tbuckley/cabot-search huggingface dataset:
Cholinergic Autonomic Dysfunction in Veterans With Gulf War Illness
Authors: Robert W. Haley, Elizabeth Charuvastra, William E. Shell, David M. Buhner, W. Wesley Marshall, Melanie M. Biggs, Steve C. Hopkins, Gil I. Wolfe, Steven Vernino
Journal: JAMA Neurology (2012)

The authors of prior small studies raised the hypothesis that symptoms in veterans of the 1991 Gulf War, such as chronic diarrhea, dizziness, fatigue, and sexual dysfunction, are due to cholinergic autonomic dysfunction.To perform a confirmatory test of this prestated hypothesis in a larger, representative sample of Gulf War veterans.Nested case-control study.Clinical and Translational Research Center, University of Texas Southwestern Medical Center, Dallas.Representative samples of Gulf War veterans meeting a validated case definition of Gulf War illness with 3 variants (called syndromes 1-3) and a control group, all selected randomly from the US Military Health Survey.Validated domain scales from the Autonomic Symptom Profile questionnaire, the Composite Autonomic Severity Score, and high-frequency heart rate variability from a 24-hour electrocardiogram.The Autonomic Symptom Profile scales were significantly elevated in all 3 syndrome groups (P< .001), primarily due to elevation of the orthostatic intolerance, secretomotor, upper gastrointestinal dysmotility, sleep dysfunction, urinary, and autonomic diarrhea symptom domains. The Composite Autonomic Severity Score was also higher in the 3 syndrome groups (P= .045), especially in syndrome 2, primarily due to a significant reduction in sudomotor function as measured by the Quantitative Sudomotor Axon Reflex Test, most significantly in the foot; the score was intermediate in the ankle and upper leg and was nonsignificant in the arm, indicating a peripheral nerve length-related deficit. The normal increase in high-frequency heart rate variability at night was absent or blunted in all 3 syndrome groups (P< .001).Autonomic symptoms are associated with objective, predominantly cholinergic autonomic deficits in the population of Gulf War veterans.
Total Hip Replacement in England
Authors: Edward F. Rosenberg
Journal: JAMA (1970)

Involvement of the hips is an often-ocurring, and frequently disastrous complication of both rheumatoid and osteoarthritis. In these conditions early symptoms of hip joint difficulties are certain forerunners of serious deterioration. Involvement of one side often is followed by involvement of the other side and pain and disability tend to increase until walking and standing become impossible. Disabling arthritis of the hips may be encountered also as a late complication of other ailments, notably coxa plana, Legg's disease, slipped femoral epiphyses, aseptic necrosis of the femoral head, Charcot's disease of the hip, Paget's disease of the pelvic bones, fat embolism, and avascular necrosis of the femoral head subsequent to dislocation. Similarly, arthritis may develop in the hip following surgical treatment for fractures of the femoral head and neck. In some instances, the hip joint deteriorates without recognizable cause in persons with "dysplastic" or poorly formed pelvic bones. There is no
Bortezomib Abolishes Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Resistance via a p21-Dependent Mechanism in Human Bladder and Prostate Cancer Cells
Authors: Laura M. Lashinger, Keyi Zhu, Simon A. Williams, Marissa Shrader, Colin P.N. Dinney, David J. McConkey
Journal: Cancer Research (2005)

Abstract Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family of cytokines that induces apoptosis in some tumor cells but not in normal cells. Unfortunately, many human cancer cell lines are refractory to TRAIL-induced cell death, and the molecular mechanisms underlying resistance are unclear. Here we report that TRAIL resistance was reversed in human bladder and prostate cancer cell lines by the proteasome inhibitor bortezomib (PS-341, Velcade). Synergistic induction of apoptosis occurred within 4 to 6 hours in cells treated with TRAIL plus bortezomib and was associated with accumulation of p21WAF-1/Cip-1 (p21) and inhibition of cyclin-dependent kinase (cdk) activity. Roscovitine, a specific cdk1/2 inhibitor, also sensitized cells to TRAIL. Silencing p21 expression reduced levels of DNA fragmentation by 50% in cells treated with bortezomib and TRAIL, confirming that p21 was required for the response. Analysis of the TRAIL pathway revealed that caspase-8 processing was enhanced in a p21-dependent fashion in cells exposed to TRAIL and bortezomib as compared with cells treated with TRAIL alone. Thus, all downstream components of the pathway (Bid cleavage, cytochrome c release, and caspase-3 activation) were amplified. These data strongly suggest that p21-mediated cdk inhibition promotes TRAIL sensitivity via caspase-8 activation and that TRAIL and bortezomib should be combined in appropriate in vivo models as a possible approach to solid tumor therapy.
Aberrant actin depolymerization triggers the pyrin inflammasome and autoinflammatory disease that is dependent on IL-18, not IL-1β
Authors: Man Lyang Kim, Jae Jin Chae, Yong Hwan Park, Dominic De Nardo, Roslynn A. Stirzaker, Hyun-Ja Ko, Hazel Tye, Louise Cengia, Ladina DiRago, Donald Metcalf, Andrew W. Roberts, Daniel L. Kastner, Andrew M. Lew, Dena Lyras, Benjamin T. Kile, Ben A. Croker, Seth L. Masters
Journal: The Journal of Experimental Medicine (2015)

Gain-of-function mutations that activate the innate immune system can cause systemic autoinflammatory diseases associated with increased IL-1β production. This cytokine is activated identically to IL-18 by an intracellular protein complex known as the inflammasome; however, IL-18 has not yet been specifically implicated in the pathogenesis of hereditary autoinflammatory disorders. We have now identified an autoinflammatory disease in mice driven by IL-18, but not IL-1β, resulting from an inactivating mutation of the actin-depolymerizing cofactor Wdr1. This perturbation of actin polymerization leads to systemic autoinflammation that is reduced when IL-18 is deleted but not when IL-1 signaling is removed. Remarkably, inflammasome activation in mature macrophages is unaltered, but IL-18 production from monocytes is greatly exaggerated, and depletion of monocytes in vivo prevents the disease. Small-molecule inhibition of actin polymerization can remove potential danger signals from the system and prevents monocyte IL-18 production. Finally, we show that the inflammasome sensor of actin dynamics in this system requires caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain, and the innate immune receptor pyrin. Previously, perturbation of actin polymerization by pathogens was shown to activate the pyrin inflammasome, so our data now extend this guard hypothesis to host-regulated actin-dependent processes and autoinflammatory disease.
Crohn's spondylitis: a family study
Authors: P. Hickling, J. A. Bird-Stewart, J. D. Young, V. Wright
Journal: Annals of the Rheumatic Diseases (1983)

We report a case of HLA B27 negative Crohn9s spondylitis with a detailed study of the proband9s family, including tissue types of all living relatives. The family included cases of psoriasis, psoriatic spondylitis, and idiopathic ankylosing spondylitis. We believe this to be the first report of these associated diseases occurring in one family. All relatives were B27 negative, including one with psoriatic spondylitis. The aetiological implications of these findings are considered.
A Case of Type 1 Diabetes With Nocturnal Hypoglycemia After Desensitization Therapy for Insulin Allergy
Authors: Takumi Kitamoto, Kenichi Sakurai, Kaori Tachibana, Hidetaka Yokoh, Ko Ishikawa, Takashi Miki, Koutaro Yokote
Journal: Diabetes Care (2013)

Antibodies against exogenously injected insulin are common with insulin treatment but seldom have serious effects on blood glucose (1). In insulin autoimmune syndrome (IAS), however, the insulin antibody causes hypoglycemia (2) in the absence of exogenous insulin treatment.

Here, we report a case of type 1 diabetes with insulin antibody, whereby the patient developed nocturnal hypoglycemia after desensitization therapy for an insulin allergy.

After receiving insulin therapy for 1 year, a 61-year-old man was admitted to our hospital because of an insulin allergy and poor control of diabetes. He had an itchy eruption at the insulin injection site. At the time of admission, the patient presented with an HbA1c level of 16.2% (154 mmol/mol); anti-GAD antibody 80.0 U/L (<1.5 U/mL); serum C-peptide level 0.01 ng/mL after glucagon injection (fasting 0.67–2.48 ng/mL); and insulin-specific IgE 41.5 UA/mL (<0.34 …
Hong Kong influenza variant.
Authors: R E Hope-Simpson
Journal: BMJ (1971)

benztropine 2 mg t.i.d., and she was dis- charged from inpatient treatment on this dosage.She began attending a psychiatric re- habilitation day hospital shortly afterwards, and one month after starting pimozide 4 mg b.d.her schizophrenic symptomatology ap- peared to be under con rol, but she was complaining of poor visual acuity.On examination there was paralysis of the ciliary muscle of both eyes, with fixed dilated pupils, and paralysis of accommodation.She was examined by an ophthalmologist at this time and no other abnormality noticed to account for this.Pimozide was reduced to 2 mg daily as a maintenance dose, and orphenadrine 50 mg t.i.d.substituted for benztropine.Her vision and pupillary re- sponses to light and accommodation gradually returned to normal over the following two weeks.It would appear, therefore, that as well as causing Parkinsonian side effects in a dosage of 8 mg daily, pimozide caused paralysis of accommodation, and interfered with normal pupillary reactions.
Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000)
Authors: Yoshinobu Kanda, Shigeru Chiba, Hisamaru Hirai, Hisashi Sakamaki, Tohru Iseki, Yoshihisa Kodera, Takahiro Karasuno, Shinichiro Okamoto, Noriyuki Hirabayashi, Koji Iwato, Atsuo Maruta, Yoshihiro Fujimori, Tatsuo Furukawa, Shin Mineishi, Keitaro Matsuo, Nobuyuki Hamajima, Masahiro Imamura
Journal: Blood (2003)
Underwater birth and neonatal respiratory distress
Authors: Zainab Kassim, Maria Sellars, Anne Greenough
Journal: BMJ (2005)

In 1992 the House of Commons Select Health Committee's report on maternity services recommended that all hospitals should provide women with the “option of a birthing pool where this is practicable.”1 A subsequent surveillance study of all NHS maternity units between 1994 and 1996 found that 0.6% of all deliveries in England and Wales occurred in water.2 Rawal and colleagues have suggested that water births have become popular among mothers and midwives because the buoyancy and warmth of the water promotes natural labour while providing a non-invasive safe and effective form of pain management.3 Practitioners and parents should remember, however, that birthing pools pose potential risks for the baby. We report on a newborn baby who developed respiratory distress due to aspiration after an underwater birth.

A full term male infant weighing 3150 g was born in the birthing pool of the labour ward of our hospital. His mother was a 34 year old, healthy primigravida who had …
First-Line Systemic Therapy Practice Patterns and Concordance With NCCN Guidelines for Patients Diagnosed With Metastatic NSCLC Treated at NCCN Institutions
Authors: Carrie Zornosa, Jonathan L. Vandergrift, Gregory P. Kalemkerian, David S. Ettinger, Michael S. Rabin, Mary Reid, Gregory A. Otterson, Marianna Koczywas, Thomas A. D'Amico, Joyce C. Niland, Rizvan Mamet, Katherine M. Pisters
Journal: Journal of the National Comprehensive Cancer Network (2012)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) allow many systemic therapy options for patients with metastatic non–small cell lung cancer (NSCLC). This analysis uses the NCCN NSCLC Outcomes Database to report on first-line therapy practice patterns and concordance with NCCN Guidelines. The analysis was limited to patients diagnosed with metastatic NSCLC between September 2006 and November 2009 at 1 of 8 participating NCCN Member Institutions. Patient characteristics, regimens used, and guidelines concordance were analyzed. Institutional variation and changes in practice over time were also measured. A total of 1717 patients were included in the analysis. Of these, 1375 (80%) were treated with systemic therapy, most often in the form of a carboplatin-based doublet (51%) or carboplatin-based doublet with targeted therapy (17%). Overall, 76% of patients received care that was concordant with NCCN Guidelines. Among patients with good performance status (n = 167), the most common reasons for not receiving first-line therapy were that therapy was not recommended (39%) or death occurred before treatment (33%). The most common reason for receiving nonconcordant drug therapy was the administration of pemetrexed or erlotinib before its incorporation into the NCCN Guidelines for first-line therapy (53%). Most patients in this cohort received care that was concordant with NCCN Guidelines. The NSCLC Outcomes Database is a valuable resource for evaluating practice patterns and concordance with NCCN Guidelines among patients with NSCLC.
Learning, Satisfaction, and Mistreatment During Medical Internship
Authors: Steven R. Daugherty, DeWitt C. Baldwin, Jr, Beverley D. Rowley
Journal: JAMA (1998)

Concerns about the working and learning environment of residency training continue to surface. Previous surveys of residents have focused on work hours and income, but have shed little light on how residents view their training experience.To provide a description of the internship year as seen by a large cross section of second-year residents.Mail survey conducted in 1991.Residency programs in the United States.Random 10% sample (N=1773) of all second-year residents listed in the American Medical Association's medical research and information database.What and who contributes most to residents' learning during internships, degree of satisfaction with the internship experience, on-call and sleep schedules, incidents of perceived mistreatment or abuse, observations of unethical behavior, and experiences of harassment or discrimination.A total of 1277 surveys (72%) of 1773 mailed were returned. Overall, respondents reported a moderate level of satisfaction with their first year of residency. On a scale of 0 to 3, residents rated other residents as contributing most (score of 2.3) to their learning, with special patients ranked second (2.1). During a typical work week, residents reported that they spent an average of 56.9 hours on call in the hospital. A total of 1185 (93%) residents reported experiencing at least 1 incident of perceived mistreatment, with 53% reporting being belittled or humiliated by more senior residents. Among women residents, 63% reported having experienced at least 1 episode of sexual harassment or discrimination. A total of 45% of residents reported having observed another individual falsifying medical records, and 70% saw a colleague working in an impaired condition, most often lack of sleep. Regression analyses suggest that satisfaction with the residency experience was associated with the presence of factors that enhanced learning, and fewer experiences of perceived mistreatment.Residents report significant problems during their internship experience. Satisfaction with internship is enhanced by positive learning experiences and lack of mistreatment.
Dual mechanism of vascular endothelial growth factor upregulation by hypoxia in human hepatocellular carcinoma
Authors: Z von Marschall
Journal: Gut (2001)

<h3>BACKGROUND/AIMS</h3> Vascular endothelial growth factor (VEGF) plays a key role in regulation of tumour associated angiogenesis. In the current study we analysed expression of VEGF and its receptors in human hepatocellular carcinoma (HCC) and investigated the molecular mechanisms of VEGF regulation by hypoxia. <h3>METHODS</h3> VEGF, kinase domain region (KDR)/fetal liver kinase 1 (flk-1), and flt-1 expression were examined by immunohistochemistry and in situ hybridisation in 15 human HCC tissues. Expression of VEGF and regulation by hypoxia were assessed in three human HCC cell lines using a quantitative competitive reverse transcription-polymerase chain reaction, ELISA, and a series of 5′ deletion reporter gene constructs of the human VEGF promoter in transient transfection assays. <h3>RESULTS</h3> We observed over expression of VEGF mRNA and protein in HCC compared with cirrhosis or normal liver. Expression of VEGF in tumour cells was strongly increased in areas directly adjacent to necrotic/hypoxic regions. Both VEGF receptors were detected in vascular endothelia of HCC while only KDR/flk-1 receptors were detected in endothelial cells of cirrhotic livers. Expression of VEGF was observed in all human HCC cell lines examined. Hypoxia (1% oxygen) resulted in profound upregulation of VEGF mRNA and protein levels. Furthermore, hypoxia treatment resulted in a doubling of VEGF mRNA stability. Deletion analysis of the human VEGF 5′ flanking region −2018 and +50 demonstrated induction of VEGF promoter activity under hypoxic conditions which was significantly decreased following deletion of the region −1286 and −789 suggesting a substantial contribution of the −975 putative hypoxia inducible factor 1 binding site to hypoxia mediated transcriptional activation of the VEGF gene. <h3>CONCLUSION</h3> These data suggest hypoxia as a central stimulus of angiogenesis in human HCC through upregulation of VEGF gene expression by at least two distinct molecular mechanisms: activation of VEGF gene transcription and an increase in VEGF mRNA stability.
Reduced Epithelial Expression of Secretory Component in Small Airways Correlates with Airflow Obstruction in Chronic Obstructive Pulmonary Disease
Authors: CHARLES PILETTE, VÉRONIQUE GODDING, ROBERT KISS, MONIQUE DELOS, ERIC VERBEKEN, CHRISTINE DECAESTECKER, KRISTEL DE PAEPE, JEAN-PIERRE VAERMAN, MARC DECRAMER, YVES SIBILLE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The epithelial polymeric immunoglobulin receptor/transmembrane secretory component (pIgR/SC) transports into secretions polymeric immunoglobulin A (pIgA), which is considered the first line of defense of the respiratory tract. The present study, done with quantitative immunohistochemistry, evaluated epithelial expression of secretory component (SC) and Clara cell protein (CC16) and neutrophil infiltration into the airways of eight patients with severe chronic obstructive pulmonary disease (COPD) who were undergoing lung transplantation, as compared with these processes in six nonsmoking patients with pulmonary hypertension who were used as controls and in lung specimens from five smokers without chronic bronchitis. Staining for SC was significantly decreased in the COPD patients as compared with the controls, both in large (mean optical density [MOD]: 23.4 [range: 21.1 to 27.8] versus 42.2 [range: 28.2 to 49.3], p = 0.003) and in small airways (MOD: 30.8 [range: 20.3 to 39.4] versus 41.5 [range: 39.2 to 46.2], p = 0.003). SC expression in small airways correlated strongly with functional parameters such as FEV1 (Kendall's tau (K) = 0.76, p = 0.008), FVC (K = 0.64, p = 0.03), and midexpiratory flow at 50% of VC (MEF50) (K = 0.74, p = 0.01). The reduced expression of SC in large airways correlated with neutrophil infiltration in submucosal glands (K = -0.47, p = 0.03). Expression of CC16 in the bronchial epithelium of COPD patients was also significantly decreased as compared with that of controls, especially in small airways (MOD: 28.3 [range: 26.8 to 32.4] versus 45.8 [range: 40.7 to 56.0], p = 0.002), but no correlation was observed with lung function tests. In conclusion, this study shows that reduced expression of SC in airway epithelium is associated with airflow obstruction and neutrophil infiltration in severe COPD.
Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress
Authors: RK Brown, H Wyatt, JF Price, FJ Kelly
Journal: European Respiratory Journal (1996)

The aim of this study was to determine whether a relationship exists between the circulating concentration of antioxidants, or markers of oxidative stress, and pulmonary function in cystic fibrosis patients. Plasma was obtained from 34 patients attending a cystic fibrosis clinic. Oxidative stress was investigated by measuring the concentrations of circulating lipid hydroperoxides and malondialdehyde (lipid peroxidation) and protein carbonyls (protein oxidation). Antioxidant status was determined from the plasma concentrations of alpha-tocopherol, ascorbic acid, uric acid and total sulphydryls. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced mid-expiratory flow (FEF25-75) were measured in 25 of the subjects by spirometry, and expressed as percentage predicted for normal height, weight and age. Lung function decreased significantly with age and was associated with decreased plasma alpha-tocopherol, ascorbic acid and sulphydryl concentrations. The reduction in pulmonary function correlated with elevated plasma malondialdehyde, but not with lipid hydroperoxide or protein carbonyl concentrations. Patients with severe lung dysfunction (FEV1 < 50% predicted) had higher plasma concentrations of lipid hydroperoxides than those with mild-to-moderate lung dysfunction (FEV1 > 50% pred). This study provides evidence that cystic fibrosis patients have inadequate antioxidant defences to cope with the elevated oxidative stress that they regularly experience. We believe that recurring oxidative lung injury contributes to the decline in pulmonary function in these patients.
Rheumatoid Arthritis treated with Organic Copper Compounds
Authors: T. J. O'Reilly
Journal: BMJ (1955)

septicaemia, meningitis, pneumococcal infections, etc., may at times be associated with toxic haemoglobinuria as a result of an acute haemolytic crisis.One is struck by the dramatic onset of favism: it can result in the destruction of more than 75% of the red cells in the blood within 24 hours.However, the response to blood transfusion is nothing short of miraculous.Favism can recur, and the only prevention is to refrain from eating the broad-bean.
A new computational approach to analyze human protein complexes and predict novel protein interactions
Authors: Sara Zanivan, Ilaria Cascone, Chiara Peyron, Ivan Molineris, Serena Marchio, Michele Caselle, Federico Bussolino
Journal: Genome biology (2007)

We propose a new approach to identify interacting proteins based on gene expression data. By using hypergeometric distribution and extensive Monte-Carlo simulations, we demonstrate that looking at synchronous expression peaks in a single time interval is a high sensitivity approach to detect co-regulation among interacting proteins. Combining gene expression and Gene Ontology similarity analyses enabled the extraction of novel interactions from microarray datasets. Applying this approach to p21-activated kinase 1, we validated α-tubulin and early endosome antigen 1 as its novel interactors.