tbuckley/cabot-search huggingface dataset:
Increased Anxiety During Anticipation of Unpredictable But Not Predictable Aversive Stimuli as a Psychophysiologic Marker of Panic Disorder
Authors: Christian Grillon, Shmuel Lissek, Stephanie Rabin, Dana McDowell, Sharone Dvir, Daniel S. Pine
Journal: American Journal of Psychiatry (2008)

Objective: Predictability is a fundamental modulator of anxiety in that the ability to predict aversive events mitigates anxious responses. In panic disorder, persistent symptoms of anxiety are caused by anticipation of the next uncued (unpredictable) panic attack. The authors tested the hypothesis that elevated anxious reactivity, specifically toward unpredictable aversive events, is a psychophysiological correlate of panic disorder. Method: Participants were exposed to one condition in which predictable aversive stimuli were signaled by a cue, a second condition in which aversive stimuli were administered unpredictably, and a third condition in which no aversive stimuli were anticipated. Startle was used to assess anxious responses to cues and contexts. Results: Relative to healthy comparison subjects, patients with panic disorder displayed equivalent levels of fear-potentiated startle to the threat cue but elevated startle potentiation in the context of the unpredictable condition. Conclusions: Patients with panic disorder are overly sensitive to unpredictable aversive events. This vulnerability could be either a premorbid trait marker of the disorder or an acquired condition caused by the experience of uncued panic attacks. As a premorbid trait, vulnerability to unpredictability could be etiologically related to panic disorder by sensitizing an individual to danger, ultimately leading to intense fear/alarm responses to mild threats. As an acquired characteristic, such vulnerability could contribute to the maintenance and worsening of panic disorder symptoms by increasing anticipatory anxiety.
Intraperitoneal Immunotherapy for Metastatic Ovarian Carcinoma: Resistance of Intratumoral Collagen to Antibody Penetration
Authors: Jaehwa Choi, Kimberly Credit, Karla Henderson, Ravi Deverkadra, Zhi He, Helge Wiig, Heather Vanpelt, Michael F. Flessner
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Convective transport of macromolecules from the peritoneal cavity into tumor is determined by its hydraulic permeability and the pressure gradient. Previous studies showed that establishing a pressure gradient into the tumor failed to result in significant penetration. This study addresses the hypothesis that the extracellular matrix is the major resistance to the penetration of an i.p. injected antibody. Experimental Design: Human ovarian tumors (SKOV-3 and OVCAR-3) were established in the abdominal wall of athymic rats. After anesthesia, the tumor serosal surface was treated for 2 hours with Krebs solution (control), collagenase (37.5 unit/mL), or hyaluronidase (10 unit/mL) followed by 3 hours of convective delivery of radiolabeled IgG. Transport of antibody into the tumor was measured with quantitative autoradiography along with the tumor interstitial pressure, concentration of collagen and hyaluronic acid, and IgG volume of distribution. Results: Antibody was excluded from 42% to 53% of tumor extracellular volume. Exposure of tumors to hyaluronidase did not enhance IgG transport despite removal of 90% of the hyaluronan from the exposed tumor. In contrast, collagenase reduced collagen content, lowered tumor interstitial pressure, and markedly enhanced antibody penetration. Conclusions: Reduction of collagen, but not hyaluronan, in the matrix of ovarian xenografts enhanced the transport of i.p. injected antibody. Although high interstitial pressure is a deterrent to convective transport of macromolecules into the tumor parenchyma, the structure of the interstitial matrix provides an inherent resistance, which must be overcome before effective delivery of an antibody.
Variant CJD still poses threat to public health, warn experts
Authors: A. O'Dowd
Journal: BMJ (2013)

The risk of variant Creutzfeldt-Jakob disease (vCJD) to public health in the United Kingdom is still very much a reality and requires funding for research and universal blood tests, scientific experts have warned.

MPs on the House of Commons Science and Technology Committee holding an evidence session on 27 November as part of their inquiry into vCJD were told by experts of the ongoing risks of the disease.

The degenerative brain disease, sometimes called the human form of bovine spongiform encephalopathy (BSE) or “mad cow disease,” emerged after widespread exposure to BSE prions in the late 1980s and early 1990s through contaminated meat products in the food chain.

At the evidence session, Andrew Miller, the committee’s chairman and Labour MP for Ellesmere Port and Neston, asked, “Do you think that variant CJD continues to pose a significant risk to public health?”

John Collinge, professor of neurology at University College London …
Intimal Smooth Muscle Cells of Porcine and Human Coronary Artery Express S100A4, a Marker of the Rhomboid Phenotype In Vitro
Authors: Anne C. Brisset, Hiroyuki Hao, Edoardo Camenzind, Marc Bacchetta, Antoine Geinoz, Jean-Charles Sanchez, Christine Chaponnier, Giulio Gabbiani, Marie-Luce Bochaton-Piallat
Journal: Circulation Research (2007)

We reported that smooth muscle cell (SMC) populations isolated from normal porcine coronary artery media exhibit distinct phenotypes: spindle-shaped (S) and rhomboid (R). R-SMCs are recovered in higher proportion from stent-induced intimal thickening compared with media suggesting that they participate in intimal thickening formation. Our aim was to identify a marker of R-SMCs in vitro and to explore its possible expression in vivo. S- and R-SMC protein extracts were compared by means of 2-dimensional polyacrylamide gel electrophoresis followed by tandem mass spectrometry. S100A4 was found to be predominantly expressed in R-SMC extracts. Using a monoclonal S100A4 antibody we confirmed that S100A4 is highly expressed by R-SMCs and hardly detectable in S-SMCs. S100A4 was colocalized with α-smooth muscle actin in stress fibers of several quiescent cells and upregulated during migration. PDGF-BB, FGF-2 or coculture with endothelial cells, which modulate S-SMCs to a R-phenotype, increased S100A4 expression in both S- and R-SMCs. Silencing of S100A4 mRNA in R-SMCs decreased cell proliferation, suggesting a functional role for this protein. In vivo S100A4 was absent in normal porcine coronary artery media, but highly expressed by SMCs of stent-induced intimal thickening. In humans, S100A4 was barely detectable in coronary artery media and markedly expressed in SMCs of atheromatous and restenotic coronary artery lesions. Our results indicate that S100A4 is a marker of porcine R-SMCs in vitro and of intimal SMCs during intimal thickening development. It is also a marker of a large population of human atheromatous and restenotic SMCs. Clarifying S100A4 function might be useful to understand the evolution of atherosclerotic and restenotic processes.
Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation
Authors: Yinzhu Jin, Cinzia Mazza, Jacinda R. Christie, Silvia Giliani, Maurilia Fiorini, Patrizia Mella, Francesca Gandellini, Donn M. Stewart, Qili Zhu, David L. Nelson, Luigi D. Notarangelo, Hans D. Ochs
Journal: Blood (2004)
Glycodelin: A New Biomarker with Immunomodulatory Functions in Non–Small Cell Lung Cancer
Authors: Marc A. Schneider, Martin Granzow, Arne Warth, Philipp A. Schnabel, Michael Thomas, Felix J.F. Herth, Hendrik Dienemann, Thomas Muley, Michael Meister
Journal: Clinical Cancer Research (2015)

In recent years, immune therapeutic strategies against non-small cell lung cancer (NSCLC) based on tissue-derived biomarkers, for example PD1/PD-L1 (CD274), have evolved as novel and promising treatment options. However, the crosstalk between tumor and immune cells is poorly understood. Glycodelin (gene name PAEP), initially described in the context of pregnancy and trophoblastic implantation, is a secreted immunosuppressive glycoprotein with an as-of-yet largely unknown function in lung cancer.In this study, we characterized the expression and role of glycodelin in NSCLC through mRNA and protein expression analyses, functional knockdown experiments, and correlations with clinicopathologic parameters.Glycodelin mRNA expression was significantly elevated in tumors (n = 336) compared with matched normal tissue (P < 0.0001). Overall survival (OS) was significantly reduced in NSCLC with high glycodelin mRNA levels in women but not in men. Glycodelin was detected in the sera of patients, and the levels correlated with recurrence and metastatic disease. Knockdown of glycodelin with siRNAs in NSCLC cell lines resulted in significant upregulation of immune system modulatory factors such as PDL1, CXCL5, CXCL16, MICA/B, and CD83 as well as proliferation stimulators EDN1 and HBEGF. Furthermore, decreased migration of tumor cells was observed.Altogether, the comprehensive characterization of glycodelin in NSCLC provides strong support for its use as a biomarker with immune modulatory function.
Skin-derived antileucoproteases (SKALPs): characterization of two new elastase inhibitors from psoriatic epidermis
Authors: J. SCHALKWIJK, A. CHANG, P. JANSSEN, G.J. JONGH, P.D. MIER
Journal: British Journal of Dermatology (1990)

Elastase inhibiting activity (EIA) was demonstrated in the epidermis from lesions and in psoriatic scale, whereas normal epidermis did not contain significant EIA. Two new elastase inhibitors were partially purified and characterized using psoriatic scale as a source. The two species (approximate molecular weights 10 and 20 kDa) were shown to be stable, and high-affinity inhibitors of human leucocyte elastase (Ki less than 10(-10) M). No activity against human cathepsin G could be demonstrated. Cultured human keratinocytes were shown to contain EIA activity similar to that found in psoriatic scale. EIA could also be demonstrated in human epidermis following the induction of an experimental inflammatory response by sellotape-stripping. We propose the acronym SKALP (skin-derived antileucoprotease) as a name for these new proteinase inhibitors.
Melorheostosis on Three-phase Bone Scintigraphy
Authors: DANIEL C. DAVIS, RICARDO SYKLAWER, RICHARD L. COLE
Journal: Clinical Nuclear Medicine (1992)

Melorheostosis is a benign sclerosing bone dysplasia with a very unusual and characteristic roentgenographic appearance. Its scintigraphic appearance also is characteristic, with asymmetric cortical activity that may cross joints to involve contiguous bones. The authors report the appearance of melorheostosis on angiogram and blood pool phases of three-phase bone scintigraphy.
Dynamic Rectal Examination: Its Significant Clinical Value
Authors: Tj. G. Wiersma, C. J. J. Mulder, J. W. A. J. Reeders
Journal: Endoscopy (1997)

The aim of the present study was to carry out a proper correlation between patients' clinical symptoms and the radiological findings obtained by dynamic rectal examination (DRE). At DRE, the small bowel and in females the vagina are routinely opacified in addition to defecography. A prospective study of 248 consecutive patients (193 women and 55 men, ratio 3.5:1) and 14 control subjects was conducted. The parameters assessed included the anorectal angle, the position of the anorectal junction, and the total movement of the pelvic floor during squeezing and defecation. Anatomical changes as rectoceles, enteroceles and intussusceptions were also observed. Based on the findings, the following conclusions can be drawn. There is no indication for measurement of the central or posterior anorectal angle. There is no indication for measurement of the perineal ascent, perineal descent, and anorectal junction level. Anterior rectoceles occur very frequently in females, and are only of clinical relevance if the patients need digital vaginal support to facilitate defecation. DRE is a sensitive method for diagnosing enteroceles and intussusceptions.
Isotype specificity of helper T cell clones. Peyer's patch Th cells preferentially collaborate with mature IgA B cells for IgA responses.
Authors: H Kiyono, M D Cooper, J F Kearney, L M Mosteller, S M Michalek, W J Koopman, J R McGhee
Journal: The Journal of Experimental Medicine (1984)

The nature of the IgA B cell precursors that receive preferential help from selected clones of T helper cells from mouse Peyer's patches (PP Th A) were studied. Activation of the PP Th A clones required the presence of antigen, sheep erythrocytes (SRBC), in a culture system supporting development of antibody-secreting plasma cells. Two types of PP Th A cells were used. Both gave vigorous IgA responses; the first also supported low IgM, and the second low IgM and IgG subclass antibody responses. Removal of sIgA+ B cells from either splenic or PP B cell cultures selectively depleted precursors of IgA antibody producers. Cultures of purified sIgA+ B cells, cloned PP Th A cells and SRBC, selectively yielded IgA antibody producers. Finally, PP Th A cells did not support IgA responses in B cell cultures derived from spleens of young mice (days 1-25), and full IgA responses were not seen until the donor mice were 6-7 wk of age. These results suggest that cloned T helper cells can recognize and collaborate with mature, IgA committed B cells.
Anaphylactoid Reactions to Isosulfan Blue Dye During Breast Cancer Lymphatic Mapping in Patients Given Preoperative Prophylaxis
Authors: Chandrajit P. Raut, M. Denise Daley, Kelly K. Hunt, Jeri Akins, Merrick I. Ross, S. Eva Singletary, Gailen D. Marshall, Funda Meric-Bernstam, Gildy Babiera, Barry W. Feig, Frederick C. Ames, Henry M. Kuerer
Journal: Journal of Clinical Oncology (2004)
Association Between Physical Activity and Risk of All-Cause Mortality and Cardiovascular Disease in Patients With Diabetes
Authors: Satoru Kodama, Shiro Tanaka, Yoriko Heianza, Kazuya Fujihara, Chika Horikawa, Hitoshi Shimano, Kazumi Saito, Nobuhiro Yamada, Yasuo Ohashi, Hirohito Sone
Journal: Diabetes Care (2013)

OBJECTIVE The association between habitual physical activity (PA) and lowered risk of all-cause mortality (ACM) and cardiovascular disease (CVD) has been suggested in patients with diabetes. This meta-analysis summarizes the risk reduction in relation to PA, focusing on clarifying dose-response associations. RESEARCH DESIGN AND METHODS Electronic literature searches were conducted for cohort studies that examined relative risk (RR) of ACM or CVD in relation to PA in patients with diabetes. For the qualitative assessment, RR for the highest versus the lowest PA category in each study was pooled with a random-effects model. We added linear and spline regression analyses to assess the quantitative relationship between increases in PA and ACM and CVD risk. RESULTS There were 17 eligible studies. Qualitatively, the highest PA category had a lower RR [95% CI] for ACM (0.61 [0.52–0.70]) and CVD (0.71 [0.60–0.84]) than the lowest PA category. The linear regression model indicated a high goodness of fit for the risk of ACM (adjusted R2 = 0.44, P = 0.001) and CVD (adjusted R2 = 0.51, P = 0.001), with the result that a 1 MET-h/day incrementally higher PA was associated with 9.5% (5.0–13.8%) and 7.9% (4.3–11.4%) reductions in ACM and CVD risk, respectively. The spline regression model was not significantly different from the linear model in goodness of fit (P = 0.14 for ACM risk; P = 0.60 for CVD risk). CONCLUSIONS More PA was associated with a larger reduction in future ACM and CVD risk in patients with diabetes. Nevertheless, any amount of habitual PA was better than inactivity.
Plasma mevalonate as a measure of cholesterol synthesis in man.
Authors: T S Parker, D J McNamara, C D Brown, R Kolb, E H Ahrens, A W Alberts, J Tobert, J Chen, P J De Schepper
Journal: Journal of Clinical Investigation (1984)

Measurement of mevalonic acid (MVA) concentrations in plasma or 24-h urine samples is shown to be useful in studies of the regulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol synthesis. Plasma MVA concentrations, measured either at 7-9 a.m. after an overnight fast, or throughout the 24-h cycle, were compared with cholesterol synthesis rates that were measured by the sterol balance method: plasma MVA concentrations were directly related to the rate of whole body cholesterol synthesis (r = 0.972; p less than 0.001; n = 18) over a tenfold range of cholesterol synthesis rates. Moreover, hourly examination of MVA concentrations throughout the day demonstrated that interventions such as fasting or cholesterol feeding cause suppression of the postmidnight diurnal rise in plasma MVA concentrations, with little change in the base-line of the rhythm. Thus, the daily rise and fall of plasma MVA appears to reflect changes in tissues and organs, such as the liver and intestine, that are known to be most sensitive to regulation by fasting or by dietary cholesterol. The hypothesis that short-term regulation of HMG-CoA reductase in tissues is quickly reflected by corresponding variations in plasma MVA was tested by using a specific inhibitor of HMG-CoA reductase, mevinolin, to block MVA synthesis. Mevinolin caused a dose-dependent lowering of plasma MVA after a single dose; and in patients who received the drug twice a day for 4 wk, it decreased 24-h urinary MVA output. Significant lowering of plasma cholesterol was achieved through administration of mevinolin at doses that only moderately limit MVA production.
Early Fixation of an Optimal Genetic Code
Authors: Stephen J. Freeland, Robin D. Knight, Laura F. Landweber, Laurence D. Hurst
Journal: Molecular Biology and Evolution (2000)

The evolutionary forces that produced the canonical genetic code before the last universal ancestor remain obscure. One hypothesis is that the arrangement of amino acid/codon assignments results from selection to minimize the effects of errors (e.g., mistranslation and mutation) on resulting proteins. If amino acid similarity is measured as polarity, the canonical code does indeed outperform most theoretical alternatives. However, this finding does not hold for other amino acid properties, ignores plausible restrictions on possible code structure, and does not address the naturally occurring nonstandard genetic codes. Finally, other analyses have shown that significantly better code structures are possible. Here, we show that if theoretically possible code structures are limited to reflect plausible biological constraints, and amino acid similarity is quantified using empirical data of substitution frequencies, the canonical code is at or very close to a global optimum for error minimization across plausible parameter space. This result is robust to variation in the methods and assumptions of the analysis. Although significantly better codes do exist under some assumptions, they are extremely rare and thus consistent with reports of an adaptive code: previous analyses which suggest otherwise derive from a misleading metric. However, all extant, naturally occurring, secondarily derived, nonstandard genetic codes do appear less adaptive. The arrangement of amino acid assignments to the codons of the standard genetic code appears to be a direct product of natural selection for a system that minimizes the phenotypic impact of genetic error. Potential criticisms of previous analyses appear to be without substance. That known variants of the standard genetic code appear less adaptive suggests that different evolutionary factors predominated before and after fixation of the canonical code. While the evidence for an adaptive code is clear, the process by which the code achieved this optimization requires further attention.
Oesophageal cancer and alcoholic spirits in central Africa
Authors: N. D. McGlashan
Journal: Gut (1969)

A geographical pathology survey of a large area in central Africa is described and a contrast is recognized between neighbouring areas with apparently many and apparently few cases of oesophageal cancer. This distribution is compared first with other known areas of high and low incidence in sub-Saharan Africa and then with the drinking of indigenous types of distilled spirits. A significant order of spatial correlation is shown between the geographical pattern of the disease and the drinking of sugar-based alcoholic spirit in central Africa. Samples of spirits from eastern Zambia, central Kenya, and the Transkei, although prepared in apparently dissimilar utensils, were all shown to be contaminated in varying degree with zinc. Nitrosamine-like compounds in native spirits were also reported in all these areas. The need for a geographical survey of indigenous drinking habits in Africa is illustrated. Since legislation against distilling is ineffective, a simple means of excluding carcinogenic compounds from illicit spirits should be ascertained and widely promulgated at village level.
Too much substance, not enough cognition
Authors: Vincent C. Müller, Stephanie Kelter
Journal: Behavioral and Brain Sciences (1998)

Millikan's account of substance concepts is based on a notion of “substance” expanded from realist notions of individuals and natural kinds. Her metaphysical notion, based on “inductive potential,” is shown to be too puristic and needs to incorporate cognizing subjects. This could preserve the realist/nondescriptionist insight that the extension of substances is determined by the world.
Cocaine-induced hepatotoxicity
Authors: John M. Porter, Marc S. Sussman, Gerald M. Rosen
Journal: Hepatology (1988)

A patient with hepatonecrosis associated with cocaine use is presented. Postmortem examination of the liver showed marked periportal inflammation and necrosis, and mild diffuse fatty infiltration. These pathologic findings are identical to those previously reported in a mouse model of cocaine hepatotoxicity.
Hydrogen sulfide as a novel mediator for pancreatic pain in rodents
Authors: S Nishimura, O Fukushima, H Ishikura, T Takahashi, M Matsunami, T Tsujiuchi, F Sekiguchi, M Naruse, Y Kamanaka, A Kawabata
Journal: Gut (2009)

<h3>Objective:</h3> Hydrogen sulfide (H<sub>2</sub>S) is formed from l-cysteine by multiple enzymes including cystathionine-γ-lyase (CSE) in mammals, and plays various roles in health and disease. Recently, a pronociceptive role for H<sub>2</sub>S in the processing of somatic pain was identified. Here, the involvement of H<sub>2</sub>S in pancreatic pain is examined. <h3>Methods:</h3> Anaesthetised rats or mice received an injection of NaHS, a donor for H<sub>2</sub>S, or capsaicin into the pancreatic duct, and the expression of spinal Fos protein was detected by immunohistochemistry. Pancreatitis was created by 6 hourly doses of caerulein in unanaesthetised mice, and pancreatitis-related allodynia/hyperalgesia was evaluated using von Frey hairs. CSE activity and protein levels in pancreatic tissues were measured using the colorimetric method and western blotting, respectively. <h3>Results:</h3> Either NaHS or capsaicin induced the expression of Fos protein in the superficial layers of the T8 and T9 spinal dorsal horn of rats or mice. The induction of Fos by NaHS but not capsaicin was abolished by mibefradil, a T-type Ca<sup>2+</sup> channel blocker. In conscious mice, repeated doses of caerulein produced pancreatitis accompanied by abdominal allodynia/hyperalgesia. Pretreatment with an inhibitor of CSE prevented the allodynia/hyperalgesia, but not the pancreatitis. A single dose of mibefradil reversed the established pancreatitis-related allodynia/hyperalgesia. Either the activity or protein expression of pancreatic CSE increased after the development of caerulein-induced pancreatitis in mice. <h3>Conclusions:</h3> The data suggest that pancreatic NaHS/H<sub>2</sub>S most probably targets T-type Ca<sup>2+</sup> channels, leading to nociception, and that endogenous H<sub>2</sub>S produced by CSE and possibly T-type Ca<sup>2+</sup> channels are involved in pancreatitis-related pain.