tbuckley/cabot-search huggingface dataset:
Saxitoxin Puffer Fish Poisoning in the United States, with the First Report of <i>Pyrodinium bahamense</i> as the Putative Toxin Source
Authors: Jan H. Landsberg, Sherwood Hall, Jan N. Johannessen, Kevin D. White, Stephen M. Conrad, Jay P. Abbott, Leanne J. Flewelling, R. William Richardson, Robert W. Dickey, Edward L.E. Jester, Stacey M. Etheridge, Jonathan R. Deeds, Frances M. Van Dolah, Tod A. Leighfield, Yinglin Zou, Clarke G. Beaudry, Ronald A. Benner, Patricia L. Rogers, Paula S. Scott, Kenji Kawabata, Jennifer L. Wolny, Karen A. Steidinger
Journal: Environmental Health Perspectives (2006)

From January 2002 to May 2004, 28 puffer fish poisoning (PFP) cases in Florida, New Jersey, Virginia, and New York were linked to the Indian River Lagoon (IRL) in Florida. Saxitoxins (STXs) of unknown source were first identified in fillet remnants from a New Jersey PFP case in 2002.We used the standard mouse bioassay (MBA), receptor binding assay (RBA), mouse neuroblastoma cytotoxicity assay (MNCA), Ridascreen ELISA, MIST Alert assay, HPLC, and liquid chromatography-mass spectrometry (LC-MS) to determine the presence of STX, decarbamoyl STX (dc-STX), and N-sulfocarbamoyl (B1) toxin in puffer fish tissues, clonal cultures, and natural bloom samples of Pyrodinium bahamense from the IRL.We found STXs in 516 IRL southern (Sphoeroides nephelus), checkered (Sphoeroides testudineus), and bandtail (Sphoeroides spengleri) puffer fish. During 36 months of monitoring, we detected STXs in skin, muscle, and viscera, with concentrations up to 22,104 microg STX equivalents (eq)/100 g tissue (action level, 80 microg STX eq/100 g tissue) in ovaries. Puffer fish tissues, clonal cultures, and natural bloom samples of P. bahamense from the IRL tested toxic in the MBA, RBA, MNCA, Ridascreen ELISA, and MIST Alert assay and positive for STX, dc-STX, and B1 toxin by HPLC and LC-MS. Skin mucus of IRL southern puffer fish captive for 1-year was highly toxic compared to Florida Gulf coast puffer fish. Therefore, we confirm puffer fish to be a hazardous reservoir of STXs in Florida's marine waters and implicate the dinoflagellate P. bahamense as the putative toxin source.Associated with fatal paralytic shellfish poisoning (PSP) in the Pacific but not known to be toxic in the western Atlantic, P. bahamense is an emerging public health threat. We propose characterizing this food poisoning syndrome as saxitoxin puffer fish poisoning (SPFP) to distinguish it from PFP, which is traditionally associated with tetrodotoxin, and from PSP caused by STXs in shellfish.
CKD-Induced Wingless/Integration1 Inhibitors and Phosphorus Cause the CKD–Mineral and Bone Disorder
Authors: Yifu Fang, Charles Ginsberg, Michael Seifert, Olga Agapova, Toshifumi Sugatani, Thomas C. Register, Barry I. Freedman, Marie-Claude Monier-Faugere, Hartmut Malluche, Keith A. Hruska
Journal: Journal of the American Society of Nephrology (2014)

In chronic kidney disease, vascular calcification, renal osteodystrophy, and phosphate contribute substantially to cardiovascular risk and are components of CKD–mineral and bone disorder (CKD-MBD). The cause of this syndrome is unknown. Additionally, no therapy addresses cardiovascular risk in CKD. In its inception, CKD-MBD is characterized by osteodystrophy, vascular calcification, and stimulation of osteocyte secretion. We tested the hypothesis that increased production of circulating factors by diseased kidneys causes the CKD-MBD in diabetic mice subjected to renal injury to induce stage 2 CKD (CKD-2 mice). Compared with non-CKD diabetic controls, CKD-2 mice showed increased renal production of Wnt inhibitor family members and higher levels of circulating Dickkopf-1 (Dkk1), sclerostin, and secreted klotho. Neutralization of Dkk1 in CKD-2 mice by administration of a monoclonal antibody after renal injury stimulated bone formation rates, corrected the osteodystrophy, and prevented CKD-stimulated vascular calcification. Mechanistically, neutralization of Dkk1 suppressed aortic expression of the osteoblastic transcription factor Runx2, increased expression of vascular smooth muscle protein 22-α, and restored aortic expression of klotho. Neutralization of Dkk1 did not affect the elevated plasma levels of osteocytic fibroblast growth factor 23 but decreased the elevated levels of sclerostin. Phosphate binder therapy restored plasma fibroblast growth factor 23 levels but had no effect on vascular calcification or osteodystrophy. The combination of the Dkk1 antibody and phosphate binder therapy completely treated the CKD-MBD. These results show that circulating Wnt inhibitors are involved in the pathogenesis of CKD-MBD and that the combination of Dkk1 neutralization and phosphate binding may have therapeutic potential for this disorder.
A paper that changed my practice, twice
Authors: A. Clark
Journal: BMJ (2002)

As a newly qualified preregistration house officer, alone on an orthopaedic ward one weekend, I was asked to review a patient complaining of pleuritic chest pain. This meant considering a short list of differential diagnoses to treat or exclude. Among these, of course, was pulmonary embolism, hence a D-dimer test seemed relevant. I can't remember much about this specific encounter, but I know I thought, worried, and procrastinated for as long as it took for the blood results to come back. Then I bleeped the medical registrar to ask what to do about the abnormal D-dimer test result.

The most memorable part of the encounter was …
Local Delivery of Paclitaxel to Inhibit Restenosis during Angioplasty of the Leg
Authors: Gunnar Tepe, Thomas Zeller, Thomas Albrecht, Stephan Heller, Uwe Schwarzwälder, Jean-Paul Beregi, Claus D Claussen, Anja Oldenburg, Bruno Scheller, Ulrich Speck
Journal: New England Journal of Medicine (2008)

Drug-eluting stents reduce restenosis in coronary arteries, but clinical trials have failed to prove their efficacy in peripheral arteries. We investigated the use of paclitaxel-coated angioplasty balloons and paclitaxel dissolved in the angiographic contrast medium during angioplasty of the leg.In a small, multicenter trial, we randomly assigned 154 patients with stenosis or occlusion of a femoropopliteal artery to treatment with standard balloon catheters coated with paclitaxel, uncoated balloons with paclitaxel dissolved in the contrast medium, or uncoated balloons without paclitaxel (control). The primary end point was late lumen loss at 6 months.The mean (+/-SD) age of the patients was 68+/-8 years, 24% were smokers, and 49% had diabetes. Twenty-seven percent of the lesions were total occlusions, and 36% were restenotic lesions. The mean lesion length was 7.4+/-6.5 cm. There were no significant differences in baseline characteristics between the groups. There were no adverse events attributable to the paclitaxel-coated balloons. At 6 months, the mean late lumen loss was 1.7+/-1.8 mm in the control group, as compared with 0.4+/-1.2 mm (P<0.001) in the group treated with paclitaxel-coated balloons and 2.2+/-1.6 mm (P=0.11) in the group treated with paclitaxel in the contrast medium. The rate of revascularization of target lesions at 6 months was 20 of 54 (37%) in the control group, 2 of 48 (4%) in the group treated with paclitaxel-coated balloons (P<0.001 vs. control), and 15 of 52 (29%) in the group treated with paclitaxel in the contrast medium (P=0.41 vs. control); at 24 months, the rates increased to 28 of 54 (52%), 7 of 48 (15%), and 21 of 52 (40%), respectively.Use of paclitaxel-coated angioplasty balloons during percutaneous treatment of femoropopliteal disease is associated with significant reductions in late lumen loss and target-lesion revascularization. No significant benefit is seen with the use of a paclitaxel-containing contrast medium. (ClinicalTrials.gov number, NCT00156624 [ClinicalTrials.gov].).
Gender Differences in the Management and Clinical Outcome of Stable Angina
Authors: Caroline Daly, Felicity Clemens, Jose L. Lopez Sendon, Luigi Tavazzi, Eric Boersma, Nicholas Danchin, Francois Delahaye, Anselm Gitt, Desmond Julian, David Mulcahy, Witold Ruzyllo, Kristian Thygesen, Freek Verheugt, Kim M. Fox
Journal: Circulation (2006)

Background— We sought to examine the impact of gender on the investigation and subsequent management of stable angina and to assess gender differences in clinical outcome at 1 year. Methods and Results— The Euro Heart Survey of Stable Angina enrolled patients with a clinical diagnosis of stable angina on initial assessment by a cardiologist. Baseline clinical details and cardiac investigations planned or performed within a 4-week period of the assessment were recorded, and follow-up data were collected at 1 year. A total of 3779 patients were included in the survey; 42% were female. Women were less likely to undergo an exercise ECG (odds ratio, 0.81; 95% CI, 0.69 to 0.95) and less likely to be referred for coronary angiography (odds ratio, 0.59; 95% CI, 0.48 to 0.72). Antiplatelet and statin therapies were used significantly less in women than in men, both at initial assessment and at 1 year, even in those in whom coronary disease had been confirmed. Women with confirmed coronary disease were less likely to be revascularized than their male counterparts and were twice as likely to suffer death or nonfatal myocardial infarction during the 1-year follow-up period (hazard ratio, 2.09; 95% CI, 1.13 to 3.85), even after multivariable adjustment for age, abnormal ventricular function, severity of coronary disease, and diabetes. Conclusions— Significant gender bias has been identified in the use of investigations and evidence-based medical therapy in stable angina. Women were also less likely to be revascularized. The observed bias is of particular concern in light of the adverse prognosis observed among women with stable angina and confirmed coronary disease.
The hepatitis B virus receptor: Book'em, Dano?
Authors: Mark E. Peeples
Journal: Hepatology (1994)

In a previous study, we have identified endonexin II (E–II) on human liver plasma membranes as a specific, Ca–dependent, small hepatitis B surface antigen (HBsAg)–binding protein. In this article, we describe the spontaneous development of anti–HBs antibodies in rabbits immunized with native or recombinant human liver E–II and in chickens immunized with the F(ab′)2 fragment of rabbit anti–human liver E–II immunoglobulin G. Anti–HBs activity was not observed in rabbits immunized with rat liver E–II. Cross–reactivity of anti–E–II antibodies to HBsAg epitopes was excluded, since anti–HBs and anti–E–II activities can be separated by E–II affinity chromatography. The existence of an anti–idiotypic antibody is further demonstrated by competitive binding of human liver E–II and this antibody (Ab2) to small HBsAg, suggesting that Ab2 mimics a specific E–II epitope that interacts with small HBsAg. In addition, it was demonstrated that anti–HBs antibodies developed in rabbits after immunization with intact human liver E–II or in chickens after immunization with F(ab′)2 fragments of rabbit anti–human liver E–II immunoglobulin G recognize the same epitopes on small HBsAg. These findings strongly indicate that human liver E–II is a very specific small HBsAg–binding protein and support the assumption that human liver E–II is the hepatitis B virus receptor protein. Binding of viral envelope proteins to specific receptors on human hepatocytes is considered to be an important step in HBV infection. In this study, we demonstrate that a 34–kDa human liver plasma membrane protein specifically binds to small HBsAg in a Ca2+–dependent manner. By partial amino acid sequence analysis of preparatively isolated 34–kDa protein comigrating with HBsAg–binding protein obtained from binding assay on IEF/SDS–PAGE, we have identified this HBsAg–binding protein as Endonexin II (E–II). Native human liver E–II inhibits binding of HBsAg to intact human hepatocytes and shows specific binding to small HBsAg. This binding can be inhibited by human liver plasma membrane proteins, recombinant E–II, or anti–E–II antibodies. Despite 90% sequence homology, rat liver E–II does not bind to small HBsAg and does not inhibit significantly (less than 20%) binding of HBsAg to intact hepatocytes. Cross–linking of small HBsAg and radiolabeled human liver E–II resulted in a specific additional protein complex on PAGE with an apparent molecular weight of 90 kDa, corresponding to a complex of E–II and small HBsAg with a ratio of 2 to 1 or 1 to 2. These findings indicate that E–II, found in human liver, is a specific HBsAg–binding protein and might play an important role in the initiation of HBV infection.
Proteomic and Lipidomic Signatures of Lipid Metabolism in NASH-Associated Hepatocellular Carcinoma
Authors: Kyle Muir, Antonious Hazim, Ying He, Marion Peyressatre, Do-Young Kim, Xiaoling Song, Laura Beretta
Journal: Cancer Research (2013)

Nonalcoholic steatohepatitis (NASH) is a common preneoplastic condition of hepatocellular carcinoma (HCC). Mice with hepatocytic deletion of Pten develop NASH and HCC later in life. This model is highly valuable for studies aimed at identifying the molecular mechanism by which metabolic disorders contribute to tumor development. We applied proteomic and lipidomic profiling approaches to Pten-null NASH liver and tumors. Circulating fatty acid composition was also characterized in these mice. The relevance to human NASH and HCC was further validated. This integrative proteomic and lipidomic study from mouse to human and from liver to blood identified the following disease signatures: (i) an HCC signature: upregulated hepatic scd1/scd2, fads2, and acsl5:acsl1 ratio, elevated vaccenic and erucic acids, and reduced margaric and linoleic acids in both liver and plasma; (ii) a NASH signature that correlates with tumor burden: upregulated hepatic elovl6, elevated oleic, adrenic, and osbond acids, and reduced cervonic acid in liver and plasma; and (iii) a NASH signature: reduced hepatic and circulating lignoceric and eicosapentaenoic acids. Altogether, these results show the role of lipid-modifying enzymes converting saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA) in HCC and the importance of an increased ratio of long chain n6-polyunsaturated fatty acids over n3-polyunsaturated fatty acids in NASH and HCC risk. They also highlight the relevance of the Pten-null model for studies related to NASH and HCC and show that circulating lipid metabolome provides a direct read of lipid changes in the liver. Most importantly, novel candidate targets for HCC diagnosis, therapy, risk assessment, and prevention were identified.
Repair of a Perforated Pulmonary Artery Due to a Swan-Ganz Catheter Using Thrombin Injection
Authors: David R. Dobies, Amanda L. Cohoon, Ashley A. Bates
Journal: Circulation (2009)

P ulmonary artery perforation is a rare but often fatal complication of right heart catheterization that is due to Swan-Ganz catheter (Edward Lifesciences, Irvine, Calif) placement. 1-3Treatment of a catheter-induced pulmonary artery rupture includes emergent intubation, lung resection, surgical pulmonary artery repair, and catheter-based pulmonary artery embolization. 4,5 This case demonstrates a new therapeutic approach of injecting topical Thrombin-JMI (GenTrac Inc, Middleton, Wisc) through the distal port of the Swan-Ganz catheter to effectively treat a pulmonary artery rupture during a right heart catheterization.
Episodic Exposure to Fine Particulate Air Pollution Decreases Circulating Levels of Endothelial Progenitor Cells
Authors: Timothy E. O'Toole, Jason Hellmann, Laura Wheat, Petra Haberzettl, Jongmin Lee, Daniel J. Conklin, Aruni Bhatnagar, C. Arden Pope
Journal: Circulation Research (2010)

Acute and chronic exposures to airborne particulate matter (PM) have been linked in epidemiological studies to a wide spectrum of cardiovascular disorders that are characterized by a dysfunctional endothelium. The pathophysiological mechanisms underlying these associations are unclear.To examine whether exposure to fine PM with an aerodynamic diameter of <2.5 microm (PM(2.5)) affects the circulating levels of endothelial progenitor cell (EPC) populations, systemic inflammation and coagulation.Phenotypically distinct EPC populations were quantified by flow cytometry in young (18 to 25 years) adult humans exposed to episodic increases in PM(2.5) along the Wasatch Mountain Front in Utah. In addition, Sca-1+/Flk-1+ cells were measured in the peripheral blood of mice exposed to concentrated particles from ambient air in Louisville, Ky. In both studies, PM exposure was negatively correlated with circulating EPC levels. In humans, statistically significant associations between PM(2.5) exposure and the plasma levels of platelet-monocyte aggregates, high-density lipoprotein, and nonalbumin protein were also observed. Episodic increases in PM(2.5) did not change plasma levels of C-reactive protein, interleukin-1beta, interleukin-6, fibrinogen, or serum amyloid A.Episodic exposure to PM(2.5) induces reversible vascular injury, reflected in part by depletion of circulating EPC levels, and increases in platelet activation and the plasma level of high-density lipoprotein. These changes were also accompanied by an increase in nonalbumin protein and may be related to mechanisms by which exposure to particulate air pollution increases the risk of cardiovascular disease and adverse cardiovascular events.
Overview of preventable industrial causes of occupational cancer.
Authors: E Ward
Journal: Environmental Health Perspectives (1995)

This paper summarizes what is known about preventable causes of occupational cancer, including single agents, complex mixtures, and broad occupational associations. Epidemiologic methods have been very successful in documenting cancer risks associated with single agents. Epidemiologic data are most conclusive when an exposure-response relationship can be demonstrated. Examples of agents for which epidemiologic studies provide evidence of an exposure-response relationship include benzene and (concurrent exposure to) ortho-toluidine and aniline. Vinyl chloride and bischloromethyl ether are examples of associations between single agents and rare histologic types of cancer. It is more difficult to conduct epidemiologic studies to identify cancer risks associated with complex mixtures. Studies of diesel exhaust and lung cancer and metal machining oils are cited as having employed advanced industrial hygiene and epidemiologic methods for studies of complex mixtures. Elevated cancer risks have also been identified in broad occupational groups, including painters and dry cleaners. Epidemiologic case-control studies are often used to detect such associations but are limited in their abilities to detect the causal agents. Major gaps exist in knowledge of occupational cancer risks among women workers and workers of color. Because epidemiologic research measures illness and mortality that have already occurred, a positive study can be interpreted to represent a failure in prevention. The challenge we face in the next decade is to identify interventions earlier in the causal pathway (toxicologic testing, biomarkers of exposure or precancerous changes, institution of engineering and good industrial hygiene practices to reduce occupational exposure levels) so that occupational cancer can be prevented.
TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease
Authors: Sruti Rayaprolu, Bianca Mullen, Matt Baker, Timothy Lynch, Elizabeth Finger, William W Seeley, Kimmo J Hatanpaa, Catherine Lomen-Hoerth, Andrew Kertesz, Eileen H Bigio, Carol Lippa, Keith A Josephs, David S Knopman, Charles L White, Richard Caselli, Ian R Mackenzie, Bruce L Miller, Magdalena Boczarska-Jedynak, Grzegorz Opala, Anna Krygowska-Wajs, Maria Barcikowska, Steven G Younkin, Ronald C Petersen, Nilüfer Ertekin-Taner, Ryan J Uitti, James F Meschia, Kevin B Boylan, Bradley F Boeve, Neill R Graff-Radford, Zbigniew K Wszolek, Dennis W Dickson, Rosa Rademakers, Owen A Ross
Journal: Molecular Neurodegeneration (2013)

Abstract Background A rare variant in the Triggering Receptor Expressed on Myeloid cells 2 ( TREM2 ) gene has been reported to be a genetic risk factor for Alzheimer’s disease by two independent groups (Odds ratio between 2.9-4.5). Given the key role of TREM2 in the effective phagocytosis of apoptotic neuronal cells by microglia, we hypothesized that dysfunction of TREM2 may play a more generalized role in neurodegeneration. With this in mind we set out to assess the genetic association of the Alzheimer’s disease-related risk variant in TREM2 (rs75932628, p.R47H) with other related neurodegenerative disorders. Results The study included 609 patients with frontotemporal dementia, 765 with amyotrophic lateral sclerosis, 1493 with Parkinson’s disease, 772 with progressive supranuclear palsy, 448 with ischemic stroke and 1957 controls subjects free of neurodegenerative disease. A significant association was observed for the TREM2 p.R47H substitution in susceptibility to frontotemporal dementia (OR = 5.06; p-value = 0.001) and Parkinson’s disease (OR = 2.67; p-value = 0.026), while no evidence of association with risk of amyotrophic lateral sclerosis, progressive supranuclear palsy or ischemic stroke was observed. Conclusions Our results suggest that the TREM2 p.R47H substitution is a risk factor for frontotemporal dementia and Parkinson’s disease in addition to Alzheimer’s disease. These findings suggest a more general role for TREM2 dysfunction in neurodegeneration, which could be related to its role in the immune response.
The PTPN22*C1858T functional polymorphism is associated with susceptibility to inflammatory polyarthritis but neither this nor other variants spanning the gene is associated with disease outcome
Authors: H Naseem, W Thomson, A Silman, J Worthington, D Symmons, A Barton
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background:</h3> The <i>PTPN22</i> gene has been widely confirmed as a susceptibility gene for rheumatoid arthritis (RA) in populations of Northern European descent. The aim of the current study was to explore the role of variants spanning the <i>PTPN22</i> gene in determining susceptibility to and outcome of inflammatory polyarthritis (IP). <h3>Patients and methods:</h3> Single nucleotide polymorphism (SNP) variants spanning the gene were genotyped using the Sequenom MassArray platform and tested, firstly for their association with susceptibility to IP. Genotype frequencies were compared between new onset IP cases (n = 843) and population controls (n = 471). Secondly, a within-cohort analysis was performed testing each variant for association with a number of clinical outcome measures reflecting disease severity including radiological erosions, physical function, measured using the Health Assessment Questionnaire (HAQ) score, and disease activity at defined time-points following disease presentation. <h3>Results:</h3> A significant association between carriage of the <i>PTPN22*1858T</i> allele and IP (odds ratio (OR) = 1.4 (95% CI 1.1–1.9), p = 0.02) was observed. The strength of the effect was similar in the RA subgroup (OR = 1.4 (95% CI 1.0–1.9), p = 0.05). No association between IP susceptibility and any of the other SNPs was detected. No association was detected for any of the SNPs tested, including the <i>PTPN22</i>*<i>C1858T</i> polymorphism, for either erosive status, Larsen score by 5 years or other markers of clinical outcome. <h3>Conclusion:</h3> The <i>PTPN22</i>*<i>C1858T</i> polymorphism is associated with susceptibility to IP, but we have found no evidence for association of this or other variants spanning the gene with clinical outcome measures.