tbuckley/cabot-search huggingface dataset:
Fulminant hepatic failure resulting from coexistent Wilson's disease and hepatitis E.
Authors: R Sallie, J Chiyende, K C Tan, D Bradley, B Portmann, R Williams, A P Mowat, G Mieli-Vergani
Journal: Gut (1994)

Fulminant hepatic failure resulting from hepatitis E and coexistent Wilson9s disease was diagnosed in a six year old girl six weeks after returning from a holiday in India. Wilson9s disease was diagnosed on the basis of histological evidence of hepatocellular copper deposition, confirmed by biochemical estimation of liver copper concentration. Although severely damaged, the liver was non-cirrhotic. Hepatitis E virus (HEV) was diagnosed by nested polymerase chain reaction, the specificity of which was confirmed by direct sequencing of amplified DNA. Replication of HEV within the liver at the time of diagnosis was confirmed by selective amplification of the antigenomic strand of the virus obtained from total liver RNA. The patient had an orthotopic liver transplantation without recurrence of hepatitis and remains well at 19 months. Viral excretion, recorded by serial amplification of HEV RNA extracted from stool samples, persisted for 30 days after liver grafting. Severe vitiligo, present preoperatively, dramatically improved after liver grafting and institution of immunosuppressive treatment. This case suggests that viral infection may play a part in the acute decompensation seen in some cases of Wilson9s disease.
LSC 2013 abstract - NF-κβ acts downstream of EGFR in regulating low dose cadmium induced primary lung cell proliferation
Authors: Subhadip Kundu, Arindam Bhattacharyya
Journal: European Respiratory Journal (2013)

Studies done so far, regarding cadmium induced cellular proliferation were based on mitogen activated protein kinase and Ca2+/calmodulin dependent protein kinase (MAPK/CaMK) dependent pathways. Cadmium treated mice primary lung epithelial cell proliferation was measured both by cell cycle analysis and Brdu incorporation assay and morphologically by atomic force microscopy. RT-PCR and western blot confirmed the specific signalling pathways. Primary lung epithelial cells were transfected with siEGFR, and molecular interactions of downstream signalling molecules were determined. We have reported RNAi induced silencing of the EGFR, which is over expressed in cadmium induced primary mice lung epithelial cells. Use of siEGFR effectively prevents expression of proinflammatory and cell proliferative markers.We have also transfected the primary lung epithelial cell with siRNA against the regulatory subunit of nuclear factor κβ (NF-κβ) and the data shows that cadmium induced lung cell proliferation is the effect of EGFR mediated NF-κβ activation.

Nf-κB regulation of EGFR

![Figure][1] 



Hypothetical Scheme

![Figure][1]  [1]: pending:yes
Nitric Oxide–Independent Vasodilator Rescues Heme-Oxidized Soluble Guanylate Cyclase From Proteasomal Degradation
Authors: Sabine Meurer, Sylke Pioch, Tatjana Pabst, Nils Opitz, Peter M. Schmidt, Tobias Beckhaus, Kristina Wagner, Simone Matt, Kristina Gegenbauer, Sandra Geschka, Michael Karas, Johannes-Peter Stasch, Harald H.H.W. Schmidt, Werner Müller-Esterl
Journal: Circulation Research (2009)

Nitric oxide (NO) is an essential vasodilator. In vascular diseases, oxidative stress attenuates NO signaling by both chemical scavenging of free NO and oxidation and downregulation of its major intracellular receptor, the alphabeta heterodimeric heme-containing soluble guanylate cyclase (sGC). Oxidation can also induce loss of the heme of sGC, as well as the responsiveness of sGC to NO. sGC activators such as BAY 58-2667 bind to oxidized/heme-free sGC and reactivate the enzyme to exert disease-specific vasodilation. Here, we show that oxidation-induced downregulation of sGC protein extends to isolated blood vessels. Mechanistically, degradation was triggered through sGC ubiquitination and proteasomal degradation. The heme-binding site ligand BAY 58-2667 prevented sGC ubiquitination and stabilized both alpha and beta subunits. Collectively, our data establish oxidation-ubiquitination of sGC as a modulator of NO/cGMP signaling and point to a new mechanism of action for sGC activating vasodilators by stabilizing their receptor, oxidized/heme-free sGC.
A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation
Authors: Mario Notari, Paolo Neviani, Ramasamy Santhanam, Bradley W. Blaser, Ji-Suk Chang, Annamaria Galietta, Anne E. Willis, Denis C. Roy, Michael A. Caligiuri, Guido Marcucci, Danilo Perrotti
Journal: Blood (2005)
Regional Hypoxia in Glioblastoma Multiforme Quantified with [18F]Fluoromisonidazole Positron Emission Tomography before Radiotherapy: Correlation with Time to Progression and Survival
Authors: Alexander M. Spence, Mark Muzi, Kristin R. Swanson, Finbarr O'Sullivan, Jason K. Rockhill, Joseph G. Rajendran, Tom C.H. Adamsen, Jeanne M. Link, Paul E. Swanson, Kevin J. Yagle, Robert C. Rostomily, Daniel L. Silbergeld, Kenneth A. Krohn
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Hypoxia is associated with resistance to radiotherapy and chemotherapy and activates transcription factors that support cell survival and migration. We measured the volume of hypoxic tumor and the maximum level of hypoxia in glioblastoma multiforme before radiotherapy with [18F]fluoromisonidazole positron emission tomography to assess their impact on time to progression (TTP) or survival. Experimental Design: Twenty-two patients were studied before biopsy or between resection and starting radiotherapy. Each had a 20-minute emission scan 2 hours after i.v. injection of 7 mCi of [18F]fluoromisonidazole. Venous blood samples taken during imaging were used to create tissue to blood concentration (T/B) ratios. The volume of tumor with T/B values above 1.2 defined the hypoxic volume (HV). Maximum T/B values (T/Bmax) were determined from the pixel with the highest uptake. Results: Kaplan-Meier plots showed shorter TTP and survival in patients whose tumors contained HVs or tumor T/Bmax ratios greater than the median (P ≤ 0.001). In univariate analyses, greater HV or tumor T/Bmax were associated with shorter TTP or survival (P &amp;lt; 0.002). Multivariate analyses for survival and TTP against the covariates HV (or T/Bmax), magnetic resonance imaging (MRI) T1Gd volume, age, and Karnovsky performance score reached significance only for HV (or T/Bmax; P &amp;lt; 0.03). Conclusions: The volume and intensity of hypoxia in glioblastoma multiforme before radiotherapy are strongly associated with poorer TTP and survival. This type of imaging could be integrated into new treatment strategies to target hypoxia more aggressively in glioblastoma multiforme and could be applied to assess the treatment outcomes.
Neural Activation Underlying Acute Grief in Women After the Loss of an Unborn Child
Authors: Anette Kersting, Patricia Ohrmann, Anya Pedersen, Kristin Kroker, Daniela Samberg, Jochen Bauer, Harald Kugel, Katja Koelkebeck, Johannes Steinhard, Walter Heindel, Volker Arolt, Thomas Suslow
Journal: American Journal of Psychiatry (2009)

The traumatic loss of an unborn child by induced termination of pregnancy because of fetal malformation is a major life event that causes intense maternal grief. Increasing evidence supports the hypothesis that the same neural structures involved in the experience of physical pain are involved in the experience of social pain and loss.To investigate neural activation patterns related to acute grief, the authors conducted a functional MRI study of 12 post-termination women and 12 noninduced women who delivered a healthy child. Brain activation was measured while participants viewed pictures of happy baby, happy adult, and neutral adult faces.Relative to comparison women, post-termination women showed greater activation in the middle and posterior cingulate gyrus, the inferior frontal gyrus, the middle temporal gyrus, the thalamus, and the brainstem in response to viewing happy baby faces. Functional connectivity between the cingulate gyrus and the thalamus during the processing of happy baby faces was significantly stronger in post-termination women.Overall, acute grief after the loss of an unborn child was closely related to the activation of the physical pain network encompassing the cingulate gyrus, the inferior frontal gyrus, the thalamus, and the brainstem. To the authors' knowledge, the stronger functional thalamocingulate connectivity in post-termination women is the first in vivo demonstration of an involvement of the neural maternal attachment network in grief after the loss of an unborn child.
Rare diseases bullet 12: Pulmonary manifestations of Behcet's disease
Authors: F Erkan
Journal: Thorax (2001)

HistoryBehçet's disease is a chronic inflammatory disorder of unknown aetiology characterised by recurrent attacks.8][9][10] Diagnosis Since Behçet's disease does not have pathognomonic symptoms or laboratory findings, the diagnosis is made on the basis of the criteria proposed by the International Study Group for Behçet's disease in 1990 (table 2). 11According to the criteria, recurrent oral ulceration must be present and at least two of the following: recurrent genital ulceration, eye lesions, skin lesions, or a positive pathergy test (development of a papule or pustule following a needle prick to the skin, as in table 2). Epidemiology3][14][15][16][17][18] The highest prevalence rate was reported from Turkey as 80-370 per 100 000.The prevalence ranges from two to 30 cases per 100 000 in
A phase II pilot trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node positive breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group
Authors: K.D. Miller, A. O’Neill, E.A. Perez, A.D. Seidman, G.W. Sledge
Journal: Annals of Oncology (2011)
The hyperthyroid heart. An analysis of systolic and diastolic properties in single rat ventricular myocytes.
Authors: R A Josephson, H A Spurgeon, E G Lakatta
Journal: Circulation Research (1990)

Single ventricular myocytes were isolated by collagenase digestion from the hearts of 6-8-month-old male Wistar rats in either the control (euthyroid) state or after 7 days of daily injection of 0.64 mg/kg thyroxine (hyperthyroid). Myocytes were field-stimulated from slack length, and contraction was measured with an inverted microscope-photodiode array-computer apparatus. The effect of pacing rate and ouabain administration on systolic and diastolic function was examined. Single myocytes isolated from hyperthyroid hearts maintain the properties of bulk muscle, because maximal twitch velocity is augmented 98% and the time course of contraction as measured by the time to peak shortening, relaxation time, or contraction duration is abbreviated 39%. Spontaneous sarcoplasmic reticulum calcium release, as measured by the occurrence of contractile waves, is increased in the hyperthyroid myocytes. This increased frequency of spontaneous sarcoplasmic reticulum calcium release is most marked under conditions known to be associated with high intracellular calcium, such as low pacing rates or digitalis glycoside administration. It can account for the hypoperformance of the hyperthyroid myocytes noted under these conditions because it is associated with depletion of sarcoplasmic reticulum calcium stores and diminution of subsequent twitch amplitude. These observations may help explain, in part, the cellular basis of the altered cardiac performance in the hyperthyroid state.
PECAM-1 is required for transendothelial migration of leukocytes.
Authors: W A Muller, S A Weigl, X Deng, D M Phillips
Journal: The Journal of Experimental Medicine (1993)

Platelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) is crucial to the process of leukocyte transmigration through intercellular junctions of vascular endothelial cells. A monoclonal antibody to PECAM, or recombinant soluble PECAM, blocks transendothelial migration of monocytes by 70-90%. Pretreating either the monocytes or the endothelial junctions with antibody blocks transmigration. If the endothelium is first activated by cytokines, anti-PECAM antibody or soluble recombinant PECAM again block transmigration of both monocytes and neutrophils. Anti-PECAM does not block chemotaxis of either cell type. Light and electron microscopy reveal that leukocytes blocked in transmigration remain tightly bound to the apical surface of the endothelial cell, precisely over the intercellular junction. Thus, the process of leukocyte emigration can be dissected into three successive stages: rolling, mediated by the selectin class of adhesion molecules; tight adhesion, mediated by the leukocyte integrins and their endothelial cell counter-receptors; and now transmigration, which, based on these studies, requires PECAM-1.
Patient compliance in a clinical trial with inhaled budesonide in children with mild asthma
Authors: G Jónasson, K H Carlsen, A Sødal, C Jonasson, P Mowinckel
Journal: European Respiratory Journal (1999)

Children's use of inhalation devices can give valuable information about their adherence to asthma therapy. The aim of this study was to examine treatment adherence of low dose inhaled budesonide or placebo administered via Turbuhaler twice daily in children with mild asthma participating in an asthma trial, by comparing diary registration with the number of doses remaining in the inhaler. A total of 163 children (age 7-16 yrs, 56 females, 107 males) with mild asthma (mean baseline forced expiratory volume in one second (FEV1) was 103% of predicted), were included into a double blind, randomized study. After a two-week run-in period, the children received inhaled budesonide, either 100 microg or 200 microg daily, and/or placebo for 12 weeks. All patients used daily diary cards throughout the study. Results from 161 patients were analysed. Mean compliance according to the diary was 93%, whereas estimated mean compliance when counting remaining doses in the Turbuhaler was 77%. Overuse of medication was found in 7% of the children. There was no significant difference in compliance between sex in the study group, whereas children aged < or =9 yrs had significantly better drug adherence than older children. No significant relationship was found between symptom score and compliance. In conclusion, even with optimal patient follow-up in a clinical trial, adherence to prophylactic asthma treatment is considerably lower than the patients own reports from the use of daily diary cards.
Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure
Authors: Manuel Romero-Gómez, Sara Montagnese, Rajiv Jalan
Journal: Journal of Hepatology (2014)

Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization.
Improvement of Gemcitabine-Based Therapy of Pancreatic Carcinoma by Means of Oncolytic Parvovirus H-1PV
Authors: Assia L. Angelova, Marc Aprahamian, Svitlana P. Grekova, Amor Hajri, Barbara Leuchs, Nathalia A. Giese, Christiane Dinsart, Alexia Herrmann, Ginette Balboni, Jean Rommelaere, Zahari Raykov
Journal: Clinical Cancer Research (2009)

Abstract Pancreatic carcinoma is a gastrointestinal malignancy with poor prognosis. Treatment with gemcitabine, the most potent chemotherapeutic against this cancer up to date, is not curative, and resistance may appear. Complementary treatment with an oncolytic virus, such as the rat parvovirus H-1PV, which is infectious but nonpathogenic in humans, emerges as an innovative option. Purpose: To prove that combining gemcitabine and H-1PV in a model of pancreatic carcinoma may reduce the dosage of the toxic drug and/or improve the overall anticancer effect. Experimental Design: Pancreatic tumors were implanted orthotopically in Lewis rats or subcutaneously in nude mice and treated with gemcitabine, H-1PV, or both according to different regimens. Tumor size was monitored by micro-computed tomography, whereas bone marrow, liver, and kidney functions were monitored by measuring clinically relevant markers. Human pancreatic cell lines and gemcitabine-resistant derivatives were tested in vitro for sensitivity to H-1PV infection with or without gemcitabine. Results: In vitro studies proved that combining gemcitabine with H-1PV resulted in synergistic cytotoxic effects and achieved an up to 15-fold reduction in the 50% effective concentration of the drug, with drug-resistant cells remaining sensitive to virus killing. Toxicologic screening showed that H-1PV had an excellent safety profile when applied alone or in combination with gemcitabine. The benefits of applying H-1PV as a second-line treatment after gemcitabine included reduction of tumor growth, prolonged survival of the animals, and absence of metastases on CT-scans. Conclusion: In addition to their potential use as monotherapy for pancreatic cancer, parvoviruses can be best combined with gemcitabine in a two-step protocol.
Circulating prolactin and breast cancer risk among pre- and postmenopausal women in the EPIC cohort
Authors: K. Tikk, D. Sookthai, T. Johnson, S. Rinaldi, I. Romieu, A. Tjønneland, A. Olsen, K. Overvad, F. Clavel-Chapelon, L. Baglietto, H. Boeing, A. Trichopoulou, P. Lagiou, D. Trichopoulos, D. Palli, V. Pala, R. Tumino, S. Rosso, S. Panico, A. Agudo, V. Menéndez, M.-J. Sánchez, P. Amiano, J.M. Huerta Castaño, E. Ardanaz, H.B. Bueno-de-Mesquita, E. Monninkhof, C. Onland-Moret, A. Andersson, M. Sund, E. Weiderpass, K.-T. Khaw, T.J. Key, R.C. Travis, M.J. Gunter, E. Riboli, L. Dossus, R. Kaaks
Journal: Annals of Oncology (2014)
Three 15-min Bouts of Moderate Postmeal Walking Significantly Improves 24-h Glycemic Control in Older People at Risk for Impaired Glucose Tolerance
Authors: Loretta DiPietro, Andrei Gribok, Michelle S. Stevens, Larry F. Hamm, William Rumpler
Journal: Diabetes Care (2013)

OBJECTIVE The purpose of this study was to compare the effectiveness of three 15-min bouts of postmeal walking with 45 min of sustained walking on 24-h glycemic control in older persons at risk for glucose intolerance. RESEARCH DESIGN AND METHODS Inactive older (≥60 years of age) participants (N = 10) were recruited from the community and were nonsmoking, with a BMI &amp;lt;35 kg/m2 and a fasting blood glucose concentration between 105 and 125 mg dL−1. Participants completed three randomly ordered exercise protocols spaced 4 weeks apart. Each protocol comprised a 48-h stay in a whole-room calorimeter, with the first day serving as the control day. On the second day, participants engaged in either 1) postmeal walking for 15 min or 45 min of sustained walking performed at 2) 10:30 a.m. or 3) 4:30 p.m. All walking was on a treadmill at an absolute intensity of 3 METs. Interstitial glucose concentrations were determined over 48 h with a continuous glucose monitor. Substrate utilization was measured continuously by respiratory exchange (VCO2/VO2). RESULTS Both sustained morning walking (127 ± 23 vs. 118 ± 14 mg dL−1) and postmeal walking (129 ± 24 vs. 116 ± 13 mg dL−1) significantly improved 24-h glycemic control relative to the control day (P &amp;lt; 0.05). Moreover, postmeal walking was significantly (P &amp;lt; 0.01) more effective than 45 min of sustained morning or afternoon walking in lowering 3-h postdinner glucose between the control and experimental day. CONCLUSIONS Short, intermittent bouts of postmeal walking appear to be an effective way to control postprandial hyperglycemia in older people.
Blood Flow-Metabolism Mismatch: Good for the Tumor, Bad for the Patient
Authors: David A. Mankoff, Lisa K. Dunnwald, Savannah C. Partridge, Jennifer M. Specht
Journal: Clinical Cancer Research (2009)

Abstract Although tightly coupled in most normal tissues, blood flow and metabolism are often not well matched in tumors. A flow-metabolism mismatch, specifically, high metabolism relative to blood flow, can be recognized in tumors by functional and molecular imaging and is associated with poor response to treatment and early relapse or disease progression. (Clin Cancer Res 2009;15(17):5294–6)
NKX2-1/TITF1/TTF-1-Induced ROR1 Is Required to Sustain EGFR Survival Signaling in Lung Adenocarcinoma
Authors: Tomoya Yamaguchi, Kiyoshi Yanagisawa, Ryoji Sugiyama, Yasuyuki Hosono, Yukako Shimada, Chinatsu Arima, Seiichi Kato, Shuta Tomida, Motoshi Suzuki, Hirotaka Osada, Takashi Takahashi
Journal: Cancer Cell (2012)
Deficiency of Cartilage-Associated Protein in Recessive Lethal Osteogenesis Imperfecta
Authors: Aileen M. Barnes, Weizhong Chang, Roy Morello, Wayne A. Cabral, MaryAnn Weis, David R. Eyre, Sergey Leikin, Elena Makareeva, Natalia Kuznetsova, Thomas E. Uveges, Aarthi Ashok, Armando W. Flor, John J. Mulvihill, Patrick L. Wilson, Usha T. Sundaram, Brendan Lee, Joan C. Marini
Journal: New England Journal of Medicine (2006)

Classic osteogenesis imperfecta, an autosomal dominant disorder associated with osteoporosis and bone fragility, is caused by mutations in the genes for type I collagen. A recessive form of the disorder has long been suspected. Since the loss of cartilage-associated protein (CRTAP), which is required for post-translational prolyl 3-hydroxylation of collagen, causes severe osteoporosis in mice, we investigated whether CRTAP deficiency is associated with recessive osteogenesis imperfecta. Three of 10 children with lethal or severe osteogenesis imperfecta, who did not have a primary collagen defect yet had excess post-translational modification of collagen, were found to have a recessive condition resulting in CRTAP deficiency, suggesting that prolyl 3-hydroxylation of type I collagen is important for bone formation.
Fungal infections of the spine.
Authors: W S Symmers
Journal: BMJ (1973)

found in practice to be of equal value and also safe in the diagnosis of two small series of mute psychiatric inpatients.2 "Poor-risk" patients, especially those sus- ceptible to respiratory or cardiovascular depression, will need extra care, but even then intravenous diazepam and lorazepam have been shown to be less hazardous than intravenous barbiturates.4Care is also necessary with epileptics receiving parenteral barbiturates or paraldehyde,5 patients taking Mandrax6 and during curarization.7Apnoea with diazepam alone has been reported in an 80-year-old patient.8Such risks must be balanced against the importance of diagnosing and treating the underlying cause of the mutism.-Iam, etc., H.