tbuckley/cabot-search huggingface dataset:
Selective Effects of Oxygen Free Radicals on Excitation-Contraction Coupling in Ventricular Muscle
Authors: Wei Dong Gao, Yongge Liu, Eduardo Marban
Journal: Circulation (1996)

Oxygen free radicals (OFRs) have been implicated in the pathogenesis of myocardial stunning, but the precise mechanism by which OFRs foster stunning remains unclear. We investigated the pathophysiology of the contractile dysfunction that occurs after direct exposure of OFRs to cardiac muscle and compared the results with the pathophysiology of stunned myocardium.Trabeculae from the right ventricles of rat hearts were loaded iontophoretically with fura-2 to determine [Ca2+]i. Steady-state force-[Ca2+]i relations were obtained by rapid electrical stimulation in the presence of ryanodine. Two exogenous OFR-generating systems were used: H2O2 + Fe(3+)-nitrilotriacetic acid (H2O2 + Fe3+) to produce hydroxyl radical, and xanthine oxidase+purine (XO + P) to produce superoxide. In muscles exposed to H2O2 + Fe3+ for 10 minutes, both twitch force and Ca2+ transients were decreased (eg, in 1.5 mmol/L external [Ca2+], force decreased from 41 +/- 7 to 23 +/- 4 mN/mm2, P < .05, and Ca2+ transient amplitude from 0.96 +/- 0.09 to 0.70 +/- 0.05 mumol/L, P < .05). Maximal Ca(2+)-activated force (Fmax) decreased slightly, from 103 +/- 5 to 80 +/- 12 mN/mm2 (P = NS). Neither the [Ca2+]i required to achieve 50% of Fmax (Ca50) nor the Hill coefficient was changed. In muscles exposed to XO + P for 20 minutes, twitch force was reduced (in 1.5 mmol/L external [Ca2+]) from 50 +/- 9 to 39 +/- 8 mN/mm2 (P < .05). Ca2+ transients, on the other hand, were not affected. Fmax decreased insignificantly from 100 +/- 16 to 81 +/- 14 mN/mm2. Ca50 increased from 0.71 +/- 0.06 to 1.07 +/- 0.07 mumol/L (P < .05), with no change in the Hill coefficient.These results indicate that exposure to the H2O2 + Fe3+ free radical-generating system reduces activator Ca2+ availability, whereas XO + P decreases the Ca2+ sensitivity of the myofilaments. Exogenously generated OFRs, particularly those produced by XO + P, mimic the effects of myocardial stunning on cardiac excitation-contraction coupling.
N-acetylglucosamine-6-phosphate deacetylase in hepatocytes, kupffer cells and sinusoidal endothelial cells from rat liver
Authors: Patrick Campbell, Jerry N. Thompson, Robert J.E. Fraser, Torvard C. Laurent, HåKan Pertoft, Lennart Rodén
Journal: Hepatology (1990)

The activity of N –acetylglucosamine–6–phosphate deacetylase, a key enzyme in the pathway of N –acetylglucosamine catabolism, was measured in hepatocytes, Kupffer cells and sinusoidal endothelial cells from rat liver and cultured human skin fibroblasts. Kupffer cells and endothelial cells had similar high levels of deacetylase activity that were more than twice the level observed in fibroblasts. In contrast, hepatocytes had extremely low activity (several hundredfold less than Kupffer cells and endothelial cells). A major implication of deacetylase deficiency in hepatocytes is that N –acetylglucosamine generated as a result of the catabolism of complex carbohydrates in these cells cannot enter glycolysis and must be largely reused for the synthesis of plasma glycoproteins and other N –acetylglucosamine–containing macromolecules.
Role of Microsomal Prostaglandin E Synthase 1 in the Kidney
Authors: Helene Francois, Carie Facemire, Anil Kumar, Laurent Audoly, Beverly Koller, Thomas Coffman
Journal: Journal of the American Society of Nephrology (2007)

Prostaglandin E(2) (PGE(2)) is one of the most ubiquitous prostanoids in the kidney, where it may influence a wide range of physiologic functions. PGE(2) is generated through enzymatic metabolism of prostanoid endoperoxides by specific PGE synthases (PGES). Several putative PGES have been identified and cloned, including the membrane-associated, inducible microsomal PGES1 (mPGES1), which is expressed in the kidney. To evaluate the physiologic role of mPGES1 in the kidney, mice with targeted disruption of mPges1 gene were studied, with a focus on responses where PGE(2) has been implicated, including urinary concentration, regulation of blood pressure, and response to a loop diuretic. The absence of mPGES1 was associated with a 50% decrease in basal excretion of PGE(2) in urine (P < 0.001). In female but not male mPGES1-deficient mice, there was a reciprocal increase in basal excretion of other prostanoids. Nonetheless, urinary osmolalities were similar in mPges1(+/+) and mPges1(-/-) mice at baseline and after 12 h of water deprivation. Likewise, there were no differences in blood pressure between mPGES1-deficient and wild-type mice on control or high- or low-salt diets. The furosemide-induced increase in urinary PGE(2) excretion that was seen in wild-type mice was attenuated in mPGES1-deficient mice. However, furosemide-associated diuresis was reduced only in male, not female, mPGES1-deficient mice. Stimulation of renin by furosemide was not affected by mPGES1 deficiency. These data suggest that mPGES1 contributes to basal synthesis of PGE(2), but there are other pathways that lead to renal PGE(2) synthesis. Moreover, there are significant gender differences in physiologic contributions of mPGES1 to control kidney function.
Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT)
Authors: Brunangelo Falini, Enrico Tiacci, Alessandra Pucciarini, Barbara Bigerna, Julia Kurth, Georgia Hatzivassiliou, Sara Droetto, Barbara Verducci Galletti, Marcello Gambacorta, Attilio Orazi, Laura Pasqualucci, Ira Miller, Ralf Küppers, Riccardo Dalla-Favera, Giorgio Cattoretti
Journal: Blood (2003)
Phase I and Clinical Pharmacological Evaluation of Aphidicolin Glycinate
Authors: C. Sessa, M. Zucchetti, E. Davoli, R. Califano, F. Cavalli, S. Frustaci, L. Gumbrell, A. Sulkes, B. Winograd, M. D'Incalci
Journal: JNCI Journal of the National Cancer Institute (1991)

The toxicity profile and the pharmacominetics of ashidicolin glycinate, a water-soluble; ilogue of aphidicolin, have been evaluated in two consecutive phase I clinical studies. In the first study, aphidicolin glycinate was given by 1-hour infusion on for 5 consecutive days, every 3 weeks (daily x 5 study); in the second study, which was planned on the basis of the pharmacokinetic information obtained in the previous study, the drug was given by 24-hour continuous infusion. Treatment was repeated every 3 weeks. In the daily x 5 study, the daily dose was escalated from 12 mg/m 2 to the maximum tolerated dose of 2250 mg/m 2 . Local toxicity was dose limiting. Elimination half-life was 2 ± 0.2 hours (mean ± SE), with aphidicolin being undetectable 6–8 hours after the end of the infusion. In the 24-hour continuous-infusion study, the dose was escalated from 435 mg/m 2 to the maximum tolerated dose of 4500 mg/m 2 . Local toxicity was dose limiting, while other toxic effects were absent. The experimentally determined concentrations at the steady state were in agreement with those predicted on the basis of the available pharmacokinetic data. The targeted concentration at the steady state of 3 μg/mL was achieved at doses greater than or equal to 3000 mg/m 2 . Twenty-four-hour continuous infusion is the recommended schedule for clinical evaluations of aphidicolin glycinate as the synchronizing agent or in combination with cisplatin. [J Natl Cancer Inst 83: 1160–1164,1991]
Arthritis and coeliac disease.
Authors: J T Bourne, P Kumar, E C Huskisson, R Mageed, D J Unsworth, J A Wojtulewski
Journal: Annals of the Rheumatic Diseases (1985)

We report six patients with coeliac disease in whom arthritis was prominent at diagnosis and who improved with dietary therapy. Joint pain preceded diagnosis by up to three years in five patients and 15 years in one patient. Joints most commonly involved were lumbar spine, hips, and knees (four cases). In three cases there were no bowel symptoms. All were seronegative. X-rays were abnormal in two cases. HLA-type A1, B8, DR3 was present in five and B27 in two patients. Circulating immune complexes showed no consistent pattern before or after treatment. Coeliac disease was diagnosed in all patients by jejunal biopsy, and joint symptoms in all responded to a gluten-free diet. Gluten challenge (for up to three weeks) failed to provoke arthritis in three patients tested. In a separate study of 160 treated coeliac patients attending regular follow up no arthritis attributable to coeliac disease and no ankylosing spondylitis was identified, though in a control group of 100 patients with Crohn9s disease the expected incidence of seronegative polyarthritis (23%) and ankylosing spondylitis (5%) was found (p less than 0.01). Arthritis appears to be a rare manifestation of coeliac disease. This relationship may provide important clues to the role of gastrointestinal antigens in rheumatic diseases.
Myocardial redox state during coronary artery bypass grafting assessed with microdialysis
Authors: Ludger Bahlmann, Martin Misfeld, Stephan Klaus, Alexander Leptien, Matthias Heringlake, Peter Schmucker, Hans-Hinrich Sievers, Urban Ungerstedt, Ernst-Guenther Kraatz
Journal: Intensive Care Medicine (2004)
Educational Disparities in Mortality Among Adults With Diabetes in the U.S.
Authors: Rosemary Dray-Spira, Tiffany L. Gary-Webb, Frederick L. Brancati
Journal: Diabetes Care (2010)

OBJECTIVE To measure relative and absolute educational disparities in mortality among U.S. adults with diabetes and to compare their magnitude with disparities observed within the nondiabetic population. RESEARCH DESIGN AND METHODS A total of 85,867 individuals (5,007 with diabetes), aged 35–84 years, who participated in the National Health Interview Survey from 1986 to 1996 were followed for mortality through 31 December 2002. Relative and absolute educational disparities in all-cause, cardiovascular disease (CVD), and non-CVD mortality were measured. RESULTS In relative terms, the risk of all-cause mortality was 28% higher in diabetic adults with the lowest versus the highest position on the educational scale (relative index of inequality 1.28 [95% CI 1.08–1.53]). This inverse relationship reflected marked disparities in CVD mortality and was found in all age, sex, and race/ethnicity groups except Hispanics. Although substantial, this relative educational gradient in mortality among adults with diabetes was smaller than in the nondiabetic population. In absolute terms, diabetic adults with the lowest position on the educational scale suffered 503 excess deaths per 10,000 person-years of follow-up compared with those with the highest position. These absolute disparities were stronger than in the nondiabetic population. The results were even more striking for CVD mortality. CONCLUSIONS The risk of mortality differs substantially according to educational level among individuals with diabetes in the U.S. Although relative educational disparities in mortality are weaker in adults with versus without diabetes, their absolute impact is greater and translates into a major mortality burden.
Effects of T cell depletion in radiation bone marrow chimeras. II. Requirement for allogeneic T cells in the reconstituting bone marrow inoculum for subsequent resistance to breaking of tolerance.
Authors: M Sykes, M A Sheard, D H Sachs
Journal: The Journal of Experimental Medicine (1988)

The ability of normal recipient-type lymphocytes to break tolerance in long-term allogenic radiation chimeras has been investigated. Reconstitution of lethally irradiated mice with a mixture of syngeneic and allogeneic T cell-depleted (TCD) bone marrow (BM) has previously been shown to lead to mixed chimerism and permanent, specific tolerance to donor and host alloantigen (3-5). If allogeneic T cells are not depleted from the reconstituting inoculum, complete allogeneic chimerism results; however, no clinical evidence for GVHD is observed, presumably due to the protective effect provided by syngeneic TCD BM. This model has now been used to study the effects of allogenic T cells administered in reconstituting BM inocula on stability of long-term tolerance. We have attempted to break tolerance in long-term chimeras originally reconstituted with TCD or non-TCD BM by challenging them with inocula containing normal, nontolerant recipient strain lymphocytes. tolerance was broken with remarkable ease in recipients of mixed marrow inocula in which both original BM components were TCD. In contrast, tolerance in chimeras originally reconstituted with non-TCD allogeneic BM was not affected by such inocula. Susceptibility to loss of chimerism and tolerance was not related to initial levels of chimerism per se, but rather to T cell depletion of allogeneic BM, since chimeras reconstituted with TCD allogeneic BM alone (mean level of allogeneic chimerism 98%) were as susceptible as mixed chimeras to the tolerance-breaking effects of such inocula. The possible contribution of GVH reactivity to this resistance was investigated using an F1 into parent strain combination. In these animals, the use of non-TCD F1 BM inocula for reconstitution did not lead to resistance to the tolerance-breaking effects of recipient strain splenocytes. These results suggest that the ability of T cells in allogeneic BM inocula to confer resistance to late graft failure may be related to their graft-vs.-host reactivity, even in situations in which they do not cause clinical GVHD. These findings may have relevance to the mechanism whereby T cell depletion of allogeneic BM leads to an increased incidence of late graft failure in clinical BM transplantation situations.
Human Chorionic Gonadotropin and Rat Mammary Cancer Prevention
Authors: I. H. Russo, M. Koszalka, J. Russo
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Human Chorionic Gonadotropin and Rat Mammary Cancer Prevention Get access I. H. Russo, I. H. Russo * Department of Pathology, Michigan Cancer FoundationDetroit, Mich * Correspondence to: Irma H. Russo, M.D., Department of Pathology, Michigan Cancer Foundation, 110 E. Warren Ave., Detroit, MI 48201. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Koszalka, M. Koszalka Department of Pathology, Michigan Cancer FoundationDetroit, Mich Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Russo J. Russo Department of Pathology, Michigan Cancer FoundationDetroit, Mich Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 15, 1 August 1990, Pages 1286–1289, https://doi.org/10.1093/jnci/82.15.1286 Published: 01 August 1990 Article history Received: 19 March 1990 Revision received: 16 May 1990 Accepted: 24 May 1990 Published: 01 August 1990
Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity
Authors: Gustavo del Real, Sonia Jiménez-Baranda, Emilia Mira, Rosa Ana Lacalle, Pilar Lucas, Concepción Gómez-Moutón, Marta Alegret, Jose María Peña, Manuel Rodríguez-Zapata, Melchor Alvarez-Mon, Carlos Martínez-A., Santos Mañes
Journal: The Journal of Experimental Medicine (2004)

Human immunodeficiency virus (HIV)-1 infectivity requires actin-dependent clustering of host lipid raft–associated receptors, a process that might be linked to Rho guanosine triphosphatase (GTPase) activation. Rho GTPase activity can be negatively regulated by statins, a family of drugs used to treat hypercholesterolemia in man. Statins mediate inhibition of Rho GTPases by impeding prenylation of small G proteins through blockade of 3-hydroxy-3-methylglutaryl coenzyme A reductase. We show that statins decreased viral load and increased CD4+ cell counts in acute infection models and in chronically HIV-1–infected patients. Viral entry and exit was reduced in statin-treated cells, and inhibition was blocked by the addition of l-mevalonate or of geranylgeranylpyrophosphate, but not by cholesterol. Cell treatment with a geranylgeranyl transferase inhibitor, but not a farnesyl transferase inhibitor, specifically inhibited entry of HIV-1–pseudotyped viruses. Statins blocked Rho-A activation induced by HIV-1 binding to target cells, and expression of the dominant negative mutant RhoN19 inhibited HIV-1 envelope fusion with target cell membranes, reducing cell infection rates. We suggest that statins have direct anti–HIV-1 effects by targeting Rho.
An unique case of primary pulmonary cryptococcosis with extensive chest wall invasion
Authors: S Mitsuoka
Journal: Thorax (2004)

An abnormality was found on the chest radiograph of a 56 year old man during a medical check up. Three months later the bloody sputum and left chest pain were aggravated; the left chest was swollen and pain increased and the patient was admitted a month later. At admission the chest radiograph revealed a left upper lobe mass and a chest CT scan showed extension into the chest wall (fig 1A and B). There …
Breast Cancer Risk Reduction, Version 2.2015
Authors: Therese B. Bevers, John H. Ward, Banu K. Arun, Graham A. Colditz, Kenneth H. Cowan, Mary B. Daly, Judy E. Garber, Mary L. Gemignani, William J. Gradishar, Judith A. Jordan, Larissa A. Korde, Nicole Kounalakis, Helen Krontiras, Shicha Kumar, Allison Kurian, Christine Laronga, Rachel M. Layman, Loretta S. Loftus, Martin C. Mahoney, Sofia D. Merajver, Ingrid M. Meszoely, Joanne Mortimer, Lisa Newman, Elizabeth Pritchard, Sandhya Pruthi, Victoria Seewaldt, Michelle C. Specht, Kala Visvanathan, Anne Wallace, Mary Ann Bergman, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2015)

Breast cancer is the most frequently diagnosed malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. To assist women who are at increased risk of developing breast cancer and their physicians in the application of individualized strategies to reduce breast cancer risk, NCCN has developed these guidelines for breast cancer risk reduction.
Mechanisms of Intermittent Ventricular Bigeminy
Authors: R. LANGENDORF, A. PICK
Journal: Circulation (1955)

In a previous report dealing with intermittent ventricular bigeminy due to ventricular premature systoles with fixed coupling in the presence of a grossly irregular dominant pacemaker, it was shown that the appearance and disappearance of the ectopic beats were dependent upon the length of the ventricular cycle ("rule of bigeminy"). In the present report, dealing with ventricular premature systoles with varying coupling in the presence of a regular dominant rhythm, the mechanism of ectopic impulse formation is shown to be either parasystole or re-entry, and the intermittence of bigeminy is due to simple interference or to a disturbance in conduction of a parasystolic or of a re-entrant impulse. Intermittent parasystole is illustrated and presented as a possible link between the two fundamental mechanisms of parasystole and re-entry.
A BRCA1-mutation associated DNA methylation signature in blood cells predicts sporadic breast cancer incidence and survival
Authors: Shahzia Anjum, Evangelia-Ourania Fourkala, Michal Zikan, Andrew Wong, Aleksandra Gentry-Maharaj, Allison Jones, Rebecca Hardy, David Cibula, Diana Kuh, Ian J Jacobs, Andrew E Teschendorff, Usha Menon, Martin Widschwendter
Journal: Genome Medicine (2014)

BRCA1 mutation carriers have an 85% risk of developing breast cancer but the risk of developing non-hereditary breast cancer is difficult to assess. Our objective is to test whether a DNA methylation (DNAme) signature derived from BRCA1 mutation carriers is able to predict non-hereditary breast cancer.In a case/control setting (72 BRCA1 mutation carriers and 72 BRCA1/2 wild type controls) blood cell DNA samples were profiled on the Illumina 27 k methylation array. Using the Elastic Net classification algorithm, a BRCA1-mutation DNAme signature was derived and tested in two cohorts: (1) The NSHD (19 breast cancers developed within 12 years after sample donation and 77 controls) and (2) the UKCTOCS trial (119 oestrogen receptor positive breast cancers developed within 5 years after sample donation and 122 controls).We found that our blood-based BRCA1-mutation DNAme signature applied to blood cell DNA from women in the NSHD resulted in a receiver operating characteristics (ROC) area under the curve (AUC) of 0.65 (95% CI 0.51 to 0.78, P = 0.02) which did not validate in buccal cells from the same individuals. Applying the signature in blood DNA from UKCTOCS volunteers resulted in AUC of 0.57 (95% CI 0.50 to 0.64; P = 0.03) and is independent of family history or any other known risk factors. Importantly the BRCA1-mutation DNAme signature was able to predict breast cancer mortality (AUC = 0.67; 95% CI 0.51 to 0.83; P = 0.02). We also found that the 1,074 CpGs which are hypermethylated in BRCA1 mutation carriers are significantly enriched for stem cell polycomb group target genes (P <10(-20)).A DNAme signature derived from BRCA1 carriers is able to predict breast cancer risk and death years in advance of diagnosis. Future studies may need to focus on DNAme profiles in epithelial cells in order to reach the AUC thresholds required of preventative measures or early detection strategies.
The BTB-ZF transcription factor Zbtb20 is driven by Irf4 to promote plasma cell differentiation and longevity
Authors: Stéphane Chevrier, Dianne Emslie, Wei Shi, Tobias Kratina, Cameron Wellard, Alexander Karnowski, Erdem Erikci, Gordon K. Smyth, Kamal Chowdhury, David Tarlinton, Lynn M. Corcoran
Journal: The Journal of Experimental Medicine (2014)

The transcriptional network regulating antibody-secreting cell (ASC) differentiation has been extensively studied, but our current understanding is limited. The mechanisms of action of known “master” regulators are still unclear, while the participation of new factors is being revealed. Here, we identify Zbtb20, a Bcl6 homologue, as a novel regulator of late B cell development. Within the B cell lineage, Zbtb20 is specifically expressed in B1 and germinal center B cells and peaks in long-lived bone marrow (BM) ASCs. Unlike Bcl6, an inhibitor of ASC differentiation, ectopic Zbtb20 expression in primary B cells facilitates terminal B cell differentiation to ASCs. In plasma cell lines, Zbtb20 induces cell survival and blocks cell cycle progression. Immunized Zbtb20-deficient mice exhibit curtailed humoral responses and accelerated loss of antigen-specific plasma cells, specifically from the BM pool. Strikingly, Zbtb20 induction does not require Blimp1 but depends directly on Irf4, acting at a newly identified Zbtb20 promoter in ASCs. These results identify Zbtb20 as an important player in late B cell differentiation and provide new insights into this complex process.
THE PROBLEM OF THE SIGNIFICANCE OF THE INCLUSION BODIES FOUND IN THE SALIVARY GLANDS OF INFANTS, AND THE OCCURRENCE OF INCLUSION BODIES IN THE SUBMAXILLARY GLANDS OF HAMSTERS, WHITE MICE, AND WILD RATS (PEIPING)
Authors: Ann G. Kuttner, Shao-Hsun Wang
Journal: The Journal of Experimental Medicine (1934)

1. Acidophilic intranuclear inclusion bodies occur in the salivary glands of Chinese infants dying from miscellaneous causes. The lesion is similar to that previously described in infants in Europe and America. 2. Attempts to prove that this lesion is due to an infectious agent by its production in animals have been unsuccessful. 3. Acidophilic intranuclear inclusion bodies have been found in the submaxillary glands of hamsters, white mice, and wild rats. 4. Evidence is presented to show that the lesion in hamsters, white mice, and wild rats is due to a virus, which is specific for each species, being transmissible to normal individuals of this breed, and which is very similar to the submaxillary gland virus of guinea pigs.