tbuckley/cabot-search huggingface dataset:
Poisoning by Organic Phosphorus Insecticides
Authors: P. L. Bidstrup
Journal: BMJ (1950)

<h3>Abstract</h3> <b>Objectives</b>: To determine prevalence of rectal bleeding in the community and to examine factors that lead some patients to consult their general practitioner about rectal bleeding while others do not. <b>Design</b>: Questionnaire survey followed by semistructured interviews of sample of respondents with rectal bleeding. <b>Setting</b>: Two general practices on Tyneside. <b>Subjects</b>: 2000 adult patients registered with the general practices were sent a validated questionnaire. Respondents with rectal bleeding were divided into consulters and non-consulters, and 30 patients from each group (matched for age, sex, and characteristics of bleeding) were interviewed. <b>Main outcome measures</b>: Prevalence of rectal bleeding, proportion of subjects with rectal bleeding who sought medical advice, and reasons for consulting or not consulting a doctor about rectal bleeding. <b>Results</b>: 287 of the 1200 respondents to the questionnaire had noticed rectal bleeding at some time in their lives, and 231 had noticed it within previous 12 months. Only 118 (41%) of all respondents with rectal bleeding had ever sought medical advice for the problem. Those aged over 60 were most likely to have consulted, as were those who reported blood mixed with their stools. Main difference between those who had sought medical advice and those who had not was that consulters were more likely than non-consulters to perceive their symptoms as serious. <b>Conclusions</b>: Although rectal bleeding is common, only minority of patients seek medical advice for their bleeding. Perception of seriousness of symptoms seems to be most important factor in deciding whether to consult a doctor for rectal bleeding.
The Effects of Taurolidine, a Novel Antineoplastic Agent, on Human Malignant Mesothelioma
Authors: Linda Nici, Barbara Monfils, Paul Calabresi
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Malignant mesothelioma (MM) is a cancer with uniformly poor responses to current therapeutic regimens. This study evaluates whether taurolidine, a novel antineoplastic agent, is effective against human MM cell lines and a murine model of human MM. Experimental Design: Cell growth inhibition and viability assays were performed on REN, LRK, and H28 cell lines after 24–72-h exposure to 0–200 μm taurolidine. Cell cycle analysis with annexin-V binding, terminal deoxynucleotidyl transferase-mediated nick end labeling assay, electron microscopy, and response to the general caspase inhibitor z-VAD-fmk were performed on MM cell lines after 24–72-h exposure to 50–150 μm taurolidine. Athymic mice were given i.p. injections of 20 × 106 REN cells, followed by i.p. taurolidine (17.5 or 20 mg), 3 days/week for up to 3 weeks. Tumors were assessed at day 30. All statistical tests were two-sided. Results: A 72-h exposure of MM cells to taurolidine showed IC50 of 28–42.7 μm and 50% viability at 49.8–135 μm. Annexin V assay for apoptosis revealed significant increases in annexin binding after 24–72-h exposure to 50–150 μm taurolidine (P &amp;lt; 0.05), which was significantly inhibited by z-VAD (P &amp;lt; 0.05). MM cells exposed to 50–150 μm taurolidine for 24–72 h showed terminal deoxynucleotidyl transferase-mediated nick end labeling staining consistent with apoptosis, as well as structural evidence of apoptosis via electron microscopy. In vivo, there were significant tumor reductions (62 to &amp;gt;99% reduction) for all dosage regimens compared with untreated controls (P &amp;lt; 0.001). In addition, all control animals exhibited ascites and diaphragmatic tumors while treated animals did not. Conclusions: Taurolidine has significant antineoplastic activity against MM in vitro and in vivo, in part, due to tumor cell apoptosis. These findings warrant further study for potential clinical usefulness.
Effect of Oral Androstenedione on Serum Testosterone and Adaptations to Resistance Training in Young Men
Authors: D S King, R L Sharp, M D Vukovich, G A Brown, T A Reifenrath, N L Uhl, K A Parsons
Journal: JAMA (1999)

Androstenedione, a precursor to testosterone, is marketed to increase blood testosterone concentrations as a natural alternative to anabolic steroid use. However, whether androstenedione actually increases blood testosterone levels or produces anabolic androgenic effects is not known.To determine if short- and long-term oral androstenedione supplementation in men increases serum testosterone levels and skeletal muscle fiber size and strength and to examine its effect on blood lipids and markers of liver function.Eight-week randomized controlled trial conducted between February and June 1998.Thirty healthy, normotestosterogenic men (aged 19-29 years) not taking any nutritional supplements or androgenic-anabolic steroids or engaged in resistance training.Twenty subjects performed 8 weeks of whole-body resistance training. During weeks 1, 2, 4, 5, 7, and 8, the men were randomized to either androstenedione, 300 mg/d (n = 10), or placebo (n = 10). The effect of a single 100-mg androstenedione dose on serum testosterone and estrogen concentrations was determined in 10 men.Changes in serum testosterone and estrogen concentrations, muscle strength, muscle fiber cross-sectional area, body composition, blood lipids, and liver transaminase activities based on assessments before and after short- and long-term androstenedione administration.Serum free and total testosterone concentrations were not affected by short- or long-term androstenedione administration. Serum estradiol concentration (mean [SEM]) was higher (P<.05) in the androstenedione group after 2 (310 [20] pmol/L), 5 (300 [30] pmol/L), and 8 (280 [20] pmol/L) weeks compared with presupplementation values (220 [20] pmol/L). The serum estrone concentration was significantly higher (P<.05) after 2 (153 [12] pmol/L) and 5 (142 [15] pmol/L) weeks of androstenedione supplementation compared with baseline (106 [11] pmol/L). Knee extension strength increased significantly (P<.05) and similarly in the placebo (770 [55] N vs 1095 [52] N) and androstenedione (717 [46] N vs 1024 [57] N) groups. The increase of the mean cross-sectional area of type 2 muscle fibers was also similar in androstenedione (4703 [471] vs 5307 [604] mm2; P<.05) and placebo (5271 [485] vs 5728 [451] mm2; P<.05) groups. The significant (P<.05) increases in lean body mass and decreases in fat mass were also not different in the androstenedione and placebo groups. In the androstenedione group, the serum high-density lipoprotein cholesterol concentration was reduced after 2 weeks (1.09 [0.08] mmol/L [42 (3) mg/dL] vs 0.96 [0.08] mmol/L [37 (3) mg/dL]; P<.05) and remained low after 5 and 8 weeks of training and supplementation.Androstenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptations to resistance training in normotestosterogenic young men and may result in adverse health consequences.
Mycobacterial virulence. Virulent strains of Mycobacteria tuberculosis have faster in vivo doubling times and are better equipped to resist growth-inhibiting functions of macrophages in the presence and absence of specific immunity.
Authors: R J North, A A Izzo
Journal: The Journal of Experimental Medicine (1993)

The kinetics of growth of two virulent strains of mycobacteria (M. tuberculosis Erdman and M. tuberculosis H37Rv) and two attenuated strains (M. tuberculosis H37Ra and M. bovis Bacillus Calmette-Guerin [BCG]) were studied in the lungs, livers, spleens, and kidneys of severe combined immunodeficient (SCID) mice and of their coisogenic CB-17 immunocompetent counterparts. It was found, in keeping with the findings of earlier investigators (Pierce, C. H., R. J. Dubos, and W. B. Schaefer. 1953. J. Exp. Med. 97:189.), that in immunocompetent mice, virulent organisms grew progressively only in the lungs, whereas the growth of attenuated organisms was controlled in all organs. In SCID mice, in contrast, virulent mycobacteria grew rapidly and progressively in all organs, as did BCG, although at a slower rate. However, H37Ra failed to grow progressively in any organs of SCID mice, unless the mice were treated with hydrocortisone. In fact, hydrocortisone treatment enabled virulent, as well as attenuated, organisms to grow strikingly more rapidly in all organs of SCID mice and in all organs of CB-17 mice. A histological study showed that in SCID mice, multiplication of mycobacteria in the liver occurs in the cytoplasm of macrophages in granulomas and presumably in macrophages in other organs. It is suggested, therefore, that the macrophages of SCID mice possess a glucocorticoid-sensitive mycobacterial mechanism that prevents virulent and avirulent mycobacteria from expressing their true minimal doubling times. In the absence of this mechanism in the lungs of hydrocortisone-treated SCID mice, the doubling times of Erdman, H37Rv, BCG, and H37Ra were 17.7, 17.4, 44.6, and 98.6 h, respectively. The possible importance of a rapid multiplication rate for mycobacterial virulence is discussed.
Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers
Authors: Gunda Herberth, Mario Bauer, Michaela Gasch, Denise Hinz, Stefan Röder, Sven Olek, Tibor Kohajda, Ulrike Rolle-Kampczyk, Martin von Bergen, Ulrich Sack, Michael Borte, Irina Lehmann
Journal: Journal of Allergy and Clinical Immunology (2013)
CD43 Regulation of T Cell Activation Is Not through Steric Inhibition of T Cell–APC Interactions but through an Intracellular Mechanism
Authors: Jiankun Tong, Eric J. Allenspach, Stephenie M. Takahashi, Purvi D. Mody, Chan Park, Janis K. Burkhardt, Anne I. Sperling
Journal: The Journal of Experimental Medicine (2004)

CD43 is a large heavily glycosylated protein highly expressed on T cells and actively excluded from the immunological synapse through interactions with ezrin-radixin-moesin proteins. Due to its size and charge, it has been proposed that the CD43 ectodomain acts as a physical barrier to T cell–APC interactions. We have addressed this hypothesis by studying the effect of reconstituting CD43 mutants into the hyperproliferative CD43−/− T cells. Reintroduction of full-length CD43 reversed the CD43−/− T cell hyperproliferation. Interestingly, despite the lack of exclusion from the interaction site, a mutant containing the CD43 ectodomain on a glycosylphosphatidylinositol linkage was ineffective. Additionally, T cell–APC conjugate formation was not affected by this ectodomain-only construct. In contrast, CD43−/− T cell hyperproliferation was reversed by an intracellular-only CD43 fused to the small ectodomain of hCD16. Mutation of this intracellular-only CD43 such that it could not move from the T cell–APC contact site had no further affect on proliferation than the moveable CD43 but did dramatically reduce interleukin-2 production. Thus, the exclusion of the CD43 intracellular region from the immunological synapse is required for CD43 regulation of interleukin-2 production, but the presence of the cytoplasmic tail, independent of its location, is sufficient to reverse CD43−/− T cell hyperproliferation.
HMG-CoA reductase inhibitor attenuates experimental autoimmune myocarditis through inhibition of T cell activation
Authors: R AZUMA, J SUZUKI, M OGAWA, H FUTAMATSU, N KOGA, Y ONAI, H KOSUGE, M ISOBE
Journal: Cardiovascular Research (2004)

Objective: This study tested the hypothesis that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor affects T cell-mediated autoimmunity through inhibition of nuclear factor-κB (NFκB) and reduces the severity of experimental autoimmune myocarditis (EAM).
Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial
Authors: J Sulo, P Chimpeni, J Hatcher, JG Kublin, CV Plowe, ME Molyneux, K Marsh, TE Taylor, WM Watkins, PA Winstanley
Journal: The Lancet (2002)
Generation of hematopoietic repopulating cells from human embryonic stem cells independent of ectopic<i>HOXB4</i>expression
Authors: Lisheng Wang, Pablo Menendez, Farbod Shojaei, Li Li, Frederick Mazurier, John E. Dick, Chantal Cerdan, Krysta Levac, Mickie Bhatia
Journal: The Journal of Experimental Medicine (2005)

Despite the need for alternative sources of human hematopoietic stem cells (HSCs), the functional capacity of hematopoietic cells generated from human embryonic stem cells (hESCs) has yet to be evaluated and compared with adult sources. Here, we report that somatic and hESC-derived hematopoietic cells have similar phenotype and in vitro clonogenic progenitor activity. However, in contrast with somatic cells, hESC-derived hematopoietic cells failed to reconstitute intravenously transplanted recipient mice because of cellular aggregation causing fatal emboli formation. Direct femoral injection allowed recipient survival and resulted in multilineage hematopoietic repopulation, providing direct evidence of HSC function. However, hESC-derived HSCs had limited proliferative and migratory capacity compared with somatic HSCs that correlated with a distinct gene expression pattern of hESC-derived hematopoietic cells that included homeobox (HOX) A and B gene clusters. Ectopic expression of HOXB4 had no effect on repopulating capacity of hESC-derived cells. We suggest that limitations in the ability of hESC-derived HSCs to activate a molecular program similar to somatic HSCs may contribute to their atypical in vivo behavior. Our study demonstrates that HSCs can be derived from hESCs and provides an in vivo system and molecular foundation to evaluate strategies for the generation of clinically transplantable HSC from hESC lines.
ADENO-ASSOCIATED SATELLITE VIRUS INTERFERENCE WITH THE REPLICATION OF ITS HELPER ADENOVIRUS
Authors: Wade P. Parks, Anna M. Casazza, Judith Alcott, Joseph L. Melnick
Journal: The Journal of Experimental Medicine (1968)

Adeno-associated satellite virus type 4 interferes with the replication of its helper adenovirus. No interferon-like soluble substance could be detected in satellite-infected cultures and other DNA- and RNA-containing viruses were not inhibited by coinfection with satellite virus under conditions which reduced adenovirus yields by more than 90% in monkey cells. Altering the concentration of adenovirus in the presence of constant amounts of satellite resulted in a constant degree of interference over a wide range of adenovirus inocula and suggested that adenovirus concentration was not a significant factor in the observed interference. The interference with adenovirus replication was abolished by pretreating satellite preparations with specific antiserum, ultraviolet light or heating at 80 degrees C for 30 min. This suggested that infectious satellite virus mediated the interference. Satellite virus concentration was found to be a determinant of interference and studies indicated that the amount of interference with adenovirus was directly proportional to the concentration of satellite virus. 8 hr after adenovirus infection, the replication of adenovirus was no longer sensitive to satellite interference. This was true even though the satellite virus was enhanced as effectively as if the cells were infected simultaneously with both viruses. Interference with adenovirus infectivity was accompanied by reduced yields of complement-fixing antigen and of virus particles which suggested that satellite virus interfered with the formation and not the function of adenovirus products. When cells were infected either with adenovirus alone or with adenovirus plus satellite, the same proportion of cells plated as adenovirus infectious centers. However, the number of plaque-forming units of adenovirus formed per cell in the satellite-infected cultures was reduced by approximately 90%, the same magnitude of reduction noted in whole cultures coinfected with satellite and adenovirus. This suggested that all cells infected with the two viruses were producing a reduced quantity of adenovirus.
Extracellular matrix rigidity modulates neuroblastoma cell differentiation and N-myc expression
Authors: Wilbur A Lam, Lizhi Cao, Vaibhavi Umesh, Albert J Keung, Shamik Sen, Sanjay Kumar
Journal: Molecular Cancer (2010)

Abstract Neuroblastoma is a pediatric malignancy characterized by tremendous clinical heterogeneity, in which some tumors are extremely aggressive while others spontaneously differentiate into benign forms. Because the degree of differentiation correlates with prognosis, and because differentiating agents such as retinoic acid (RA) have proven to decrease mortality, much effort has been devoted to identifying critical regulators of neuroblastoma differentiation in the cellular microenvironment, including cues encoded in the extracellular matrix (ECM). While signaling between tumor cells and the ECM is classically regarded to be based purely on biochemical recognition of ECM ligands by specific cellular receptors, a number of recent studies have made it increasingly clear that the biophysical properties of the ECM may also play an important role in this cross-talk. Given that RA-mediated neuroblastoma differentiation is accompanied by profound changes in cell morphology and neurite extension, both of which presumably rely upon mechanotransductive signaling systems, it occurred to us that mechanical cues from the ECM might also influence RA-mediated differentiation, which in turn might regulate clinically-relevant aspects of neuroblastoma biology. In this study, we tested this hypothesis by subjecting a series of neuroblastoma culture models to ECM microenvironments of varying mechanical stiffness and examined the regulatory role of ECM stiffness in proliferation, differentiation, and expression of tumor markers. We find that increasing ECM stiffness enhances neuritogenesis and suppresses cell proliferation. Remarkably, increasing ECM stiffness also reduces expression of N-Myc, a transcription factor involved in multiple aspects of oncogenic proliferation that is used for evaluating prognosis and clinical grading of neuroblastoma. Furthermore, the addition of RA enhances all of these effects for all ECM stiffnesses tested. Together, our data strongly support the notion that the mechanical signals from the cellular microenvironment influence neuroblastoma differentiation and do so synergistically with RA. These observations support further investigation of the role of microenvironmental mechanical signals in neuroblastoma proliferation and differentiation and suggest that pharmacological agents that modulate the underlying mechanotransductive signaling pathways may have a role in neuroblastoma therapy.
Shared Circuitry
Authors: Kory J. Lavine, David M. Ornitz
Journal: Circulation Research (2009)

Ischemic heart disease is the most common cause of heart failure and is among the leading causes of mortality worldwide. Therapies used for the treatment of this disease aim to restore blood flow to severely narrowed or occluded coronary arteries by either catheter-based or surgical means. Although these strategies prove efficacious for many patients, a substantial number of individuals fail to improve following these procedures. Recently, a noninvasive strategy has been proposed, focusing on the use of endogenous growth factors that trigger the growth of new coronary arteries. Using the developing heart as a model, several groups have identified some of the key pathways that not only govern the development of the coronary vascular system but also promote the growth of the adult coronary vasculature. Here, we review the major morphological events and signaling cascades that mediate the formation of the coronary vasculature in the embryo. We further describe the mechanism by which many of these same pathways also regulate the adult coronary vasculature and their potential use in the treatment of ischemic heart disease.
Sphingosine-Induced Apoptosis in Rhabdomyosarcoma Cell Lines Is Dependent on Pre-Mitochondrial Bax Activation and Post-Mitochondrial Caspases
Authors: Darren C. Phillips, Sophie Martin, Belinda T. Doyle, Janet A. Houghton
Journal: Cancer Research (2007)

Abstract Sphingolipids is the collective term ascribed to components of the sphingomyelin cycle. Modulation of the cellular levels of individual sphingolipids can induce a diverse range of cellular responses including apoptosis, proliferation, and cell cycle arrest. We present data showing that rhabdomyosarcoma cell lines, independent of lineage (alveolar rhabdomyosarcoma and embryonal rhabdomyosarcoma), are particularly sensitive to the induction of apoptosis as a result of an elevation in the cellular levels of sphingosine (d-erythro-sphingosine). Sphingosine-mediated apoptosis does not require its metabolism to the related proapoptotic molecule ceramide and is stereospecific because exposure of the rhabdomyosarcoma cell line RD to the l-erythro and dl-threo isoforms of sphingosine did not induce apoptosis. Importantly, for efficient induction of apoptosis, sphingosine required Bax activation and consequential translocation to the mitochondria. This resulted in selective mitochondrial release of cytochrome c and Smac/Diablo but not other mitochondrial related factors (apoptosis-inducing factor, endonuclease G, and HtrA2/Omi). Using small interfering RNA, reduced Bax expression conferred the impaired release of mitochondrial cytochrome c to the cytoplasm following sphingosine exposure, inhibiting the induction of apoptosis. Furthermore, dissipation of the inner mitochondrial membrane potential and enhanced production of reactive oxygen species were not observed. Bax activation and cytochrome c release were independent of caspases; however, caspase-3 and caspase-9 activity distal to the mitochondria was essential for the execution of apoptosis. [Cancer Res 2007;67(2):756–64]
The relationship of vascular injury and myocardial hemorrhage to necrosis after reperfusion.
Authors: M C Fishbein, J Y-Rit, U Lando, K Kanmatsuse, J C Mercier, W Ganz
Journal: Circulation (1980)

Early reperfusion may salvage ischemic myocardium; late reperfusion often intensifies morphologic changes of necrosis and causes hemorrhage. To determine whether hemorrhage after reperfusion increases the extent of myocardial infarction, six closed-chest, anesthetized dogs underwent balloon occlusion of the left anterior descending coronary artery for 5.5 hours, followed by 30 minutes of reflow. Colloidal carbon was injected distal to the balloon before reperfusion to label injured vessels. After sacrifice, the area of myocardial necrosis was measured by planimetry of 1-cm-thick serial slices of left ventricle stained with triphenyl tetrazolium chloride. Areas of hemorrhage and vascular injury were also measured. In all hearts, the extent of hemorrhage and vascular injury was less than the extent of necrosis (10.2 +/- 4.6% vs 19.8 +/- 8.6% [mean +/- SD], p &lt; 0.01). Further, hemorrhage was always within the area of necrosis, primarily in the subendocardial portion. Hemorrhage after reperfusion occurred only in necrotic tissue where carbon labeling indicated severe vascular injury before reperfusion, suggesting that the hemorrhage was the consequence of preexisting microvascular injury, not its cause.
ELIMINATING CREATININE KINASE-MB (CKMB) IN RULING OUT ACUTE MYOCARDIAL INFARCTION (MI) WHEN TROPONIN (TN) IS AVAILABLE CAN LEAD TO SAVING HUNDREDS OF MILLIONS OF HEALTHCARE DOLLARS
Authors: Anitha Raiamanickam. Yuanyuan Zhang, Claudine Jurkovitz, Ruth Aguiar, Xin Xu, Paul Kolm, Angela DiSabatino, William Weintraub, Ehsanur Rahman
Journal: Journal of the American College of Cardiology (2012)