tbuckley/cabot-search huggingface dataset:
Plasma Parathyroid Hormone and the Risk of Cardiovascular Mortality in the Community
Authors: Emil Hagström, Per Hellman, Tobias E. Larsson, Erik Ingelsson, Lars Berglund, Johan Sundström, Håkan Melhus, Claes Held, Lars Lind, Karl Michaëlsson, Johan Ärnlöv
Journal: Circulation (2009)

Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking.The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60; P<0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (<6.8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L; normal glomerular filtration rate, >50 mL . min(-1) . 1.73 m(-2) and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality.Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.
Prenatal Presentation of a Metastasizing Rhabdoid Tumor With Homozygous Deletion of the <i>SMARCB1</i> Gene
Authors: Shahrzad Negahban, Inga Nagel, Hossein Soleimanpour, Azita Aledavood, Neda Bagheri, Mehdi Paydar, Khosrow Daneshbod, Martin Hasselblatt, Stefan Gesk, Reiner Siebert, Yahya Daneshbod
Journal: Journal of Clinical Oncology (2010)
Problem solving treatment and group psychoeducation for depression: multicentre randomised controlled trial
Authors: C. Dowrick, G. Dunn, J. L. Ayuso-Mateos, O. S. Dalgard, H. Page, V. Lehtinen, P. Casey, C. Wilkinson, J. L. Vazquez-Barquero, G. Wilkinson
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To determine the acceptability of two psychological interventions for depressed adults in the community and their effect on caseness, symptoms, and subjective function. <b>Design:</b> A pragmatic multicentre randomised controlled trial, stratified by centre. <b>Setting:</b> Nine urban and rural communities in Finland, Republic of Ireland, Norway, Spain, and the United Kingdom. <b>Participants:</b> 452 participants aged 18 to 65, identified through a community survey with depressive or adjustment disorders according to the international classification of diseases, 10th revision or <i>Diagnostic and Statistical Manual of Mental Disorders</i>, fourth edition. <b>Interventions:</b> Six individual sessions of problem solving treatment (n=128), eight group sessions of the course on prevention of depression (n=108), and controls (n=189). <b>Main outcome measures:</b> Completion rates for each intervention, diagnosis of depression, and depressive symptoms and subjective function. <b>Results:</b> 63% of participants assigned to problem solving and 44% assigned to prevention of depression completed their intervention. The proportion of problem solving participants depressed at six months was 17% less than that for controls, giving a number needed to treat of 6; the mean difference in Beck depression inventory score was −2.63 (95% confidence interval −4.95 to −0.32), and there were significant improvements in SF-36 scores. For depression prevention, the difference in proportions of depressed participants was 14% (number needed to treat of 7); the mean difference in Beck depression inventory score was −1.50 (−4.16 to 1.17), and there were significant improvements in SF-36 scores. Such differences were not observed at 12 months. Neither specific diagnosis nor treatment with antidepressants affected outcome. <b>Conclusions:</b> When offered to adults with depressive disorders in the community, problem solving treatment was more acceptable than the course on prevention of depression. Both interventions reduced caseness and improved subjective function.
Computation and cognition: issues in the foundations of cognitive science
Authors: Zenon W. Pylyshyn
Journal: Behavioral and Brain Sciences (1980)

Abstract The computational view of mind rests on certain intuitions regarding the fundamental similarity between computation and cognition. We examine some of these intuitions and suggest that they derive from the fact that computers and human organisms are both physical systems whose behavior is correctly described as being governed by rules acting on symbolic representations. Some of the implications of this view are discussed. It is suggested that a fundamental hypothesis of this approach (the “proprietary vocabulary hypothesis”) is that there is a natural domain of human functioning (roughly what we intuitively associate with perceiving, reasoning, and acting) that can be addressed exclusively in terms of a formal symbolic or algorithmic vocabulary or level of analysis. Much of the paper elaborates various conditions that need to be met if a literal view of mental activity as computation is to serve as the basis for explanatory theories. The coherence of such a view depends on there being a principled distinction between functions whose explanation requires that we posit internal representations and those that we can appropriately describe as merely instantiating causal physical or biological laws. In this paper the distinction is empirically grounded in a methodological criterion called the “cognitive impenetrability condition.” Functions are said to be cognitively impenetrable if they cannot be influenced by such purely cognitive factors as goals, beliefs, inferences, tacit knowledge, and so on. Such a criterion makes it possible to empirically separate the fixed capacities of mind (called its “functional architecture”) from the particular representations and algorithms used on specific occasions. In order for computational theories to avoid being ad hoc, they must deal effectively with the “degrees of freedom” problem by constraining the extent to which they can be arbitrarily adjusted post hoc to fit some particular set of observations. This in turn requires that the fixed architectural function and the algorithms be independently validated. It is argued that the architectural assumptions implicit in many contemporary models run afoul of the cognitive impenetrability condition, since the required fixed functions are demonstrably sensitive to tacit knowledge and goals. The paper concludes with some tactical suggestions for the development of computational cognitive theories.
Cryoglobulins are not essential
Authors: M TRENDELENBURG, J A SCHIFFERLI
Journal: Annals of the Rheumatic Diseases (1998)

In 1933 Wintrope and Buell described “an extraordinary hyperproteinemia” in a patient suffering from multiple myeloma. She “presented symptoms of coldness, blanching and a peculiar mottling of the extremities, as well as other signs of disturbed circulation, and was found to have, in her blood, a voluminous quantity of a substance which invariably was precipitated immediately on withdrawal of the blood from the body”.1 

Since then several authors have analysed the cryoprecipitation reaction as well as the cryoprecipitated proteins.2 3 In 1974, Brouet and colleagues proposed a classification based on the type of protein that constitutes the cryoprecipitate.4 This classification has always had the disadvantage of associating diseases with very different aetiology and outcome, in the same group. In addition to cryoglobulinaemia secondary to well defined pathologies, Brouet and colleagues realised that a large proportion (30%) of patients had no known disease. This group of idiopathic cryoglobulinaemia has been referred to as “essential” cryoglobulinaemia. Since our initial report in 1990,5 it has become clear that most of these essential cryoglobulinaemias are in fact associated with hepatitis C virus infection. The description of a cryoglobulinaemia therefore has to take into account this important new finding.

The definition is based on an in vitro observation. A cryoglobulin is a globulin that precipitates when the serum is incubated at a temperature <37°C. Each cryoglobulin has an individual thermal curve with well defined kinetics of precipitation. Sometimes there is a good correlation between the thermal amplitude and the clinical signs (purpura after cold exposure) but in general cryoprecipitation is perceived as an in vitro artefact, with little or no direct pathological consequences in organs other than the skin. Indeed it is thought that the accumulation of cryoglobulins, for instance in the renal glomeruli, could not be explained for by a …
Contradictory State Administrative Regulation of Minimally Invasive Cosmetic Procedures in Kentucky and North Carolina
Authors: Jason D. Gillum, Robert P. Dellavalle
Journal: JAMA Dermatology (2013)

The regulation of minimally invasive cosmetic procedures (MICPs), such as laser skin rejuvenation and hair removal, should be of keen interest to dermatologists for a number of reasons, the most important of which is patient safety.
FcγRIIa mediates C-reactive protein-induced inflammatory responses of human vascular smooth muscle cells by activating NADPH oxidase 4
Authors: J RYU, C LEE, J SHIN, C PARK, J KIM, S PARK, K HAN
Journal: Cardiovascular Research (2007)

We investigated the mechanism by which C-reactive protein (CRP) affects pro-inflammatory activities of vascular smooth muscle cells (VSMCs).RT-PCR, flow cytometry, and immunoblotting assays consistently showed the expression of FcgammaRIIa by cultured VSMCs isolated from human coronary arteries. Immunofluorescence staining of human coronary artery plaque showed the co-localization of FcgammaRIIa with alpha-actin(+) VSMCs in atheromatous regions. Confocal microscopic image analysis of H(2)DCFDA-labeled cells showed that CRP induced intracellular reactive oxygen species (ROS) generation by FcgammaRIIa(+) HEK293T cells. Moreover, CRP time- and dose-dependently generated ROS in VSMCs through FcgammaRIIa activation. VSMCs mainly express NADPH oxidase 4 isoform (Nox4), the suppression of which using a specific siRNA completely abolished CRP-induced ROS generation by VSMCs. The downregulation of p22(phox), a component of the active Nox4 complex, by transfecting with specific decoy oligomers and functional blocking of FcgammaRIIa not only inhibited the CRP-induced ROS generation but also reduced the degree of AP-1 and NF-kappaB activation, the production of MCP-1, IL-6, and ET-1, and the apoptotic changes of VSMCs in response to CRP.CRP-induced ROS generation by VSMCs, which requires functional activation of FcgammaRIIa and NADPH oxidase 4, orchestrates pro-inflammatory activities of VSMCs and may eventually promote atherogenesis and plaque rupture.
The Extraction of the Stone of Madness
Authors: D. O'Neill
Journal: BMJ (2012)

The Extraction of the Stone of Madness by Hieronymus Bosch

Museo del Prado/Madrid

As technology and basic science feature more prominently in clinical practice, a corresponding challenge is to keep these advances in perspective for trainees and students. Philosophers from Kant to Habermas have warned against scientism—seeing science as the principal form of knowledge rather than as one of many forms. But at every post-take ward round, the complexities of the psychological and social aspects of medicine struggle unequally with the seductive, but often illusory, certainties of hard data.

It is not just our junior colleagues who are waylaid in this way; the general public is equally bedazzled by technology. …
Gene modified cellular vaccine (GMCV) composed of autologous adipose-derived mesenchymal stem cells (AAD-MSCS) transfected with lipid-cation HSP70 activated innate and adaptive immunity after targeting metastatic pancreatic Ca cells
Authors: J. Giannios
Journal: Gut (2011)

<h3>Introduction</h3> Metastatic pancreatic Ca leads to fatalities due to resistance in conventional anticancer therapies. By activation of immunological mechanisms we aim to circumvent the chemoresistant mechanisms. <h3>Methods</h3> Animal models characterized by metastatic pancreatic Ca refractory to conventional treatment were developed and treated with IV administration of the Gene-Modified Cellular Vaccine(GMCV) termed as SV/AS (under patent),which is composed of Autologous Adipose-derived Mesenchymal Stem Cells (AADMSCs), which were transfected with lipid-cation imunodominant molecule Hsp70. <h3>Results</h3> Post-treatment, we observed molecular remission in all tumour/metastatic sites, and activation of CD4+ T-cells by antigen presenting cells (APC), enhancement of MHC class I expression, generation of tumor-specific cytotoxicity with CTLs induced by the antigenic fingerprint/repertoire, activation of natural-killer (NK) cells, generation of peptide-specific tumour immunity induced by CD91 and C19 overexpression on dendritic cells (DCs),CD40 on macrophages, and LOX-1,CD14 and TLR2–4 on monocytes. Furthermore, hsp70 induced Th1-type immune response inducing secondary necrosis, which is the most potent immunogenic mode of cell death, and phagocytosis of tumour cells by activated macrophages leading to a lethal bystander effect. Finally, we observed repair of damaged tissue and organs by renewal of injured cells. <h3>Conclusion</h3> The Gene Modified Cellular Vaccine (GMCV) consisting of autologous adipose mesenchymal stem cells expressing Hsp70 activated the innate and adaptive immunity leading to eradication of metastatic pancreatic Ca cells, while there was stem cell renewal of injured cells.
Matrix Metalloproteinases 9 and 10 Inhibit Protein Kinase C–Potentiated, p53-Mediated Apoptosis
Authors: Eric Meyer, Jean-Yves Vollmer, Raymonde Bovey, Ivan Stamenkovic
Journal: Cancer Research (2005)

Abstract p53, a major sensor of DNA damage, is a transcription factor that, depending on its phosphorylation status, regulates the cell cycle, DNA repair, or apoptosis. The protein kinase C (PKC) family of isozymes is also implicated in cell cycle and programmed cell death (PCD) control and has recently been shown to influence p53 function. Using three human colon adenocarcinoma cell lines SW480, EB-1, and HCT116 that either lack p53 function and were engineered to express inducible wild-type p53 (wt p53), or that constitutively express wt p53, we show that phorbol ester–mediated PKC activation potentiates p53-induced PCD. Despite the effectiveness of PKC/p53 synergy in inducing SW480 tumor cell death, however, a fraction of the cells invariably survive. To address the putative mechanisms that underlie resistance to PKC/p53-induced cell death, we generated a phorbol 12-myristate 13-acetate/p53–resistant SW480 subline and compared the gene expression profile of resistant and parental cells by DNA microarray analysis. The results of these experiments show that PKC/p53-resistant cells express a higher level of several matrix metalloproteinases (MMP), including MMP-9, MMP-10, and MMP-12, and corresponding real-time PCR assays indicate that p53 is a negative regulator of MMP-9 gene expression. Using MMP inhibitors and MMP-specific small interfering RNA, we show that MMP function confers protection from PKC/p53-induced apoptosis and identify the protective MMPs as MMP-9 and MMP-10. Taken together, these observations provide evidence that MMPs are implicated in tumor cell resistance to the synergistic proapoptotic effect of PKC and p53.
Expression of bcl-2 Protein, an Inhibitor of Apoptosis, and Bax, an Accelerator of Apoptosis, in Ventricular Myocytes of Human Hearts With Myocardial Infarction
Authors: Jun Misao, Yukihiro Hayakawa, Michiya Ohno, Satoshi Kato, Takako Fujiwara, Hisayoshi Fujiwara
Journal: Circulation (1996)

Background In general, myocyte death in myocardial infarctions (MIs) is attributed to necrosis, but recently the involvement of apoptosis has been suggested. The ratio of bcl-2 protein, an inhibitor of apoptosis, to Bax protein, an inducer of apoptosis, determines survival or death after an apoptotic stimulus. We speculated that bcl-2 or Bax expression is induced by ischemia and that it may be related to myocyte death in human hearts. Methods and Results We studied immunohistochemically 37 autopsied human hearts (acute MI, n=15; old MI, n=12; normal hearts as a control, n=10) with the use of bcl-2 and Bax antibodies. There were no myocytes with positive bcl-2 immunoreactivity in the controls or hearts with old MI. However, myocytes with positive bcl-2 immunoreactivity were seen in 9 of 15 hearts (60%) with acute MI, in that it was localized only in salvaged areas surrounding the infarcted tissues. Myocytes with slightly positive Bax immunoreactivity were observed in the control hearts. In the salvaged myocytes surrounding the infarcted tissues, Bax was overexpressed in 2 of 15 hearts (13%) with acute MI but in 10 of 12 hearts (83%) with old MI. Conclusions bcl-2 protein is induced in salvaged myocytes at the acute stage of infarction, but Bax protein is overexpressed at the old stage. The expression of bcl-2 and the overexpression of Bax may play an important pathophysiological role in the protection or acceleration of the apoptosis of human myocytes after ischemia and/or reperfusion.
Use of vasodilator drug in shock.
Authors: S. P. Singh
Journal: BMJ (1966)

seem to appear rather late in the development of this disorder, for these antibodies were not detected in parietal cell antibodypositive individuals with hydrochloric acid in their gastric juice and in only 13 out of 50 parietal cell antibody-positive subjects with achlorhydria.Because we think that parietal cell antibodies are an earlier and more frequent symptom pointing to the possible development of pernicious anaei than intrinsic factor antibodies we consider the detection of the latter antibodies of little value as an early diagnostic procedure.Some years ago we stated that the method for the detection of parietal cell antibodies is a valuable test for selecting those relatives of patients with pernicious anaemia who run the risk of developing this disease.8Dr. J. H. Dagg and colleagues (10 September, p. 619) have shown that this method also can be used for the detection of latent pernicious anaemia in patients with iron-deficiency ansemia.On the basis of the evidence available at present we like to think that the method for the detection of parietal cell antibodies should be employed as a routine procedure in all con- ditions frequently associated with the occur- rence of these antibodies.Parietal cell antibody-positive individuals should be in- vestigated for the presence of hydrochloric acid in their gastric juice, and when they are found to be achlorhydric the intrinsic factor secretory capacity of their gastric mucosa should be examined.If they lack intrinsic factor they should receive prophylactic treat- ment with vitamin B,, before a deficiency of this vitamin may lead to irreversible neurological complications.-Weare, etc.
Locally Advanced Pancreatic Cancer: Where Should We Go From Here?
Authors: Philip Agop Philip
Journal: Journal of Clinical Oncology (2011)

R-DHAP can modulate bcl-6 expression through epigenetic mechanisms, which allows the release of TP53 and therefore alters the development of germinal center centroblasts. 11In contrast, ABClike DLBCL has been associated with constitutive activation of nuclear factor B, which may induce the cytokines interleukin-6 and interleukin-10 to act through Janus-activated kinases and the signal transducer and activators of transcription pathways as well as B-cell receptor pathways. 5,15 This information may help us to develop more rationally designed combinations of agents for these subtypes of DLBCL.If we are able to better predict which patients are likely to benefit from specific therapies, we could enrich the population treated for better outcomes with less toxicity.Although the Bio-CORAL study does not confirm that the cell of origin should be used to modify the salvage therapy for patients with different subtypes of DLBCL, it is hypothesis generating and the basis for future molecularly directed, randomized clinical trials.Use of the molecular information on cell of origin and stromal elements of various subtypes of lymphomas may assist in the development of improved combinations that produce superior survival outcomes.
Detection of Hepatitis B Virus DNA in Serum by a Simple Spot Hybridization Technique: Comparison with Results for Other Viral Markers
Authors: Jacques Scotto, Michelle Hadchouel, Christiane Hery, Jeannine Yvart, Pierre Tiollais, Christian Brechot
Journal: Hepatology (1983)

A simplified spot method for determination in serum of hepatitis B virus DNA (HBV DNA) by molecular hybridization is proposed. For simultaneous testing of 30 serum samples, it reduced to about 1 hr the duration of the steps preceding hybridization proper. The method also greatly reduced the loss of DNA during these steps and allowed more sensitive detection in samples of only 25 or 50 μ1. HBV DNA was determined in 181 serum samples by this method, and the results were pooled with 67 previous determinations by the Southern blot technique. Results for the pool were then compared to those obtained with radioimmunoassay for serological HBV markers. Ninety-six of the 248 samples were HBV DNA positive. Eleven others gave variable or inconclusive results, probably due to low viral particle titers. Seventy-two HBsAg- and HBeAg-positive sera contained HBV DNA, confirming that HBeAg is a marker of active viral replication. Fourteen other HBsAg- and HBeAg-positive sera, obtained from eight patients, were either HBV DNA negative or oscillated between negative and positive, or, again, were weakly positive; serological follow-up in 7 patients showed seroconversion to anti-HBe in 5, 3 of which became HBsAg negative. Eight of the HBsAg-positive sera were negative or borderline for HBeAg but contained HBV DNA and may, therefore, have been infective; seven of these sera had anti-HBe. Six HBsAg-negative sera contained HBV DNA and may also have been infective; five of these exhibited HBV antibodies. These results indicate that molecular hybridization not only provides a more sensitive and direct method for detecting hepatitis B virus in serum but also defines additional serological patterns with predictive or epidemiological value.