tbuckley/cabot-search huggingface dataset:
The conventional autopsy in modern medicine
Authors: Tariq Ayoub, Jade Chow
Journal: Journal of the Royal Society of Medicine (2008)

Summary In many countries, including the UK, where relatives' consent is required, clinical autopsy rates (i.e. autopsies other than those required by law) have been declining since the 1950s. In the UK, even in teaching hospitals, the clinical autopsy rate has fallen to only 10% of deaths or less. At this rate of decline, clinical autopsies – and the pathologists who perform them – face extinction. The future practice of medicine will be blind to the many adverse consequences of clinical actions or omissions. The reasons for this decline are manifold and these have to be addressed if autopsy is to stand a chance of survival. The future of autopsy lies in promoting public support for autopsies, in some cases adapting the autopsy to address specific questions, thus making more effective use of information from autopsies. Only by ensuring that the next generation of doctors have experienced the powerful educational benefit of examining the body after death will the importance of autopsy to modern medicine be understood.
Basal Ganglia Surface Morphology and the Effects of Stimulant Medications in Youth With Attention Deficit Hyperactivity Disorder
Authors: Loren J. Sobel, Ravi Bansal, Tiago V. Maia, Juan Sanchez, Luigi Mazzone, Kathleen Durkin, Jun Liu, Xuejun Hao, Iliyan Ivanov, Ann Miller, Laurence L. Greenhill, Bradley S. Peterson
Journal: American Journal of Psychiatry (2010)

Objective Disturbances in the basal ganglia portions of cortico-striato-thalamo-cortical circuits likely contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The authors examined the morphologic features of the basal ganglia nuclei (caudate, putamen, and globus pallidus) in children with ADHD. Method A total of 104 individuals (combined-type ADHD patients: N=47; healthy comparison subjects: N=57), aged 7 to 18 years, were examined in a cross-sectional case-control study using anatomical magnetic resonance imaging. Conventional volumes and the surface morphology for the basal ganglia were measured. Results Overall volumes were significantly smaller only in the putamen. Analysis of the morphological surfaces revealed significant inward deformations in each of the three nuclei, localized primarily in portions of these nuclei that are components of limbic, associative, and sensorimotor pathways in the cortico-striato-thalamo-cortical circuits in which these nuclei reside. The more prominent these inward deformations were in the patient group, the more severe the ADHD symptoms. Surface analyses also demonstrated significant outward deformations of all basal ganglia nuclei in the ADHD children treated with stimulants compared with those ADHD youth who were untreated. These stimulant-associated enlargements were in locations similar to the reduced volumes detected in the ADHD group relative to the comparison group. The outward deformations associated with stimulant medications attenuated the statistical effects of the primary group comparisons. Conclusions These findings potentially represent evidence of anatomical dysregulation in the circuitry of the basal ganglia in children with ADHD and suggest that stimulants may normalize morphological features of the basal ganglia in children with the disorder.
Depressed beta-adrenergic receptor- and endothelium-mediated vasodilation in conscious dogs with heart failure.
Authors: K Kiuchi, N Sato, R P Shannon, D E Vatner, K Morgan, S F Vatner
Journal: Circulation Research (1993)

Peripheral vasodilator responsiveness was examined in pacing-induced heart failure (HF) in 11 conscious dogs chronically instrumented for measurement of systemic (total peripheral resistance [TPR]) and local (iliac blood flow) vascular resistance. Dose responses to isoproterenol (ISO), acetylcholine (ACh), and nitroglycerin (NTG) were examined in the same dogs before pacing (control) and after 4 to 7 weeks of rapid ventricular pacing, which induced congestive HF, characterized by increased left ventricular end-diastolic pressure (6.7 +/- 0.4 [control] versus 28 +/- 1.5 [HF] mm Hg) and decreased cardiac output (-30 +/- 5%) and left ventricular dP/dt (-53 +/- 3%), as well as ascites and peripheral edema. In the control state, TPR fell by 57 +/- 2% in response to ISO (100 ng/kg), by 61 +/- 3% in response to ACh (3 micrograms/kg), and by 55 +/- 2% in response to NTG (10 micrograms/kg). In HF, smaller decreases (P &lt; .05) in TPR were observed with the same doses of ISO (-50 +/- 2%) and ACh (-49 +/- 2%) but not with NTG (-58 +/- 3%). Depressed responses to systemic ISO and ACh, but not NTG, were observed in HF in the presence of ganglionic blockade and also after local administration of smaller doses of the drugs in the absence of ganglionic blockade, but where systemic effects were not elicited. Inhibition of nitric oxide synthase increased TPR to a greater degree before HF (+154 +/- 28% [control]) than after (+80 +/- 22% [HF]) and eliminated the depressed responses to ACh but not to ISO. beta-Adrenergic receptor density, as determined by 125I-cyanopindolol binding in membrane preparations from mesenteric vessels was significantly decreased after HF (130 +/- 3 [control] versus 100 +/- 8 [HF] fmol/mg, P &lt; .05) without any change in affinity. Thus, peripheral vascular beta-adrenergic receptor downregulation occurs in HF, independent of altered endothelium-mediated peripheral vasodilation.
Effects of inhibiting Na+/H+-exchange or angiotensin converting enzyme on atrial tachycardia-induced remodeling
Authors: K Shinagawa
Journal: Cardiovascular Research (2002)

Background: Inhibitors of the Na+/H+-exchanger (NHE1) and of angiotensin-converting enzyme (ACE) have been shown to reduce short-term (<6 h) tachycardia-induced atrial electrical remodeling. The role of NHE1 and ACE in longer-term electrical remodeling, as might occur with persistent AF, has not been studied. Methods: Dogs were subjected to atrial-tachypacing (400 bpm) for 7 days during treatment with 240 mg/day (standard clinical dose) of the NHE1 inhibitor cariporide (CariL, n=6), 1000 mg/day cariporide (CariH, n=6), 2 mg/kg/day of the ACE inhibitor enalapril (E, n=6), or no-drug controls (n=7). To ensure steady state concentrations at the onset of pacing, treatment began 3 days before the initiation of atrial tachypacing. Results were compared to those of unpaced dogs (n=9). Results: Atrial tachypacing reduced atrial effective refractory period (ERP), e.g. at a basic cycle length of 300 ms from 126±4 ms (unpaced, mean±S.E.) to 79±8 ms (no-drug controls, P<0.001). ERP abbreviation was unchanged by CariL (83±8 ms), CariH (80±7 ms), or E (76±5 ms). Atrial tachypacing increased mean duration of the longest AF episode in each dog (DAF) from 130±80 s (unpaced) similarly in all groups: 864±364 s, no-drug controls; 609±376 s, CariL; 709±353 s, CariH; 645±365 s, E (P=NS for differences among groups). Sustained AF requiring cardioversion for termination was induced in 0% of unpaced dogs vs. 33% of CariL, 33% of CariH, 33% of E, and 43% of control dogs. AF inducibility by single extrastimuli increased from 4±2% in unpaced dogs to 48±13% (P<0.01) in no-drug control dogs, an effect not changed by CariL (33±14%), CariH (35±17%) or E (48±16%). Conclusions: In contrast to short-term (several-hour) atrial tachycardia-induced remodeling, remodeling by 7-day tachycardia is not affected by NHE1 or ACE inhibition. These results support the notion that short-term atrial tachycardia remodeling involves different mechanisms from longer-term remodeling, and urges caution in extrapolating results from studies of short-term remodeling to effects in longer-term remodeling as often occurs clinically.
Purification and Characterization of a Major Allergen from the House Dust Mite <i>Dermatophagoides farinae</i>
Authors: A. Holck, S. Dale, K. Sletten
Journal: Allergy (1986)

A major allergen from an extract of the house dust mite, Dermatophagoides farinae , was shown to be extremely heterogenic with respect to charge. A slightly basic component of this allergen with a pI of 8, was purified by isoelectric focusing m two steps. The purified component, denoted antigen 19/20 IIa, seemed to be representative for the allergenic activity of the major allergen. The amino acid analysis suggested that antigen 19/20 IIa had a molecular weight of 9400 and contained one residue of galactosamine. SDS polyacrylamide gel electrophoresis did indicate a somewhat higher molecular weight of 14,500. Antibodies against the purified component cross reacted with a crude extract of the mite Dermatophagoides pteronyssinus.
C<scp>ELL</scp>-C<scp>ELL</scp> S<scp>IGNALING</scp> D<scp>URING</scp> S<scp>YNAPSE</scp> F<scp>ORMATION IN THE</scp> CNS
Authors: Peter Scheiffele
Journal: Annual Review of Neuroscience (2003)

▪ Abstract Synapses join individual nerve cells into a functional network. Specific cell-cell signaling events regulate synapse formation during development and thereby generate a highly reproducible connectivity pattern. The accuracy of this process is fundamental for normal brain function, and aberrant connectivity leads to nervous system disorders. However, despite the overall precision with which neuronal circuits are formed, individual synapses and synaptic networks are also plastic and can readily adapt to external stimuli or perturbations. In recent studies, several trans-synaptic signaling systems have been identified that can mediate various aspects of synaptic differentiation in the central nervous system. It appears that these individual pathways functionally cooperate, thereby generating robustness and flexibility, which ensure normal nervous system function.
Interleukin-12 inhibits antigen-induced airway hyperresponsiveness in mice.
Authors: J C Kips, G J Brusselle, G F Joos, R A Peleman, J H Tavernier, R R Devos, R A Pauwels
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The airway inflammation observed in allergic asthma is thought to be orchestrated by an antigen-driven T-helper-2 (Th2) lymphocyte response. In vitro data indicate that the presence of interleukin-12 (IL-12) during the primary stimulation of T-lymphocytes with antigen favors the development of Th1 cells. The aim of the present study was to examine the effect of IL-12 in vivo on antigen-induced airway changes in a murine model. C57BL/6 mice were actively sensitized to ovalbumin; 14 d later, they were exposed daily for 7 d to aerosolized ovalbumin. This resulted in airway eosinophilia, production of ovalbumin-specific IgE, and airway hyperresponsiveness to carbachol. Administration of recombinant murine IL-12 (rmIL-12) during the active immunization prevented these antigen-induced changes. In contrast, administration of rmIL-12 to actively immunized mice during the daily aerosol exposure (but not at the time of immunization) abolished airway eosinophilia and hyperresponsiveness without influencing the production of specific IgE. These results suggest that IL-12 can suppress antigen-induced airway changes despite the presence of circulating specific IgE.
The Clinical Relevance of Stromal Matrix Metalloproteinase Expression in Ovarian Cancer
Authors: Aparna A. Kamat, Mavis Fletcher, Lynn M. Gruman, Peter Mueller, Adriana Lopez, Charles N. Landen, Liz Han, David M. Gershenson, Anil K. Sood
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Matrix metalloproteinases (MMP) are proteolytic enzymes implicated in cancer progression and metastasis. We sought to determine the role of epithelial (tumor cell–derived) and stromal (host-derived) expression of MMPs in predicting the clinical outcome of patients with epithelial ovarian cancer (EOC). Experimental Design: MMP-2, MMP-9, and membrane type 1 (MT1)-MMP expression was evaluated using immunohistochemistry in 90 invasive EOCs, and samples were scored for epithelial and stromal staining. Results were correlated with clinicopathologic characteristics using univariate and multivariate analyses. Results: High expression of MMP-2, MMP-9, and MT1-MMP in tumor epithelium was detected in 54%, 97%, and 100% of cases, and in stromal compartments, in 38%, 70%, and 38% of cases, respectively. High stromal expression of MMP-2, MMP-9, and MT1-MMP was significantly associated with aggressive features such as high stage, high grade ascites, and positive lymph node status. Kaplan-Meier analysis showed that high epithelial and stromal expression of MMP-2, MMP-9, and MT1-MMP were each significantly associated with shorter disease-specific survival (DSS; P &amp;lt; 0.01). On tree-structured survival analysis, patients with strong epithelial MT1-MMP expression had the shortest DSS, whereas patients with moderate epithelial MT1-MMP and low stromal MMP-9 expression had the longest DSS (P &amp;lt; 0.01). On multivariate analysis, high stromal expression of MMP-9 (P = 0.01) and MT1-MMP (P = 0.04), strong epithelial MT1-MMP (P = 0.01) and high stage (P = 0.04) were independent predictors of poor DSS. Conclusions: Overexpression of stromal MMP-9 and MT1-MMP is independently associated with shorter DSS in EOC. Thus, host-derived MMPs are valuable predictors of clinical outcome in EOC.
Activation of Syk in Neutrophils by Antineutrophil Cytoplasm Antibodies Occurs via Fcγ Receptors and CD18
Authors: Peter Hewins, Julie M. Williams, Michael J.O. Wakelam, Caroline O.S. Savage
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Antineutrophil cytoplasm antibodies (ANCA) activate TNF-α–primed neutrophils to undergo a respiratory burst. The intracellular signals that mediate activation have not been studied extensively but could increase the understanding of the pathogenesis small vessel vasculitis. It was demonstrated that ANCA-IgG induced phosphorylation of the tyrosine kinase Syk in TNF-α–primed neutrophils from healthy donors. Syk was not phosphorylated in response to ANCA F(ab′)2. Furthermore, Syk phosphorylation was attenuated by blockade of both low-affinity Fcγ receptors and CD18. Similarly, low-affinity Fcγ receptor blockade reduced ANCA-induced superoxide production. In patient-derived neutrophils, the high-affinity Fcγ receptor FcγRI was also demonstrated to be involved in ANCA-induced superoxide production. However, Syk phosphorylation was not attenuated by blockade of the FcγRI, present on neutrophils from vasculitis patients. The tyrosine kinase inhibitor 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine inhibited the ANCA-induced respiratory burst and Syk phosphorylation, suggesting that Src kinases lie upstream of Syk activation but downstream of ANCA engagement of Fcγ receptors. Piceatannol, another tyrosine kinase inhibitor, also inhibited ANCA-induced Syk phosphorylation and the ANCA-stimulated respiratory burst, supporting the proposed functional role for Syk in ANCA signaling. ANCA-induced phosphorylation of Cbl and intracellular calcium transients, potential downstream mediators of Syk activation, were also blocked by tyrosine kinase inhibitors. While it has previously been shown that pertussis toxin diminishes the ANCA-induced respiratory burst, indicating heterotrimeric G protein involvement, Syk phosphorylation and calcium transients were unaffected by pertussis toxin. Collectively, these data show that Syk phosphorylation is induced during ANCA-triggered neutrophil activation.
Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump
Authors: Jacqueline R. M. Plass, Olaf Mol, Janette Heegsma, Mariska Geuken, Klaas Nico Faber, Peter L. M. Jansen, Michael Müller
Journal: Hepatology (2002)

The bile salt export pump (BSEP or ABCB11) mediates the adenosine triphosphate-dependent transport of bile salts across the canalicular membrane of the hepatocyte. Mutations in the corresponding ABCB11 gene cause progressive familial intrahepatic cholestasis type 2. The aim of this study was to investigate the regulation of human ABCB11 gene transcription by bile salts. First, a 1.7-kilobase human ABCB11 promoter region was cloned. Sequence analysis for possible regulatory elements showed a farnesoid X receptor responsive element (FXRE) at position −180. The farnesoid X receptor (FXR) functions as a heterodimer with the retinoid X receptor α (RXRα) and can be activated by the bile salt chenodeoxycholic acid (CDCA). Luciferase reporter gene assays showed that the ABCB11 promoter is positively controlled by FXR, RXRα, and bile salts in a concentration-dependent manner. Mutation of the FXRE strongly represses the FXR-dependent induction. Second, endogenous ABCB11 transcription regulation was studied in HepG2 cells, stably expressing the rat sodium-dependent taurocholate transporter (rNtcp) cells. ABCB11 expression was induced by adding bile salts to the culture medium, and this effect was maximized by combining it with cotransfection of rFxr and hRXRα. Reducing endogenous FXR levels using RNA interference fully repressed the bile salt-induced ABCB11 expression. In conclusion, these results show that FXR is required for the bile salt-dependent transcriptional control of the human ABCB11 gene and that the cellular amount of FXR is critical for the level of activation of ABCB11 transcription.
Colonic stenting versus emergency surgery for acute left-sided malignant colonic obstruction: a multicentre randomised trial
Authors: Jeanin E van Hooft, Willem A Bemelman, Bas Oldenburg, Andreas W Marinelli, Martijn F Lutke Holzik, Marina J Grubben, Mirjam A Sprangers, Marcel G Dijkgraaf, Paul Fockens
Journal: The Lancet Oncology (2011)
MicroRNA in Cardiovascular Calcification
Authors: Claudia Goettsch, Joshua D. Hutcheson, Elena Aikawa
Journal: Circulation Research (2013)

Cardiovascular calcification is a prominent feature of chronic inflammatory disorders-such as chronic kidney disease, type 2 diabetes mellitus, and atherosclerosis-that associate with significant morbidity and mortality. The concept that similar pathways control both bone remodeling and vascular calcification is widely accepted, but the precise mechanisms of calcification remain largely unknown. The central role of microRNAs (miRNA) as fine-tune regulators in the cardiovascular system and bone biology has gained acceptance and has raised the possibility for novel therapeutic targets. Additionally, circulating miRNAs have been proposed as biomarkers for a wide range of cardiovascular diseases, but knowledge of miRNA biology in cardiovascular calcification is very limited. This review focuses on the role of miRNAs in cardiovascular disease, with emphasis on osteogenic processes. Herein, we discuss the current understanding of miRNAs in cardiovascular calcification. Furthermore, we identify a set of miRNAs common to diseases associated with cardiovascular calcification (chronic kidney disease, type 2 diabetes mellitus, and atherosclerosis), and we hypothesize that these miRNAs may provide a molecular signature for calcification. Finally, we discuss this novel hypothesis with emphasis on known biological and pathological osteogenic processes (eg, osteogenic differentiation, release of calcifying matrix vesicles). The aim of this review is to provide an organized discussion of the known links between miRNA and calcification that provide emerging concepts for future studies on miRNA biology in cardiovascular calcification, which will be critical for developing new therapeutic strategies.
Effectiveness and safety of tocilizumab therapy for patients with rheumatoid arthritis and renal insufficiency: a real-life registry study in Japan (the ACTRA-RI study)
Authors: Shunsuke Mori, Tamami Yoshitama, Toshihiko Hidaka, Naoyuki Hirakata, Yukitaka Ueki
Journal: Annals of the Rheumatic Diseases (2015)

Renal involvement is frequently present in patients with rheumatoid arthritis (RA). Approximately 15–25% of patients with RA have renal insufficiency, defined as a glomerular filtration rate (GFR) <60 mL/min.1 Although concomitant use of methotrexate (MTX) has been proven to be more effective than administration of biological agents alone,2 MTX elimination is delayed in patients with renal insufficiency, which can increase the risk of adverse events.3 ,4 Therefore we often use MTX at reduced dosage for these patients in daily practice, which may result in inadequate responses.

The ACTRA-RI (Actemra for RA patients with renal insufficiency) study was designed to evaluate the efficacy and safety of tocilizumab (TCZ) therapy in the real-life registry of patients with RA and renal insufficiency. For this study, we registered all patients with RA who had begun TCZ therapy in participating hospitals as of January 2014 (total 405 patients with RA: 102 with renal insufficiency and 303 without). An estimated GFR (eGFR) was first calculated using an equation that had been …
Effect of Human Leukocyte Antigen Class I Expression of Tumor Cells on Outcome of Intravesical Instillation of Bacillus Calmette-Guerin Immunotherapy for Bladder Cancer
Authors: Hiroshi Kitamura, Toshihiko Torigoe, Ichiya Honma, Eiji Sato, Hiroko Asanuma, Yoshihiko Hirohashi, Noriyuki Sato, Taiji Tsukamoto
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Various immune systems play important roles in the clinical efficacy of intravesical Bacillus Calmette-Guerin (BCG) instillation for bladder cancer. However, human leukocyte antigen (HLA) class I molecules on tumor cells and various immune system cells infiltrating to/around the tumor have not been evaluated, although many prognostic factors, including clinical, pathologic, and molecular ones, have been investigated. The aim of this study was to determine immunologic prognostic factors of BCG immunotherapy for bladder cancer. Experimental Design: Immunohistochemical staining for HLA class I, CD4, CD8, CD20, CD68, TIA-1, S-100, and FOXP3 was carried out on specimens from 30 patients who underwent BCG immunotherapy from whom both pretreatment and posttreatment specimens were obtained. We did univariate and multivariate analyses of factors affecting recurrence-free survival. The positive, weakly positive, and negative groups of cells that infiltrated to/around the tumor were compared with recurrence-free survival using the Kaplan-Meier method and log-rank test. Results: HLA class I was a significant prognostic factor both in univariate and multivariate analyses. The 5-year recurrence-free survivals of the patients with HLA class I–positive tumors and those with HLA class I–negative tumors were 55.7% and 19.1%, respectively (P = 0.019). There was a significant association between infiltration of CD8, CD20, and CD68-positive cells after BCG therapy and therapeutic effects. Conclusions: Our data show that expression of HLA class I molecules on tumor cells contributes significantly to the therapeutic effect of BCG immunotherapy for bladder cancer. It is suggested that CTLs may be one of main effectors in this therapy.
A comparison of twice-weekly MPD-PUVA and three times-weekly skin typing-PUVA regimens for the treatment of psoriasis
Authors: D.A. BUCKLEY, E. HEALY, S. ROGERS
Journal: British Journal of Dermatology (1995)

Journal Article A comparison of twice‐weekly MPD‐PUVA and three times‐weekly skin typing‐PUVA regimens for the treatment of psoriasis Get access D.A. BUCKLEY, D.A. BUCKLEY City of Dublin Skin and Cancer Hospital, Hume Street, Dublin 2, Ireland Dr D.A. Buckley, Department of Dermatology, The General Hospital, Steelhouse Lane, Birmingham B4 6NP, U.K. Search for other works by this author on: Oxford Academic Google Scholar E. HEALY, E. HEALY Department of Dermatology, Royal Victoria Infirmary, Newcastle Upon Tyne, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. ROGERS S. ROGERS City of Dublin Skin and Cancer Hospital, Hume Street, Dublin 2, Ireland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 133, Issue 3, 1 September 1995, Pages 417–422, https://doi.org/10.1111/j.1365-2133.1995.tb02670.x Published: 01 September 1995 Article history Accepted: 09 November 1994 Published: 01 September 1995