta-analysis, they said, because more research had been published …