tbuckley/cabot-search huggingface dataset:
Efficacy and safety of bronchial artery embolization for the control of hemoptysis in patients with mycobacterium avium complex lung disease
Authors: Kenichi Okuda, Masahiro Kawashima, Kimihiko Masuda, Junko Suzuki, Nobuharu Ohshima, Hirotoshi Matsui, Akira Yamane, Atsuhisa Tamura, Hideaki Nagai, Shinobu Akagawa, Ken Ohta
Journal: European Respiratory Journal (2014)

Rationale:  Hemoptysis frequently develops in the clinical course of Mycobacterium avium complex (MAC) lung disease. Bronchial artery embolization (BAE) is considered as one of the useful treatments of massive and persistent hemoptysis. The aim of this study was to analyze the clinical characteristics of patients with hemoptysis associated with MAC and to evaluate efficacy and safety of BAE.   Methods:  Among 529 patients who were admitted to our institute with MAC lung disease from January 2007 to December 2012, we retrospectively reviewed the background, imaging findings and clinical course of the patients who underwent BAE using coils due to hemoptysis.   Results:  Forty-three patients with a median age of 72 years (ranged from 35 to 88) and male:female ratio of 9:34 were included in this study, demonstrating nodular/bronchiectasis in 27 (62.8%) and fibrocavitary pattern in 16 (37.2%) on CT scan. A median length from the initial diagnosis of MAC lung disease to BAE was 60 months and MAC was under treatment with antibiotics in 21 (48.8%) patients at the time of BAE. Non-rebleeding rate during 12 months after BAE was 79.1%. Presence of aspergilloma (p   Conclusion:  BAE is an effective and safe method to control hemoptysis in patients with MAC lung disease. It is important to carefully observe the patients with risk factors for rebleeding such as aspergilloma and multiple vessels embolized at BAE.
Genetically modified enterotoxigenic Escherichia coli vaccines induce mucosal immune responses without inflammation
Authors: A. Daley, R. Randall, M. Darsley, N. Choudhry, N. Thomas, I. R Sanderson, N. M Croft, P. Kelly
Journal: Gut (2007)

<h3>Objective:</h3> Enterotoxigenic <i>Escherichia coli</i> (ETEC) is a major cause of acute diarrhoea in children in the developing world, in travellers and in the military. Safe, effective vaccines could reduce morbidity and mortality. As immunity to ETEC is strain specific, the ability to create vaccines in vitro which express multiple antigens would be desirable. It was hypothesised that three genetically attenuated ETEC strains, one with a genetic addition, would be immunogenic and safe, and they were evaluated in the first licensed UK release of genetically modified oral vaccines. <h3>Methods:</h3> Phase 1 studies of safety and immunogenicity were carried out at a Teaching Hospital in London. Varying oral doses of any of three oral vaccines, or placebo, were administered to volunteers of both sexes (n = 98). Peripheral blood responses were measured as serum antibodies (IgG or IgA) by ELISA, antibody-secreting cell (ASC) responses by enzyme-linked immunospot (ELISPOT), and antibody in lymphocyte supernatant (ALS) by ELISA. Mucosal antibody secretion was measured by ELISA for specific IgG and IgA in whole gut lavage fluids (WGLFs). <h3>Results:</h3> Significant mucosal IgA responses were obtained to colonisation factors CFA/I, CS1, CS2 and CS3, both when naturally expressed and when genetically inserted. Dose–response relationships were most clearly evident in the mucosal IgA in WGLF. Vaccines were well tolerated and did not elicit interleukin (IL) 8 or IL6 secretion in WGLF. <h3>Conclusions:</h3> Genetically modified ETEC vaccines are safe and induce significant mucosal IgA responses to important colonisation factors. Mucosal IgA responses were clearly seen in WGLF, which is useful for evaluating oral vaccines.
THE DERMO-EPIDERMAL INTERFACE IN HEALTH AND DISEASE.
Authors: J. B. ROSS
Journal: British Journal of Dermatology (1965)

Journal Article THE DERMO‐EPIDERMAL INTERFACE IN HEALTH AND DISEASE. Get access J. B. ROSS J. B. ROSS Late Registrar, Department of Dermatology, The Royal Victoria Infirmary, Newcastle upon Tyne, 1 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 77, Issue 2, 1 February 1965, Pages 77–87, https://doi.org/10.1111/j.1365-2133.1965.tb14603.x Published: 01 February 1965
Joint Loading Modality: Its Application to Bone Formation and Fracture Healing
Authors: Ping Zhang, George Malacinski, Hiroki Yokota
Journal: British Journal of Sports Medicine (2007)

Sports related injuries such as impact and stress fractures often require a rehabilitation program to stimulate bone formation and accelerate fracture healing. This review introduces a recently developed joint loading modality and evaluates its potential applications to bone formation and fracture healing in post-injury rehabilitation. Bone is a dynamic tissue whose structure is constantly altered in response to its mechanical environments. Indeed, many loading modalities can influence the bone remodeling process. The joint loading modality is, however, able to enhance anabolic responses and accelerate wound healing without inducing significant in situ strain at the site of bone formation or fracture healing. This review highlights the unique features of this loading modality and discusses its potential underlying mechanisms as well as possible clinical applications.
Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors
Authors: David B. Miklos, Haesook T. Kim, Emmanuel Zorn, Ephraim P. Hochberg, Luxuan Guo, Alex Mattes-Ritz, Sebastien Viatte, Robert J. Soiffer, Joseph H. Antin, Jerome Ritz
Journal: Blood (2003)
The Critical Role of Hematopoietic Cells in Lipopolysaccharide-induced Airway Inflammation
Authors: John W. Hollingsworth, Benny J. Chen, David M. Brass, Katie Berman, M. Dee Gunn, Donald N. Cook, David A. Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Rapid and selective recruitment of neutrophils into the airspace in response to LPS facilitates the clearance of bacterial pathogens. However, neutrophil infiltration can also participate in the development and progression of environmental airway disease. Previous data have revealed that Toll-like receptor 4 (tlr4) is required for neutrophil recruitment to the lung after either inhaled or systemically administrated LPS from Escherichia coli. Although many cell types express tlr4, endothelial cell expression of tlr4 is specifically required to sequester neutrophils in the lung in response to systemic endotoxin. To identify the cell types requiring trl4 expression for neutrophil recruitment after inhaled LPS, we generated chimeric mice separately expressing tlr4 on either hematopoietic cells or on structural lung cells. Neutrophil recruitment into the airspace was completely restored in tlr4-deficient mice receiving wild-type bone marrow. By contrast, wild-type animals receiving tlr4-deficient marrow had dramatically reduced neutrophil recruitment. Moreover, adoptive transfer of wild-type alveolar macrophages also restored the ability of tlr4-deficient recipient mice to recruit neutrophils to the lung. These data demonstrate the critical role of hematopoietic cells and alveolar macrophages in initiating LPS-induced neutrophil recruitment from the vascular space to the airspace.
Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome
Authors: Maria Dalamaga, Konstantinos Karmaniolas, John Chamberland, Athina Nikolaidou, Antigoni Lekka, Amalia Dionyssiou-Asteriou, Christos S Mantzoros
Journal: Metabolism (2013)
Association Among Hyperinsulinemia, Family History of Diabetes, and Diminutive Stature in Normoglycemic Premenopausal Women
Authors: F.J. Guerrero-Igea, J.A. Lepe-Jimenez, A. Garrido-Serrano, S. Palomo-Gil
Journal: Diabetes Care (2001)

Diabetic Ketoacidosis Associated With Orlistat Treatment Orlistat is a drug frequently prescribed as an adjuvant in weight control therapy (1-2).Orlistat inhibits gastric and pancreatic lipases in the lumen of the gastrointestinal tract to decrease the systemic absorption of dietary fat (1,2).In clinical trials, steatorrhoea and other gastrointestinal disorders are the most frequently reported side effects (3).Other reported adverse effects include hypertension (4) and depression (5).No cases of severe hyperglycemia or diabetic ketoacidosis (DKA) have been previously reported with this drug.We report an 18-year-old Caucasian woman with type 1 diabetes for the past 3 years who had a progressive increase in weight, reaching 89 kg, and a height of 164 cm (BMI 33 kg/m 2 ).She was administered several weight-reducing regimens, but to no avail.One month before her hospitalization, she began taking, on her own, orlistat (120 mg three times per day) in addition to a low-calorie diet.This was accompanied by one to three watery bowel movements per day.She was progressively lethargic, and her insulin dose requirement increased from 86 to 98 U/day, in three preprandial injections of regular insulin with one evening dose of long-acting insulin.She had no other underlying illnesses and was not on any other medication.Her home blood glucose monitoring revealed progressive worsening of her diabetes control.On the day of presentation in the emergency room, she was complaining of severe lethargy, abdominal discomfort, nausea, and two episodes of vomiting.Laboratory data showed severe hyperglycemia (blood glucose 550 mg/dl), acidosis (pH 7.0), hyperosmolar state (Na 153 mEq/l, K 3.0 mEq/l, BUN 60 mg/dl, creatinine 1.8 mg/ dl), severe ketosis (ketone bodies 40 mg/ dl), and positive urinary ketones.She was afebrile (37.2°C), weighed 85 kg, had an HbA 1c 12%, and was dehydrated (ϳ10% of her body weight).Orlistat was stopped, and the patient was started on intravenous hydration and insulin.The patient showed significant improvement over a period of 5 days.On discharge, she was back on her baseline insulin dosage of 82 U/day, and she was hemodynamically stable.In this patient, orlistat, probably secondary to the watery stools, seemed to have progressively caused dehydration and a decrease in intravascular volume.Initially, this lead to insulin resistance and increased insulin requirements, followed by DKA.This is the first report of DKA precipitated by orlistat in a type 1 diabetic patient.We advise caution and close monitoring of patients with type 1 diabetes who are given orlistat for obesity management.
Novel cerebrovascular pathology in mice fed a high cholesterol diet
Authors: Sonia Franciosi, Miguel A Gama Sosa, Daniel F English, Elizabeth Oler, Twethida Oung, William GM Janssen, Rita De Gasperi, James Schmeidler, Dara L Dickstein, Christoph Schmitz, Sam Gandy, Patrick R Hof, Joseph D Buxbaum, Gregory A Elder
Journal: Molecular Neurodegeneration (2009)

Hypercholesterolemia causes atherosclerosis in medium to large sized arteries. Cholesterol is less known for affecting the microvasculature and has not been previously reported to induce microvascular pathology in the central nervous system (CNS).Mice with a null mutation in the low-density lipoprotein receptor (LDLR) gene as well as C57BL/6J mice fed a high cholesterol diet developed a distinct microvascular pathology in the CNS that differs from cholesterol-induced atherosclerotic disease. Microvessel diameter was increased but microvascular density and length were not consistently affected. Degenerative changes and thickened vascular basement membranes were present ultrastructurally. The observed pathology shares features with the microvascular pathology of Alzheimer's disease (AD), including the presence of string-like vessels. Brain apolipoprotein E levels which have been previously found to be elevated in LDLR-/- mice were also increased in C57BL/6J mice fed a high cholesterol diet.In addition to its effects as an inducer of atherosclerosis in medium to large sized arteries, hypercholesterolemia also induces a microvascular pathology in the CNS that shares features of the vascular pathology found in AD. These observations suggest that high cholesterol may induce microvascular disease in a range of CNS disorders including AD.
Experts call for more allergy specialists in UK
Authors: A. O'Dowd
Journal: BMJ (2010)

The United Kingdom has a worryingly low number of specialists to diagnose food allergies in children, experts say.

It is estimated that the number of admissions of children to hospital for food allergies has risen 500% since 1990. The British Society for Allergy and Clinical Immunology, the professional and academic body that represents the specialty of allergy, has this week called for the number of specialists to be boosted.

Following up on the findings of a recently published joint report with the Royal College of Physicians and Royal College of Pathologists, Allergy Services: Still Not Meeting the …
Do changes in pulmonary capillary wedge pressure adequately reflect myocardial ischemia during anesthesia? A correlative preoperative hemodynamic, electrocardiographic, and transesophageal echocardiographic study.
Authors: M E van Daele, G R Sutherland, M M Mitchell, A G Fraser, O Prakash, E N Rulf, J R Roelandt
Journal: Circulation (1990)

Pulmonary capillary wedge pressure (PCWP) is monitored during anesthesia in an attempt to detect changes in myocardial function in patients at risk of preoperative cardiac complications. Because the sensitivity with which preoperative PCWP monitoring indicates myocardial ischemia is uncertain, we monitored PCWP, 12-lead electrocardiogram, and left ventricular wall motion abnormalities as defined by transesophageal echocardiography (TEE) in 98 anesthetized patients before coronary artery bypass grafting. Measurements were made five times in each patient, before and after induction of anesthesia. Myocardial ischemia was identified by TEE in 14 patients; in 10 of these, it was associated with concomitant ST segment depression of at least 1 mm. The onset of ischemia, as defined by TEE, was accompanied by a mean increase in PCWP of 3.5 +/- 4.8 mm Hg, as compared with a mean change of 0 +/- 2.2 mm Hg between observations not associated with the onset of ischemia (p less than 0.01). An increase in PCWP of at least 3 mm Hg, tested as an indicator of ischemia, had a sensitivity of 25% and a positive predictive value of 15%; after correction for background changes associated with anesthetic induction, the sensitivity of this indicator was 33%, and its positive predictive value was 16%. These figures were not improved by selecting cutoff points higher or lower than 3 mm Hg. In this study, the onset of myocardial ischemia was associated with a small yet significant increase in mean PCWP at group level.(ABSTRACT TRUNCATED AT 250 WORDS)
Please Santa, bring me freedom
Authors: Kamran Abbasi
Journal: BMJ (2004)

Freedom has become the political buzzword of the 21st century. George Bush's agenda is to bring democracy and freedom to the rest of the peoples of the world, while his own are slaves to work, crippled by personal debt, and trapped in loneliness or loveless relationships—the shackles of the rich. Now that the surviving Afghanis and Iraqis are enjoying the benefits of Western freedoms, what will this mean for their health? No empirical studies have explored the relation between the extent of freedom allowed by political regimes and the effect on a nation's health—until now.

Carlos Alvarez-Dardet and colleagues use …
Phase II study of epirubicin and vinorelbine with granulocyte colony-stimulating factor: A high-activity, dose-dense weekly regimen for advanced breast cancer
Authors: C Nisticò, C Garufi, S Barni, L Frontini, D A Gallà, D Giannarelli, A Vaccaro, A M D'Ottavio, E Terzoli
Journal: Annals of Oncology (1999)
Platelet-derived growth factor-D and Rho GTPases regulate recruitment of cancer-associated fibroblasts in cholangiocarcinoma
Authors: Massimiliano Cadamuro, Giorgia Nardo, Stefano Indraccolo, Luigi Dall'Olmo, Luisa Sambado, Lidia Moserle, Irene Franceschet, Michele Colledan, Marco Massani, Tommaso Stecca, Nicolò Bassi, Stuart Morton, Carlo Spirli, Romina Fiorotto, Luca Fabris, Mario Strazzabosco
Journal: Hepatology (2013)

Cholangiocarcinoma (CCA) is characterized by an abundant stromal reaction. Cancer-associated fibroblasts (CAFs) are pivotal in tumor growth and invasiveness and represent a potential therapeutic target. To understand the mechanisms leading to CAF recruitment in CCA, we studied (1) expression of epithelial-mesenchymal transition (EMT) in surgical CCA specimens and CCA cells, (2) lineage tracking of an enhanced green fluorescent protein (EGFP)-expressing human male CCA cell line (EGI-1) after xenotransplantation into severe-combined-immunodeficient mice, (3) expression of platelet-derived growth factors (PDGFs) and their receptors in vivo and in vitro, (4) secretion of PDGFs by CCA cells, (5) the role of PDGF-D in fibroblast recruitment in vitro, and (6) downstream effectors of PDGF-D signaling. CCA cells expressed several EMT biomarkers, but not alpha smooth muscle actin (α-SMA). Xenotransplanted CCA masses were surrounded and infiltrated by α-SMA-expressing CAFs, which were negative for EGFP and the human Y-probe, but positive for the murine Y-probe. CCA cells were strongly immunoreactive for PDGF-A and -D, whereas CAFs expressed PDGF receptor (PDGFR)β. PDGF-D, a PDGFRβ agonist, was exclusively secreted by cultured CCA cells. Fibroblast migration was potently induced by PDGF-D and CCA conditioned medium and was significantly inhibited by PDGFRβ blockade with Imatinib and by silencing PDGF-D expression in CCA cells. In fibroblasts, PDGF-D activated the Rac1 and Cdc42 Rho GTPases and c-Jun N-terminal kinase (JNK). Selective inhibition of Rho GTPases (particularly Rac1) and of JNK strongly reduced PDGF-D-induced fibroblast migration.CCA cells express several mesenchymal markers, but do not transdifferentiate into CAFs. Instead, CCA cells recruit CAFs by secreting PDGF-D, which stimulates fibroblast migration through PDGFRβ and Rho GTPase and JNK activation. Targeting tumor or stroma interactions with inhibitors of the PDGF-D pathway may offer a novel therapeutic approach.
Interstitial laser photocoagulation of normal lung parenchyma in rats
Authors: D I Fielding, G Buonaccorsi, A Hanby, M R Hetzel, S G Bown
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Management of peripheral lung tumours may be risky in patients with poor lung function or in the elderly. A new possibility is interstitial laser photocoagulation (ILP) in which tumours are gently coagulated using thin laser fibres placed percutaneously under radiological guidance. This could have a useful palliative role in selected patients, but to be safe the effects on normal lung parenchyma must first be understood. This paper describes the creation and healing of ILP lesions in the normal rat lung. <h3>METHODS</h3> ILP was performed using single laser fibres placed percutaneously in the left lung of normal rats under general anaesthetic with radiological guidance (laser power 1–3 W at 805 nm, treatment time 250–1000 s). The lesion size and healing were studied in rats killed at times from three days to six months after treatment, the bursting pressure was measured, and any complications noted. <h3>RESULTS</h3> Zones of necrosis up to 12 mm in diameter were produced, the size depending on the laser power and treatment time. Histological examination showed typical thermal effects with complete healing with fibrosis by two months. The effect was very localised with remarkably little effect on the structure and function of the rest of the lung. Adverse effects in the lung parenchyma only occurred if the ILP lesion involved the hilar vessels or the oesophagus, causing pulmonary congestion and perforation, respectively. Pneumothorax was seen in 6% of cases. <h3>CONCLUSIONS</h3> ILP with a single fibre can produce a localised zone of necrosis in normal lung parenchyma which heals safely and which has little effect on the rest of the lung. Further study of this technique using multiple fibres in a larger animal model is warranted to see if it is feasible and safe to produce a large enough volume of necrosis to be of value in the treatment of small peripheral lung tumours in patients who are unsuitable for surgery or palliative radiotherapy.
Human Ovarian Carcinoma β-N-Acetylglucosaminidase Isoenzymes and Their Role in Extracellular Matrix Degradation
Authors: Barbara Woynarowska, Hanna Wikiel, Ralph J. Bernacki
Journal: Cancer Research (1989)

Abstract  Degradation and invasion of basement membrane by tumor cells involves the cooperative hydrolysis of proteoglycans, collagens, and glycoproteins mediated by a number of enzymes including proteases, collagenases, and glycosidases. In order to study these processes  in vitro , a tissue culture system was developed in which bovine corneal endothelial cell extracellular matrix (ECM) serves as a substrate for attachment and degradation by human ovarian carcinoma cells. Using this system, a correlation was observed between solubilization of glycoconjugates present in ECM and extracellular levels of β- N -acetylglucosaminidase (EC 3.2.1.30). To determine the role of individual isoenzymes of β- N -acetylglucosaminidase (β-NAG) in ECM degradation, the cellular and secreted forms of the enzyme were fractionated and characterized. Three intracellular isoenzyme forms, A, I, and B, were isolated from invasive human ovarian carcinoma cell line A-121. In cell homogenate, forms A and B corresponded to 65 and 33% of total β-NAG activity, respectively. Form I was found to be localized in the plasma membrane fraction of these cells. Two secreted forms of β-NAG (A S  and B S ) were detected in serum-free medium. The separated intracellular and secreted isoenzymes demonstrated similar  K  m  values, ranging from 1 to 5 mm, with  p -nitro-β- N -acetylglucosaminide substrate. Treatment of [ 3 H]glucosamine-labeled ECM with the separated isoenzymes of β-NAG resulted in time- and concentration-dependent releases of radioactivity with potency of I > B » A. These results suggest that human ovarian carcinoma cell β- N -acetylglucosaminidase isoenzymes (forms B and A) contribute to ECM degradation as secreted enzymes and form I as a membrane enzyme.
RANKL Expression, Function, and Therapeutic Targeting in Multiple Myeloma and Chronic Lymphocytic Leukemia
Authors: Benjamin Joachim Schmiedel, Carolin Andrea Scheible, Tina Nuebling, Hans-Georg Kopp, Stefan Wirths, Miyuki Azuma, Pascal Schneider, Gundram Jung, Ludger Grosse-Hovest, Helmut Rainer Salih
Journal: Cancer Research (2012)

Abstract Bone destruction is a prominent feature of multiple myeloma, but conflicting data exist on the expression and pathophysiologic involvement of the bone remodeling ligand RANKL in this disease and the potential therapeutic benefits of its targeted inhibition. Here, we show that RANKL is expressed by primary multiple myeloma and chronic lymphocytic leukemia (CLL) cells, whereas release of soluble RANKL was observed exclusively with multiple myeloma cells and was strongly influenced by posttranscriptional/posttranslational regulation. Signaling via RANKL into multiple myeloma and CLL cells induced release of cytokines involved in disease pathophysiology. Both the effects of RANKL on osteoclastogenesis and cytokine production by malignant cells could be blocked by disruption of RANK–RANKL interaction with denosumab. As we aimed to combine neutralization of RANKL with induction of antibody-dependent cellular cytotoxicity of natural killer (NK) cells against RANKL-expressing malignant cells and as denosumab does not stimulate NK reactivity, we generated RANK-Fc fusion proteins with modified Fc moieties. The latter displayed similar capacity compared with denosumab to neutralize the effects of RANKL on osteoclastogenesis in vitro, but also potently stimulated NK cell reactivity against primary RANKL-expressing malignant B cells, which was dependent on their engineered affinity to CD16. Our findings introduce Fc-optimized RANK-Ig fusion proteins as attractive tools to neutralize the detrimental function of RANKL while at the same time potently stimulating NK cell antitumor immunity. Cancer Res; 73(2); 683–94. ©2012 AACR.