tbuckley/cabot-search huggingface dataset:
Abstract 604: The ginger compound, 6-shogaol, inhibits prostate cancer cell growth through reduced activation of signal transducer and activator of transcription 3 (Stat3)
Authors: Achinto Saha, Eric S. Silver, Jonathan L. Sessler, John DiGiovanni
Journal: Cancer Research (2012)

Abstract Prostate cancer is the most common non-skin neoplasm and second leading cause of death in men in the USA with an estimated 240,890 new cases and 33,720 deaths from this disease in 2011. The risk for developing prostate cancer increases with age and overall 1 in 6 men will be diagnosed with this disease. Despite much recent progress, prostate cancer continues to represent a major cause of cancer-related mortality and morbidity in men. Ginger (Zingiber officinale) has been widely used as a spice, and as a medicinal herb in traditional herbal medicine. It is a natural dietary ingredient with antioxidant, anti-inflammatory, and anticarcinogenic properties. Ginger contains several pungent constituents such as gingerols, shogaols, paradols, and gingerdiols. The shogaols are predominant constituents in the dried ginger. Several studies reported that 6-shogaol has anticancer and anti-inflammatory activity. However the mechanism(s) involved in anticancer effect of 6-shogaol has not been clearly elucidated. In the current study, we found that 6-shogaol inhibited the proliferation of human prostate cancer cells including LNCap, DU145 and PC-3 in a concentration dependent manner. In order to find the mechanism associated with the antiproliferative effect of 6-Shogaol, we performed Western blotting and found that this compound inhibited the constitutive (DU145) and IL-6 (LNCap and DU145) induced phosphorylation of Stat3(Tyr705). 6-shogaol also inhibited constitutive and IL-6 induced phosphorylation of Stat3(Ser727) in both cell lines. It also decreased the level of several Stat3 regulated molecules such as cyclin D1 and survivin. Next we measured the apoptosis inducing activity of 6-shogaol and found that this compound induced apoptosis in LNCap and DU145 cells also in a concentration dependent manner. In order to confirm the mechanism involved in apoptosis induction, we measured the level of various apoptosis markers and found that 6-shogaol induced cleavage of PARP and caspase7 in both LNCap and DU145 cell lines. Quantitative real time PCR data showed that 6-shogaol decreased the mRNA level of Bcl2, CCL5, IL-6, IL-7 and increased the expression of Bax, p21, IRF1 and SOCS1. Collectively, the current data lead us to suggest that 6-shogaol may possess properties for further consideration as a therapeutic and/or chemopreventive agent for human prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 604. doi:1538-7445.AM2012-604
Acute Renal Failure and Pigmentation Due to Phenazopyridine (Pyridium®)
Authors: FILOTEO A. ALANO
Journal: Annals of Internal Medicine (1970)

Two patients developed evidence of acute renal failure after receiving larger than recommended doses of phenazopyridine (Pyridium®) for urinary tract analgesia. Both patients had evidence of preexisting renal disease. The patients developed skin pigmentation, pigmentation of the urine, and highly pigmented casts and crystals in the urine sediment. Both had transient oliguria and impaired renal function. One patient died suddenly from pulmonary embolus: Postmortem examination showed pigmented tubular casts and degenerative and regenerative changes in the epithelial cells of the collecting ducts. The localization of the lesions was similar to that reported in studies of phenazopyridine toxicity. Phenazopyridine should be used with caution and in reduced doses in patients with evidence of renal impairment.
MCL1 is deregulated in subgroups of diffuse large B-cell lymphoma
Authors: S-S Wenzel, M Grau, C Mavis, S Hailfinger, A Wolf, H Madle, G Deeb, B Dörken, M Thome, P Lenz, S Dirnhofer, F J Hernandez-Ilizaliturri, A Tzankov, G Lenz
Journal: Leukemia (2012)
Expression of Slow Skeletal Troponin I in Adult Mouse Heart Helps to Maintain the Left Ventricular Systolic Function During Respiratory Hypercapnia
Authors: Dalia Urboniene, Fernando A.L. Dias, James R. Peña, Lori A. Walker, R. John Solaro, Beata M. Wolska
Journal: Circulation Research (2005)

Compared with the adult, neonatal heart muscle is less sensitive to deactivation by acidic pH. We hypothesized that expression of slow skeletal troponin I (ssTnI), the embryonic isoform, in adult heart would help maintain left ventricular (LV) systolic function during respiratory hypercapnia. We assessed LV function by transthoracic 2D-targeted M-mode and pulsed Doppler echocardiography in transgenic (TG) mice in which cardiac TnI was replaced with ssTnI and in nontransgenic (NTG) littermates. Anesthetized mice were ventilated with either 100% oxygen or 35% CO2 balanced with oxygen. Arterial blood pH with 35% CO2 decreased to the same levels in both groups of animals. In the absence of propranolol, the LV fractional shortening was higher in TG compared with NTG mice throughout most of the experimental protocol. LV diastolic function was impaired in TG compared with NTG mice both at 100% oxygen and 35% CO2 because E-to-A wave ratio of mitral flow was significantly lower, and E-wave deceleration time and LV isovolumic relaxation time were longer in TG compared with NTG mice. When compensatory mechanisms that occur through stimulation of beta-adrenergic receptors during hypercapnia were blocked by continuous perfusion with propranolol, we found that NTG mice died within 3 to 4 minutes after switching to 35% CO2, whereas TG mice survived. Our experiments demonstrate the first evidence that specific replacement of cardiac TnI with ssTnI has a protective effect on the LV systolic function during hypercapnic acidosis in situ.
Lipopolysaccharides prime whole human blood and isolated neutrophils for the increased synthesis of 5-lipoxygenase products by enhancing arachidonic acid availability: involvement of the CD14 antigen.
Authors: M E Surette, R Palmantier, J Gosselin, P Borgeat
Journal: The Journal of Experimental Medicine (1993)

Stimulation of heparinized blood with 1 microM formyl-methionyl-leucyl-phenylalanine (FMLP) resulted in the formation of &amp;lt; 30 pmol/ml plasma of 5-lipoxygenase (5-LO) products. The preincubation of blood with 1 microgram/ml of lipopolysaccharide (LPS) (Escherichia coli 0111-B4) for 30 min before stimulation with FMLP resulted in the accumulation of 250-300 pmol of 5-LO products per ml plasma. The major products detected were leukotriene B4 and (5S)-hydroxy-6,8,11,14-eicosatetraenoic acid which were produced in equivalent amounts. The priming activity was detectable with as little as 1-10 ng LPS per ml blood and was optimal using 1-10 micrograms LPS/ml blood. The priming for 5-LO product synthesis was optimal after 20-30 min of preincubation with LPS and declined at preincubation times &amp;gt; 30 min. The priming effect of LPS was also observed using the complement fragment C5a or interleukin 8 as agonists. Polymorphonuclear leukocytes (PMN) and peripheral blood mononuclear cells accounted for 80 and 20% of the synthesis of 5-LO products, respectively. The ability of LPS to prime isolated PMN was dependent on the presence of plasma and was inhibited by the anti-CD14 antibody IOM2, indicating a CD14-dependent priming mechanism. The priming of whole blood with tumor necrosis factor alpha (TNF-alpha) and LPS was additive and the presence of mononuclear cells did not enhance the ability of LPS to prime PMN, indicating that the priming activity of LPS is independent of LPS-induced TNF-alpha synthesis. The mechanism by which LPS enhance 5-LO product synthesis in PMN was investigated. Treatment of PMN with LPS strongly enhanced the release of arachidonic acid after stimulation with FMLP. The release of arachidonic acid was optimal 2-3 min after stimulation with FMLP, attaining levels 5-15-fold greater than those observed in unprimed cells stimulated with FMLP. These results demonstrate that LPS dramatically increases the ability of blood to generate 5-LO products, and support the putative role of leukotrienes in pathological states involving LPS.
THE CURE OF INGUINAL HERNIA
Authors: A. J. Hull
Journal: BMJ (1917)

548-~~~.DCA J_BAY years ago, and has been built up within the lives of many of us.It lhas opened out a wide prospect and gives promise of revolutionizing medical study.Tlle imnpulse that the work of Harvey gave to Britislh plhysiology is shown by nam-ing those who followed him in the next one hundred years.
Sailing and science: an interdisciplinary perspective
Authors: V Higgins
Journal: British Journal of Sports Medicine (2006)

Edited by Gisela Sjogaard (series editor Jens Bangsbo). Published by Blackwell Publishing, 2001, £17.99, 144 pp, softcover. ISBN 8716123506

A number of papers presented at the Annual European College of Sports Science Conference held in Copenhagen Denmark in1997 are combined to form this book. Sailing was chosen to be the featured sport as …
Gastrointestinal Candida colonisation promotes sensitisation against food antigens by affecting the mucosal barrier in mice
Authors: N Yamaguchi
Journal: Gut (2006)

Controversy still exists as to whether gastrointestinal colonisation by Candida albicans contributes to aggravation of atopic dermatitis. We hypothesised that Candida colonisation promotes food allergy, which is known to contribute to a pathogenic response in atopic dermatitis. We tested this using a recently established murine Candida colonisation model.Candida colonisation in the gastrointestinal tract was established by intragastric inoculation with C albicans in mice fed a synthetic diet. To investigate sensitisation against food antigen, mice were intragastrically administered with ovalbumin every other day for nine weeks, and antiovalbumin antibody titres were measured weekly. To examine gastrointestinal permeation of food antigen, plasma concentrations of ovalbumin were measured following intragastric administration of ovalbumin.Ovalbumin specific IgG and IgE titres were higher in BALB/c mice with Candida colonisation than in normal mice. Gastrointestinal permeation of ovalbumin was enhanced by colonisation in BALB/c mice. Histological examination showed that colonisation promoted infiltration and degranulation of mast cells. Candida colonisation did not enhance ovalbumin permeation in mast cell deficient W/Wv mice but did in congenic littermate control +/+ mice. Reconstitution of mast cells in W/Wv mice by transplantation of bone marrow derived mast cells restored the ability to increase ovalbumin permeation in response to Candida colonisation.These results suggest that gastrointestinal Candida colonisation promotes sensitisation against food antigens, at least partly due to mast cell mediated hyperpermeability in the gastrointestinal mucosa of mice.
Protective Role of Interleukin-10 in Ozone-Induced Pulmonary Inflammation
Authors: Gillian S. Backus, Reuben Howden, Jennifer Fostel, Alison K. Bauer, Hye-Youn Cho, Jacqui Marzec, David B. Peden, Steven R. Kleeberger
Journal: Environmental Health Perspectives (2010)

BackgroundThe mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators.ObjectivesWe investigated the molecular mechanisms underlying interleuken-10 (IL-10)–mediated attenuation of O3-induced pulmonary inflammation in mice.MethodsIl10-deficient (Il10−/−) and wild-type (Il10+/+) mice were exposed to 0.3 ppm O3 or filtered air for 24, 48, or 72 hr. Immediately after exposure, differential cell counts and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also used global mRNA expression analyses of lung tissue with Ingenuity Pathway Analysis to identify patterns of gene expression through which IL-10 modifies O3-induced inflammation.ResultsMean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10−/− mice than in Il10+/+ mice after exposure to O3 at all time points tested. O3-enhanced nuclear NF-κB translocation was elevated in the lungs of Il10−/− compared with Il10+/+ mice. Gene expression analyses revealed several IL-10–dependent and O3-dependent mediators, including macrophage inflammatory protein 2, cathepsin E, and serum amyloid A3.ConclusionsResults indicate that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several genetic targets through which IL-10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O3-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals.
Kinetics of Taurocholate Efflux From Freshly Isolated Suspensions and Primary Cultures of Rat Hepatocytes
Authors: Veerapol Kukongviriyapan, Neill H. Stacey
Journal: Hepatology (1990)

Isolated rat hepatocytes have been advocated as a model to study aspects of mechanism of chemical-induced interference with biliary excretory function. Some technical problems do exist in studying efflux, such as the reuptake of the previously excreted substrate. Another concern is the loss of liver-specific functions in hepatocytes with continuing time in culture. It is important to address such technical aspects and to determine whether the process of efflux is compromised in primary cultures of hepatocytes. In the presence of Na+ the apparent efflux of taurocholate from hepatocytes was shown to be significantly confounded by reuptake of substrate. The unidirectional efflux was best demonstrated in buffer where choline replaced Na+. A comparison of efflux kinetics for cultured cells to those in suspension showed that both apparent affinity for transport carriers and transport capacity were greater in the former. The simple diffusion component for efflux increased with the time in culture, but affinity for transport carriers and transport capacity remained unchanged over 6 to 24 hr. However, it was not possible to determine meaningful kinetic constants after 24 hr in culture because the uptake of taurocholate was so low. Primary cultured hepatocytes may therefore be of limited value in the study of efflux of bile salts in the longer term, mainly because of the inability of cells to take up and accumulate a sufficiently high level of bile salts.
Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology.
Authors: A C van der Wal, A E Becker, C M van der Loos, P K Das
Journal: Circulation (1994)

The study was designed to verify the concept of plaques "at risk" and whether inflammation could play a role in plaque rupture and thrombosis.In 20 patients who had died of acute myocardial infarction, the thrombosed coronary artery was identified and the site of plaque rupture was traced in serial sections. The cellular characteristics of the fibrous cap at the immediate site of rupture were analyzed and compared with the adjacent cap tissue by use of monoclonal antibodies reactive with macrophages, T lymphocytes, and smooth muscle cells. A deep intimal rupture, extending into the lipid core, was encountered in 12 plaques, whereas 8 had superficial erosions only. Ten atherosclerotic plaques had a distinctly attenuated fibrous cap covering a large atheroma, 7 showed a thick fibrocellular cap overlying a lipid pool, and 3 showed a fibrocellular lesion without a clear lipid core. Macrophages, and to a lesser extent T lymphocytes, were the dominant cells at the immediate site of either rupture or superficial erosion in each instance. These sites, moreover, were always characterized by abundant expression of HLA-DR antigens on both inflammatory cells and adjacent smooth muscle cells, suggesting an active inflammatory reaction. In terms of overall cellular composition of the ruptured plaques, the dominant cell types were macrophages and T cells in 11, smooth muscle cells in 3, and mixtures of both in 6.The underlying atherosclerotic plaque morphology in complicated coronary artery lesions causing acute myocardial infarction is heterogeneous with respect to both plaque architecture and cellular composition. However, the immediate site of plaque rupture or erosion is always marked by an inflammatory process. This suggests that inflammation plays a role in destabilizing the fibrous cap tissue and, thus, in enhancing the risk of coronary thrombosis.
Enhanced synthesis of cysteinyl leukotrienes in atopic dermatitis
Authors: J. FAULER, CH. NEUMANN, D. TSIKAS, J.C. FROLICH
Journal: British Journal of Dermatology (1993)

Synthesis of cysteinyl leukotrienes was assessed in patients with atopic dermatitis (AD; n=8) and healthy volunteers (n=8) by measuring urinary excretion of leukotriene E4 (LTE4), the main index metabolite of cysteinyl leukotrienes in man. Using this non‐invasive method we demonstrated a significant (P<0.05) 4.5‐fold increase in excretion of LTE4 compared with healthy volunteers. The identity of LTE4 was unequivocally demonstrated by gas chromatography‐mass spectrometry/mass spectrometry (GC‐MS/MS). LTE4 was routinely measured by radioimmunoassay (RIA), and quantitative measurement of LTE4 by RIA was validated by GC‐MS/MS. There was a linear correlation between LTE4 measured by RIA and by GC‐MS/MS (r=0.994). Tn representative samples, LTE4 was also quantitatively assessed by GC‐MS/MS. In these samples, LTE4 values obtained by GC‐MS/MS differed <10% from those obtained by RIA. The present findings suggest that cysteinyl leukotrienes play a role in AD.
Delayed Onset of Malaria — Implications for Chemoprophylaxis in Travelers
Authors: Eli Schwartz, Monica Parise, Phyllis Kozarsky, Martin Cetron
Journal: New England Journal of Medicine (2003)

Most antimalarial agents used by travelers act on the parasite's blood stage and therefore do not prevent late-onset illness, particularly that due to species that cause relapsing malaria. We examined the magnitude of this problem among Israeli and American travelers.We examined malaria surveillance data from Israel and the United States to determine the traveler's destination, the infecting species, the type of chemoprophylaxis used, and the incubation period.In Israel, from 1994 through 1999, there were 300 cases of malaria among returning travelers in which one species of plasmodium could be identified. In 134 of these cases (44.7 percent), the illness developed more than two months after the traveler's return; nearly all of these cases were due to infection with Plasmodium vivax or P. ovale. In 108 of the 134 cases (80.6 percent), the patient had used an antimalarial regimen according to national guidelines. In the United States, from 1992 through 1998, there were 2822 cases of malaria among travelers in which the cause could be evaluated. Late illness developed in 987 (35.0 percent) of these travelers. The infection was due to P. vivax in 811 travelers, P. ovale in 66, P. falciparum in 59, and P. malariae in 51; 614 (62.2 percent) of those with late-onset illness had appropriately taken an effective antimalarial agent.In more than one third of malaria-infected travelers, the illness developed more than two months after their return. Most of these late-onset illnesses are not prevented by the commonly used and effective blood schizonticides. Agents that act on the liver phase of malaria parasites are needed for more effective prevention of malaria in travelers.
Role of Tissue-Specific Blood Flow and Tissue Recruitment in Insulin-Mediated Glucose Uptake of Human Skeletal Muscle
Authors: Riccardo C. Bonadonna, Maria Pia Saccomani, Stefano Del Prato, Enzo Bonora, Ralph A. DeFronzo, Claudio Cobelli
Journal: Circulation (1998)

Background —Conflicting evidence exists concerning whether insulin-induced vasodilation plays a mechanistic role in the regulation of limb glucose uptake. It can be predicted that if insulin augments blood flow by causing tissue recruitment, this mechanism would enhance limb glucose uptake. Methods and Results —Twenty healthy subjects were studied with the forearm perfusion technique in combination with the euglycemic insulin clamp technique. Ten subjects were studied at physiological insulin concentrations (≈400 pmol/L) and the other 10 at supraphysiological insulin concentrations (≈5600 pmol/L). Four additional subjects underwent a saline control study. Pulse injections of a nonmetabolizable extracellular marker (1-[ 3 H]- l -glucose) were administered into the brachial artery, and its washout curves were measured in one ipsilateral deep forearm vein and used to estimate the extracellular volume of distribution and hence the amount of muscle tissue drained by the deep forearm vein. Both during saline infusion and at physiological levels of hyperinsulinemia we observed no changes in blood flow and/or muscle tissue drained by the deep forearm vein. However, supraphysiological hyperinsulinemia accelerated total forearm blood flow (45.0±1.8 versus 36.5±1.3 mL · min −1 · kg −1 , P &lt;0.01) and increased the amount of muscle tissue drained by the deep forearm vein (305±46 versus 229±32 g, P &lt;0.05). The amount of tissue newly recruited by insulin was strongly correlated to the concomitant increase in tissue glucose uptake ( r =0.789, P &lt;0.01). Conclusions —Acceleration of forearm blood flow mediated by supraphysiological hyperinsulinemia is accompanied by tissue recruitment, which may be a relevant determinant of forearm (muscle) glucose uptake.
Low T-Lymphocyte Ratios in Homosexual Men
Authors: Robert J. Biggar
Journal: JAMA (1984)

To investigate risk factors for immunologic abnormalities among homosexual men, T-lymphocyte helper/suppressor (OKT4/OKT8) ratios were determined in 78 healthy Danish homosexual men. Ratios in 26 men (33%) were low (less than 1.00). Visiting the United States in 1980 to 1981 was a strong (7.7-fold) risk factor for having a ratio less than 1.00. Among nine travelers who visited only once, the risk of having a low ratio increased significantly if the visit had occurred in 1981. A risk of similar magnitude (6.9-fold) was found among the three men who had not been to the United States but who reported homosexual contact with a Danish man who became ill with Kaposi's sarcoma. Risk of low ratios did not correlate with age or years of homosexual activity. Promiscuity was not a significant risk factor, but these men generally had fewer sex partners than that which has been reported from the United States. Neither nitrite inhalant use nor cytomegalovirus antibody (prevalence or titer) was associated with low ratios. These data support the hypothesis that a transmissible biologic agent may be etiologically responsible for the low helper/suppressor ratios in homosexual men.
Adult T-cell lymphoma leukemia in western countries
Authors: Jean Pierre Farcet, Mathieu Kuentz, Chantal Andre, Jean Marc Darves, Félix Reyes, Bernard Dreyfus, Henri Rochant
Journal: American Journal of Hematology (1983)

Abstract A new T‐cell disorder has recently emerged: the so‐called adult T‐cell lymphoma leukemia (ATLL) initially described in Japan. Subsequently, ATLL cases were recognized in patients from the Caribbean. We summarize the clinical and hematological features of 19 published cases from Western countries, in addition to a new case we encountered. The leukemic cells display characteristic morphological features and a T 3 + T 4 + T 8 − T 6 − surface antigenic phenotype. Overall survival is of short duration, but remission could be obtained in our case despite a subsequent relapse in skin and CNS. Geographic clusters of ATLL cases have led to the discovery of the possible role of a new retrovirus, HTLV, in the genesis of this rare malignancy.