tbuckley/cabot-search huggingface dataset:
Serum vitellogenin levels and reproductive impairment of male Japanese Medaka (Oryzias latipes) exposed to 4-tert-octylphenol.
Authors: S Gronen, N Denslow, S Manning, S Barnes, D Barnes, M Brouwer
Journal: Environmental Health Perspectives (1999)

The induction of synthesis of the "female" yolk precursor protein vitellogenin (VTG) in male fish by estrogenic chemicals in the environment has been demonstrated in many recent reports. However, little is known about the organismal and biological significance of this phenomenon. To examine the relationship between VTG production in male fish and reproductive impairment, adult male medaka were exposed to 4-tert-octylphenol (OP), a known environmental estrogen, in concentrations ranging from 20 to 230 ppb for 21 days, under flow-through conditions. Following exposure, male fish were mated, in the absence of OP, with unexposed females. Breeding groups composed of exposed males and control females produced about 50% fewer eggs than control groups. VTG levels in serum of male fish increased with increasing OP exposure concentration and decreased after OP exposure was discontinued. Nevertheless, significant correlations (p<0.01) were observed between VTG levels in exposed male fish and 1) OP exposure concentrations, 2) percent of fertilized eggs, and 3) survival of embryos. OP-induced VTG synthesis and reproductive impairment appear to be closely linked phenomena. Histological examination indicated spermatogenesis in OP-exposed fish was inhibited, and some exposed fish had oocytes in their testes. Finally, OP caused a significant increase in the number of abnormally developing embryos, suggesting that OP may be genotoxic as well as estrogenic.
A8.12 MIR-125B controls mitochondrial functions and dynamics in monocytes
Authors: I Duroux-Richard, C Roubert, M Ammari, J Présumey, JR Grün, T Häupl, A Grützkau, C-H Lecellier, C Jorgensen, F Apparailly
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Monocytes play essential roles in immune defense but are also implicated in pathological inflammatory responses due to excessive and prolonged activation. How survival and apoptotic regulators control monocyte lifespan to avoid pathological conditions associated with chronic inflammatory response such as observed in rheumatoid arthritis (RA) remains elusive. As part of the molecular rheostat machinery, micro (mi)RNAs represent an important class of regulatory molecules. MiR-125b, a highly conserved miRNA, has emerged as a key regulator of hematopoietic stem cells development and homeostasis. The aim of our study was to identify endogenous miR-125b target genes that contribute to altering monocyte responses. <h3>Materials and Methods</h3> We used gain- and loss-of-function methods to evaluate the effect of miR-125b on the human monocytic cell line THP-1. A transcriptome analysis was performed to identify putative targets that were validated using a luciferase reporter construct containing the 3'UTR of candidate genes. Apoptosis was analysed by Caspase 3/7 assays. Monocyte oxygen consumption rate was investigated using the Seahorse Extracellular Flux Analyzer. TOM20 staining was used to monitor the mitochondrial network. <h3>Results</h3> Transcriptome analysis showed deregulation of several genes involved in apoptosis. Among these, the BH3-only pro-apoptotic BIK and the mitochondrial fission process 1 (MTP18) genes were identified as putative miR-125b targets. Using reporter systems, the binding of miR-125b to both 3'UTR target sequences was validated. Enforced expression of miR-125b in THP-1 decreased BIK and MTP18 expression levels and monocyte viability though augmentation of caspase 3/7 activity. LPS-induced expression of miR-125b reduced mitochondrial respiration and triggered mitochondrial fusion through BIK and MTP18 silencing respectively. Importantly, BIK and MTP18 knock-down mimicked miR-125b over-expression phenotype while miR-125b inhibitor reversed phenotype. <h3>Conclusions</h3> Our present work identified BIK and MTP18 as novel cellular targets of miR-125b in human monocytes. Our data also suggest a novel role for miR-125b in miR-125b in regulating metabolic adaptation of monocytes to inflammation, as well as mitochondrial fusion and fission, thus extending its involvement in cell biology and RA pathogenesis.
An Alternative and Effective HIV Vaccination Approach Based on Inhibition of Antigen Presentation Attenuators in Dendritic Cells
Authors: Xiao-Tong Song, Kevin Evel-Kabler, Lisa Rollins, Melissa Aldrich, Feng Gao, Xue F Huang, Si-Yi Chen
Journal: PLoS Medicine (2005)

Current efforts to develop HIV vaccines that seek to stimulate immune responses have been disappointing, underscoring the inability of natural immune responses to control HIV-1 infection. Here we tested an alternative strategy to induce anti-HIV immune responses by inhibiting a host's natural immune inhibitor.We used small interfering RNA (siRNA) to inhibit suppressor of cytokine signaling (SOCS) 1, a key negative regulator of the JAK/STAT pathway, and investigated the effect of this silencing on the ability of dendritic cells (DCs) to induce anti-HIV-1 immunity. We found that SOCS1-silenced DCs broadly induced enhanced HIV-1 envelope (Env)-specific CD8+ cytotoxic T lymphocytes and CD4+ T helper cells, as well as antibody responses, in mice. Importantly, SOCS1-silenced DCs were more resistant to HIV Env-mediated suppression and were capable of inducing memory HIV Env-specific antibody and T cell responses. SOCS1-restricted signaling, as well as production of proinflammatory cytokines such as interleukin-12 by DCs, play a critical role in regulating the anti-HIV immune response. Furthermore, the potency of HIV DNA vaccination is significantly enhanced by coimmunization with SOCS1 siRNA expressor DNA.This study demonstrates that SOCS1 functions as an antigen presentation attenuator to control both HIV-1-specific humoral and cellular responses. This study represents the first, to our knowledge, attempt to elicit HIV-specific T cell and antibody responses by inhibiting a host's antigen presentation attenuator, which may open a new and alternative avenue to develop effective therapeutic and prophylactic HIV vaccines.
Diseases of the Gastrointestinal Tract (Liver)
Authors: A G Bearn, H G Kunkel
Journal: Annual Review of Medicine (1955)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Use of phylogenetic analysis to distinguish adaptation from exaptation
Authors: Daniel G. Blackburn
Journal: Behavioral and Brain Sciences (2002)

One important difference between adaptive and nonadaptive explanations can be found in the evolutionary sequence of structural and functional modifications. Phylogenetic analysis (cladistics) provides a powerful methodology for distinguishing exaptation from adaptation, by indicating whether character traits have predated, accompanied, or followed evolution of particular functions. Such analysis yields falsifiable hypotheses that can help to distinguish causal relationships from mere correlation.
The Dead-Donor Rule and the Future of Organ Donation
Authors: Robert D. Truog, Franklin G. Miller, Scott D. Halpern
Journal: New England Journal of Medicine (2013)

The ethics of organ transplantation have been premised on the "dead-donor rule": vital organs should be taken only from persons who are dead. But why shouldn't some living patients, such as those near death but on life support, be allowed to donate organs?
New Granulocyte Antigens Demonstrated by Microgranulocytotoxicity Assay
Authors: J. S. Thompson, V. L. Overlin, J. M. Herbick, C. D. Severson, F. H. J. Claas, J. D. 'Amaro, C. P. Burns, R. G. Strauss, J. A. Koepke
Journal: Journal of Clinical Investigation (1980)

Although granulocyte transfusions and bone marrow transplantation are becoming common clinical modalities, our knowledge of surface nonerythroid, nonlymphoid, non-HLA hematopoetic antigens remains very incomplete. Accordingly, we have systematically screened sera from recipients of multiple granulocyte and whole blood transfusions, and immunoneutropenic patients for antibodies directed primarily at granulocytes.
Distribution of a liquid meal within the stomach and gastric emptying after vagotomy and drainage operations.
Authors: O Lawaetz, Y Aritas, N J Brown, D N Ralphs, E Sjontoft
Journal: Gut (1982)

The intragastric distribution of a radionuclide labelled liquid meal was studied in 62 patients with duodenal ulceration by means of a gamma camera imaging system. A total of 85 gastric emptying studies (23 preoperative and 62 postvagotomy tests) revealed three distinct patterns of distribution. The activity distribution in the stomach after vagotomy showed a slower rate of return and a decreased accumulation of the meal in the proximal part of the stomach compared with the pattern in the intact stomach. The return of the liquid meal to the proximal stomach was considered to be a physiological process controlled by vagal reflexes and changed by a vagotomy. These observations made during emptying of a liquid meal seem to give rise to a better differentiation of the motor patterns after various types of gastric operations. With a quantification of the intragastric patterns of distribution it may be possible in a prospective study to give a more graded evaluation of changes induced by vagotomy than is possible with the traditional characterisation of gastric emptying.
Clarifying the Dispute over Academic–Industry Relationships
Authors: Thomas S. Huddle
Journal: The American Journal of Bioethics (2011)

Click to increase image sizeClick to decrease image size Acknowledgments 1. See remarks beginning with “Although I have focused on distortion from financial input, I have no doubt that ideological commitment can be just as distortive” (Greenland 2009 Greenland, S. 2009. Accounting for uncertainty about investigator bias: Disclosure is informative. Journal of Epidemiology and Community Health, 63: 593–598. [Crossref], [PubMed] , [Google Scholar], 597).
Chloroform induction of ornithine decarboxylase activity in rats.
Authors: R E Savage, C Westrich, C Guion, M A Pereira
Journal: Environmental Health Perspectives (1982)

Chloroform is a drinking water contaminant that has been demonstrated to be carcinogenic to mice and rats resulting in an increased incidence of liver and kidney tumors, respectively. The mechanism of chloroform carcinogenicity might be by tumor initiation and/or promotion. Since induction of ornithine decarboxylase (ODC) activity has been proposed as a molecular marker for tumor promoters, we have investigated the effect of chloroform on ODC activity in rats. Chloroform induced a dose-dependent increase of hepatic ODC with an apparent threshold at 100 mg/kg body weight. Female rats were two to four times more susceptible to to chloroform. Upon daily dosing of chloroform for 7 days the liver became less susceptible, with the last dose of chloroform resulting in only 10% of the activity observed after a single dose. Nuclear RNA polymerase I activity was also induced by chloroform. Chloroform, rather than increasing the activity of renal ODC, resulted in a 35% reduction. The induction by chloroform of hepatic ODC activity might be associated with regenerative hyperplasia while the renal carcinogenicity of chloroform could not be demonstrated to be associated with ODC induction.
Antiarrhythmic activity, electrocardiographic effects and pharmacokinetics of the encainide metabolites O-desmethyl encainide and 3-methoxy-O-desmethyl encainide in man.
Authors: J T Barbey, K A Thompson, D S Echt, R L Woosley, D M Roden
Journal: Circulation (1988)

Although encainide is an effective antiarrhythmic agent, plasma concentrations and pharmacologic effects are not well correlated. One explanation is the generation of active metabolites: while in most patients (extensive metabolizers; EMs) concentrations of the metabolites O-desmethyl encainide (ODE) and 3-methoxy-O-desmethyl encainide (3MODE) are higher than those of encainide, a small subset (poor metabolizers; PMs) lack the ability to extensively biotransform encainide. Considerable data from studies in vitro and animal studies, as well as indirect evidence in patients, indicate that ODE and 3MODE produce the effects seen during long-term encainide therapy in EMs. We now report the initial direct evaluation of the pharmacologic actions of these metabolites of encainide in man. Nine patients with ventricular arrhythmias, seven of the EM phenotype and two of the PM phenotype, were studied. Chronic high-frequency ventricular arrhythmias were suppressed by encainide therapy in seven of nine; monitoring arrhythmia frequency during withdrawal of encainide allowed definition of plasma concentrations of encainide and metabolites associated with arrhythmia suppression. Intravenous infusions of both ODE and 3MODE suppressed chronic ventricular arrhythmias, while infusions of placebo had no effect. ODE clearance was a function of metabolizer phenotype, with higher clearance (mean 914 ml/min; range 554 to 1,314) in EMs than in PMs (434, 298 ml/min); moreover, 3MODE was detected during ODE infusions in all seven EMs but in neither PM. 3MODE clearance was more uniform (mean 289 ml/min in EMs [range 180-410] vs 300 and 78 ml/min in the two PMs) and ODE was not detected in any subject during 3MODE infusion. Encainide itself was not detected after any infusion of ODE or 3MODE. During withdrawal of encainide therapy, ODE plasma concentration at the time of arrhythmia recurrence was 55 +/- 40 ng/ml (mean +/- SD), while ODE by infusion was effective at a concentration of 37 +/- 15 ng/ml. Similarly, plasma concentration of 3MODE at the time of arrhythmia recurrence after withdrawal of chronic encainide was 116 +/- 35 ng/ml and that during 3MODE infusion was 105 +/- 50 ng/ml. While both compounds prolonged QRS duration, ODE was the more potent, increasing QRS by 9.2 +/- 1.6% per 100 ng/ml vs 1.2 +/- 0.5% per 100 ng/ml for 3MODE. On the other hand, 3MODE prolonged the corrected JT interval by 1.9 +/- 0.6% per 100 ng/ml, while ODE shortened it by 2.7 +/- 1.9% per 100 ng/ml.(ABSTRACT TRUNCATED AT 400 WORDS)
Robin Frank Holloway Horn
Authors: Melvin Green
Journal: BMJ (2006)

Paediatrician who became a pioneer in the management of cystic fibrosisTony Jackson made a considerable contribution to the transformation of cystic fibrosis from a fatal disease of infancy to a chronic disease of adults.He applied the developing technology and pharmaceutical developments to everyday practice, supported families and patients, and, after retirement, gave strategic direction to the Cystic Fibrosis Trust research and medical advisory committee, of which he was chairman.The trust awarded him its John Panchaud medal.
Staphylococcus Phage Types In a Nursery Epidemic
Authors: Pearl Ma
Journal: JAMA (1973)

To the Editor.—  A nursery epidemic by phage nontypable Staphylococcus aureus in Cook County Hospital in Chicago and another in our hospital presented an epidemiological problem.  Four newborn babies suffered from staphylococcal impetigo in May 1973 in our hospital. Hexachlorophene was not used—even for rinsing the babies. All pustule cultures yielded phage nontypable S. aureus that were sensitive to erythromycin, kanamycin, lincomycin, oxacillin, tetracycline, cephalothin, and chloramphenicol, but resistant to penicillin and ampicillin. A survey of 140 nasopharyngeal and throat cultures of doctors and nursing personnel revealed isolates with a similar antibiogram from two pediatric residents and one nurse. They were relieved from duty in the nursery and received treatment while the phage typing of the isolates was carried out. The phage typing report is shown in the Table. The only common denominator was phage nontypability of the isolates from the babies and from one resident. The colonies of the
-Adrenoceptor function changes with age of subject in myocytes from non-failing human ventricle
Authors: C.H. Davies, N. Ferrara, S.E. Harding
Journal: Cardiovascular Research (1996)

The contractile response to beta-adrenoceptor stimulation has been found to be reduced in single myocytes from failing human ventricle. A portion of that reduction was statistically related to the age of the patient. We have developed a method for obtaining viable contracting myocytes from small biopsies of human ventricle, enabling experiments to be performed on non-failing left ventricle from patients undergoing coronary artery surgery. These subjects are generally in an older age range than those we have previously obtained from donor hearts. The present study compares responses to isoproterenol and high Ca2+ between myocytes from older (> 50 years, n = 8) and younger (< 40 years, n = 5) subjects. Myocytes from older patients did not differ in their contraction amplitude (10.7 +/- 1.0 cf. 10.8 +/- 1.1% cell shortening), or contraction and relaxation velocities in high Ca2+ at a driving frequency of 0.2 Hz (32 degrees C). The sensitivity to isoproterenol, as determined from the EC50 value (concentration for half-maximal effect), was also similar between age groups (1.16 +/- 0.64 nM young, cf. 2.76 +/- 2.0 nM old), although higher than in myocytes from failing hearts (22.3 +/- 7.5 nM, n = 11). However, for the older group there was a significant depression in maximum contraction amplitude with isoproterenol (8.5 +/- 0.6 cf. 11.5 +/- 1.0% cell shortening, P < 0.05) and in the ratio between this and the maximum Ca2+ response (isoproterenol/Ca2+ ratio, 0.79 +/- 0.05 cf. 1.16 +/- 0.12, P < 0.05). Concomitantly, the maximum contraction and relaxation velocities achieved in the presence of isoproterenol were also depressed in older subjects (P < 0.02 for both). We conclude that age and/or coronary disease with unimpaired left ventricular function selectively reduces the maximum effect of isoproterenol but not the concentration at which this occurs.
Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Leucovorin Plus Oxaliplatin in Metastatic Colorectal Cancer: A Final Report of the AIO Colorectal Study Group
Authors: Rainer Porschen, Hendrik-Tobias Arkenau, Stephan Kubicka, Richard Greil, Thomas Seufferlein, Werner Freier, Albrecht Kretzschmar, Ullrich Graeven, Axel Grothey, Axel Hinke, Wolff Schmiegel, Hans-Joachim Schmoll
Journal: Journal of Clinical Oncology (2007)

To compare the use of capecitabine plus oxaliplatin (CAPOX) with infusional fluorouracil (FU)/folinic acid plus oxaliplatin (FUFOX) as first-line therapy for patients with metastatic colorectal cancer (MCRC).A total of 474 patients with MCRC received either CAPOX (capecitabine 1,000 mg/m2 bid, days 1 to 14 plus oxaliplatin 70 mg/m2 days 1 and 8, repeated every 22 days) ) or FUFOX (oxaliplatin 50 mg/m2 followed by leucovorin 500 mg/m2 plus FU 2,000 mg/m2 as a 22-hour infusion days 1, 8, 15, and 22, repeated every 36 days). The primary end point was progression-free survival (PFS). Secondary end points were response rate (RR), overall survival (OS), time to treatment failure, and toxicity. The study was designed to determine noninferiority for the CAPOX regimen.Median PFS was 7.1 months in the CAPOX arm and 8.0 months in the FUFOX arm (hazard ratio [HR], 1.17; 95% CI, 0.96 to 1.43; P = .117). Median OS was 16.8 months (CAPOX) and 18.8 months (FUFOX; HR, 1.12; 95% CI, 0.92 to 1.38; P = .26). Overall RRs were 48% for CAPOX (95% CI, 41% to 54%) and 54% for FUFOX (95% CI, 47% to 60%). Both regimens were generally well tolerated, although there was a significantly higher incidence of grade 2/3 hand-foot syndrome (HFS) in the CAPOX arm (P = .028).CAPOX resulted in a slightly inferior efficacy than FUFOX. With respect to PFS, the best estimate of the HR of 1.17 was within the prespecified equivalence range. However, a relevant inferiority cannot be excluded. Both regimens were generally well tolerated but there was a significantly higher rate of grade 2/3 HFS in the CAPOX arm.
Fatal varicella zoster infection in a severe steroid dependent asthmatic patient receiving methotrexate.
Authors: A H Morice, W K Lai
Journal: Thorax (1995)

A case is described of fatal haemorrhagic varicella zoster in a steroid dependent asthmatic patient concurrently receiving methotrexate. The future management of patients on immunosuppressive steroid sparing drugs is discussed.
Pseudo-obstruction of the large bowel.
Authors: J Neely
Journal: BMJ (1970)

expected in patients who are conscious after overdosage of nitrazepam.I find this quite confusing, and as a clini- cian who prescribes both nitrazepam and methaqualone I cannot see how judgements as to "safety" in overdosage can be equated with "preference," presumably as such preference must take into account the effectiveness of a drug in normal dosage for a specific purpose-in this case induction of sleep.-Iam, etc.
Echocardiographic Identification of Cardiovascular Sources of Emboli To Guide Clinical Management of Stroke: A Cost-Effectiveness Analysis
Authors: Robert L. McNamara
Journal: Annals of Internal Medicine (1997)

Background: No consensus exists about the use of imaging strategies to identify potential cardiovascular sources of emboli in patients who have had strokes. Objective: To determine the cost-effectiveness of various cardiac imaging strategies after stroke. Design: A Markov model decision analysis was used to evaluate the benefits and costs of nine diagnostic strategies, including transthoracic echocardiography, transesophageal echocardiography, sequential approaches, selective imaging, and no imaging. Setting: Simulated clinical practice in the United States. Patients: Hypothetical patients with a first stroke who were in normal sinus rhythm. Measurements: Echocardiographic detection rates of potential sources of emboli were ascertained by doing a systematic review of the literature. Values for event rates, anticoagulation effects, utilities, and costs were obtained from the literature and Medicare data. Results: When visualized left atrial thrombus was used as the only indication for anticoagulation, transesophageal echocardiography performed only in patients with a history of cardiac problems cost $9000 per quality-adjusted life-year; transesophageal echocardiography in all patients cost $13 000 per quality-adjusted life-year. Cost savings and decreased morbidity and mortality rates associated with reduction in preventable recurrent strokes substantially offset examination costs and risks of anticoagulation. These results were moderately sensitive to efficacy of anticoagulation and incidence of intracranial bleeding during anticoagulation and were mildly sensitive to prevalence of left atrial thrombus, rate of recurrent stroke in patients with thrombus, quality of life after stroke, cost of transesophageal echocardiography, and specificity of transesophageal echocardiography. Transthoracic echocardiography, alone or in sequence with transesophageal echocardiography, was not cost-effective compared with transesophageal echocardiography. Conclusion: Physicians should consider doing transesophageal echocardiography in all patients with new-onset stroke.
In Utero Undernutrition in Male Mice Programs Liver Lipid Metabolism in the Second-Generation Offspring Involving Altered Lxra DNA Methylation
Authors: Débora Martínez, Thais Pentinat, Sílvia Ribó, Christian Daviaud, Vincent W. Bloks, Judith Cebrià, Nuria Villalmanzo, Susana G. Kalko, Marta Ramón-Krauel, Rubén Díaz, Torsten Plösch, Jörg Tost, Josep C. Jiménez-Chillarón
Journal: Cell Metabolism (2014)