tbuckley/cabot-search huggingface dataset:
Immunogold labelling of epidermal Langerhans cells on tissue sections of normal human skin
Authors: G. PANFILIS, G.C. MANARA, C. FERRARI
Journal: British Journal of Dermatology (1986)

A colloidal gold staining procedure was developed for immuno-electron microscopy, which allowed the demonstration of T6 surface antigens of epidermal Langerhans cells on sections of normal human skin with consistent ultrastructural preservation of subcellular structures. All the observed Birbeck granule-bearing Langerhans cells revealed immunogold labelling along the plasma membrane. The penetration of the tissue by the gold particles was adequate, as was the sensitivity and the specificity of the reaction. A major advantage of the present method in comparison with immunoperoxidase techniques is the absence of non-specific staining of the membranes of keratinocytes facing the labelled plasma membrane of the Langerhans cells.
Realizing the Clinical Potential of Cancer Nanotechnology by Minimizing Toxicologic and Targeted Delivery Concerns
Authors: Sanjay Singh, Arati Sharma, Gavin P. Robertson
Journal: Cancer Research (2012)

Nanotechnology has the potential to make smart drugs that would be capable of targeting cancer but not normal cells and to load combinations of cooperating agents into a single nanosized particle to more effectively treat this disease. However, to realize the full potential of this technology, the negative aspects associated with these nanoparticles need to be overcome. This review discusses concerns in the field limiting realization of the full clinical potential of this technology, which are toxicity and targeted delivery. Strategies to overcome these hurdles are also reviewed, which could lead to attainment of the full clinical potential of this exciting technology.
Role of Nitric Oxide in Sepsis-associated Pulmonary Edema
Authors: FRANK HINDER, HENNING D. STUBBE, HUGO VAN AKEN, RENÉ WAURICK, MICHAEL BOOKE, JÖRG MEYER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Transient pulmonary hypertension after inhibition of nitric oxide synthase (NOS) does not alter pulmonary reflection coefficients or lymph flows in endotoxemic sheep. To test the effects of persistent pulmonary hypertension induced by N ω-nitro-l-arginine methylester (l-NAME) and of inhaled NO on pulmonary edema, 18 sheep (three groups) were chronically instrumented with pulmonary artery catheters, femoral arterial fiberoptic thermistor catheters, and tracheostomy. The awake, spontaneously breathing animals received Salmonella typhi endotoxin (lipopolysaccharide; LPS) (10 ng/kg/ min) for 28 h. After 24 h, an airflow of 6 L/min was delivered through the tracheostomy. One group of animals (l-NAME/air) received l-NAME intravenously (25 mg/kg + 5 mg/kg/h) and breathed air. The second group (l-NAME/NO) was given l-NAME and NO (40 ppm) was added to the airflow. The third group was given NaCl 0.9% and breathed air (NaCl/air). Extravascular lung water was measured through the double-indicator dilution technique. Endotoxemia caused pulmonary edema, which was aggravated by l-NAME. Breathing of NO normalized pulmonary artery pressure (Ppa) and ameliorated pulmonary edema. Inhalation of NO may therefore be a therapeutic option for pulmonary edema associated with pulmonary hypertension.
PHACOS, a functionalized bacterial polyester with bactericidal activity against methicillin-resistant Staphylococcus aureus
Authors: Nina Dinjaski, Mar Fernández-Gutiérrez, Shivaram Selvam, Francisco J. Parra-Ruiz, Susan M. Lehman, Julio San Román, Ernesto García, José L. García, Andrés J. García, María Auxiliadora Prieto
Journal: Biomaterials (2013)
Differential Effect of B Lymphocyte–induced Maturation Protein (Blimp-1) Expression on Cell Fate during B Cell Development
Authors: Eric J. Messika, Peter S. Lu, Yen-Jen Sung, Tony Yao, Jen-Tsan Chi, Yueh-hsiu Chien, Mark M. Davis
Journal: The Journal of Experimental Medicine (1998)

The B lymphocyte–induced maturation protein (Blimp-1) upregulates the expression of syndecan-1 and J chain and represses that of c-myc. We have transfected Blimp-1 into two sublines of the BCL1 B cell lymphoma that represent distinct stages of B cell development in secondary lymphoid tissues. After interleukin (IL)-2 and IL-5 stimulation, the BCL1 3B3 cells differentiate into centrocyte-like cells, whereas the BCL1 5B1b cells blast and appear to be blocked at the centroblast stage. This blasting effect and the increase in IgM secretion that follows it can be blocked by a dominant negative form of Blimp-1. At the same time, the ectopic expression of Blimp-1 in these partially activated cells induces an apoptotic response that also can be suppressed by the same dominant negative protein. A similar effect was noticed when Blimp-1 was expressed in the mature L10A and the immature WEHI-231 lines, indicating this may be a general effect at earlier stages of the B cell development, and distinct from the ability of Blimp-1 to induce maturation in late stages of differentiation. Truncation mutants indicate that the induction of the apoptotic response relies mainly on 69 amino acids within Blimp-1's proline-rich domain. We propose that Blimp-1 expression defines a checkpoint beyond which fully activated B cells proceed to the plasma cell stage, whereas immature and partially activated cells are eliminated at this point.
Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients
Authors: R.A. Feelders, A.J.G. Swaak, J.A. Romijn, A.M.M. Eggermont, E.T. Tielens, G. Vreugdenhill, E. Endert, H.G. van Eijk, A. Berghout
Journal: Metabolism (1999)
Reply to Nakayama and Tamura
Authors: Alberto Quaglia, Ahlam Mustafa, Ragai R. Mitry, Bernard Portmann
Journal: Hepatology (2010)

We thank Dr. Nakayama and Dr. Tamura for their interest in our recent contribution to Image of the Month1 and for allowing us to share their broad knowledge on copper, metallothionein, and porphyrin autofluorescence. Their elaborate spectroscopic and biochemical explanations are beyond our area of expertise, and we do not have direct experience with the Long-Evans cinnamon rat model of Wilson disease. We made the simple histological observation that autofluorescent granules in human liver tissue from well-characterized patients with Wilson disease or chronic cholestasis stain with both orcein and rhodanine in keeping with a high content in sulfhydril groups and copper, respectively. The large size of the fluorescent granules suggested that we were not dealing with metallothionein-copper alone, but with a large amount of copper incorporated into the not entirely characterized lysosomal complex of metallothionein polymers with a glycoprotein component, as supported by periodic acid–Schiff staining. We realized that copper-metallothionein autofluorescence was well-known in earlier literature, and wondered about its possible practical use and the potential role of autofluorescence in liver pathology as quoted in an excellent review on the subject.2 We thought it was worth sharing this matter in the Image of the Month forum and remain glad to have generated some academic debate. Alberto Quaglia*, Ahlam Mustafa*, Ragai R. Mitry*, Bernard Portmann*, * King's College Hospital, Institute of Liver Studies London, UK.
Lectures in Chest Medicine
Authors: Harry B. Greenberg
Journal: JAMA (1970)

Presenting an interesting view of respiratory disease, the ten lectures that make up this book examine many topical issues and dispel some antequated ideas. After noting that "only a patient who lacks the necessary mental equipment to cough into a handkerchief need be isolated," Edge discusses the concepts that have revolutionized the management of pulmonary tuberculosis. It has become practicable, he observes, to put tuberculous adults in semicubicalized hospital wards that contain persons with other diseases. And, citing the negligible relapse rate, he considers antituberculosis chemotherapy almost always successful. Treating sarcoidosis, on the other hand, yields uncertain results. According to James, Sharma, and Carstairs, some forms of sarcoidosis resolve spontaneously but others lead to disabling fibrosis. For these they recommend adrenal corticosteroids and in selected instances chloroquine and oxyphenbutazone. Edge also uses steroids to halt the ravages of polyarteritis and sometimes of lupus. He considers the patient's prognosis mostly dependent
Red for danger: the effects of red hair in surgical practice
Authors: A. L. Cunningham, C. P. Jones, J. Ansell, J. D. Barry
Journal: BMJ (2010)

<h3>Background</h3> Little is known about optimal fluid therapy for patients with sepsis without shock who present to the ED. In this study, we aimed to quantify the effect of a fluid challenge on non-invasively measured Cardiac Index (CI) in patients presenting with sepsis without shock. <h3>Methods</h3> In a prospective cohort study, CI, stroke volume (SV) and systemic vascular resistance (SVR) were measured non-invasively in 30 patients presenting with sepsis without shock to the ED of a large teaching hospital in the Netherlands between May 2018 and March 2019 using the ClearSight system. After baseline measurements were performed, a passive leg raise (PLR) was done to simulate a fluid bolus. Measurements were then repeated 30, 60, 90 and 120 s after PLR. Finally, a standardised 500 mL NaCl 0.9% intravenous bolus was administered after which final measurements were done. Fluid responsiveness was defined as &gt;15% increase in CI after a standardised fluid challenge. <h3>Measurements and main results</h3> Seven out of 30 (23%) patients demonstrated a &gt;15% increase in CI after PLR and after a 500 mL fluid bolus. Fluid responders had a higher estimated glomerular filtration rate (eGFR) (64 (44–78) vs 37 (23–47), p=0.009) but otherwise similar patient and treatment characteristics as non-responders. Baseline measurements of cardiac output (CO), CI, SV and SVR were unrelated to PLR fluid responsiveness. The change in CI after PLR was strongly positive correlated to the change in CI after a 500 mL NaCl 0.9% fluid bolus (r=0.88, p&lt;0.001). <h3>Conclusion</h3> The results of the present study demonstrate that in patients with sepsis in the absence of shock, three out of four patients do not demonstrate a clinically relevant increase in CI after a standardised fluid challenge. Non-invasive CO monitoring in combination with a PLR test has the potential to identify patients who might benefit from fluid resuscitation and may contribute to a better tailored treatment of these patients.
Author's reply to Robson and Lip
Authors: D. Spence
Journal: BMJ (2013)

I did not suggest that anticoagulation is ineffective in atrial fibrillation1 2: its effectiveness is not in dispute. The issue is the relative benefit of anticoagulation. If the background rate of stroke declines as it has, the absolute benefit of anticoagulation will also decline. The risk from the medical treatments of aspirin, warfarin, or new agents is fixed. …
In sero veritas: what serum markers teach us about HCV infection of primary human hepatocytes
Authors: Thomas Pietschmann
Journal: Gut (2013)

HCV has chronically infected an estimated number of 160 million individuals worldwide.1 In the course of 10–20 years of persistent infection, approximately 20% of these patients are at risk of developing severe liver disease, including fibrosis, cirrhosis and hepatocellular carcinoma.2 Besides the ability to establish chronic infection, the pronounced genetic variability of HCV and the diverse course of chronic infection ranging from relatively benign to exacerbating liver disease are hallmarks of hepatitis C. Moreover, response to classical antiviral treatment based on pegylated interferon alpha (PEG-IFN-α) and ribavirin is substantially influenced by viral and host factors, since viral genotypes 1 and 4 are more resilient to therapy compared with genotypes 2 and 3 and as polymorphisms in the vicinity of the IFN28B locus predict the chances to naturally clear HCV infection and of response to IFN-based therapies.3 ,4 The high degree of virus variability is also a formidable challenge in the emerging era of directly acting antivirals for treatment of hepatitis C by mediating drug escape through resistance mutations. Moreover, many molecules, most prominently the already licensed protease inhibitors telaprevir and boceprevir, display a genotype-dependent antiviral activity. Therefore, both viral and host genetic variability complicate provision of efficacious, safe, well-tolerated and cost-effective therapies to the large number of HCV patients.

At the same time, HCV has been resistant to disclosing its secrets as the road for development of suitable cell culture and animal models to dissect mechanism of virus replication and liver disease has been paved with many roadblocks. For instance, infection of cultured cells by primary patient-derived virus from sera …
Energy metabolism and contractile function after 15 beats of moderate myocardial ischemia.
Authors: A E Arai, G A Pantely, W J Thoma, C G Anselone, J D Bristow
Journal: Circulation Research (1992)

Difficulties in studying myocardial metabolism with adequate time resolution have led to contradictory conclusions regarding the mechanisms causing contractile abnormalities during the early stages of ischemia. In acutely instrumented swine, we investigated whether abnormalities in subendocardial ATP, phosphocreatine, or lactate content develop rapidly enough during the first few heart beats after onset of partial myocardial ischemia to contribute to contractile failure. Within the first 15 beats of a 40-50% reduction in left anterior descending coronary artery blood flow, regional myocardial function was significantly reduced but continuing to deteriorate. Rapidly frozen transmural left ventricular biopsies obtained on the 15th heart beat (+/- 1.5 beats) after the onset of ischemia revealed significant decrements in subendocardial phosphocreatine and ATP levels to 77% (p less than 0.05) and 84% (p less than 0.005) of control values, respectively, but minimal change in lactate content. Metabolic effects as assessed by transmural averages took longer to become detectable; thus, there was a tendency to underestimate the importance of subendocardial metabolic effects on myocardial function. When left ventricular preload was assessed during this early time period, left ventricular end-diastolic wall thickness only decreased by 3%, and left ventricular end-diastolic pressure did not change significantly despite a large fall in coronary perfusion pressure. Thus, in an in vivo pig model with techniques optimized to detect subendocardial metabolic changes within the period of very early moderate myocardial ischemia, abnormalities in high energy phosphate compounds occurred rapidly enough to contribute to developing myocardial dysfunction, whereas preload-mediated mechanisms related to vascular distending pressure could not explain the functional deterioration under these conditions.
Acute Chemical Emergencies
Authors: Stefanos N. Kales, David C. Christiani
Journal: New England Journal of Medicine (2004)

Acute chemical emergencies can occur as a result of an industrial accident, occupational exposure, a natural disaster, or an act of terrorism. This article reviews empirical principles for rapid recognition and treatment of the clinical syndromes, or toxidromes, caused by asphyxiants, cholinesterase inhibitors, respiratory irritants, and blistering agents. Treatment should be provided as soon as possible after an acute chemical exposure, usually before laboratory tests can confirm the specific chemicals involved.
CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells
Authors: Eric J. Kunkel, Chang H. Kim, Nicole H. Lazarus, Mark A. Vierra, Dulce Soler, Edward P. Bowman, Eugene C. Butcher
Journal: Journal of Clinical Investigation (2003)

The dissemination of IgA-dependent immunity between mucosal sites has important implications for mucosal immunoprotection and vaccine development. Epithelial cells in diverse gastrointestinal and nonintestinal mucosal tissues express the chemokine MEC/CCL28. Here we demonstrate that CCR10, a receptor for MEC, is selectively expressed by IgA Ab-secreting cells (large s/cIgA+CD38hiCD19int/–CD20–), including circulating IgA+ plasmablasts and almost all IgA+ plasma cells in the salivary gland, small intestine, large intestine, appendix, and tonsils. Few T cells in any mucosal tissue examined express CCR10. Moreover, tonsil IgA plasmablasts migrate to MEC, consistent with the selectivity of CCR10 expression. In contrast, CCR9, whose ligand TECK/CCL25 is predominantly restricted to the small intestine and thymus, is expressed by a fraction of IgA Ab-secreting cells and almost all T cells in the small intestine, but by only a small percentage of plasma cells and plasmablasts in other sites. These results point to a unifying role for CCR10 and its mucosal epithelial ligand MEC in the migration of circulating IgA plasmablasts and, together with other tissue-specific homing mechanisms, provides a mechanistic basis for the specific dissemination of IgA Ab-secreting cells after local immunization.
287 EVALUATING VIROLOGIC RESPONSE WITHIN 2–4 WEEKS HAS HIGH POSITIVE/NEGATIVE PREDICTIVE VALUES FOR SUSTAINED VIROLOGIC RESPONSE IN PATIENTS WITH GENOTYPE 1 CHRONIC HEPATITIS C DURING TREATMENT
Authors: A. Neumann, M. Shiffman, P. Ferenci, G. Foster, E. Yoshida, S. Pianko, M. Sulkowski, S. Zeuzem, Y. Benhamou, D. Nelson, J. McHutchison, E. Pulkstenis, G. Subramanian
Journal: Journal of Hepatology (2010)
Structural changes in ageing skin
Authors: W. MONTAGNA, K. CARLISLE
Journal: British Journal of Dermatology (1990)

Journal Article Structural changes in ageing skin Get access W. MONTAGNA, W. MONTAGNA Oregon Regional Primate Research Center, Beaverton, Oregon, U.S.A. W. Montagna, M.D., Oregon Regional Primate Research Center, 505 NW, 185th Avenue, Beaverton, OR 97006, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar K. CARLISLE K. CARLISLE Oregon Regional Primate Research Center, Beaverton, Oregon, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 122, Issue s35, 1 April 1990, Pages 61–70, https://doi.org/10.1111/j.1365-2133.1990.tb16127.x Published: 01 April 1990
New therapeutic targets in HCC: Reptin ATPase and HCC senescence
Authors: Carmen Berasain
Journal: Journal of Hepatology (2010)

Cellular senescence is a process characterized by permanent cell cycle arrest. It is the consequence of the finite proliferative capacity of normal cells (replicative senescence) and the response to stress and damage from exogenous and endogenous sources. Several years ago it was shown that senescence is an innate tumour suppressive mechanism associated with the activation of oncogenes, which limits the progression of pre-malignant lesions [1]. As a consequence, escape from senescence is a prerequisite for the progression to malignancy. There are three main mechanisms that trigger cellular senescence and that must be quelled in cancer cells: activation of the p53 pathway, upregulation of the CDKN2A locus, and telomere shortening [2]. Genetic and epigenetic aberrations in any or all of these pathways are common marks of all types of human cancer. However, the senescence resistance associated with transformed cells is reversible [3], and senescence-inducing drugs could represent an ideal opportunity to increase the arsenal of anti-cancer weapons [2]. In the present issue of The Journal of Hepatology the work of Menard et al. describes a new example of tumour progression blockage linked to the induction of replicative senescence in a xenograft model of liver cancer [4]. Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and is characterized by a poor prognosis. In many cases no effective therapy at all can be offered to patients with HCC [5]. Surgical interventions such as tumour ablation or transplantation are restricted to a selected group of patients with very specific clinical features, and non-resectable tumours are resistant to conventional chemotherapy. New strategies such as radiotherapy and gene therapy alone or in combination with cell therapy are at early stages of clinical development [6]. Given the survival benefits of the molecular inhibitor Sorafenib in patients at advanced stages [7] the use of single or combined targeted therapies appears as a promising therapeutic alternative. Recent studies demonstrate the existence of an increasing number of pathways that might be altered by drugs in HCC cells [5]. The molecular profiling of HCC and the identification of patient subclasses according to drug responsiveness will lead to a more per-
Knowledge and comfort
Authors: Samiran Nundy
Journal: BMJ (2004)

in the multivariate analyses.Riders wearing high visibility clothing and white helmets are likely to be more safety conscious than other riders.However, we were able to adjust for sociodemographic variables, the propensity for risk taking behaviour, and environmental characteristics.Bright colours worn during the day, daytime use of headlight, and reflective or fluorescent clothing are thought to enhance conspicuity by increasing the brightness contrast between the surface or object it is on and the background environment.The finding that helmet colour was associated with injury crash risk whereas frontal colour of clothing was not was unexpected.A possible explanation for our findings is that 80% of the controls wore black, blue, or brown top clothing and black or blue clothing from the waist down.Accordingly our study may not have had the power to detect an effect of brightly coloured clothing if it existed.Our study was also limited by the one "catch-all" category for reflective and or fluorescent clothing.These materials offer maximum conspicuity advantage in differing ambient light conditionsfluorescence at twilight and reflective material at night.We were unable to determine the individual contributions of these materials. Implications for prevention of injuriesThis study took place in a predominantly urban area and in a country where motorcycles make up a small percentage of all registered motor vehicles.Factors contributing to poor conspicuity, such as contrast from the background environment and ambient illumination, may differ between settings.The population attributable risks are not generalisable as they depend on the background prevalence of the risk factors in specific populations.However, there is no reason to believe that the relative risk estimates for the conspicuity measures investigated would not be generalisable to other settings.This seems to be the first population based aetiological study investigating motorcycle conspicuity and risk of crash related injury and death.The study suggests that low physical conspicuity is a contributing factor in a significant proportion of road traffic crashes causing injury.The social costs of motorcycling deaths and disability are high, not only through premature deaths and hospital admissions but also through costs of rehabilitation, lost income, sickness benefits, insurance, property, and legal expenses as well as personal costs of grief and suffering.This study supports the introduction of both active and passive injury prevention strategies through laws requiring daytime use of headlights and measures encouraging greater visibility of motorcycle riders on the roads.