tbuckley/cabot-search huggingface dataset:
Modification of immune function through exposure to dietary aflatoxin in Gambian children.
Authors: Paul C Turner, Sophie E Moore, Andrew J Hall, Andrew M Prentice, Christopher P Wild
Journal: Environmental Health Perspectives (2002)

Aflatoxins are immunotoxins that frequently contaminate staple foods in The Gambia and other parts of sub-Saharan Africa, resulting in high exposure throughout life. Impaired infant immune system development may be a key predictor of mortality from infectious disease. In this study we aimed to determine the effect of dietary aflatoxin exposure on a number of immune parameters in Gambian children. A cohort of 472 Gambian children 6-9 years of age was recruited. Serum aflatoxin-albumin (AF-alb) adducts were analyzed to provide a measure of exposure. Immune parameters included secretory IgA (sIgA) in saliva, cell-mediated immunity (CMI), determined using the CMI multitest where test antigens are applied to the skin, and antibody responses to both rabies and pneumococcal polysaccharide vaccines. Birth weight, current anthropometry, and micronutrient status were also recorded. AF-alb adducts were detected in 93% of the children (geometric mean level 22.3 pg/mg; range 5-456 pg/mg). AF-alb level was strongly influenced by month of sampling. In a multivariable analysis, sIgA was markedly lower in children with detectable AF-alb compared with those with nondetectable levels [50.4 micro g/mg protein (95% confidence interval [CI] 48.0-52.8) and 70.2 micro g/mg protein (95% CI 61.1-79.2), respectively; p < 0.0001]. Antibody response to one of four pneumococcal serotypes, but not rabies vaccine, was weakly associated with higher levels of AF-alb. There was no association between CMI responses to test antigens and AF-alb. These data confirm that children in rural Gambia are frequently exposed to high levels of aflatoxin. The study provides evidence that sIgA in saliva may be reduced because of dietary levels of aflatoxin exposure. Given the high burden of infection-related mortality in West Africa, further investigation of the immune effects of aflatoxin exposure in children is merited.
Evaluation of an Ambulatory Medical-Care Delivery System
Authors: Sidney R. Garfield, Morris F. Collen, Robert Feldman, Krikor Soghikian, Robert H. Richart, James H. Duncan
Journal: New England Journal of Medicine (1976)

Abstract We designed a medical-care-delivery system specifically to relieve the impaired access to care that has invariably accompanied the elimination of personal fees by prepaid plans, Medicare and other third-party payment plans. The solution involved the entry of patients through a paramedically staffed health-evaluation service that effectively separated patients into three basic health-status groups—the well and worried well (68.4 per cent); the asymptomatic sick (3.9 per cent); and the sick (27.7 per cent)—a process that permitted matching the needs of each group with appropriate services. The system achieved increased physician accessibility to new patients by 20 times, reduced the waiting time for new appointments from six to eight weeks to a day or two, saved physician time and costs for entry work-up by 70 to 80 per cent, reduced total resources used throughout the year by $32,550 per 1000 entrants, and proved very satisfactory to patients and generally so to staff. (N Engl J Med 294:426–431, 1976)
Desensitization of adenosine receptor-mediated inhibition of lipolysis. The mechanism involves the development of enhanced cyclic adenosine monophosphate accumulation in tolerant adipocytes.
Authors: B B Hoffman, H Chang, E Dall'Aglio, G M Reaven
Journal: Journal of Clinical Investigation (1986)

Adipocytes contain adenosine receptors, termed A1 receptors, which inhibit lipolysis by decreasing adenylate cyclase activity. The inhibition of lipolysis by adenosine agonists in vivo acutely suppresses the plasma concentrations of free fatty acids (FFA) and triglycerides. We have found that infusions of the adenosine receptor agonist phenylisopropyladenosine (PIA) initially decreases plasma FFA concentrations; however, with prolonged exposure (6 d), rats become very tolerant to the effects of the drug. Adipocytes isolated from epididymal fat pads from PIA-infused rats have altered lipolytic responses. When lipolysis is stimulated with a relatively high concentration of isoproterenol (10(-7) M), PIA does not inhibit lipolysis in adipocytes from the infused animals. However, PIA inhibits isoproterenol-stimulated cyclic AMP (cAMP) accumulation in adipocytes from the infused rats although with decreased sensitivity compared with controls. The explanation for the impaired antilipolytic effect appears to be due to the fact that isoproterenol-stimulated cAMP accumulation is markedly increased in cells from infused rats. Indeed, basal lipolysis and lipolysis stimulated with lower concentrations of isoproterenol (10(-9), 10(-8) M) are effectively inhibited by PIA. cAMP accumulation is greatly increased in adipocytes from infused rats when stimulated by isoproterenol, ACTH, and forskolin. The results have some striking analogies to changes induced in nerve cells by prolonged exposure to narcotics. These data suggest that tolerance to PIA develops in adipocytes as a consequence of enhanced cAMP accumulation.
P30 Lung injury and its prognostic significance in acute liver failure
Authors: V. K. Audimoolam, M. McPhail, S. Desai, C. Willars, W. Bernal, J. A. Wendon, G. Auzinger
Journal: Gut (2011)

<h3>Introduction</h3> Acute liver failure (ALF) is a multi system illness. Data on the incidence and outcome of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) complicating ALF is scant1. We analysed radiological, gas exchange and ventilator data of consecutive patients admitted with ALF/subacute liver failure (SALF) to a tertiary liver intensive therapy unit (LITU). <h3>Aim</h3> The main objective of this assessment was to identify the incidence of ALI/ARDS in ALF/SALF and the impact it has on outcome. <h3>Method</h3> All patients with ALF/SALF receiving mechanical ventilation who were admitted between January 2007 and February 2011 were included. Patients were categorised according to the ARDS network consensus definition as: No lung injury present (NALI), ALI (P/F &lt;300 mm Hg) and ARDS (P/F &lt;200 mm Hg). Chest radiographs were independently assessed by two observers for the presence of bilateral infiltrates. Absence of left atrial pressure elevation was based on haemodynamic and echocardiographic assessment. <h3>Results</h3> 146 (M: F 71:75) patients with ALF/SALF were studied. 31 patients (21%) fulfilled ARDS network criteria, 14 ARDS (9.6%), 17 ALI (11.6%), within the first 72 h following LITU admission. ARDS patients required higher levels of positive end expiratory pressure (10 vs 6 ALI and 7cmH<sub>2</sub>O NALI, p=0.016) and had a worse oxygenation index (10.7 vs 4.3 ALI, 4.5 NALI, p≤0.001). There was a trend towards reduced compliance of the respiratory system in ARDS and ALI patients (p=0.07 vs NALI) and an increased number of ventilator days (NALI 10d, ALI 12d, ARDS 17d). Duration of LITU stay (p=0.175) and survival (p=0.877) were not affected by the presence of ALI/ARDS. Type of liver disease presentation ALF/SALF, poor prognostic markers of liver failure, that is, lactate, INR, bilirubin, presence of encephalopathy and intracranial hypertension did not correlate with lung injury presentation. Also no association with inotrope requirements (p=0.495), need for extracorporeal renal support (p=0.565) and severity of organ failure scores was found. <h3>Conclusion</h3> The incidence of lung injury is relatively low in ALF of mixed aetiology. Less than 10% of patients fulfilled ARDS criteria. Overall presence of ALI/ARDS appeared to have a limited impact on outcome.
Preclinical Evaluation of TriMix and Antigen mRNA-Based Antitumor Therapy
Authors: Sandra Van Lint, Cleo Goyvaerts, Sarah Maenhout, Lode Goethals, Aurélie Disy, Daphné Benteyn, Joeri Pen, Aude Bonehill, Carlo Heirman, Karine Breckpot, Kris Thielemans
Journal: Cancer Research (2012)

The use of tumor-associated antigen (TAA) mRNA for therapeutic purposes is under active investigation. To be effective, mRNA vaccines need to deliver activation stimuli in addition to TAAs to dendritic cells (DC). In this study, we evaluated whether intranodal delivery of TAA mRNA together with TriMix, a mix of mRNA encoding CD40 ligand, constitutive active Toll-like receptor 4 and CD70, results in the in situ modification and maturation of DCs, hence, priming of TAA-specific T cells. We showed selective uptake and translation of mRNA in vivo by lymph node resident CD11c(+) cells. This process was hampered by codelivery of classical maturation stimuli but not by TriMix mRNA. Importantly, TriMix mRNA induced a T-cell-attracting and stimulatory environment, including recruitment of antigen-specific CD4(+) and CD8(+) T cells and CTLs against various TAAs. In several mouse tumor models, mRNA vaccination was as efficient in CTL induction and therapy response as vaccination with mRNA-electroporated DCs. Together, our findings suggest that intranodal administration of TAA mRNA together with mRNA encoding immunomodulating molecules is a promising vaccination strategy.
443 Higher efficacy of sequential therapy of lamivudine and interferon-A (IFN) vs. lamivudine monotherapy in patients with HBEAG positive chronic hepatitis B (CHB): A prospective randomized controlled trial
Authors: B.C. Sharma, S.K. Sarin, S. Kumar, R.C. Guptan, R. Kumar, S.N. Kazim, V. Malhotra
Journal: Journal of Hepatology (2004)
Theranostic nanoparticles based on PEGylated hyaluronic acid for the diagnosis, therapy and monitoring of colon cancer
Authors: Ki Young Choi, Eun Jung Jeon, Hong Yeol Yoon, Beom Suk Lee, Jin Hee Na, Kyung Hyun Min, Sang Yoon Kim, Seung-Jae Myung, Seulki Lee, Xiaoyuan Chen, Ick Chan Kwon, Kuiwon Choi, Seo Young Jeong, Kwangmeyung Kim, Jae Hyung Park
Journal: Biomaterials (2012)
Which SSRI? A Meta-Analysis of Pharmacotherapy Trials in Pediatric Obsessive-Compulsive Disorder
Authors: Daniel A. Geller, Joseph Biederman, S. Evelyn Stewart, Benjamin Mullin, Andrés Martin, Thomas Spencer, Stephen V. Faraone
Journal: American Journal of Psychiatry (2003)

The authors conducted a meta-analysis of published randomized, controlled medication trials in children and adolescents with obsessive-compulsive disorder (OCD) to assess evidence for differential efficacy based on type of drug, study design, and outcome measure.A systematic literature search was performed for articles pertaining to the pharmacological treatment of pediatric and/or adolescent OCD. All baseline, posttreatment, and change scores with standard deviations reported in each study were included in the analyses. Effect sizes for dependent measures were expressed as standardized mean differences. The analysis included data on efficacy for four selective serotonin reuptake inhibitors (SSRIs) (paroxetine, fluoxetine, fluvoxamine, and sertraline) and clomipramine, four study designs, four dependent outcome measures, and two types of outcome scores (change and posttreatment scores). Multivariate regression was performed to assess the degree to which the effect sizes varied with the methodological features of each study.Twelve studies with a total of 1,044 participants met all inclusion criteria for the analysis. The pooled standardized mean difference for the results of all studies was 0.46 and showed a highly significant difference between drug and placebo treatment. Only one of the four outcome measures evaluated was not sensitive to change with treatment. A multivariate regression analysis of drug effect with other variables controlled showed that clomipramine was significantly superior to each of the SSRIs but that the SSRIs were comparably effective.Although highly significant, the overall effect sizes for medication were modest. Similarities and differences between the variables studied that emerged in the meta-analysis may have implications for both clinical care and future research.
Developmental increases in rat hepatic microsomal UDP-glucuronosyltransferase activities toward xenoestrogens and decreases during pregnancy.
Authors: Junya Matsumoto, Hiroshi Yokota, Akira Yuasa
Journal: Environmental Health Perspectives (2002)

Xenoestrogens, such as bisphenol A and diethylstilbestrol, are glucuronidated by an isoform of UDP-glucuronosyltransferase named UGT2B1 in the livers of adult male rats. In this study, we found that nonylphenol and octylphenol are also conjugated with glucuronic acid by adult rat liver microsomes. Although UDP-glucuronosyltransferase activities toward these xenoestrogens were not detected in the fetal rat liver, a linear increase in enzymatic activities during neonatal development was observed. At 3 weeks after birth, the activities had reached the same level as that of adult rats. The protein and mRNA contents of UGT2B1 also were not detected in the fetal rat liver, but a developmental increase in newborn rat liver was detected by Western and Northern blotting analysis. Additionally, rat hepatic microsomal UDP-glucuronosyltransferase activities toward these xenoestrogens were reduced by about half during pregnancy of mother rats. The results suggest that the reproductive organs of fetal and early-stage neonatal rats, which are sensitive to sex hormones, face a high risk of exposure to free active xenoestrogens.
Serum pro-hepcidin: measuring active hepcidin or a non-functional precursor?
Authors: Matthew Brookes, Naveen Sharma, Chris Tselepis, Tariq Iqbal
Journal: Gut (2004)

We read with great interest the paper “Pro-hepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia” ( Gut 2004; 53 :735–43) .

We have two observations. Firstly it was shown that pro-hepcidin and hepcidin were colocalised within the liver and in Hep-G cells. However, it was not possible, using serum ELISA, to identify the C terminus of …
Effects of phenobarbital on bilirubin metabolism and its response to phototherapy in the jaundiced gunn rat
Authors: Arnold N. Cohen, Jaime Kapitulnik, Donald J. Ostrow, Eugene A. Zenone, Cecile Cochrane, Lillian Celic, Heidemarie Cheney
Journal: Hepatology (1985)

Jaundiced Gunn rats, treated with phenobarbital (60 mg per kg i.p. for 7 to 10 days) showed 25 and 36% decreases in mean plasma bilirubin levels in two experiments (p &lt; 0.01). Kinetic studies with tracer 14 C–bilirubin revealed that there was no change in bilirubin turnover or total pool size due to phenobarbital, but a 49% increase in the hepatic pool and a 27% decrease in the cutaneous pool of bilirubin. The increase in the hepatic pool accounted for over 90% of the bilirubin lost from the plasma. Such pretreatment with phenobarbital did not alter the decline in plasma bilirubin or total bilirubin pool due to subsequent phototherapy. Phenobarbital followed by phototherapy produced a significantly greater reduction in plasma bilirubin levels than either treatment alone. These studies demonstrate that phenobarbital does decrease plasma bilirubin in Gunn rats primarily by shifting the pigment to the liver, and suggests that combined treatment with phenobarbital and phototherapy might be of value in patients with congenital hyperbilirubinemia due to glucuronyl transferase deficiency.
IMMUNOLOGICAL SPECIFICITY OF MATERIAL SEDIMENTABLE AT HIGH SPEED PRESENT IN NORMAL AND TUMOR TISSUES
Authors: Jacob Furth, Elvin A. Kabat
Journal: The Journal of Experimental Medicine (1941)

Materials sedimentable at high speed (approximately 27,000 R.P.M.) were found in all normal and neoplastic tissues studied. They are carriers of the Forssman antigen and of the Wassermann hapten. These heavy materials exhibit species, organ, and individual specificity and produce several antibodies which can be demonstrated by absorption tests. Heavy materials from chicken sarcoma and chicken spleen could not be distinguished by complement fixation tests.
TONSIL AND ADENOID OPERATIONS UNDER ANESTHESIA BY NITROUS OXID, AND NITROUS OXID AND OXYGEN: A PRELIMINARY REPORT.
Authors: W. E. CASSELBERRY
Journal: JAMA (1898)

The desirability of an anesthetic that would obviate the general objections pertaining to chloroform and ether in operation on tonsils and adenoids has been the source of much research. The chief objection to chloroform lies in its danger; bromid of ethyl has scarcely attained any greater confidence; ether, while reasonably safe, is so prolonged in its effects as to be inconvenient for this purpose. Nitrous oxid alone has been employed by a few operators, notably at the Central London Throat Hospital, but the available operating period from a single administration is almost too brief for the satisfactory removal of both the tonsils and adenoids. Experience has proven this anesthetic, however, to be safer than any other and to possess the advantage of a rapid revival of the patient; therefore following Gardner, Hunt and Hewitt of England, and Van Arsdale of New York, we have sought to modify the action of
Moxifloxacin-containing Regimens of Reduced Duration Produce a Stable Cure in Murine Tuberculosis
Authors: Eric L. Nuermberger, Tetsuyuki Yoshimatsu, Sandeep Tyagi, Kathy Williams, Ian Rosenthal, Richard J. O'Brien, Andrew A. Vernon, Richard E. Chaisson, William R. Bishai, Jacques H. Grosset
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

In a recent experimental study using the mouse model of tuberculosis, treatment with a combination of rifampin, moxifloxacin, and pyrazinamide was able to shorten the time to negative lung cultures by up to 2 months compared with the standard regimen of rifampin, isoniazid, and pyrazinamide. To confirm that this substitution of moxifloxacin for isoniazid permits a shorter duration of treatment, a second study was performed in which mice were assessed for relapse after treatment with combination therapy for 3, 4, 5, or 6 months. Although no relapse was observed among mice treated for at least 4 months with rifampin, moxifloxacin, and pyrazinamide, mice treated with rifampin, isoniazid, and pyrazinamide required 6 months of treatment before no relapse could be detected. For mice treated with rifampin, moxifloxacin, and pyrazinamide, similar efficacy was noted whether pyrazinamide was administered for 1 month, 2 months, or the entire duration of therapy. These results suggest that the use of rifampin, moxifloxacin, and pyrazinamide may substantially shorten the duration of therapy needed to cure human tuberculosis and that the full benefit of pyrazinamide in this regimen may be realized after just 1 month of treatment.
Response to Letter Regarding Article, “Circulating Endothelial Progenitor Cells in Patients With Eisenmenger Syndrome and Idiopathic Pulmonary Arterial Hypertension”
Authors: Gerhard-Paul Diller, Elisabeth Bédard, Stephen J. Wort, Michael A. Gatzoulis, Sven van Eijl, Omar Ali, Martin R. Wilkins, John Wharton, Darlington O. Okonko, Luke S. Howard, Thomas Thum, Johann Bauersachs, J. Simon R. Gibbs, Adrian J. Hobbs
Journal: Circulation (2009)
The CD28/CTLA-4:B7 receptor system in experimental autoimmune encephalomyelitis.
Authors: P S Linsley
Journal: Journal of Clinical Investigation (1995)

Experimental autoimmune encephalomyelitis (EAE) is a T cell- mediated autoimmune disorder widely used as a model for human multiple sclerosis (MS).In this issue of The Journal, Cross et al. (1) describe the successful treatment of murine EAE using a soluble form of the T cell activation molecule, CTLA-4.To- gether with two other recent studies (2, 3), this demonstrates a crucial role of the CD28/CTLA-4:B7 receptor system in EAE and suggests potential therapies for human MS. Role of CD28 in T cell activation
Molecular Evolution of Two Paralogous Tandemly Repeated Heterochromatic Gene Clusters Linked to the X and Y Chromosomes of Drosophila melanogaster
Authors: Galina L. Kogan, Vitalii N. Epstein, Alexei A. Aravin, Vladimir A. Gvozdev
Journal: Molecular Biology and Evolution (2000)

Here we report the peculiarities of molecular evolution and divergence of paralogous heterochromatic clusters of the testis- expressed X-linked Stellate and Y-linked Su(Ste) tandem repeats. It was suggested that Stellate and Su(Ste) clusters affecting male fertility are the amplified derivatives of the unique euchromatic gene βCK2tes encoding the putative testis-specific β-subunit of protein kinase CK2. The putative Su(Ste)-like evolutionary intermediate was detected on the Y chromosome as an orphon outside of the Su(Ste) cluster. The orphon shows extensive homology to the Su(Ste) repeat, but contains several Stellate-like diagnostic nucleotide substitutions, as well as a 10-bp insertion and a 3′ splice site of the first intron typical of the Stellate unit. The orphon looks like a pseudogene carrying a drastically damaged Su(Ste) open reading frame (ORF). The putative Su(Ste) ORF, as compared with the Stellate one, carries numerous synonymous substitutions leading to the major codon preference. We conclude that Su(Ste) ORFs evolved on the Y chromosome under the pressure of translational selection. Direct sequencing shows that the efficiency of concerted evolution between adjacent repeats is 5–10 times as high in the Stellate heterochromatic cluster on the X chromosome as that in the Y-linked Su(Ste) cluster, judging by the frequencies of nucleotide substitutions and single-nucleotide deletions.
Endoscopic Pancreatocholangiography: Progress and Problem
Authors: F.J. Ingelfinger
Journal: New England Journal of Medicine (1972)

In Nagoya, Japan, an endoscopic team under Tatsuzo Kasugai is using duodenal fiberscopes to cannulate the papilla of Vater, with a recent success rate of 97 per cent.1 , 2 This rate, claimed for cannulation of intact patients given no more than atropine, meperidine, and an intravenous antispasmodic, bests what many an experienced surgeon might attain in intubating the papilla under direct vision for purposes of operative pancreatography. Nor is the Nagoya group unique in its dexterity, for several other Japanese endoscopists enjoy what appear to be comparable skills. Japan, indeed, has become the world center for endoscopic cannulation of the papilla, . . .
The Dangerous Kitchen
Authors: Paul H. Martin
Journal: JAMA (1963)

<h3>To the Editor:</h3> —After several years of studying accidental poisonings of young children who have been referred to our health department by two poison control centers, I am firmly convinced that the kitchen is the most dangerous room in the home. This conclusion has been reached after a study of hundreds of poisonings of children, all of whom were under 5 years of age. There appear to be two major reasons why so many of these poisonings occur in the kitchen. First, this room has become the medicine cabinet of the home. No doubt the parent feels that placing the medicine on a high shelf will afford adequate protection. However, our public health nurses have found repeatedly that the child has made a set of steps by the use of stools, chairs, pulled out drawers and so forth. They believe that, given enough time, the active, inquisitive child can reach