tbuckley/cabot-search huggingface dataset:
Oxidative stress and redox regulation of lung inflammation in COPD
Authors: I. Rahman, I. M. Adcock
Journal: European Respiratory Journal (2006)

Reactive oxygen species, either directly or via the formation of lipid peroxidation products, may play a role in enhancing inflammation through the activation of stress kinases (c-Jun activated kinase, extracellular signal-regulated kinase, p38) and redox-sensitive transcription factors, such as nuclear factor (NF)-κB and activator protein-1. This results in increased expression of a battery of distinct pro-inflammatory mediators. Oxidative stress activates NF-κB-mediated transcription of pro-inflammatory mediators either through activation of its activating inhibitor of κB-α kinase or the enhanced recruitment and activation of transcriptional co-activators. Enhanced NF-κB-co-activator complex formation results in targeted increases in histone modifications, such as acetylation leading to inflammatory gene expression. Emerging evidence suggests the glutathione redox couple may entail dynamic regulation of protein function by reversible disulphide bond formation on kinases, phosphatases and transcription factors. Oxidative stress also inhibits histone deacetylase activity and in doing so further enhances inflammatory gene expression and may attenuate glucocorticoid sensitivity. The antioxidant/anti-inflammatory effects of thiol molecules (glutathione, N -acetyl- L -cysteine and N -acystelyn, erdosteine), dietary polyphenols (curcumin-diferuloylmethane, cathechins/quercetin and reserveratol), specific spin traps, such as α-phenyl- N -tert-butyl nitrone, a catalytic antioxidant (extracellular superoxide dismutase (SOD) mimetic, SOD mimetic M40419 and SOD, and catalase manganic salen compound, eukarion-8), porphyrins (AEOL 10150 and AEOL 10113) and theophylline have all been shown to play a role in either controlling NF-κB activation or affecting histone modifications with subsequent effects on inflammatory gene expression in lung epithelial cells. Thus, oxidative stress regulates both key signal transduction pathways and histone modifications involved in lung inflammation. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in chronic obstructive pulmonary disease are also discussed.
Outbreak of Type A Botulism and Development of a Botulism Surveillance and Antitoxin Release System in Argentina
Authors: Rodrigo G. Villar
Journal: JAMA (1999)

Botulism is an important public health problem in Argentina, but obtaining antitoxin rapidly has been difficult because global supplies are limited. In January 1998, a botulism outbreak occurred in Buenos Aires.To determine the source of the outbreak, improve botulism surveillance, and establish an antitoxin supply and release system in Argentina.Cohort study in January 1998 of 21 drivers of a specific bus route in urban Buenos Aires.Occurrence of botulism and implication of a particular food as the vehicle causing this outbreak.Nine (43%) of 21 bus drivers developed botulism, presenting with gastroenteritis, symptoms of acute cranial nerve dysfunction including ptosis, dysphagia, blurred vision, and motor weakness. One driver experienced respiratory failure. Type A toxin was detected from 3 of 9 patients' serum samples. All drivers received botulism antitoxin; there were no fatalities. Consumption of matambre (Argentine meat roll) was significantly associated with illness. Among 11 persons who ate matambre, 9 developed illness, compared with none of those who did not eat it (P<.001). The matambre had been cooked in water at 78 degrees C to 80 degrees C for 4 hours, sealed in heat-shrinked plastic wrap, and stored in refrigerators that did not cool adequately. Subsequently, a botulism surveillance and antitoxin release system was established.Insufficient cooking time and temperatures, storage in heat-shrinked plastic wrap, and inadequate refrigeration likely contributed to Clostridium botulinum spore survival, germination, and toxin production. A rapid-response botulism surveillance and antitoxin release system in Argentina should provide more timely distribution of antitoxin to patients and may serve as a model for other nations.
RAD51 can inhibit PDGF-B–induced gliomagenesis and genomic instability
Authors: Ulrica K. Westermark, Nanna Lindberg, Pernilla Roswall, Daniel Bråsäter, Hildur R. Helgadottir, Sanna-Maria Hede, Anders Zetterberg, Maria Jasin, Monica Nistér, Lene Uhrbom
Journal: Neuro-Oncology (2011)

Faithful replication and DNA repair are vital for maintenance of genome integrity. RAD51 is a central protein in homologous recombination repair and during replication, when it protects and restarts stalled replication forks. Aberrant RAD51 expression occurs in glioma, and high expression has been shown to correlate with prolonged survival. Furthermore, genes involved in DNA damage response (DDR) are mutated or deleted in human glioblastomas, corroborating the importance of proper DNA repair to suppress gliomagenesis. We have analyzed DDR and genomic instability in PDGF-B–induced gliomas and investigated the role of RAD51 in glioma development. We show that PDGF-B–induced gliomas display genomic instability and that co-expression of RAD51 can suppress PDGF-B–induced tumorigenesis and prolong survival. Expression of RAD51 inhibited proliferation and genomic instability of tumor cells independent of Arf status. Our results demonstrate that the RAD51 pathway can prevent glioma initiation and maintain genome integrity of induced tumors, suggesting reactivation of the RAD51 pathway as a potential therapeutic avenue.
Glucose Metabolism in the First 3 Years after Renal Transplantation in Patients Receiving Tacrolimus versus Cyclosporine-Based Immunosuppression
Authors: Elly M. van Duijnhoven, Maarten H. L. Christiaans, Johannes M. M. Boots, Fred H. M. Nieman, Bruce H. R. Wolffenbuttel, Johannes P. van Hooff
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The long-term effects of tacrolimus and cyclosporine on pancreatic islet cell function in renal transplant recipients are unclear. Therefore, a prospective, randomized, longitudinal study was performed that compared glucose metabolism in adult kidney allograft recipients on tacrolimus versus cyclosporine-based immunosuppression. Twenty-three white renal allograft recipients, randomized for either therapy with cyclosporine or tacrolimus, underwent intravenous glucose tolerance tests 6 times during the first 3 yr after transplantation. Concomitant therapy (low-dose steroids and azathioprine) was the same in both groups. Insulin sensitivity index (kG), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus and cyclosporine were measured. The occurrence of posttransplantation diabetes mellitus was prospectively monitored. Statistical analysis was performed by ANOVA for repeated measures, and parametric and nonparametric tests were also performed. Although only one patient treated with cyclosporine developed posttransplantation diabetes mellitus, kG levels were below normal in up to one-third of both patients who received tacrolimus and cyclosporine. The only significant difference between patients who received tacrolimus and those who received cyclosporine was in pancreatic secretion capacity at week 3 after transplantation, when the increment of C-peptide secretion was 57% lower and the increment of insulin secretion was 48% lower for patients receiving tacrolimus. In both groups, from week 3 to month 6, there was a tendency toward an increase in kG, despite a significant increase in fasting glucose and insulin resistance calculated by homeostasis model assessment. After month 6, there were no significant changes in any of the parameters of glucose metabolism, indicating that long-term use of either tacrolimus or cyclosporine does not cause chronic, cumulative pancreatic toxicity.
Analysis of DNA polymerase reaction products for detecting hepatitis B virus in serum—comparison with spot hybridization technique
Authors: Fumio Imazeki, Masao Omata, Osamu Yokosuka, Yasuhisa Matsuyama, Yoshimi Ito, Kunio Okuda
Journal: Hepatology (1985)

An assay for DNA polymerase reaction products using slab gel electrophoresis and autoradiography was compared with the spot hybridization technique for the detection of hepatitis B virus DNA in 317 blood samples. The former could identify the nature and size of DNA on electrophoresis, and reduce potentially false-positive results due to artifacts. Discordant results between the two methods occurred in 36 of 317 samples; 22 were positive by the spot technique alone, and 14 were positive by the analysis of DNA polymerase reaction products alone. However, the samples positive with the spot test alone showed weak radioactive signals on electrophoresis/autoradiography that were often interpreted as "inconclusive" by blind observations. Correlation of hepatitis B e antigen/antibody with hepatitis B virus DNA was studied in 91 patients with various chronic liver diseases. Discordant results, i.e., presence of the DNA in antibody positive sera, or its absence in the antigen positive sera, were obtained in 15 (19%) cases. Such patients tended to have advanced liver disease with fluctuating serum aminotransferase levels. Analysis of DNA polymerase reaction products by slab gel electrophoresis and autoradiography is not only sensitive, but is also as specific as the Southern blot technique in the detection of hepatitis B virus DNA in serum, and may prove useful in selected samples, especially where no cloned hepatitis B virus DNA is available, or in search of new hepatitis B virus-like viruses.
CD36 Mediates the Innate Host Response to β-Amyloid
Authors: Joseph B. El Khoury, Kathryn J. Moore, Terry K. Means, Josephine Leung, Kinya Terada, Michelle Toft, Mason W. Freeman, Andrew D. Luster
Journal: The Journal of Experimental Medicine (2003)

Accumulation of inflammatory microglia in Alzheimer's senile plaques is a hallmark of the innate response to β-amyloid fibrils and can initiate and propagate neurodegeneration characteristic of Alzheimer's disease (AD). The molecular mechanism whereby fibrillar β-amyloid activates the inflammatory response has not been elucidated. CD36, a class B scavenger receptor, is expressed on microglia in normal and AD brains and binds to β-amyloid fibrils in vitro. We report here that microglia and macrophages, isolated from CD36 null mice, had marked reductions in fibrillar β-amyloid–induced secretion of cytokines, chemokines, and reactive oxygen species. Intraperitoneal and stereotaxic intracerebral injection of fibrillar β-amyloid in CD36 null mice induced significantly less macrophage and microglial recruitment into the peritoneum and brain, respectively, than in wild-type mice. Our data reveal that CD36, a major pattern recognition receptor, mediates microglial and macrophage response to β-amyloid, and imply that CD36 plays a key role in the proinflammatory events associated with AD.
The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A
Authors: Christian Faul, Mary Donnelly, Sandra Merscher-Gomez, Yoon Hee Chang, Stefan Franz, Jacqueline Delfgaauw, Jer-Ming Chang, Hoon Young Choi, Kirk N Campbell, Kwanghee Kim, Jochen Reiser, Peter Mundel
Journal: Nature Medicine (2008)
A randomized, double-blind, placebo-controlled trial of the combined effect of doxycycline hyclate 20-mg tablets and metronidazole 0.75% topical lotion in the treatment of rosacea
Authors: Jorge Sanchez, Aida Lugo Somolinos, Pablo I. Almodóvar, Guy Webster, Mark Bradshaw, Christopher Powala
Journal: Journal of the American Academy of Dermatology (2005)
ITS QUANTIFICATION AND SURGICAL TREATMENT
Authors: DOWLING D. MUNRO, JULIAN L. VERBOV, DAVID J. O'GORMAN, ANTHONY VIVIER
Journal: British Journal of Dermatology (1974)

Thirteen patients were treated for their axillary hyperhidrosis by excision of axillary skin under general anaesthesia. The operation was performed by dermatologists. Significant benefit was obtained by ten of the thirteen patients. The sweat levels were measured in a control group, and in patients before operation, and at intervals up to 1 year post-operatively. This is a good operation; minor complications are common, but resolve quickly.
Medical Defence Union
Authors: A. W. Tomkins
Journal: BMJ (1889)

In experimental autoimmune encephalomyelitis (EAE), the production of proinflammatory cytokines by neuroantigen-specific T cells is thought to initiate and maintain the inflammatory autoimmune pathology. Because gene knockout strategies have shown that IFN-γ and TNF are not essential for EAE development, there is increasing interest in establishing the role of other proinflammatory cytokines, primarily IL-17 in EAE. We used an IL-17 ELISPOT assay to track the neuroantigen-specific IL-17-producing T cells at single-cell resolution in various organs of SJL mice undergoing PLP 139–151-induced EAE. Overall, the migration patterns and population kinetics of the PLP 139–151-specific IL-17-producing CD4 cells were reminiscent of the IFN-γ-producing cells, with the exception of IL-17 producers far outnumbering the IFN-γ and IL-2 producers in the inflamed CNS. The selective enrichment of IL-17-producing CD4 cells in the CNS is suggestive of the pathogenic role of an independent (non-Th1) IL-17-producing proinflammatory effector T cell class in EAE.
Comparison of three techniques of inhalation on the airway response to terbutaline.
Authors: M J Cushley, R A Lewis, A E Tattersfield
Journal: Thorax (1983)

The relative efficiency of the metered dose inhaler (MDI), the MDI attached to a pear shaped extension tube (PET), and the Inspiron Mini-Neb nebuliser were assessed in eight normal and eight asthmatic subjects. Subjects inhaled the same increasing doses of terbutaline with each technique on different occasions and the response was measured as specific airway conductance (sGaw) and, in the asthmatic patients only, as FEV1. The PET produced greater bronchodilatation than either the MDI or the nebuliser in both normal and asthmatic subjects. Serum terbutaline concentrations were similar after the PET and MDI in the normal subjects, but were lower with the PET in the asthmatic patients. The nebuliser produced about the same amount of bronchodilatation as the MDI--slightly less in the normal subjects and slightly more when assessed as FEV1 in the asthmatic subjects. Serum terbutaline concentrations were lower after the nebuliser than after the MDI in both groups of subjects. For patients with moderately severe airways obstruction requiring large doses of beta agonist, the nebuliser will produce an amount of bronchodilatation similar to the MDI with lower blood levels. Overall, the PET produced greater bronchodilatation than either of the other two methods of inhalation, with low serum terbutaline concentrations similar to those produced by the nebuliser in the asthmatic patients.
The Semiconserved Head Structure of <i>Plasmodium falciparum</i> Erythrocyte Membrane Protein 1 Mediates Binding to Multiple Independent Host Receptors
Authors: Qijun Chen, Andreas Heddini, Antonio Barragan, Victor Fernandez, S. Frieda A. Pearce, Mats Wahlgren
Journal: The Journal of Experimental Medicine (2000)

Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature. Blockage of the blood flow, hampered oxygen delivery, and severe malaria may follow if binding is excessive. The NH2-terminal head structure (Duffy binding–like domain 1 [DBL1α]–cysteine-rich interdomain region [CIDR1α]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate–like glucosaminoglycan, and CD36. DBL2δ was found to mediate additional binding to PECAM-1/CD31. The exceptional binding activity of the PfEMP1 head structure and its relatively conserved nature argues that it holds an important role in erythrocyte sequestration and therefore in the virulence of the malaria parasite.
Don't forget syphilis
Authors: Pete Clark, Penny A Cook, Lorraine Lighton, Qutub Syed, Mark A Bellis
Journal: BMJ (2002)

Editor—We agree with Doherty et al that regional and national surveillance systems are required to identify increases in the incidence of syphilis.1 It is therefore ironic that the authors' data on the syphilis outbreak in Manchester are incorrect, although enhanced surveillance systems have been in operation for over three years. 

The medical response to any sexually transmitted infection outbreak depends on the accuracy of epidemiological data. The Manchester Outbreak Control Group (comprising local specialists in genitourinary medicine, health promotion experts, and voluntary groups supported by the Communicable Disease Surveillance Centre North West and the Centre for Public Health at Liverpool John Moores University) has established a surveillance and communication system to ensure that statutory and voluntary sector organisations throughout Manchester have access to accurate up to date epidemiological information on request. If Doherty et al's article were the only source of information healthcare professionals in the Manchester area had access to, they would be forgiven for believing that the current outbreak is one third its actual size.

The correct number of cases between February 1999 and January 2002 should read 239, more than twice the previously published number. Similarly, quoting figures to January 2002 leaves the impression that the outbreak is over. This is not the case as a further 67 new cases were diagnosed between January and June 2002 (table). 

This lack of consultation highlights the need not only for enhanced epidemiological surveillance locally but also for enhanced communication nationally. Throughout the outbreak, the Manchester Outbreak Control Group has provided first class epidemiological data. Findings from investigations have influenced local and national strategies and been published in peer reviewed journals.2–5

This misrepresentation of the situation in Manchester has not been well received as the departments for genitourinary medicine there are struggling to cope with the increased workload from the continuing syphilis outbreak, exacerbated by some of the highest rates of sexually transmitted infection in the United Kingdom. To get ahead of the curve we first of all need to describe it accurately.
Bosentan and improved pulmonary endothelial function in pulmonary arterial hypertension
Authors: R. Ilsar, J. Levitt, M.K.C. Ng, L. Kritharides, M.R. Adams, D.S. Celermajer
Journal: European Respiratory Journal (2010)

To the Editors:

Pulmonary arterial hypertension (PAH) is characterised by pulmonary endothelial dysfunction and smooth muscle cell proliferation 1. Miniaturised catheter-based technology has recently enabled in vivo assessment of both endothelial dysfunction and pulmonary artery thickening in vivo 2, 3.

Bosentan, an oral dual endothelin-1 receptor antagonist, has been shown to improve clinical outcomes in PAH 4. In vitro , bosentan has been shown to improve human endothelial cell function 5 and reduce neointimal and smooth muscle proliferation. In pigs in vivo , bosentan has been shown to partially restore hypoxia-induced reductions in nitric oxide 6. The effect of bosentan on human pulmonary artery structure and function in vivo , however, has not been studied.

We hypothesised that bosentan therapy might improve pulmonary microvascular endothelial function and pulmonary artery remodelling in patients with established PAH. Therefore, we assessed the effect of 6 months of clinically indicated bosentan therapy in patients with advanced PAH on: 1) pulmonary microvascular function, assessed by Doppler-derived pulmonary blood flow responses to vasoactive agents; and 2) segmental pulmonary artery structure, measured by pulmonary intravascular ultrasound (IVUS).

Eight bosentan-naive subjects (three males and five females; five subjects with idiopathic and three with scleroderma-related PAH; mean±sem age 66±4 yrs; weight 79±5 kg) were studied. The institutional review board (Royal Prince Alfred Hospital, Sydney, NSW, Australia) approved the study protocol and informed consent was obtained from all subjects. All patients were in New York Heart Association (NYHA) functional class III, had mean pulmonary arterial pressure ( P pa) >25 mmHg at rest (without demonstrable reversibility) and had pulmonary capillary wedge pressure ≤15 mmHg.

Clinically indicated right heart catheterisation, assessing suitability for bosentan prescription, was performed. Thereafter, pulmonary artery IVUS assessment was performed in a distal segmental pulmonary artery of both upper and lower lobes …
Purification and partial characterization of the opacity-associated proteins of Neisseria gonorrhoeae.
Authors: M S Blake, E C Gotschlich
Journal: The Journal of Experimental Medicine (1984)

Gonococci, grown on agar, frequently give rise to opaque colonies. This opacity phenotype is associated with the presence of one or more outer membrane proteins of approximately 28,000 mol weight. These proteins are included within a class of proteins named proteins II. A method is described to isolate and purify the opacity-associated proteins from Neisseria gonorrhoeae. This method uses high concentrations of calcium and a zwitterionic detergent at pH 4.0. Under these conditions proteins II are readily solubilized from the outer membrane. Further purification is achieved by ion exchange and molecular sieve chromatography in the presence of the zwitterionic detergent. The opacity-associated proteins are very basic with isoelectric points varying between 9.0 to 10.0. Further evidence for their basic nature is their behavior on ion exchange chromatography and their amino acid composition.
Zinc in Neurotransmission
Authors: Katalin Tóth
Journal: Annual Review of Nutrition (2011)

A subset of glutamatergic synapses in the central nervous system contains zinc; it is sequestered into the lumen of synaptic vesicles, where it colocalizes with glutamate. Extracellularly applied zinc is known to interact with various postsynaptic receptors and channels; however, the role of endogenous vesicular zinc is still an enigma. The aim of this review is to present the physiology of tonic and phasic zinc modulation of excitatory and inhibitory signals and to discuss the potential role of zinc in synaptic plasticity. Zinc homeostasis is known to be altered under pathological conditions. The importance of the careful investigation of the potential sources of zinc involved in physiological and pathological processes is highlighted.