tbuckley/cabot-search huggingface dataset:
A child with localized vulval pemphigoid and IgG autoantibodies targeting the C-terminus of collagen XVII/BP180
Authors: None Schumann, None Amann, None Tasanen, None Müller, None Zillikens, None Metze, None Luger, None Bruckner-Tuderman, None Bonsmann
Journal: British Journal of Dermatology (1999)

Localized vulval pemphigoid of childhood (LVPC) has previously been reported in six girls. Clinical features and immunopathological data have suggested it to be a morphological variant of bullous pemphigoid. Epitope targets of the autoantibodies of these patients have not been defined in detail. We describe a 9-year-old girl with possible cicatricial LVPC and circulating IgG antibodies directed against native collagen XVII/BP180, its 120-kDa soluble ectodomain and against the C-terminus of collagen XVII/BP180. No reactivity was detected towards the NC16A domain of collagen XVII/BP180. Linear IgG and C3 deposits were found along the cutaneous basement membrane zone. On 1 mol/L salt-split skin, IgG autoantibodies were shown to bind to the epidermis, and the HLA type II allele DQB1*0301, a marker with significantly increased occurrence in patients with ocular and oral cicatricial pemphigoid, was identified in this patient. Our data suggest that LVPC is a variant of bullous pemphigoid in which direct immunofluorescence microscopy combined with immunoblot analysis can deliver valuable diagnostic information for differential diagnosis. However, differentiation between the scarring and non-scarring course of the disease cannot be made with the present diagnostic markers and therefore careful follow-up of patients with LVPC is required.
Health economics and the modern management of psoriasis
Authors: A.D. Burden
Journal: British Journal of Dermatology (2010)

Journal Article Health economics and the modern management of psoriasis Get access A.D. Burden A.D. Burden Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. E‐mail: David.Burden@ggc.scot.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 4, 1 October 2010, Pages 670–671, https://doi.org/10.1111/j.1365-2133.2010.10006.x Published: 01 October 2010
Abstract 11559: Determination of Cardiac Troponin with a Single-Molecule High-Sensitivity Assay and Outcomes in Patients with Stable Coronary Artery Disease: Analysis from PROVE IT-TIMI 22
Authors: Ryan G O'Malley, David A Morrow, Marc P Bonaca, Petr Jarolim, Benjamin M Scirica, Sabina A Murphy, Michael J Conrad, Christopher P Cannon, Eugene Braunwald, Marc S Sabatine
Journal: Circulation (2012)

Cardiac troponin (cTn), an established biomarker in acute coronary syndromes (ACS), is also an emerging risk predictor in patients (pts) with stable ischemic heart disease (SIHD). We assessed the p...
Phase III trial of conventional-dose chemotherapy alone or with high-dose chemotherapy for metastatic germ cell tumors (GCT) patients (PTS): A cooperative group trial by Memorial Sloan-Kettering Cancer Center, ECOG, SWOG, and CALGB
Authors: D. F. Bajorin, C. R. Nichols, K. A. Margolin, J. Bacik, P. G. Richardson, N. J. Vogelzang, L. Einhorn, M. Mazumdar, G. J. Bosl, R. J. Motzer
Journal: Journal of Clinical Oncology (2006)

4510 Background: First-line high-dose chemotherapy (HDCT) for poor-prognosis GCT PTS demonstrated improved relapse-free and overall survival compared to historical controls receiving conventional-dose regimens (JCO 1996;14:2546). Retrospective studies also showed correlations between long-term outcome and initial declines of alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (HCG). This trial sought to determine: 1) if early intervention with HDCT resulted in an outcome superior to standard-dose chemotherapy and 2) whether AFP and HCG declines during cycles 1 &amp; 2 correlated with long-term treatment outcome. Methods: PTS with untreated intermediate- or poor-risk GCT by International criteria (IGCCCG) were randomized to either 2 cycles of standard BEP (bleomycin, etoposide &amp; cisplatin) followed by 2 cycles of HDCT (cyclophosphamide, etoposide, carboplatin) plus stem-cell rescue (BEP + HDCT) or to 4 cycles of BEP. The primary endpoint was the percent of PTS in complete response at 1 year (CR-1 yr). Based on an historical CR-1 yr of 45% for BEP, targeted accrual was 109 PTS/arm to detect a 20% improvement in PTS receiving BEP + HDCT with an alpha of 5% and 80% power. Randomization used random permuted blocks; strata were risk status (poor/intermediate) and treatment center. An independent DSMB performed one interim analysis of CR-1yr and survival in May 2000. Results: 219 PTS were randomized; 108 to BEP + HDCT and 111 to BEP alone. Final analysis demonstrated a CR-1yr of 52% for BEP + HDCT and 48% for BEP alone (P = .53 via actuarial methods). Slow marker decline PTS (AFP and/or HCG) during cycles 1 &amp; 2 of BEP had a shorter progression-free and overall survival compared to satisfactory decline PTS (P ≤ .02) Among 70 PTS with unsatisfactory marker decline in cycles 1 &amp; 2, the CR-1 yr was 61% for PTS receiving HDCT for cycles 3 &amp; 4 versus 31% for those receiving 2 more cycles of BEP (P = .008). Conclusions: The routine inclusion of HDCT for intermediate- and poor-risk GCT does not improve treatment outcome. Serum marker decline during the first 2 cycles of BEP chemotherapy provides a clinically useful estimate of outcome. Research support provided by the NIH. [Table: see text]
Abstract 16362: Serum-Free Differentiation and Enrichment of Functional Human Vascular Smooth Muscle Cells From Embryonic Stem Cells
Authors: Omar A El-Mounayri, Anton Mihic, Eric A Shikatani, Mark Gagliardi, Nicole Dubois, Ralph DaCosta, Ren-Ke Li, Gordon Keller, Mansoor Husain
Journal: Circulation (2011)

Background: Currently, surface markers enabling cell sorting of viable vascular smooth muscle cells (SMCs) from mixed cell populations or tissues for therapeutic or diagnostic purposes are not available. Here we define a method to enrich for functional human vascular SMCs derived from human embryonic stem cells (hESCs). Methods & Results: Embryoid bodies (EBs) subjected to serum-free cardiovascular-directed differentiation were characterized over 30 days for SMC-specific gene expression by qRT-PCR, immunohistochemistry (IHC), and flow cytometry. EBs were composed of endothelial cells, fibroblasts, cardiomyocytes, and SMCs. Flow cytometry of day 28 EBs reveals that the SMCs form a distinct sub-population, which can integrate with endothelial cells in an in vitro angiogenesis assay. To enrich for SMCs, day 28 EBs were dissociated and cultured as monolayers. Passaging monolayers in serum-free conditions resulted in the loss of cardiomyocyte, endothelial and fibroblast populations. qRT-PCR and IHC analyses sh...
Non Invasive Respiratory Support
Journal: Thorax (1996)

Book reviews stinal lymphadenopathy is not surprising.Paediatric series have emphasised the usefulness of bronchoscopy for the diagnosis of endobronchial disease associated with medi- astinal lymph node tuberculosis.2In adults Auregan et al reported that only three from a series of 140 patients with tuberculous medi- astinal lymphadenopathy had a normal fibr- eoptic bronchoscopic examination and that 135 patients had one or more bronchial fistu- lae.3We therefore agree with Baran and col- leagues that bronchoscopy is of significant diagnostic value in patients with isolated tuberculous mediastinal lymphadenopathy and may avoid more invasive procedures such as mediastinoscopy.However, rigid bron- choscopy with large sampling and/or trans- bronchial biopsy is probably not necessary in most patients.We believe that fibreoptic bronchoscopy with bronchial biopsy speci- mens should be considered as a first line examination in patients with apparently isolated tuberculous mediastinal lymphadenopathy.
Anti-PD1 Pembrolizumab Can Induce Exceptional Fulminant Type 1 Diabetes
Authors: Caroline Gaudy, Céline Clévy, Sandrine Monestier, Noémie Dubois, Yanis Préau, Stéphanie Mallet, Marie-Aleth Richard, Jean-Jacques Grob, René Valéro, Sophie Béliard
Journal: Diabetes Care (2015)

A 44-year-old Caucasian woman with no history of diabetes was admitted to the emergency department in 2014 for vomiting and confusion, with polyuria, polydipsia, and a very recent weight loss (15 days). Biological tests revealed severe hyperglycemia and diabetic ketoacidosis (glycemia 50.45 mmol/L, ketones 3+, pH 7.25, HCO3− 3 mEq/L), with acute renal failure (39 mL/min/1.73 m2) and elevated serum lipase. Pancreatitis was ruled out by an abdominal computed tomography scan. Intravenous insulin resulted in rapid glycemic control. Surprisingly, HbA1c was subnormal (6.85%). Furthermore, anti-GAD and anti-IA2 antibodies were negative and serum C-peptide was undetectable. All these parameters led to the unusual diagnosis of fulminant type 1 diabetes (FD). FD is a rare subtype of type 1 diabetes …
Intratumor heterogeneity of EGFR mutations in lung cancer tissues and its correlation with the response to gefitinib
Authors: Kikuya Kato, Kazuya Taniguchi, Jiro Okami, Ken Kodama, Masahiko Higashiyama
Journal: Clinical Cancer Research (2006)

B25  Cancer tissues consist of various cancer cells with different genetic alterations. From the viewpoint of anti-cancer drug therapy, it is important to assess the ratio between responder and non-responder cells. Due to lack of biomarkers discriminating responder and non-responder cells, such studies are generally difficult. However, with molecular target drugs, the studies may be possible using target molecules as the biomarker. In particular, gefitinib is an ideal example, because responders carry somatic mutation(s) in the kinase domain of EGFR. This correlation is gaining a consensus at least in the Asian population. We collected primary non-small cell lung cancer tissues from twenty Japanese patients treated with gefitinib. All tissues were confirmed to carry EGFR mutations by PCR direct sequencing. For accurate quantitation of the responder/non-responder cell ratio, we randomly sampled about 60 small regions containing only cancer cells by laser microbeam dissection, and determined the mutation status of each region. To prevent contamination of different types of cells, we minimized the size of the region to 100x100x40 micrometers, which contained about thirty cells. The mutation status was determined by SNaP shot (Applied Biosystems), a primer extension assay using an oligonucleotide primer designed for each mutation. Regions were classified either of wild type cell (WT), heterozygote of EGFR mutation (HT) or homozygote of EGFR mutation (HO). WT corresponded to non-responder cells, and HT and HO to responder cells. From the number of regions of each category, the responder/non-responder cell ratio was calculated. Fourteen tissues consisted only of responder cells (group I): twelve tissues of only HT, and two tissues of HT and HO. Six tissues consisted of responder and non-responder cells (group II): non-responder cells occupied 7, 8, 10, 22, 67, 95 % of the total cancer cell population, respectively. The case with 95% non-responder cells was the only PD (progressive disease) case in this collection. Both of time to progression and overall survival were significantly reduced in the group II (p
Prevalence of sleep apnoea, sleepiness and behavioural/emotional disturbances in adults with Down's syndrome in Scotland
Authors: Elizabeth Hill, Donna Fairley, Sarah Van Putten, Sally-Anne Cooper, John Forbes, Linda Williams, Renata Riha
Journal: European Respiratory Journal (2012)

Introduction   Adults with Down9s syndrome (DS) are predisposed to sleep apnoea (SA). Prevalence is, as yet, unknown.   Aims and objectives   To assess prevalence of SA, sleepiness and behavioural and emotional disturbances in adults with DS in Scotland.   Methods   A sleep questionnaire, including the pictorial Epworth Sleepiness Scale (pESS) and subscales of the Developmental Behaviour Checklist for Adults (DBC-A), was sent to 650 adults (age ≥16yrs) with DS.  All respondents were offered sleep studies (Embletta® Gold, Embla Systems LLC).  Standard statistical analysis was undertaken.   Results   Response rate was 42% (246 valid). 16 respondents had existing SA; 11 were treated. Mean age was 31±11 years. BMI was 30±7 kg/m 2 , higher in females (p=0.009). Mean pESS score was 7±5, with males sleepier (p=0.016). 176 respondents reported snoring; 85 snored often or frequently. 60 reported apnoeas.  To date, 23 patients (15 males) have had sleep studies, 20 being valid. Mean age was 26±9 yrs. Mean BMI was 30±7 kg/m 2 ; females were heavier (p=0.001). Median AH (apnoeas+hypopnoeas per hour in bed) was 28.6 (IQR 14.8-48.2). Median ODI (≥4% O 2  desaturations per hour in bed) was 6.5 (IQR 2.1-30.9). Snorers scored higher on pESS (r=0.459, p=0.042) and DBC-A disruptive subscale (r=0.463, p=0.040). BMI correlated with the anxiety/antisocial subscale (r=0.606, p=0.010).   Conclusion   This is the first population survey of SA in DS adults. Females were less sleepy than males, despite being more obese. Snoring was associated with sleepiness and disruptive behaviour. Heavier patients were more anxious. The study is ongoing.   Acknowledgements   Chief Scientist Office, Scotland; Fondation Jerome Lejeune, France.
Fibrates and cholestasis
Authors: Nisanne S. Ghonem, David N. Assis, James L. Boyer
Journal: Hepatology (2015)

Cholestasis, including primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), results from an impairment or disruption of bile production and causes intracellular retention of toxic bile constituents, including bile salts. If left untreated, cholestasis leads to liver fibrosis and cirrhosis, which eventually results in liver failure and the need for liver transplantation. Currently, the only therapeutic option available for these patients is ursodeoxycholic acid (UDCA), which slows the progression of PBC, particularly in stage I and II of the disease. However, some patients have an incomplete response to UDCA therapy, whereas other, more advanced cases often remain unresponsive. For PSC, UDCA therapy does not improve survival, and recommendations for its use remain controversial. These considerations emphasize the need for alternative therapies. Hepatic transporters, located along basolateral (sinusoidal) and apical (canalicular) membranes of hepatocytes, are integral determinants of bile formation and secretion. Nuclear receptors (NRs) are critically involved in the regulation of these hepatic transporters and are natural targets for therapy of cholestatic liver diseases. One of these NRs is peroxisome proliferator‐activated receptor alpha (PPARα), which plays a central role in maintaining cholesterol, lipid, and bile acid homeostasis by regulating genes responsible for bile acid synthesis and transport in humans, including cytochrome P450 (CYP) isoform 7A1 (CYP7A1), CYP27A1, CYP8B1, uridine 5'‐diphospho‐glucuronosyltransferase 1A1, 1A3, 1A4, 1A6, hydroxysteroid sulfotransferase enzyme 2A1, multidrug resistance protein 3, and apical sodium‐dependent bile salt transporter. Expression of many of these genes is altered in cholestatic liver diseases, but few have been extensively studied or had the mechanism of PPARα effect identified. In this review, we examine what is known about these mechanisms and consider the rationale for the use of PPARα ligand therapy, such as fenofibrate, in various cholestatic liver disorders. (H epatology 2015;62:635–643
Are schizophrenia and affective disorder related? A selective literature review
Authors: M A Taylor
Journal: American Journal of Psychiatry (1992)

Although most modern investigators accept the Kraepelinian view that schizophrenia and affective disorder are biologically distinct, others have suggested the psychoses are on a continuum of liability. This article is a selective review of evidence for the continuum model.The author focuses on family, twin, and adoption data that do not support the Kraepelinian view of psychosis. Evidence characterized to a lesser extent includes the frequency of intermediate forms of illness (i.e., schizoaffective disorder), the inability to separate psychoses by classical symptoms into well-defined clusters, and the inability of laboratory measures to clearly define psychotic subgroups.The data demonstrate that schizophrenia and affective disorder do co-occur in some families. Whether this co-occurrence reflects true overlap is unclear, and significant pathophysiological heterogeneity may underlie clinical continuity. In some recent studies the inclusion of nonmelancholic depressions in the affective illness category may have masked overlap.The author suggests that the Kraepelinian view of psychoses may need modification. Future research should focus on factors that may reveal overlap between schizophrenia and affective disorder: severity of schizophrenia and affective disorder in probands, severity of depression in relatives, the effect of the unipolar-bipolar disorder relationship on the co-occurrence of affective disorder and schizophrenia, and the relationship of nongenetic factors that might alter the clinical expression of a shared genotype. Also, investigators should not presume a dichotomy or continuum but should examine pure and mixed pedigrees and look for state- and trait-related endophenotypes, the convergence of which would provide the basis for focused molecular genetic study.
Abstract 4374: G-CSF Treatment Improves Cardiac Function In postmyocarditic Cardiomyopathy By Enhanced Circulation And Homing Of CD34+ Progenitor Cell Populations
Authors: Stefan Brunner, Hans D Theiss, Monika Leiss, Rebekka Fischer, Markus Vallaster, Bruno C Huber, Alexandra Keithahn, Martina Sauter, Karin Klingel, Wolfgang-Michael Franz
Journal: Circulation (2008)

Objective : Recently, it was shown that the physiologic repair mechanism of mobilization and homing of bone marrow-derived stem cells (BMCs) is impaired in dilated cardiomyopathy. In our study we aimed to analyze circulation and homing of CD34 + progenitor cell populations in a murine model of dilated cardiomyopathy due to coxsackie virus B3 (CVB3) induced myocarditis and the influence of G-CSF treatment on BMC homing and cardiac function. Methods and Results : First, SWR/J (H-2q)-mice were infected by intraperitoneal injection of 10 5 pfu CVB3. Healthy, age-matched SWR/J (H-2q)-mice served as controls. 12 weeks after infection, DCM was verified by MRI/Millar-tip-catheter and histology. In DCM mice, CD34 + BMC populations (CD34 + CD31 + , CD34 + Sca-1 + , CD34 + c-kit + and CD34 + CXCR-4 + ) measured by flow cytometry were significantly increased in peripheral blood, decreased in bone marrow and remained unchanged in the hearts in comparison to controls. Different from ischemic heart diseases, myocardial homing factors (SDF-1, SCF, HIF-1a, VCAM and HGF) assessed by real-time PCR were not upregulated in the CVB3-DCM group. Finally, 18 DCM-CVB3 mice were analyzed by MRI 8 weeks after CVB3 infection and randomized into G-CSF-or saline-treatment (100 μg/20μl s.c. daily for 2× 5 days). 12 weeks after infection, cardiac function was assessed using MRI: Change of ejection fraction was significantly better in the G-CSF-group compared to the controls (4.1±1.8 vs. −2.5±2.2%; p=0.03). The improvement of cardiac function was associated with enhanced homing of BMC subpopulations. Conclusions : We have shown that postmyocarditic cardiomyopathy is associated with a reduced migration of BMCs to the cardiomyopathic hearts due to a lack of increase of homing factors. This defect can partly be overcome by G-CSF-administration resulting in an increased number of stem cells in the myocardium and leading to a moderately improved cardiac function. Therefore our data provides new insights in the pathogenesis of dilated cariomyopathy and presents a promising non-invasive approach to ameliorate heart failure.
Effects of Intensive Glucose Lowering in Type 2 Diabetes
Authors: Hertzel C Gerstein, Michael E Miller, Robert P Byington, David C Goff, J Thomas Bigger, John B Buse, William C Cushman, Saul Genuth, Faramarz Ismail-Beigi, Richard H Grimm, Jeffrey L Probstfield, Denise G Simons-Morton, William T Friedewald
Journal: New England Journal of Medicine (2008)

Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors.
Multiscale entropy analysis of RR time series obtained from polysomnographic recordings in wide age spectrum group
Authors: Jakub Radlinski, Zbigniew Baran, Waldemar Tomalak
Journal: European Respiratory Journal (2012)

Costs and complication of polysomnography lead to attempts to develop cheaper and simpler methods. The analysis of heart rate seems to be promising, however the heart rate9s dynamics is biased by several physiological factors. The aim of that study was to check influence of age on multiscale entropy (MSE) of RR time series.  64 patients undergoing routine diagnostic in sleep lab were recruited (36 male, 28 female, age 1,5 – 63 yrs mean: 25,2 ± 20 yrs, RDI: 0 – 4,9 1/h mean:1,9 ± 1,5 1/h). The full night PSG (ASSM 2007) were performed. The R-R intervals were detected in recorded ECG signal (250Hz), and the multiscale entropy (Goldberg9s MSE) was calculated (m=2, r=0.15, scale= 1-20).  We found high correlation between entropy in SE(1) and age (Fig. 1) in adults, however in the children group (age  After removing subjects younger than 15yrs the correlation increase (R=0.58, p  We conclude that entropy is biased by age in adults and the lack of such relation in young group needs further investigations.
Through a Clear Cell, Darkly: HIF2α/PLIN2–Maintained Fat Droplets Protect ccRCCs from ER Stress
Authors: Jingwei Sim, Randall S. Johnson
Journal: Cancer Discovery (2015)

Qiu and colleagues describe how a structural component of lipid droplets is markedly induced in pseudohypoxic renal tumors, where it maintains endoplasmic reticulum (ER) homeostasis. This adaptation is indispensable in tumor cells-where growth demands and a fluctuating blood supply place unnatural stresses on ER function-and is therefore an attractive therapeutic target.