tbuckley/cabot-search huggingface dataset:
Human papillomavirus-associated induction of human β-defensins in anal intraepithelial neoplasia
Authors: A Kreuter, M Skrygan, T Gambichler, N H Brockmeyer, M Stücker, C Herzler, A Potthoff, P Altmeyer, H Pfister, U Wieland
Journal: British Journal of Dermatology (2009)

Antimicrobial peptides and proteins (AMPs) are widely distributed effector molecules of the innate immune system with well-known antibacterial activity. However, there is a paucity of information regarding antiviral effects of AMPs.The present study was performed to analyse expression of AMPs in human papillomavirus (HPV)-associated anal skin lesions of human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), a special high-risk group for persistent HPV infections and anal dysplasia.Skin lesions were analysed for the presence of LL-37, RNase 7, and human beta-defensin (hBD)-1, hBD-2 and hBD-3. Moreover, HPV typing and HPV DNA load determination for HPV types 6, 11, 16, 18, 31 and 33 were performed to evaluate possible correlations between expression of AMPs and lesional HPV types.Skin biopsies of 45 HIV-positive MSM with anal intraepithelial neoplasia (AIN), anal condylomata acuminata or unaffected anal mucosa, as well as condylomata acuminata of eight HIV-negative MSM, were analysed for AMP mRNA expression. Additionally, immunohistochemical analysis for hBD-2 and hBD-3 was performed in a total of 45 samples. hBD-2 and hBD-3 gene and protein expression was significantly increased in both AIN and condyloma, whereas LL-37, RNase 7 and hBD-1 gene expression did not differ significantly from unaffected anal mucosa. AMP expression correlated neither with the number of HPV types nor with the high-risk and low-risk HPV DNA loads of the quantified types. No significant differences in AMP expression were observed in condylomata of HIV-positive and HIV-negative MSM.hBD-2 and hBD-3 expression was shown to be significantly upregulated in HPV-associated anal skin lesions of both HIV-positive and HIV-negative MSM. Their biological significance in the innate immunity against these lesions needs further research.
Rapid Effect of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibition on Coronary Endothelial Function
Authors: Sven Wassmann, Anna Faul, Benno Hennen, Bruno Scheller, Michael Böhm, Georg Nickenig
Journal: Circulation Research (2003)

Treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decreases cardiovascular event rates in hypercholesterolemic patients. Whether statins exert effects within 24 hours on the coronary vasculature in patients with endothelial dysfunction has not been elucidated. Twenty-seven patients with stable angina pectoris and average low-density lipoprotein cholesterol concentrations of 138±9 mg/dL at baseline were allocated to treatment with placebo (14 patients) or 40 mg/d pravastatin (13 patients) in a randomized, double-blind, prospective trial. Coronary endothelial function was assessed before and 24 hours after single treatment by quantitative coronary angiography during intracoronary infusion of nitroglycerin or increasing concentrations of acetylcholine (0.01, 0.1, and 1 μmol/L). Coronary blood flow reserve was measured by Doppler velocimetry during adenosine infusion. Intracoronary acetylcholine infusion induced abnormal vasoconstriction in both groups before treatment, indicating coronary endothelial dysfunction. Treatment with a single oral 40-mg dose of pravastatin significantly attenuated acetylcholine-mediated vasoconstriction after 24 hours (mean±SE decrease in luminal diameter before and after treatment: 0.01 μmol/L, 6.1±2.2% versus 3.0±1.2%; 0.1 μmol/L, 15.6±2.6% versus 7.4±1.8%; P &lt;0.05; 1 μmol/L, 22.9±2.9% versus 13.2±2.6%; P &lt;0.05). There was no significant difference in the response to acetylcholine in the placebo group (8.1±2.4% versus 9.7±2.4%, 16.1±2.9% versus 16.8±3.2%, and 21.4±3.9% versus 23.3±4.2%). The response to nitroglycerin infusion was not altered in both groups. Increase in coronary blood flow in response to adenosine and coronary flow reserve remained unchanged during placebo and statin treatment. Serum concentrations of blood lipids and high-sensitive C-reactive protein were not significantly altered after 24 hours in response to placebo or pravastatin therapy. Statin treatment improves endothelium-dependent coronary vasomotion within 24 hours in the absence of significant cholesterol reduction. The full text of this article is available online at http://www.circresaha.org.
The Receptor Interacting Protein 1 Inhibits p53 Induction through NF-κB Activation and Confers a Worse Prognosis in Glioblastoma
Authors: Seongmi Park, Kimmo J. Hatanpaa, Yang Xie, Bruce E. Mickey, Christopher J. Madden, Jack M. Raisanen, Deepti B. Ramnarain, Guanghua Xiao, Debabrata Saha, David A. Boothman, Dawen Zhao, Robert M. Bachoo, Russell O. Pieper, Amyn A. Habib
Journal: Cancer Research (2009)

Abstract Nuclear factor-κB (NF-κB) activation may play an important role in the pathogenesis of cancer and also in resistance to treatment. Inactivation of the p53 tumor suppressor is a key component of the multistep evolution of most cancers. Links between the NF-κB and p53 pathways are under intense investigation. In this study, we show that the receptor interacting protein 1 (RIP1), a central component of the NF-κB signaling network, negatively regulates p53 tumor suppressor signaling. Loss of RIP1 from cells results in augmented induction of p53 in response to DNA damage, whereas increased RIP1 level leads to a complete shutdown of DNA damage–induced p53 induction by enhancing levels of cellular mdm2. The key signal generated by RIP1 to up-regulate mdm2 and inhibit p53 is activation of NF-κB. The clinical implication of this finding is shown in glioblastoma, the most common primary malignant brain tumor in adults. We show that RIP1 is commonly overexpressed in glioblastoma, but not in grades II and III glioma, and increased expression of RIP1 confers a worse prognosis in glioblastoma. Importantly, RIP1 levels correlate strongly with mdm2 levels in glioblastoma. Our results show a key interaction between the NF-κB and p53 pathways that may have implications for the targeted treatment of glioblastoma. [Cancer Res 2009;69(7):2809–16]
Phase II study of 6-thioguanine, procarbazine, dibromodulcitol, lomustine, and vincristine chemotherapy with radiotherapy for treating malignant glioma in children
Authors: V.A. Levin, Kathleen Lamborn, William Wara, Richard Davis, Michael Edwards, Jane Rabbitt, Mary Malec, Michael D. Prados
Journal: Neuro-Oncology (2000)

We conducted a single-arm phase II study to evaluate the efficacy and safety of radiotherapy combined with 6-thioguanine, procarbazine, dibromodulcitol, lomustine, and vincristine (TPDCV) chemotherapy for treating malignant astrocytoma in children and anaplastic ependymoma in patients of all ages. Between 1984 and 1992, 42 patients who had malignant astrocytomas (glioblastomas multiforme, anaplastic astrocytomas, or mixed anaplastic oligoastrocytomas) were treated with TPDCV chemotherapy and radiation therapy. Of these patients, 40 were younger than 18 years, but 2 were older (22 and 23 years) when treated. Cranial radiation averaged 58 Gy. TPDCV chemotherapy was given for 1 year or until progression. Between 1989 and 1991, 17 patients with malignant ependymoma were treated with TPDCV chemotherapy and craniospinal radiation. Radiation was given at an average dose of 54 Gy to the tumor, 28 Gy to the whole brain, and 31 Gy to the spinal axis. TPDCV chemotherapy was given for 1 year or until tumor progressed. Of the patients with glioblastoma multiforme, 13 of 17 died; the median time to progression was 49 weeks, and median survival was 85 weeks. The four patients surviving at this writing were followed a median 537 weeks (range 364-635 weeks). Of the patients with nonglioblastoma malignant astrocytoma, 14 of 25 died; the median time to progression was 224 weeks. Median survival was not reached in this group. The median follow-up for those surviving was 494 weeks. For the patients with ependymoma, 11 of 17 died with a median time to progression of 141 weeks. The median follow-up for the eight who survive was 469 weeks. Nine patients died with a median survival of 183 weeks. The combination of TPDCV and radiotherapy has activity against childhood anaplastic astrocytoma, glioblastoma multiforme, and anaplastic ependymoma. The results of this study for children with glioblastoma were comparable to results in the literature, while the results for children with anaplastic astrocytoma appeared better than most reports. The combination of TPDCV chemotherapy and radiation therapy for anaplastic ependymomas appears to be active and at least as good as published reports using radiation therapy alone.
Lower Level of Endogenous Dopamine in Patients With Cocaine Dependence: Findings From PET Imaging of D <sub>2</sub> /D <sub>3</sub> Receptors Following Acute Dopamine Depletion
Authors: Diana Martinez, Kaitlin Greene, Allegra Broft, Dileep Kumar, Fei Liu, Rajesh Narendran, Mark Slifstein, Ronald Van Heertum, Herbert D. Kleber
Journal: American Journal of Psychiatry (2009)

Objective: Previous positron emission tomography (PET) imaging studies have demonstrated that cocaine dependence is associated with a decrease in dopamine type 2 and 3 (D 2 /D 3 ) receptor binding in cocaine-dependent individuals relative to healthy comparison subjects. However, given the nature of PET imaging, it is possible that the measured decrease in radiotracer binding results from an increase in baseline dopamine levels. The purpose of this study was to measure D 2 /D 3 receptors following acute dopamine depletion in cocaine-dependent volunteers relative to healthy comparison subjects. Method: Cocaine-dependent volunteers (N=15) and healthy matched comparison subjects (N=15) were scanned using PET, with the dopamine receptor radiotracer [ 11 C]raclopride, at baseline and again following acute depletion of endogenous dopamine via alpha-methyl-para-tyrosine (AMPT) administration. Changes in radiotracer binding were measured in the subdivisions of the striatum (caudate, putamen, and ventral striatum) in addition to the striatum as a whole. Results: Findings revealed that cocaine-dependent volunteers exhibited lower levels of endogenous dopamine relative to comparison subjects, which was measured as an increase in [ 11 C]raclopride binding following AMPT administration. The increase in [ 11 C]raclopride binding in the striatum was 11.1% (SD=4.4%) in healthy comparison subjects and 5.7% (SD=5.9%) in cocaine-dependent volunteers. Similar differences were seen in the subdivisions of the striatum. Conclusions: The decrease in striatal D 2 /D 3 receptors associated with cocaine dependence cannot be attributed to higher levels of endogenous dopamine.
Rapid effect of inhaled steroids on nocturnal worsening of asthma
Authors: G Frezza
Journal: Thorax (2003)

Inhaled steroids are the most commonly used anti-inflammatory agents for asthma and are increasingly recognised as having a more rapid onset of action than was previously thought. We have investigated the effect of a single dose of inhaled steroid on nocturnal worsening of asthma.Ten patients with steroid naive moderate asthma and nocturnal asthma participated in a randomised, double blind, placebo controlled, crossover trial. Participants spent three nights in the laboratory, one week apart. On each night they underwent spirometric testing at 16.00 hours and received one of the three treatments (placebo, beclomethasone 1000 micro g, or fluticasone 1000 micro g) delivered by metered dose inhaler. Spirometric tests were repeated at 04.00 hours the following morning.Following placebo administration the mean (SE) overnight fall in FEV(1) was 0.65 (0.27) l compared with -0.02 (0.13) l following fluticasone (p=0.019) and 0.23 (0.12) l following beclomethasone (p=0.048 v placebo).A single dose of inhaled steroid (within the therapeutic range) reduced the fall in FEV(1) in patients with nocturnal asthma when administered at 16.00 hours. Nocturnal worsening of asthma is a useful model for testing inhaled steroid activity in a single night study.
Renal Impairment in Multiple Myeloma: Time Is of the Essence
Authors: Colin A. Hutchison, Frank Bridoux
Journal: Journal of Clinical Oncology (2011)

TO THE EDITOR: The recently published consensus statement fromtheInternationalMyelomaWorkingGroup 1 onthemanagement of renal impairment in patients with multiple myeloma provides a much needed overview of the topic. Unfortunately, however, the consensus statement fails to emphasis two key concepts: first, time to treatment, and second, consideration of the severity of renal impairment. As stated in the article, 1 when patients with multiple myeloma presentwithasevereacutekidneyinjury,itismostcommonlyaresult of cast nephropathy, often with a preceding trigger. This tubulointerstitial disorder is a direct consequence of the high monoclonal free lightchain(FLC)levelspresentinthepatient’ssera.Immunoglobulin FLCs, as a result of their low molecular weight, are freely filtered through the glomerulus. They are then reabsorbed in the proximal tubule through endocytosis, which is mediated by the tandem receptorsmegalinandcubilinthatarelocalizedontheapicalbrushborder. FLCs are then additionally processed in the endolysosomal compartment of the proximal tubular cell, where they are degraded by lysosomal enzymes, namely cathepsin B. 2
Patterns of acid reflux in complicated oesophagitis.
Authors: D Robertson, M Aldersley, H Shepherd, C L Smith
Journal: Gut (1987)

Oesophageal manometry and 24 hour ambulatory pH recordings from the distal oesophagus were carried out in 25 patients with complications of oesophagitis (stricture, Barrett9s oesophagus or oesophageal ulcer) and compared with 25 patients with uncomplicated oesophagitis. Acid reflux was more severe in the complicated group with 26.2% of time below pH 4 compared with 11.3% in uncomplicated patients (p less than 0.01). This difference was most marked at night, when complicated patients had long periods of acid reflux with 35.6% time less than pH 4 compared with 5.2% uncomplicated (p less than 0.001). The mean duration of nocturnal acid reflux was 15.4 minutes (2.1 minutes uncomplicated, p less than 0.001). Oesophageal motility was markedly abnormal in all groups, but with no demonstrable differences in lower oesophageal sphincter pressure or peristalsis between the groups. Patients with complications of oesophagitis have different patterns of acid reflux from uncomplicated patients, with prolonged nocturnal bathing of the oesophageal mucosa, which may be the cause of stricture formation, metaplasia, or ulceration.
In Vivo Gene Transfer Into Injured Carotid Arteries
Authors: Andrew H. Schulick, Kurt D. Newman, Renu Virmani, David A. Dichek
Journal: Circulation (1995)

Background Adenoviral vectors are very attractive agents for use in in vivo arterial gene transfer. In a previous study, we demonstrated high-efficiency adenovirus-mediated gene transfer into medial smooth muscle cells of balloon-injured rat carotid arteries. We now further characterize this system by investigating the reproducibility of recombinant gene expression, the presence of acute adenovirus-associated toxicity in the vessel wall, and the optimal virus concentration for transduction. Methods and Results Balloon-injured rat carotid arteries were incubated with (1) an adenovirus expressing a β-galactosidase gene (Av1LacZ4), (2) a related adenovirus without the recombinant gene (Addl312), or (3) control solutions. Recombinant gene expression was determined 3 days after gene transfer by measurement of β-galactosidase activity in vessel extracts and by counting of smooth muscle cells in microscopic sections that were histochemically stained to detect recombinant β-galactosidase activity. Adenovirus-associated toxicity was assessed in microscopic cross sections by counting of total smooth muscle cell nuclei in the media (to identify cell loss) and characterization of medial cellular infiltrates with histochemical stains for specific inflammatory cells (neutrophils, lymphocytes, macrophages, and monocytes). Maximum recombinant gene expression after incubation with Av1LacZ4 was produced by virus concentrations ranging from 2×10 10 to 5×10 10 plaque-forming units (pfu)/mL. Surprisingly, use of a higher concentration of Av1LacZ4 virus (1×10 11 pfu/mL) resulted in loss of recombinant gene expression. In addition, infusion of either Av1LacZ4 or Addl312 at 1×10 11 pfu/mL resulted in statistically significant decreases in medial smooth muscle cell number (53% decrease, P &lt;0.01 for Av1LacZ4; 39% decrease, P &lt;.05 for Addl312) compared with vessels infused with control solution. This decrease in smooth muscle cell number was not present after the infusion of virus at lower concentrations. The number of neutrophils in vessel cross sections was significantly increased (fivefold; P &lt;.05) after infusion of Av1LacZ4 at 1×10 11 pfu/mL compared with vessels infused with control solution. Lymphocytes, macrophages, and monocytes were present only in low numbers in all vessel cross sections and were not increased consequent to adenovirus infusion. Conclusions This model of focal in vivo adenovirus-mediated gene transfer into the media of injured arteries is highly reproducible and allows high-level recombinant gene expression over a fairly narrow range of virus concentrations. Acute adenovirus-associated tissue toxicity, as demonstrated by medial smooth muscle cell loss and neutrophilic infiltrates, places an upper limit on virus concentration and associated recombinant gene expression and suggests the presence of a “window” of virus concentration in which either therapeutic or biological effects of recombinant genes can be studied in the absence of associated acute toxicity.
Comparison of red and green light in the treatment of Bowen’s disease by photodynamic therapy
Authors: C.A. Morton, C. Whitehurst, J.V. Moore, R.M. Mackie
Journal: British Journal of Dermatology (2000)

Journal Article Comparison of red and green light in the treatment of Bowen's disease by photodynamic therapy Get access C.A. Morton, C.A. Morton University Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. : Dr Colin A. Morton, MD MRCP, Department of Dermatology, Falkirk Royal Infirmary, Major's Loan, Falkirk FK1 5QE, U.K. Tel.: +44 1324 624000. E‐mail: camorton@fdri2.fdri.scot.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar C. Whitehurst, C. Whitehurst Laser Oncology Programme, Cancer Research Campaign Department of Experimental Radiation Oncology, Paterson Institute for Cancer Research, Christie Hospital, Manchester M20 4BX, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.V. Moore, J.V. Moore Laser Oncology Programme, Cancer Research Campaign Department of Experimental Radiation Oncology, Paterson Institute for Cancer Research, Christie Hospital, Manchester M20 4BX, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.M. Mackie R.M. Mackie University Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 4, 1 October 2000, Pages 767–772, https://doi.org/10.1046/j.1365-2133.2000.03773.x Published: 01 October 2000
Comparison of oral amoxicillin and intravenous benzyl penicillin for community acquired pneumonia in children (PIVOT trial): a multicentre pragmatic randomised controlled equivalence trial
Authors: M. Atkinson, M. Lakhanpaul, A. Smyth, H. Vyas, V. Weston, J. Sithole, V. Owen, K. Halliday, H. Sammons, J. Crane, N. Guntupalli, L. Walton, T. Ninan, A. Morjaria, T. Stephenson
Journal: Thorax (2007)

<h3>Objective:</h3> To ascertain whether therapeutic equivalence exists for the treatment of paediatric community acquired pneumonia by the oral and intravenous (IV) routes. <h3>Methods:</h3> A multicentre pragmatic randomised controlled non-blinded equivalence trial was undertaken in eight paediatric centres in England (district general and tertiary hospitals). Equivalence was defined as no more than a 20% difference between treatments of the proportion meeting the primary outcome measure at any time. 246 children who required admission to hospital and had fever, respiratory symptoms or signs and radiologically confirmed pneumonia were included in the study. Exclusion criteria were wheeze, oxygen saturations &lt;85% in air, shock requiring &gt;20 ml/kg fluid resuscitation, immunodeficiency, pleural effusion at presentation requiring drainage, chronic lung condition (excluding asthma), penicillin allergy and age &lt;6 months. The patients were randomised to receive oral amoxicillin for 7 days (n = 126) or IV benzyl penicillin (n = 120). Children in the IV group were changed to oral amoxicillin after a median of six IV doses and received 7 days of antibiotics in total. The predefined primary outcome measure was time for the temperature to be &lt;38°C for 24 continuous hours and oxygen requirement to cease. Secondary outcomes were time in hospital, complications, duration of oxygen requirement and time to resolution of illness. <h3>Results:</h3> Oral amoxicillin and IV benzyl penicillin were shown to be equivalent. Median time for temperature to settle was 1.3 days in both groups (p&lt;0.001 for equivalence). Three children in the oral group were changed to IV antibiotics and seven children in the IV group were changed to different IV antibiotics. Median time to complete resolution of symptoms was 9 days in both groups. <h3>Conclusion:</h3> Oral amoxicillin is effective for most children admitted to hospital with pneumonia (all but those with the most severe disease who were excluded from this study). Prior to this study, the British Thoracic Society guidelines on childhood pneumonia could not draw on evidence to address this issue. This will spare children and their families the trauma and pain of cannulation, and children will spend less time in hospital.