tbuckley/cabot-search huggingface dataset:
Dietary Intake of Antioxidant Nutrients and the Risk of Incident Alzheimer Disease in a Biracial Community Study
Authors: Martha Clare Morris, Denis A Evans, Julia L Bienias, Christine C Tangney, David A Bennett, Neelum Aggarwal, Robert S Wilson, Paul A Scherr
Journal: JAMA (2002)

ContextOxidative processes have been suggested as elements in the development of Alzheimer disease (AD), but whether dietary intake of vitamin E and other antioxidant nutrients prevents its development is unknown.ObjectiveTo examine whether intake of antioxidant nutrients, vitamin E, vitamin C, and beta carotene is associated with incident AD.Design, Setting, and ParticipantsProspective study, conducted from 1993 to 2000, of individuals selected in a stratified random sample of community-dwelling residents. The 815 residents 65 years and older were free of AD at baseline and were followed up for a mean of 3.9 years. They completed food frequency questionnaires an average of 1.7 years after baseline.Main Outcome MeasureIncident AD diagnosed in clinical evaluations with standardized criteria.ResultsIncreasing vitamin E intake from foods was associated with decreased risk of developing AD after adjustment for age, education, sex, race, APOE ∊4, and length of follow-up. Relative risks (95% confidence intervals [CIs]) from lowest to highest quintiles of intake were 1.00, 0.71 (0.24-2.07), 0.62 (0.26-1.45), 0.71 (0.27-1.88), and 0.30 (0.10-0.92) (P for trend = .05). The protective association of vitamin E was observed only among persons who were APOE ∊4 negative. Adjustment for other dietary factors reduced the protective association. After adjustment for baseline memory score, the risk was 0.36 (95% CI, 0.11-1.17). Intake of vitamin C, beta carotene, and vitamin E from supplements was not significantly associated with risk of AD.ConclusionThis study suggests that vitamin E from food, but not other antioxidants, may be associated with a reduced risk of AD. Unexpectedly, this association was observed only among individuals without the APOE ∊4 allele.
Hemolysates reduce iron released from transferrin
Authors: Hui Zhan, Simeon Pollack, Janet Weaver
Journal: American Journal of Hematology (1989)

Transferrin donates iron to reticulocytes as follows: it binds to a receptor on the reticulocyte surface; the complex is endocytosed; both irons are released and the transferrin is recycled to the cell exterior. It has been proposed that the trigger for iron release after transferrin endocytosis is acidification of the endocytic vesicle. But this could account for removal of only one of transferrin's two irons, since only one of the irons is labile at acid pH. Moreover, iron continues to be removed from transferrin when acidification of the vesicle is blocked by a chloride-transport inhibitor. Thus a detailed explanation of iron removal from transferrin remains elusive. In earlier work we showed that iron can be removed from transferrin by whole hemolysates and also by the combined action of hemoglobin and ATP at pH 7. We now show that the iron released from transferrin by hemolysates, and by hemoglobin and ATP, is in the Fe(II) oxidation state. We also show that ADP and DPG can substitute for ATP and that NADH and NADPH can substitute for the hemoglobin, although with these substitutions Fe(II) is generated less efficiently. The reductive release of iron from transferrin is rapid enough to account for all the iron processed by a young reticulocyte. We speculate that transferrin iron may be reduced to Fe(II) before reaching the mitochondria.
What does “reduced central blood volume in cirrhosis” really mean?
Authors: G. A. Morali, L. M. Blendis
Journal: Hepatology (1990)

The pathogenesis of ascites formation in cirrhosis is uncertain. It is still under debate whether the effective blood volume is reduced (underfilling theory) or whether the intravascular compartment is expanded (overflow theory). This problem has not yet been solved because of insufficient tools for measuring the central blood volume. We have developed a method that enables us to determine directly the central blood volume, i.e., the blood volume in the heart cavities, lungs, and central arterial tree. In 60 patients with cirrhosis and 16 control subjects the central blood volume was assessed according to the kinetic theory as the product of cardiac output and mean transit time of the central vascular bed. Central blood volume was significantly smaller in patients with cirrhosis than in controls (mean 21 vs. 27 ml/kg estimated ideal body weight, p &lt; 0.001; 25% vs. 33% of the total blood volume, p &lt;0.0001). The lowest values (18 ml/kg) were found in patients with gross ascites and a reduced systemic vascular resistance. In patients with cirrhosis central blood volume was inversely correlated to the hepatic venous pressure gradient (r = −0.41, p &lt;0.01), and the total blood volume was inversely correlated to the systemic vascular resistance (r = −0.49, p &lt; 0.001), the latter being significantly reduced in the patient group. Patients with cirrhosis apparently are unable to maintain a normal central blood volume. This may be due to arteriolar vasodilation, portosystemic collateral flow, or sequestration of fluid in the peritoneal cavity, or any combination thereof. The present results indicate that central circulatory underfilling is an integral part of the hemodynamic and homeostatic derangement observed in cirrhosis.
BIOASSAYS OF CYSTIC-FIBROSIS FACTOR
Authors: BarbaraH Bowman, H.Hugh Fudenberg, JohnF Herndon, Kurt Hirschhorn, Kaye Kilburn, Seymour Lederberg, JohnA Mangos, RichardC Talamo, William Rutter, James Weisiger, AlexanderG Bearn
Journal: The Lancet (1974)
Chest radiographic staging in allergic bronchopulmonary aspergillosis: relationship with immunological findings
Authors: JL Kiely, L Spense, M Henry, MF Hurley, N Kelleher, CP Bredin
Journal: European Respiratory Journal (1998)

The question of whether a chest radiographic severity staging system could be correlated with standard blood/serum diagnostic indices in allergic bronchopulmonary aspergillosis (ABPA) was addressed in 41 patients. Asthma and positive Aspergillus fumigatus (AF) serology were considered essential diagnostic inclusion criteria. Eosinophil count, serum immunoglobulin (Ig)E and immediate skin hypersensitivity were also tested to grade patients as "definite" or "likely" ABPA. Definite cases had all five of these factors present, whereas likely cases had three or more. Chest radiographs were examined by experienced radiologists blinded to the clinical data. The six-stage radiographic score (0-5) was based on the severity and duration of changes seen: stage 0: normal; stage 1: transient hyperinflation; stage 2: transient minor changes; stage 3: transient major changes; stage 4: permanent minor changes; and stage 5: permanent major changes. Significant positive correlations (p&lt;0.05) were observed between peak AF titres (expressed as an index), peak eosinophil count and radiographic severity stage. When considered as subgroups, these correlations approached, but did not reach, significance for the group with "likely" ABPA (n=28), but in the group with definite ABPA (n=13), there was a high correlation between radiographic score and peak AF index (r=0.59), as well as peak eosinophil count (r=0.62). This study suggests that the peak Aspergillus fumigatus index and eosinophil counts correlate best with the severity of radiographic stages in allergic bronchopulmonary aspergillosis. This chest radiographic staging system may be useful in the clinical assessment and management of patients with allergic bronchopulmonary aspergillosis, particularly in those patients with more severe radiographic stages.
Disease inhibition by major histocompatibility complex binding peptide analogues of disease-associated epitopes: more than blocking alone.
Authors: M H Wauben, C J Boog, R van der Zee, I Joosten, A Schlief, W van Eden
Journal: The Journal of Experimental Medicine (1992)

Peptide analogues of disease-associated epitopes were studied for inhibition of experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA) in Lewis rats. EAE- and AA-associated analogues were selected as competitors because of their in vitro inhibitory activity on proliferation of encephalitogenic and arthritogenic T cells. Although the EAE-associated competitor had a superior major histocompatibility complex (MHC) binding affinity, the AA-associated competitor was a better inhibitor of the in vitro proliferation of arthritogenic T cells. Furthermore, although in vivo EAE was inhibited by both competitors, AA was only inhibited by the AA-associated competitor. Remarkably, in contrast to what was expected of a regular MHC competitor peptide, the AA-associated peptide analogue also prevented AA upon immunization before disease induction and appeared to induce T cell responses that crossreacted with the original disease-associated epitope. Therefore, it is concluded that antigen-specific regulatory mechanisms were involved in synergy with MHC competition. The integration of both qualities into a single "competitor-modulator" analogue peptide may lead to the development of novel, more effective, disease-specific immunomodulatory peptides.
Impaired lymphocyte reactivity against tumour cells in patients with coeliac disease
Authors: B. P. Maclaurin, W. T. Cooke, N. R. Ling
Journal: Gut (1971)

The lymphocytes of patients with coeliac disease are shown to have a significant diminution of proliferative and cytotoxic capacity as compared to normal lymphocytes when challenged <i>in vitro</i> with tumour cells from a lymphoma cell line. This impaired responsiveness is partly related to an intrinsic cellular defect but an inhibiting factor in the serum of coeliac patients has also been demonstrated. The impaired coeliac lymphocyte response in this <i>in-vitro</i> test system may serve as an indicator of a comparable defect in immune surveillance <i>in vivo.</i> This would account for the increased incidence of lymphosarcoma known to arise in patients with longstanding coeliac disease and might also explain the raised incidence of other gut-related tumours in these patients.
Inhibition by iodine of the release of thyroxine from the thyroid glands of patients with thyrotoxicosis
Authors: Leonard Wartofsky, Bernard J. Ransii, Sidney H. Ingbar
Journal: Journal of Clinical Investigation (1970)

A method has been devised which is free of many of the shortcomings of serial epithyroid counting techniques as an index of the rate of thyroid hormone secretion. By means of this method, the effect of treatment with Lugol's iodine on the rate of thyroidal secretion of thyroxine (T(4)) has been assessed in eight patients with thyrotoxicosis due to diffuse or multinodular goiter. The technique involves administration of a tracer dose of inorganic (125)I followed several days later by an intravenous tracer dose of (131)I-labeled T(4). Serial observations of serum protein-bound (PB) (125)I and (131)I are accompanied by frequent measurements of endogenous serum T(4) (T(4)-(127)I) concentration. Regardless of whether or not its administration was anteceded and accompanied by the administration of large doses of methimazole, iodine induced a rapid decrease in serum T(4)-(127)I concentration which could not be explained by an increase in the peripheral turnover of T(4), as judged from the metabolism of the (131)I-labeled hormone. Hence, the decreased serum T(4) concentration could only have resulted from decreased secretion of the hormone by the gland. Analyses of specific activity relationships between PB(125)I or T(4)-(127)I and PB(131)I made possible estimations of the extent to which iodine had decreased the rate of secretion of T(4). From such analysis, and in view of other considerations, it is concluded that the rapid decrease in T(4) secretion induced by iodine is not the result of an acute, sustained inhibition of T(4) synthesis, but rather results from an abrupt decrease in the fractional rate of thyroidal T(4) release.
Locked Knee and Osteochondritis Dissecans
Authors: Christopher Elsworth
Journal: Journal of the Royal Society of Medicine (1983)

Two patients presenting with a locked knee are described. In both cases a loose body from an osteochondritis dissecans defect had wedged beneath the anterior horn of the lateral meniscus, creating a block to extension which could not be reduced. Arthroscopy and arthroscopic methods proved unsuccessful in the removal of the loose body.
Acting on an environmental health disaster: the case of the Aral Sea.
Authors: I Small, J van der Meer, R E Upshur
Journal: Environmental Health Perspectives (2001)

The Aral Sea area in Central Asia has been encountering one of the world's greatest environmental disasters for more than 15 years. During that time, despite many assessments and millions of dollars spent by large, multinational organizations, little has changed. The 5 million people living in this neglected and virtually unknown part of the world are suffering not only from an environmental catastrophe that has no easy solutions but also from a litany of health problems. The region is often dismissed as a chronic problem where nothing positive can be achieved. Within this complicated context, Medecins Sans Frontieres, winner of the Nobel Peace Prize in 1999, is actively trying to assess the impact of the environmental disaster on human health to help the people who live in the Aral Sea area cope with their environment. Medecins Sans Frontieres has combined a direct medical program to improve the health of the population while conducting operational research to gain a better understanding of the relationship between the environmental disaster and human health outcomes. In this paper we explore the health situation of the region and the broader policy context in which it is situated, and present some ideas that could potentially be applied to many other places in the world that are caught up in environmental and human health disasters.
P769 SINGLE NUCLEOTIDE POLYMORPHISMS NEAR IL28B AND IL28A GENES AND RISK OF LIVER CIRRHOSIS AMONG PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION
Authors: M.-H. Lee, H.-I. Yang, T.-W. Shaw, S.-N. Lu, Y.-J. Lin, C.-L. Jen, Y. Yuan, G. L'Italien, C.-J. Chen
Journal: Journal of Hepatology (2014)
PTU-044 Hepatic/endothelial cell co-culture; establishing optimal conditions for liver tissue engineering
Authors: M Navarro, L Nelson, K Burgess, O Tura, K Samuel, J Plevris
Journal: Gut (2012)

<h3>Introduction</h3> Development of 3D hepatic organoids utilising human cell derivatives for in vitro drug testing and bioartificial liver support systems is challenging. Tissue engineering thick, complex structures such as human liver organoids (micro-tissue; &gt;500 mm) will require vascularisation of 3D cultures—coupled with biomatrix support scaffolds—to both maintain integrity and promote formation of endothelial channels (sinusoid-like structures) to facilitate oxygen and nutrient transfer to hepatocytes in 3D culture. Key challenges involve directing nascent microvessels into an appropriate environment defined prominently by heterotypic cell–cell contacts and meeting high metabolic demands. In this preliminary study, we aimed to optimise heterotypic co-culture of either Human Umbilical Vein Endothelial Cells (HUVECs) or Endothelial Outgrowth Cells (EOCs) with hepatic C3A cells, using appropriate biomatrix scaffolds. <h3>Methods</h3> Different ratios of HUVECs: C3A or EOCs:C3A to form co-cultures were studied using contrast/confocal microscopy and flow cytometry following appropriate immunostaining. Flow cytometry was used to study integrin expression (Cd49a, Cd49b, Cd49f, Cd49e), endothelial markers (CD31) and EpCam, as an hepatic marker. Fingerprint <i>unbiased</i> metabolomics analysis was used to assess function of co-cultured cells. Matrigel and MaxGel (Sigma) were tested as candidate bioscaffolds and were compared with standard 2D cultures on plastic and collagen for each cell line as controls. <h3>Results</h3> A ratio 3:1 (HUVECs:C3A) was optimal for growth using endothelial culture medium (Lonza EGM-2 medium, UK). Cell phenotype was maintained for 7 days in co-culture with strong integrin (Cd49a, Cd49b, Cd49f, Cd49e), and CD31 expression on HUVECs and EpCam on C3A cells, while a reduction of HUVEC cell number was noted with a parallel increase of C3A cells by day 7—to form more sheet-like structures in co-culture. Metabolomics analysis of culture media showed enhanced urea cycle, lipid synthesis and amino acid utilisation of C3A cells in co-culture. Matrigel promoted formation of microvessel structures, with interconnected channels, in both EOCs and HUVECs; and was superior to MaxGel. MaxGel in 3D sandwich culture promoted differentiated (cuboidal) morphology of C3As, but not EoCs. <h3>Conclusion</h3> Optimisation of both cell ratios and cell numbers, as well as selection of appropriate culture media are critical factors in developing a successful hepatic co-culture system with the ability to form sinusoid-like/microvessel structures. This study represents an early step towards understanding the requirements of vascularised liver tissue for future clinical/pharmaceutical applications. <h3>Competing interests</h3> None declared.
Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials
Authors: Joachim Sieper, Benjamin Porter-Brown, Liz Thompson, Olivier Harari, Maxime Dougados
Journal: Annals of the Rheumatic Diseases (2013)

BUILDER-1 and BUILDER-2 aimed to assess the efficacy and safety of tocilizumab (TCZ) in patients with ankylosing spondylitis (AS).BUILDER-1 was a two part, phase II-III parallel-group trial in patients with AS naive to antitumour necrosis factor (aTNF) treatment. Patients in part 1 received TCZ 8 mg/kg or placebo for 12 weeks. In part 2 (beginning after part 1 enrolment ended), newly enrolled patients received TCZ 4 or 8 mg/kg or placebo for 24 weeks. The same treatment arms were used in BUILDER-2, a phase III study in aTNF-inadequate responders. The primary endpoint for both studies was the proportion of patients achieving 20% improvement in the Assessments in Axial SpondyloArthritis international Society (ASAS). Secondary and exploratory endpoints included ASAS40 response rates, Bath Ankylosing Spondylitis Disease Activity Index improvement, changes in joint counts, enthesitis score and C reactive protein (CRP).102 patients were randomised in BUILDER-1 part 1; 99 (48 TCZ, 51 placebo) completed 12 weeks. Week 12 ASAS20 response rates were 37.3% and 27.5% in the TCZ and placebo arms, respectively (p=0.2823). Secondary and exploratory endpoints did not differ between treatment arms. CRP levels declined with TCZ treatment, suggesting adequate IL-6 receptor blockade. As a result, BUILDER-1 part 2 and BUILDER-2 were terminated. TCZ safety results were consistent with previous observations in rheumatoid arthritis, except for a cluster of anaphylactic and hypersensitivity events at Bulgarian study sites. No apparent explanation for this clustering could be found.BUILDER-1 failed to demonstrate TCZ efficacy in treating aTNF-naive patients with AS.
SJG-136 (NSC 694501), a Novel Rationally Designed DNA Minor Groove Interstrand Cross-Linking Agent with Potent and Broad Spectrum Antitumor Activity
Authors: John A. Hartley, Victoria J. Spanswick, Natalie Brooks, Peter H. Clingen, Peter J. McHugh, Daniel Hochhauser, R. Barbara Pedley, Lloyd R. Kelland, Michael C. Alley, Robert Schultz, Melinda G. Hollingshead, Karen M. Schweikart, Joseph E. Tomaszewski, Edward A. Sausville, Stephen J. Gregson, Philip W. Howard, David E Thurston
Journal: Cancer Research (2004)

Abstract SJG-136 (NSC 694501) is a rationally designed pyrrolobenzodiazepine dimer that binds in the minor groove of DNA. It spans 6 bp with a preference for binding to purine-GATC-pyrimidine sequences. The agent has potent activity in the National Cancer Institute (NCI) anticancer drug screen with 50% net growth inhibition conferred by 0.14 to 320 nmol/L (7.4 nmol/L mean). Sensitive cell lines exhibit total growth inhibition and 50% lethality after treatment with as little as 0.83 and 7.1 nmol/L SJG-136, respectively. COMPARE and molecular target analysis of SJG-136 data versus that of &amp;gt;60,000 compounds tested in the NCI 60 cell line screen shows that, although the agent has similarity to other DNA binding agents, the pattern of activity for SJG-136 does not fit within the clusters of any known agents, suggesting that SJG-136 possesses a distinct mechanism of action. Testing in the NCI standard hollow fiber assay produced prominent growth inhibition in 20 of 24 i.p. and 7 of 24 s.c. test combinations with 5 of 12 cell lines exhibiting cell kill. In addition, SJG-136 produced antitumor activity in mice bearing CH1 and CH1cisR xenografts, a cisplatin-resistant human ovarian tumor model, and also in mice bearing LS174T xenografts, a human colon tumor model. SJG-136 produces DNA interstrand cross-links between two N-2 guanine positions on opposite strands and separated by 2 bp. In human tumor cell lines, the cross-links form rapidly and persist compared with those produced by conventional cross-linking agents such as nitrogen mustards. In mice bearing the LS174T human colon xenograft, DNA interstrand cross-links can be detected in tumor cells using a modification of the single cell gel electrophoresis (comet) assay after administration of a therapeutic dose. Cross-links in the tumor increase with dose and are clearly detectable at 1 hour after i.v. administration. The level of cross-linking persists over a 24-hour period in this tumor in contrast to cross-links produced by conventional cross-linking agents observed over the same time period.
Annual incidence and mortality of bullous pemphigoid in the Grampian Region of North-east Scotland
Authors: V.S. Gudi, M.I. White, N. Cruickshank, R. Herriot, S.L. Edwards, F. Nimmo, A.D. Ormerod
Journal: British Journal of Dermatology (2005)

Data on the annual incidence of bullous pemphigoid (BP) in the U.K. are scarce.To estimate the annual incidence of BP in Grampian Region (North-east Scotland) and to assess the causes of mortality in this cohort of patients.Details were obtained of all patients with a diagnosis of BP recorded in the database of the Pathology Department, Aberdeen Royal Infirmary between January 1991 and December 2001. Community Health Index population data were obtained from the Grampian Health Board and the annual incidence and age- and sex-specific incidence were calculated. Mortality data were obtained from the Patient Administration System and causes of death obtained from the Office of the Registrar for Births and Deaths for Scotland.Eighty-three patients met criteria for diagnosis of BP. The annual incidence of BP in Grampian region was estimated to be 14 cases per million per year. There was a clear and marked rise in the incidence in patients over the age of 80 years. Forty-eight per cent of patients with BP died within 2 years of diagnosis. The all-cause age-standardized mortality ratio was 576%. When compared with cause-specific mortality in the Grampian population over 60 years of age, respiratory disease accounted for a higher than expected number of deaths in our cohort of patients with BP (odds ratio 5.3, 95% confidence interval 3.0-9.4).North-east Scotland appears to have a relatively high incidence of BP when compared with incidence rates in continental Europe. The mortality rate in patients with BP is considerable, especially within the first 2 years of diagnosis.
Influence of BCG-Potentiated Immunotherapy in Tumor-Bearing Mice 2
Authors: Eugenia Hawrylko
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Influence of BCG-Potentiated Immunotherapy in Tumor-Bearing Mice Get access Eugenia Hawrylko, M.D. Eugenia Hawrylko, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 2, August 1977, Pages 359–365, https://doi.org/10.1093/jnci/59.2.359 Published: 01 August 1977 Article history Received: 14 September 1976 Accepted: 01 March 1977 Published: 01 August 1977