tbuckley/cabot-search huggingface dataset:
Ambient Air Pollution and Atherosclerosis in Los Angeles
Authors: Nino Künzli, Michael Jerrett, Wendy J. Mack, Bernardo Beckerman, Laurie LaBree, Frank Gilliland, Duncan Thomas, John Peters, Howard N. Hodis
Journal: Environmental Health Perspectives (2004)

Associations have been found between long-term exposure to ambient air pollution and cardiovascular morbidity and mortality. The contribution of air pollution to atherosclerosis that underlies many cardiovascular diseases has not been investigated. Animal data suggest that ambient particulate matter (PM) may contribute to atherogenesis. We used data on 798 participants from two clinical trials to investigate the association between atherosclerosis and long-term exposure to ambient PM up to 2.5 μm in aerodynamic diameter (PM2.5). Baseline data included assessment of the carotid intima-media thickness (CIMT), a measure of subclinical atherosclerosis. We geocoded subjects’ residential areas to assign annual mean concentrations of ambient PM2.5. Exposure values were assigned from a PM2.5 surface derived from a geostatistical model. Individually assigned annual mean PM2.5 concentrations ranged from 5.2 to 26.9 μg/m3 (mean, 20.3). For a cross-sectional exposure contrast of 10 μg/m3 PM2.5, CIMT increased by 5.9% (95% confidence interval, 1–11%). Adjustment for age reduced the coefficients, but further adjustment for covariates indicated robust estimates in the range of 3.9–4.3% (p-values, 0.05–0.1). Among older subjects (≥60 years of age), women, never smokers, and those reporting lipid-lowering treatment at baseline, the associations of PM2.5 and CIMT were larger with the strongest associations in women ≥60 years of age (15.7%, 5.7–26.6%). These results represent the first epidemiologic evidence of an association between atherosclerosis and ambient air pollution. Given the leading role of cardiovascular disease as a cause of death and the large populations exposed to ambient PM2.5, these findings may be important and need further confirmation.
Contribution of the two Gs-coupled PGE2-receptors EP2-receptor and EP4-receptor to the inhibition by PGE2 of the LPS-induced TNFα-formation in Kupffer cells from EP2-or EP4-receptor-deficient mice. Pivotal role for the EP4-receptor in wild type Kupffer cells
Authors: Alexandra Fennekohl, Yukihiko Sugimoto, Eri Segi, Takayuki Maruyama, Atsushi Ichikawa, Gerhard P Püschel
Journal: Journal of Hepatology (2002)
Lack of common TCRA and TCRB clonotypes in CD8+/TCRαβ+ T-cell large granular lymphocyte leukemia: a review on the role of antigenic selection in the immunopathogenesis of CD8+ T-LGL
Authors: Y Sandberg, M J Kallemeijn, W A Dik, D Tielemans, I L M Wolvers-Tettero, E J van Gastel-Mol, T Szczepanski, Y Pol, N Darzentas, J J M van Dongen, A W Langerak
Journal: Blood Cancer Journal (2014)

Abstract Clonal CD8 + /T-cell receptor (TCR)αβ + T-cell large granular lymphocyte (T-LGL) proliferations constitute the most common subtype of T-LGL leukemia. Although the etiology of T-LGL leukemia is largely unknown, it has been hypothesized that chronic antigenic stimulation contributes to the pathogenesis of this disorder. In the present study, we explored the association between expanded TCR-Vβ and TCR-Vα clonotypes in a cohort of 26 CD8 + /TCRαβ + T-LGL leukemia patients, in conjunction with the HLA-ABC genotype, to find indications for common antigenic stimuli. In addition, we applied purpose-built sophisticated computational tools for an in-depth evaluation of clustering of TCRβ (TCRB) complementarity determining region 3 (CDR3) amino-acid LGL clonotypes. We observed a lack of clear TCRA and TCRB CDR3 homology in CD8 + /TCRαβ + T-LGL, with only low level similarity between small numbers of cases. This is in strong contrast to the homology that is seen in CD4 + /TCRαβ + T-LGL and TCRγδ + T-LGL and thus underlines the idea that the LGL types have different etiopathogenesis. The heterogeneity of clonal CD8 + /TCRαβ + T-LGL proliferations might in fact suggest that multiple pathogens or autoantigens are involved.
Pediatric ALK+ anaplastic large cell lymphoma with t(3;8)(q26.2;q24) translocation and <i>c‐myc</i> rearrangement terminating in a leukemic phase
Authors: Sara Monaco, Lawrence Tsao, V.V. Murty, S.V. Nandula, Virginia Donovan, J. Oesterheld, Govind Bhagat, Bachir Alobeid
Journal: American Journal of Hematology (2006)

Abstract Pediatric ALK‐positive anaplastic large cell lymphoma (ALK+ ALCL) is usually associated with a favorable prognosis. ALK+ ALCL associated with a leukemic phase is uncommon, but has been associated with an aggressive clinical course and unfavorable prognosis. Overexpression of c‐myc has been shown to be a consistent finding in ALK+, but not ALK‐negative ALCL (ALK− ALCL), and the c‐myc gene is considered a downstream target of deregulated ALK signaling. We describe a pediatric ALK+ ALCL with a leukemic phase at relapse. Similar to other rare cases described in the literature, it followed an aggressive clinical course despite multiple regimens of chemotherapy and bone marrow transplantation. Lymphoma cells showed aberrant ALK expression and c‐myc overexpression. In addition to the characteristic t(2;5)(p23;q35) translocation, a t(3;8)(q26.2;q24) translocation was also present, and c‐myc gene rearrangement was confirmed by FISH analysis. The findings in this case demonstrate the association of peripheral blood leukemic involvement and aggressive clinical course, and suggest that other factors, such as c‐myc rearrangement, may be responsible for the aggressive clinical behavior in ALK+ ALCL. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
IMPLICATIONS OF GLOBAL AND REGIONAL LEFT VENTRICULAR LONGITUDINAL STRAIN ON SURGICAL MITRAL VALVE REPAIR OUTCOMES
Authors: Ibtihal Al Amri, Philippe Debonnaire, Tomasz Witkowski, Robert Klautz, Jerry Braun, Martin Schalij, Jeroen Bax, Nina Ajmone Marsan, Victoria Delgado
Journal: Journal of the American College of Cardiology (2013)
Abstract 5419: Thiamine deficiency induces HIF-1 α stabilization and target gene expression.
Authors: Rebecca Sweet, Lauren Lim, Jason Zastre
Journal: Cancer Research (2013)

Abstract Introduction: Thiamine deficiencies have been reported in a number of common pathologies including diabetes, neurodegenerative disorders and in particular, cancer. Deficiencies can arise due to drug mediated reductions in cellular availability of thiamine or due to limited diffusion into solid tumors. Biochemically, a metabolic consequence of thiamine deficiency is a reduction in enzyme activity and expression of pyruvate dehydrogenase complex (PDH), which converts pyruvate to acetyl-CoA. Evidence suggests that trans-activation of hypoxia inducible factor 1-alpha (HIF-1α) regulated genes is mediated through stoichiometric changes in the metabolic intermediate pyruvate, independent of low oxygen termed pseudo-hypoxia. The resulting dysfunction of PDH and accumulation of pyruvate during TD may facilitate a pseudo-hypoxic state and mediate trans-activation of HIF-1α regulated genes. Therefore, we hypothesize that thiamine deficiency induces a pseudo-hypoxic state resulting in a stabilization of HIF-1α. Methods: The impact of TD treatments on cellular pyruvate levels was determined after 48h of TD treatment using a pyruvate assay. Protein expression of HIF-1α was assessed in nuclear lysates of SK-N-BE cells treated with 1% O2 and TD for 12, 24, and 48h by Western blot. Expression of the known HIF-1α regulated gene, GLUT1 was measured by qRTPCR after 12, 24 and 48h hypoxia (1% O2) and thiamine depletion. Results: An approximately 2 fold increase in cellular pyruvate was observed after 48h of TD exposure. A corresponding increase in HIF-1α protein expression in both 1% O2 and TD was found after 48h exposure. SK-N-BE cells demonstrated a 6 and 10 fold increase in expression of GLUT1 and SLC19A3, respectively after 48h of 1% O2 exposure. TD treatment exhibited an approximately 2 fold increase in expression of both GLUT1 and SLC19A3 after 48h treatments. Conclusions: An increase in pyruvate production and the induction of HIF-1α protein expression after TD treatment suggests the role of TD acting as a feed forward mechanism for HIF-1α stabilization and gene regulation. These results demonstrate nutritional regulation of the pro-oncogenic transcription factor, HIF-1α and an important connection of cellular thiamine to adaptive glycolytic metabolism. Citation Format: Rebecca Sweet, Lauren Lim, Jason Zastre. Thiamine deficiency induces HIF-1 α stabilization and target gene expression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5419. doi:10.1158/1538-7445.AM2013-5419
Interstitial-Cell Tumors of the Testis in Children
Authors: Frank A. Pomer, Richard E. Stiles, James H. Graham
Journal: New England Journal of Medicine (1954)

INTERSTITIAL-cell tumors of the testis constitute an interesting and relatively rare pathological entity. Tumors of the testis in themselves make up only from 0.5 to 2 per cent of all cancer in males, and the specific interstitial-cell tumor represents but 1 per cent of this total group.1 , 2 During the past few years there have been several excellent reviews in the literature,3 4 5 6 7 8 9 with a total of 46 cases reported to date. Of these, 13 have occurred in the prepubertal age group. The case reported below represents the fourteenth case occurring in a child.Normal HistologyLeydig, in 1850, first described the . . .
Detection of Pre–S1 Proteins in Serum and Liver of Hbsag–Positive Patients: A New Marker for Hepatitis B Virus Infection
Authors: Lorenz Theilmann, Mo-Quen Klinkert, Karl Gmelin, Jochen Salfeld, Heinz Schaller, Eberhard Pfaff
Journal: Hepatology (1986)

The presence of pre-S1 proteins in serum and liver of individuals with acute and chronic hepatitis B virus infection was investigated in Western blots using antibodies against a fusion protein, containing amino acids 20-120 of the pre-S region. Pre-S1 proteins were present in 20 of 38 HBsAg-positive sera. All sera positive for pre-S1 proteins were also positive for hepatitis B virus DNA indicating the presence of hepatitis B virions, and 16 of these sera were also positive for HBeAg. In five sera positive for hepatitis B virus DNA, pre-S1 proteins were not found. In an additional study, pre-S1 proteins could be detected in 4 of 6 patients with acute hepatitis B virus infection during the first 2 weeks after admission to the hospital. The presence of pre-S1 proteins showed a good correlation with the detection of hepatitis B virus DNA. After seroconversion from HBeAg to anti-HBe, both hepatitis B virus DNA and pre-S1 proteins were no longer detectable. Pre-S1 proteins were present in three liver tissue specimens from two patients with acute hepatitis B virus infection and from one patient with cirrhosis of the liver. The proteins were not found in the liver of two HBsAg-positive patients with hepatocellular carcinoma (primary liver carcinoma), negative for HBeAg. Pre-S1 proteins can be detected in serum, positive for hepatitis B virus DNA and in liver tissue of hepatitis B virus-infected individuals. The presence of these proteins appears to correspond with the presence of hepatitis B virus DNA, both markers indicating hepatitis B virus replication.
Recent Advances in Parkinson's Disease
Authors: Danilo B. Soriano
Journal: JAMA (1972)

Here is another timely book of the Contemporary Neurology Series, this one presenting the background of the drug, levodopa (L-dopa), highly effective in the treatment of parkinsonism. With various chapters written by scientists who pioneered in the field, the book is indeed stimulating, and the presentation of materials well organized and straightforward. Well described is the complex mechanism of physiology, biochemistry, and pathology and the ultimate use of levodopa in the treatment of this hitherto severely disabling disease. Various interesting questions are discussed, including the significance of a Babinski response in a patient with parkinsonism; the two types of idiopathic parkinsonism; the aphrodisiac effect of levodopa; the significance of "bloody" urine in a patient treated with this drug; the dangers of its use in patients with glaucoma; and numerous others. The chapter on adverse clinical side effects deals with the subject exhaustively and shows statistics from three pioneering institutions. The
Re: Giorgio Guazzoni, Andrea Cestari, Richard Naspro, et al. Intra- and Peri-Operative Outcomes Comparing Radical Retropubic and Laparoscopic Radical Prostatectomy: Results from a Prospective, Randomized, Single-Surgeon Study. Eur Urol 2006;50:98–104
Authors: Marco Carini, Lorenzo Masieri, Andrea Minervini, Sergio Serni
Journal: European Urology (2006)
Molecular Pathogenesis and a Consequent Classification of Multiple Myeloma
Authors: P. Leif Bergsagel, W. Michael Kuehl
Journal: Journal of Clinical Oncology (2005)

There appear to be two pathways involved in the pathogenesis of premalignant non-immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Nearly half of tumors are nonhyperdiploid, and mostly have one of five recurrent IgH translocations: 16% 11q13 (CCN D1), 3% 6p21 (CCN D3), 5% 16q23 (MAF), 2% 20q12 (MAFB), and 15% 4p16 (FGFR3 and MMSET). The remaining hyperdiploid tumors have multiple trisomies involving chromosomes 3, 5, 7, 9, 11, 15, 19, and 21, and infrequently one of these five translocations. Although cyclin D1 is not expressed by healthy lymphoid cells, it is bi-allelically dysregulated in a majority of hyperdiploid tumors. Virtually all MM and MGUS tumors have dysregulated and/or increased expression of cyclin D1, D2, or D3, providing an apparent early, unifying event in pathogenesis. The patterns of translocations and cyclin D expression (TC) define a novel classification that includes eight groups: 11q; 6p; MAF; 4p; D1 (34%); D1+D2 (6%); D2 (17%); and none (2%). The hyperdiploid D1 group is virtually absent in extramedullary MM and MM cell lines, suggesting a particularly strong dependence on interaction with the bone marrow microenvironment. Despite shared progression events (RAS mutations, MYC dysregulation, p53 mutations, and additional disruption of the retinoblastoma pathway), the phenotypes of MGUS and MM tumors in the eight TC groups is determined mainly by early oncogenic events. Similar to acute lymphocytic leukemia, MM seems to include several diseases (groups) that have differences in early or initiating events, global gene expression patterns, bone marrow dependence, clinical features, prognosis, and response to therapy.
Length of cancer trials has more than halved over past 30 years
Authors: Roger Dobson
Journal: BMJ (2005)

The average length of cancer trials has fallen over the last 30 years from seven to three years, a new research report has shown ( British Journal of Cancer 2005;92: 811-4



The analysis shows that the median duration of trials that recruited at least 90% of the target number of participants fell from 7.2 years during the period 1971-5 to 2.7 years in the period 1996-2000.

The study's authors, from the UK Medical Research Council's Clinical Trials Unit, used the national register of cancer trials (NRCT) of the …
Developmental hemodynamic changes in the chick embryo from stage 18 to 27.
Authors: E B Clark, N Hu
Journal: Circulation Research (1982)

We report the hemodynamic parameters of stage 18, 21, 24, and 27 chick embryos (from 3 to 5 days of incubation). Dorsal aortic blood velocity and mean vitelline artery blood pressure are measured with a 20 MHz pulsed-Doppler meter and servo-null pressure system respectively. We also measure heart rate, dorsal aortic diameter and embryo weight of each developmental stage. From these data, we calculate mean dorsal aortic blood flow, mean dorsal aortic blood flow per cardiac cycle, mean dorsal aortic blood flow per milligram embryo weight, vascular resistance and cardiac work. Blood flow increases geometrically with each embryo stage but remains constant when normalized for embryo weight. Mean arterial pressure increases linearly and vascular resistance decreases geometrically. Cardiac work increases in proportion to embryo weight. These results define the parameters of normal hemodynamic function during early embryonic development.
Tc-99m Bone Scintigraphy of Large Knee Joint Effusions in Osteoarthritis
Authors: Erik N. Nelson, M Elizabeth Oates
Journal: Clinical Nuclear Medicine (2004)

A 60-year-old man reported bilateral lower extremity pain and swelling. A Tc-99m HDP bone scan showed symmetric, moderately intense uptake within the femoral condyles and tibial plateaux, and marked, symmetric suprapatellar soft tissue activity. Radiographs confirmed large bilateral suprapatellar joint effusions and changes compatible with osteoarthritis. Percutaneous aspiration revealed inflammatory cells without crystals.
Getting on in and off on medical politics ...
Authors: C. Gray
Journal: BMJ (1997)

How did that get decided? How on earth did he get elected? Why was she awarded those discretionary points? Why is the duty roster so unfair? Why is the new consultant post not funded? What are “they” up to? No one asked me!

“Oh”, people will say, “it's politics-what can you expect?”. The haunt of scoundrels, the dishonest art, the least valued and second oldest profession: politics is not respected, especially in the glare of an election year.

Young doctors-particularly young female doctors-may well wonder how it all works. How can they get their good ideas implemented? How can one's voice be heard in the specialty or hospital medical committee? What happened to ideals and morality? Should one enter the public life of organisations for part or all of one's career? Or is putting your head above the parapet the one sure way to get it knocked off?

Lots of politics seem to be going on at all levels and we are not short of great issues of the day. But few of us bother to have anything to do with it, and professional societies and associations struggle to fill their committees and events, especially with doctors under 50. Political outfits everywhere are crying out for new blood and ideas. Medical elections traditionally draw a low turnout of voters. Yet most power lies in the hands of small groups of individuals-compare oligarchy (rule by the few) to “medarchy”-rule by (mostly) middle aged white men.

Medical politics spans the range between the doings of a local medical society or BMA division through Westminster and into Europe. Politics writ large is the national drama of general elections and government policy; writ small it is the lifeblood of all organisations, and unless you are self employed, your …
Hesitations and clarifications on a model to abandon feedback
Authors: Louisa M. Slowiaczek
Journal: Behavioral and Brain Sciences (2000)

Hesitations about accepting whole-heartedly Norris et al.'s suggestion to abandon feedback in speech processing models concern (1) whether accounting for all available data justifies additional layers of complexity in the model and (2) whether characterizing Merge as non- interactive is valid. Spoken word recognition studies support the nature of Merge's lexical level and suggest that phonemes should comprise the prelexical level.
Thephorin Ointment in Pruritic Dermatoses
Authors: Charles S. D'Avanzo
Journal: New England Journal of Medicine (1949)

SINCE the report of Fourneau1 and his French associates, there has been a widespread interest in the use of the so-called antihistaminics or histamine antagonists for diseases with an allergic background. Until quite recently, the antihistaminic drugs have been administered orally with good effect, especially in certain dermatoses such as the acute urticarias and urticarial drug reactions and some of the physical allergies.The success achieved with the oral administration of the antihistaminic drugs in the allergic type of dermatoses led to their topical use in similar diseases. In 1947 Mayer2 reported experimental evidence that the local application of 5 . . .
Molecular Evolution of the Mammalian Alpha 2B Adrenergic Receptor
Authors: Ole Madsen, Diederik Willemsen, Björn M. Ursing, Ulfur Arnason, Wilfried W. de Jong
Journal: Molecular Biology and Evolution (2002)

The alpha 2B adrenergic receptor (A2AB) is a heptahelical G protein–coupled receptor for catecholamines. We compared the almost complete coding region (about 1,175 bp) of the A2AB gene from 48 mammalian species, including eight newly determined sequences, representing all the 18 eutherian and two marsupial orders. Comparison of the encoded proteins reveals that residues thought to be involved in agonist binding are highly conserved, as are the regions playing a role in G protein–coupling. The three extracellular loops are generally more variable than the transmembrane domains and two of the intracellular loops, indicating a lower functional constraint. However, the greatest variation is observed in the very long, third intracellular loop, where only a few residues and a polyglutamyl tract are preserved. Although this polyglutamyl domain displays a great variation in length, its presence in all described A2ABs confirms its proposed role in agonist-dependent phosphorylation of the third intracellular loop. Phylogenetic analyses of the A2AB data set, including Bayesian methods, recognized the superordinal clades Afrotheria, Laurasiatheria, and Euarchontoglires, in agreement with recent molecular evidence, albeit with lower support. Within Afrotheria, A2AB strongly supports the paenungulate clade and the association of the continental African otter shrew with Malagasy tenrecs. Among Laurasiatheria, A2AB confirms the nesting of whales within the artiodactyls, as a sister group to hippopotamus. Within the Euarchontoglires, there is constant support for rodent monophyly.
Effect of stopping low-phenylalanine diet on intellectual progress of children with phenylketonuria.
Authors: I Smith, M E Lobascher, J E Stevenson, O H Wolff, H Schmidt, S Grubel-Kaiser, H Bickel
Journal: BMJ (1978)

Forty-seven patients at the Hospital for Sick Children, London, who had phenylketonuria and were on a low-phenylalanine diet (21 early-treated--that is, treatment started before the age of 4 months--and 26 late-treated) were placed on a normal diet between the ages of 5 and 15 years. They showed significant falls in mean IQ of about six points after the diet was withdrawn. Twenty-two similar patients (five early-treated and 17 late-treated) at the Universitäts-Kinderklinik, Heidelberg, who were placed on a relaxed low-phenylalanine rather than a normal diet, showed smaller and non-significant falls in mean IQ. During the period of strict diet none of the patients in London or Heidelberg showed any consistent falls in IQ. These results suggest that complete withdrawal of the low-phenylalanine diet during childhood leads to a fall in intellectual progress in many patients.
BLT-humanized C57BL/6 Rag2−/−γc−/−CD47−/− mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection
Authors: Kerry J. Lavender, Wendy W. Pang, Ronald J. Messer, Amanda K. Duley, Brent Race, Katie Phillips, Dana Scott, Karin E. Peterson, Charles K. Chan, Ulf Dittmer, Timothy Dudek, Todd M. Allen, Irving L. Weissman, Kim J. Hasenkrug
Journal: Blood (2013)