tbuckley/cabot-search huggingface dataset:
Maternal Exposure to Polycyclic Aromatic Hydrocarbons and 5’-CpG Methylation of Interferon-γ in Cord White Blood Cells
Authors: Wan-yee Tang, Linda Levin, Glenn Talaska, Yuk Yin Cheung, Julie Herbstman, Deliang Tang, Rachel L Miller, Frederica Perera, Shuk-Mei Ho
Journal: Environmental Health Perspectives (2012)

Maternal factors are implicated in the onset of childhood asthma. Differentiation of naïve CD4+ T lymphocytes into pro-allergic T-helper 2 cells induces interleukin (IL)4 expression and inhibits interferon (IFN)γ expression accompanied by concordant methylation changes in the promoters of these genes. However, it has yet to be established whether maternal exposure to polycyclic aromatic hydrocarbons (PAHs) can alter these gene promoters epigenetically during fetal development.In this study we sought to elucidate the relationship between maternal PAH exposure and promoter methylation status of IFNγ and IL4.We assessed the effects of benzo[a]pyrene (BaP), a representative airborne PAH, on the methylation status of the IFNγ and IL4 promoters in Jurkat cells and two lung adenocarcinoma cell lines, and on gene expression. In addition, we evaluated methylation status of the IFNγ promoter in cord white blood cells from 53 participants in the Columbia Center for Children's Environmental Health cohort. Maternal PAH exposure was estimated by personal air monitoring during pregnancy.In vitro exposure of the cell models to low, noncytotoxic doses (0.1 and 1 nM) of BaP elicited increased promoter hypermethylation and reduced expression of IFNγ, but not IL4. IFNγ promoter methylation in cord white blood cells was associated with maternal PAH exposure in the cohort study subsample.Consistent with the results for the cell lines, maternal exposure to PAHs was associated with hypermethylation of IFNγ in cord blood DNA from cohort children. These findings support a potential role of epigenetics in fetal reprogramming by PAH-induced environmental diseases.
OBSTRUCTIVE SLEEP APNEA AND ATRIAL FIBRILLATION: FINDINGS FROM ORBIT-AF
Authors: Fredrik Holmqvist, Ni Guan, Zhaoyin Zhu, Peter Kowey, Larry Allen, Gregg Fonarow, Elaine Hylek, Kenneth Mahaffey, Paul Chang, DaJuanicia Holmes, Eric Peterson, Jonathan Piccini, Bernard J. Gersh
Journal: Journal of the American College of Cardiology (2014)
History of Ginseng
Authors: Leonard Slazinski
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Although the wellresearched article by Ronald K. Siegel, PhD, "Ginseng Abuse Syndrome: Problems With the Panacea" (241:1614, 1979) described the pharmacologic effects of ginseng adequately, I believe that the history of this herb should be discussed in greater detail, because the health food industry has been active in ascribing and promoting an exotic, novel quality to ginseng that is not deserved. Ginseng has been known in the United States since colonial times. The plant<i>Panax ginseng (Schinseng)</i>grows wild in the forests of many states and from earliest times has been gathered for export, not for home consumption. Daniel Boone was active in the ginseng trade in 1788, and George Washington mentions the gathering of the plant in his diary.<sup>1</sup>All of the US ginseng production, wild or cultivated, was exported to the Orient, and the plant played a large part in opening trade with China.
FDA faces barrage of criticism over plans to assess safety of supplements
Authors: K. Epstein
Journal: BMJ (2012)

<h3>Abstract</h3> Novel biological therapies have revolutionised the management of Rheumatoid Arthritis (RA) but no cure currently exists. Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling, including via secretion of extracellular vesicles (EVs) in the cell secretome. We evaluated the therapeutic potential of MSCs-derived small EVs in an antigen-induced model of arthritis (AIA). EVs isolated from MSCs cultured normoxically (21% O<sub>2</sub>, 5% CO<sub>2</sub>), hypoxically (2% O<sub>2</sub>, 5% CO<sub>2</sub>) or with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed post-arthritis induction through swelling and histopathological analysis of synovial joint structure. Activated CD4+ T cells from healthy mice were cultured with EVs or MSCs to assess deactivation capabilities prior to application of standard EVs <i>in vivo</i> to assess T cell polarisation within the immune response to AIA. All EVs treatments reduced knee-joint swelling whilst only normoxic and pro-inflammatory primed EVs improved histopathological outcomes. In vitro culture with EVs did not achieve T cell deactivation. Polarisation towards CD4+ helper cells expressing IL17a (Th17) was reduced when normoxic and hypoxic EV treatments were applied in vitro. Normoxic EVs applied into the AIA model reduced Th17 polarisation and improved Th17:Treg homeostatic balance. Priming of MSCs in EV production can be applied to alter the therapeutic efficacy however normoxic EVs present the optimal strategy for broad therapeutic benefit. The varied outcomes observed in MSCs priming may promote EVs optimised for therapies targeted for specific therapeutic priorities. EVs present an effective novel technology with potential for cell-free therapeutic translation.
Stabilization of hypoxia inducible factor rather than modulation of collagen metabolism improves cardiac function after acute myocardial infarction in rats
Authors: Sebastian Philipp, Jan Steffen Jürgensen, Jens Fielitz, Wanja M. Bernhardt, Alexander Weidemann, Astrid Schiche, Bernhard Pilz, Rainer Dietz, Vera Regitz‐Zagrosek, Kai‐Uwe Eckardt, Roland Willenbrock
Journal: European Journal of Heart Failure (2006)
A Population Study of Endomyocardial Fibrosis in a Rural Area of Mozambique
Authors: Ana Olga Mocumbi, Maria Beatriz Ferreira, Daniel Sidi, Magdi H. Yacoub
Journal: New England Journal of Medicine (2008)

Endomyocardial fibrosis is the most common restrictive cardiomyopathy worldwide. It has no specific treatment and carries a poor prognosis, since most patients present with advanced heart failure. On the basis of clinical series, regional variations in distribution have been reported within several countries in Africa, Asia, and South America, but large-scale data are lacking on the epidemiologic features and early stages of the disease.We used transthoracic echocardiography to determine the prevalence of endomyocardial fibrosis in a rural area of Mozambique. We screened a random sample of 1063 subjects of all age groups selected by clustering. Major and minor diagnostic criteria were defined, and a severity score was developed and applied. Cases were classified according to the distribution and severity of the lesions in the heart.The estimated overall prevalence of endomyocardial fibrosis was 19.8%, or 211 of 1063 subjects (95% confidence interval [CI], 17.4 to 22.2). The prevalence was highest among persons 10 to 19 years of age (28.1%, or 73 of 260 subjects [95% CI, 22.6 to 33.6]) and was higher among male than among female subjects (23.0% vs. 17.5%, P=0.03). The most common form was biventricular endomyocardial fibrosis (a prevalence of 55.5%, or 117 of 211 subjects [95% CI, 48.8 to 62.2]), followed by right-sided endomyocardial fibrosis (a prevalence of 28.0%, or 59 of 211 subjects [95% CI, 21.9 to 34.1]). Most affected subjects had mild-to-moderate structural and functional echocardiographic abnormalities. Only 48 persons with endomyocardial fibrosis (22.7%) were symptomatic. The frequency of familial occurrence was high.Endomyocardial fibrosis is common in a rural area of Mozambique. By using echocardiography, we were able to detect early, asymptomatic stages of the disease. These findings may aid in the study of the pathogenesis of the disease and in the development of new management strategies.
Homologous-Blood Syndrome during Extracorporeal Circulation in Man
Authors: Robert S. Litwak, Ralph Slonim, B. George Wisoff, Howard L. Gadboys
Journal: New England Journal of Medicine (1963)

IT has previously been demonstrated that circulating blood volume significantly diminishes after perfusion despite careful replacement of all measured blood loss.1 Clinical and experimental evidence has developed implicating large-volume homologous-blood exchange as the cause of both the hypovolemia and the postperfusion hypotension.2 , 3 The magnitude of the volumetric and hemodynamic changes appears to be directly related to the quantity of homologous blood infused. These changes have not been demonstrated experimentally after exchange of autologous blood.3 Separate exchange of the homologous-blood compartments (erythrocytes, plasma and buffy coat) did not eliminate the manifestations of hypotension and isotopic hypovolemia in the laboratory animal. However, . . .
Childhood deaths in Africa: uses and limitations of verbal autopsies
Authors: R.W. Snow, M.T. Winstanley, V.M. Marsh, CRJC. Newton, C. Waruiru, I. Mwangi, P.A. Winstanley, K. Marsh, R.W. Snow, D. Forster, P.A. Winstanley, K. Marsh, J.R.M. Armstrong
Journal: The Lancet (1992)
Interleukin-5 and the posttreatment eosinophilia in patients with onchocerciasis.
Authors: A P Limaye, J S Abrams, J E Silver, K Awadzi, H F Francis, E A Ottesen, T B Nutman
Journal: Journal of Clinical Investigation (1991)

To understand the role of the eosinophilopoietic cytokine IL-5 in humans, the posttreatment eosinophilic response in a group of microfilaria (mf)-positive patients with onchocerciasis (n = 10) was examined before and after treatment with diethylcarbamazine (6 mg/kg for 7 d). Sequential blood samples were assessed at 24 and 1 h before treatment (baseline values), then at frequent intervals over the next 14 d. Symptom scores, skin microfilariae (mf), and peripheral blood eosinophil counts were recorded as a function of time after treatment, and serum levels of IL-5 were quantitated by a highly sensitive (sensitivity greater than or equal to 20 pg/ml) monoclonal-based ELISA. Pretreatment eosinophil counts ranged from 240 to 1,186 eosinophils/microliter (geometric mean, 675), and the mf counts from 10 to 218 per mg skin (geometric mean, 79). After an initial decline in the peripheral eosinophil count to 28 +/- 8% of pretreatment levels at 8 h after beginning treatment, the eosinophil counts steadily increased over the next 2 wk, reaching a maximum at 14 d (257 +/- 38% of pretreatment levels). Serum levels of IL-5 rose sharply from pretreatment levels to a peak of 70.5 +/- 11 pg/ml by 24 h after treatment. Serum IL-5 remained elevated over the next 2-3 d and declined toward baseline by approximately 6 d after treatment, at which time the eosinophil levels were steadily increasing. IL-3 and granulocyte macrophage colony-stimulating factor, two other cytokines implicated in eosinophilopoeisis, were not detectable in the serum at any time before or after treatment. The rise in serum IL-5 before the posttreatment eosinophilia seen in this group of patients with onchocerciasis demonstrates a temporal relationship between IL-5 and the subsequent development of eosinophilia and implicates IL-5 as an important mediator of eosinophilia in humans.
Tetrahydrofurandiol Stimulation of Phospholipase A <sub>2</sub> , Lipoxygenase, and Cyclooxygenase Gene Expression and MCF-7 Human Breast Cancer Cell Proliferation
Authors: Barry M. Markaverich, Jan Crowley, Mary Rodriquez, Kevin Shoulars, Trellis Thompson
Journal: Environmental Health Perspectives (2007)

We characterized an endocrine disruptor from ground corncob bedding material that interferes with male and female sexual behavior and ovarian cyclicity in rats and stimulates estrogen receptor (ER)-positive and ER-negative breast cancer cell proliferation. The agents were identified as an isomeric mixture of tetrahydrofurandiols (THF-diols; 9,12-oxy-10,13-dihydroxy-octadecanoic acid and 10,13-oxy-9,12-dihydroxyoctadecanoic acid). Synthetic THF-diols inhibited rat male and female sexual behavior at oral concentrations of 0.5-1 ppm, and stimulated MCF-7 human breast cancer cell proliferation in vitro.Because THF-diols are derived from lipoxygenase and cyclooxygenase pathways, we suspected that these compounds may regulate cell proliferation by modulating specific enzymatic sites involved in linoleic acid metabolism including phospholipase A(2) (PLA2), lipoxygenases (LOX-5 and LOX-12), cyclooxygenases (COX-1 and COX-2), and closely coupled enzymes including aromatase (AROM).MCF-7 human breast cancer cells were treated with inhibitors for PLA2 (quinacrine), lipoxygenases (LOX-5 and LOX-12; baicalein, REV-5091, nordihydroguaiaretic acid), cyclooxygenases (COX-1, COX-2, indomethacin), and AROM (formestane). The effects of these enzyme inhibitors on cell proliferation in response to THF-diols or estradiol (E(2)) were assessed. THF-diol modulation of the expression (RNA and protein) of these enzymes was also evaluated by quantitative real-time PCR (QPCR) and Western blot analyses.The enzyme inhibition and gene expression (RNA and protein) studies identified PLA2, LOX-5, LOX-12, COX-2, and perhaps AROM as likely sites of THF-diol regulation in MCF-7 cells. COX-1 was not affected by THF-diol treatment.THF-diol stimulation of MCF-7 cell proliferation is mediated through effects on the expression of the PLA2, COX-2, LOX-5, and LOX-12 genes and/or their respective enzyme activities. The products of these enzymes, including prostaglandins, hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecenoic acids (HODEs), are well-established mitogens in normal and malignant cells. Therefore, it is likely that these compounds are involved in the mechanism of action of THF-diols in breast cancer cells. Although the formestane inhibition studies suggested that AROM activity might be modulated by THF-diols, this was not confirmed by the gene expression studies.
Alexithymia and Outcome in Psychotherapy
Authors: Hans Joergen Grabe, Jörg Frommer, Annegret Ankerhold, Cornelia Ulrich, Ralf Gröger, Gabriele Helga Franke, Sven Barnow, Harald J. Freyberger, Carsten Spitzer
Journal: Psychotherapy and Psychosomatics (2008)

&lt;i&gt;Background:&lt;/i&gt; About 25% of all patients seeking psychotherapeutic treatment are considered to be alexithymic. Alexithymia has been assumed to be negatively associated with therapeutic outcome. On the other hand, it is unclear to which extent alexithymia itself may be modified by psychotherapeutic interventions. &lt;i&gt;Methods:&lt;/i&gt; From 414 consecutively admitted inpatients, 297 were followed up after 4 weeks (t1) and after 8–12 weeks (t2) upon discharge. Patients were treated with psychodynamic group therapy in a naturalistic setting. The Toronto Alexithymia Scale (TAS-20) and the Symptom Checklist-90 were administered. &lt;i&gt;Results:&lt;/i&gt; Twenty-seven percent of the patients were alexithymic (TAS-20 ≧61) at baseline. Multivariate models with repeated measurements indicated significant changes in Global Severity Index of the Symptom Checklist-90 in both alexithymic and nonalexithymic subjects. However, alexithymic subjects had significantly higher Global Severity Index scores than nonalexithymic subjects at t0, t1 and t2 (p &lt; 0.001). The TAS-20 scores demonstrated a high relative stability in the total sample. However, in the alexithymic group, the TAS-20 scores changed considerably from baseline to discharge [66.3 (SD = 4.7) to 55.9 (SD = 9.9); t = 8.69; d.f. = 79; p &lt; 0.001]. &lt;i&gt;Conclusion:&lt;/i&gt; The inpatient treatment program including psychodynamic group therapy significantly reduced psychopathological distress and alexithymic features in alexithymic patients. Still, these patients suffered from higher psychopathological distress at discharge than nonalexithymics. Therefore, alexithymic features may negatively affect the long-term outcome.
THE RÔLE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY
Authors: Claus W. Jungeblut, Gladys Newnan
Journal: The Journal of Experimental Medicine (1930)

1. Guinea pigs blocked by intravenous injection of either India ink or trypan blue succumbed with fatal shock after the intravenous injection of heterophile immune serum, although the time of death was somewhat delayed as compared with normal controls. 2. Local blockade of the skin of guinea pigs with trypan blue inhibited completely the development of the characteristic skin reaction following intracutaneous injection of Forssman serum within the blocked area. 3. Infiltration of the skin of guinea pigs with India ink afforded no protection against the full development of the toxic skin reaction.
The Apolipoprotein ε4 Allele Determines Prognosis and the Effect on Prognosis of Simvastatin in Survivors of Myocardial Infarction
Authors: Lars Ulrik Gerdes, Christian Gerdes, Kari Kervinen, Markku Savolainen, Ib Christian Klausen, Peter Steen Hansen, Y. Antero Kesäniemi, Ole Færgeman
Journal: Circulation (2000)

Carriers of the epsilon4 allele of the apolipoprotein E gene are at a higher risk of coronary heart disease than individuals with other genotypes. We examined whether the risk of death or a major coronary event in survivors of myocardial infarction depended on apolipoprotein E genotype and whether the benefits of treatment with simvastatin differed between genotypes.Cox proportional hazards models were used to analyze 5.5 years of follow-up data from 966 Danish and Finnish myocardial infarction survivors enrolled in the Scandinavian Simvastatin Survival Study. A total of 16% of the 166 epsilon4 carriers in the placebo group died compared with 9% of the 312 patients without the allele, which corresponds to a mortality risk ratio of 1.8 (95% confidence interval, 1.1 to 3.1). The risk ratio was unaffected by considerations of sex, age, concurrent angina, diabetes, smoking, and serum lipids in multivariate analyses. Simvastatin treatment reduced the mortality risk to 0.33 (95% confidence interval, 0.16 to 0.69) in epsilon4 carriers and to 0.66 (95% confidence interval, 0. 35 to 1.24) in other patients (P=0.23 for treatment by genotype interaction). Apolipoprotein E genotype did not predict the risk of a major coronary event. Baseline serum levels of lipoprotein(a) also predicted mortality risk and could be combined with epsilon4-carrier status to define 3 groups of patients with different prognoses and benefits from treatment.Myocardial infarction survivors with the epsilon4 allele have a nearly 2-fold increased risk of dying compared with other patients, and the excess mortality can be abolished by treatment with simvastatin.
Anticholinergic Syndrome With Procainamide Toxicity
Authors: Maurice D. Prendergast
Journal: JAMA (1984)

<h3>To the Editor.—</h3> The use of high-dose procainamide for resistant ventricular arrhythmias has been reported by Greenspan and Horowitz.<sup>1</sup>We wish to describe an anticholinergic syndrome associated with procainamide administered within the dosage range reported in their patients. <h3>Report of a Case.—</h3> A 21-year-old man underwent aortic and mitral valve replacements for rheumatic heart disease three months prior to admission to the hospital. He was subsequently admitted for control of recurrent ventricular tachycardia. Medications on admission included quinidine sulfate, 300 mg orally every six hours; digoxin, 0.25 mg orally each day; and warfarin sodium, 5 mg orally each day. His ventricular dysrhythmia proved resistant to conventional lidocaine dosage, and he was given a 200-mg intravenous (IV) procainamide loading dose followed by a maintenance IV infusion of 3 mg/min. Renal and hepatic function test results were within the normal range on admission. Twelve hours later, slow-release procainamide, 500 mg orally
Tbx20 regulates a genetic program essential to adult mouse cardiomyocyte function
Authors: Tao Shen, Ivy Aneas, Noboru Sakabe, Ralf J. Dirschinger, Gang Wang, Scott Smemo, John M. Westlund, Hongqiang Cheng, Nancy Dalton, Yusu Gu, Cornelis J. Boogerd, Chen-leng Cai, Kirk Peterson, Ju Chen, Marcelo A. Nobrega, Sylvia M. Evans
Journal: Journal of Clinical Investigation (2011)

Human mutations in or variants of TBX20 are associated with congenital heart disease, cardiomyopathy, and arrhythmias. To investigate whether cardiac disease in patients with these conditions results from an embryonic or ongoing requirement for Tbx20 in myocardium, we ablated Tbx20 specifically in adult cardiomyocytes in mice. This ablation resulted in the onset of severe cardiomyopathy accompanied by arrhythmias, with death ensuing within 1 to 2 weeks of Tbx20 ablation. Accounting for this dramatic phenotype, we identified molecular signatures that posit Tbx20 as a central integrator of a genetic program that maintains cardiomyocyte function in the adult heart. Expression of a number of genes encoding critical transcription factors, ion channels, and cytoskeletal/myofibrillar proteins was downregulated consequent to loss of Tbx20. Genome-wide ChIP analysis of Tbx20-binding regions in the adult heart revealed that many of these genes were direct downstream targets of Tbx20 and uncovered a previously undescribed DNA-binding site for Tbx20. Bioinformatics and in vivo functional analyses revealed a cohort of transcription factors that, working with Tbx20, integrated multiple environmental signals to maintain ion channel gene expression in the adult heart. Our data provide insight into the mechanisms by which mutations in TBX20 cause adult heart disease in humans.
Combined Deletion of Vhl and Kif3a Accelerates Renal Cyst Formation
Authors: Holger Lehmann, Daniele Vicari, Peter J. Wild, Ian J. Frew
Journal: Journal of the American Society of Nephrology (2015)

A subset of familial and sporadic clear cell renal cell carcinomas (ccRCCs) is believed to develop from cystic precursor lesions. Loss of function of the von Hippel-Lindau tumor suppressor gene (VHL) predisposes renal epithelial cells to loss of the primary cilium in response to specific signals. Because the primary cilium suppresses renal cyst formation, loss of the cilium may be an initiating event in the formation of ccRCC. To test this hypothesis, we analyzed the consequences of inducible renal epithelium-specific deletion of Vhl together with ablation of the primary cilium via deletion of the kinesin family member 3A (Kif3a) gene. We developed a microcomputed tomography-based imaging approach to allow quantitative longitudinal monitoring of cystic burden, revealing that combined loss of Vhl and Kif3a shortened the latency of cyst initiation, increased the number of cysts per kidney, and increased the total cystic burden. In contrast with findings in other cystic models, cysts in Kif3a mutant mice did not display accumulation of hypoxia-inducible factor 1-α (HIF1α), and deletion of both Hif1a and Kif3a did not affect cyst development or progression. Vhl/Kif3a double mutation also increased the frequency of cysts that displayed multilayered epithelial growth, which correlated with an increased frequency of misoriented cystic epithelial cell divisions. These results argue against the involvement of HIF1α in promoting renal cyst growth and suggest that the formation of simple and atypical renal cysts that resemble ccRCC precursor lesions is greatly accelerated by the combined loss of Vhl and the primary cilium.