tbuckley/cabot-search huggingface dataset:
Increased nitric oxide synthase expression in arterial vessels of cirrhotic rats with ascites
Authors: M Morales-Ruiz
Journal: Hepatology (1996)

Arterial vasodilatation is thought to play a major role in the pathogenesis of systemic hemodynamics and renal disturbances occurring in cirrhotic patients. Recent investigations suggest that an increased vascular nitric oxide (NO) production could be implicated in this abnormality. The current study assessed whether increased expression of inducible and/or endothelial nitric oxide synthase (iNOS and eNOS, respectively) occurs in arterial vessels of cirrhotic rats. The investigation was performed in thoracic and abdominal aortas and mesenteric arteries of 10 control rats and 16 cirrhotic rats with ascites. iNOS and eNOS messenger RNA (mRNA) expression were evaluated by polymerase chain reaction and ribonuclease protection assay, respectively. Endothelial NOS protein expression was assessed by Western blot. No iNOS mRNA was detected in arterial vessels of control rats. In contrast iNOS mRNA was consistently detected in all arteries of cirrhotic rats with ascites, the weakest signal being observed in the thoracic aorta and the strongest in the mesenteric artery. Enhanced eNOS mRNA abundance was found in the aorta of cirrhotic animals as compared with controls. Higher eNOS protein expression was noted in the thoracic aorta of cirrhotic rats. These results indicate the existence of increased eNOS and iNOS expression in arterial vessels of cirrhotic rats, suggesting that transcriptional activation of vascular NOSs and the associated nitric oxide hyperproduction may be of major importance in the pathogenesis of arterial vasodilation in cirrhosis.
Vitaxin, a Humanized Monoclonal Antibody to the Vitronectin Receptor (α <sub>v</sub> β <sub>3</sub> ), Reduces Neointimal Hyperplasia and Total Vessel Area After Balloon Injury in Hypercholesterolemic Rabbits
Authors: Kimberly R. Coleman, Gregory A. Braden, Mark C. Willingham, David C. Sane
Journal: Circulation Research (1999)

Abstract —The vitronectin receptor (α v β 3 ) mediates several biological processes that are critical to the formation of a neointima after coronary interventions. Blockade of α v β 3 could reduce neointima formation by inhibiting smooth muscle cell migration, decreasing transforming growth factor-β 1 expression, enhancing apoptosis, or reducing neovasculature. The effects of short-term administration of Vitaxin, a humanized monoclonal antibody to α v β 3 , on the responses to balloon injury were tested in hyperlipidemic rabbits. Balloon angioplasty was performed on the iliac arteries of male New Zealand White rabbits that were fed an atherogenic diet for 1 week before injury and until euthanization at 4 weeks. Rabbits were given either saline (control) or 1 of 2 dosing regimens of Vitaxin (high dose, 5.0 mg/kg, and low dose, 0.5 mg/kg), which were administered intra-arterially before injury and intramuscularly on days 2 and 3. High-dose and low-dose Vitaxin were equally effective in decreasing neointima formation even in the presence of hypercholesterolemia, a stimulus to α v β 3 expression. Vitaxin reduced transforming growth factor-β 1 and enhanced apoptosis in injured arteries. Despite these positive effects, Vitaxin administration was associated with a reduction in artery size, indicating a negative effect on remodeling. Vitaxin has a potential role in preventing intimal hyperplasia, especially if the negative effects on remodeling can be overcome, by dose adjustment or other strategies.
AN OPEN ASSESSMENT OF BECOTIDE® (BECLOMETHASONE DIPROPIONATE) NASAL SPRAY IN SEASONAL ALLERGIC RHINITIS
Authors: THORVALD LÖFKVIST, GUNNAR SVENSSON
Journal: Allergy (1975)

The effect of beclomethasone dipropionate (Becotide) intranasally on hay-fever has been studied in 38 adult volunteers with grass pollen allergy. The trial was carried out as an open assessment with simultaneous pollen count during the months of June and July, 1974. With the dose 300 mug/day intranasally, 95 per cent of the subjects regarded the treatment as successful for the nasal symptoms. No effect on eye symptoms was recorded, and no evident side-effects were noted.
Anti-tumour necrosis factor (TNF) alpha treatment of rheumatoid arthritis (infliximab) selectively down regulates the production of interleukin (IL) 18 but not of IL12 and IL13
Authors: V Pittoni, M Bombardieri, F R Spinelli, R Scrivo, C Alessandri, F Conti, A Spadaro, G Valesini
Journal: Annals of the Rheumatic Diseases (2002)

To measure interleukin (IL)18 serum concentrations in patients with rheumatoid arthritis (RA) undergoing infliximab treatment (tumour necrosis factor (TNF) alpha blockade) and to evaluate the concomitant modification of IL12 and IL13 serum concentrations, two cytokines belonging to the Th1 and Th2 profile respectively and biologically related to IL18.Ten patients with RA not responding to disease modifying antirheumatic drugs (DMARDs) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks. Serum samples were collected from all patients before each infusion and assayed for IL18, IL12, and IL13 by enzyme linked immunosorbent assay (ELISA); IL18 was also measured eight weeks after the last infusion.Serum concentrations of IL18 in all patients were already markedly reduced from baseline after two weeks (p<0.005). Serum IL18 was also decreased in a stable manner after six (p<0.01) and 14 weeks (p<0.01) compared with baseline concentrations. No significant modifications were found in serum concentrations of IL12 and IL13 at any time point.There was a rapid and persistent decrease in serum concentrations of IL18 in all the patients studied. This result provides evidence of an in vivo regulation of IL18 by TNFalpha and suggests that anti-TNFalpha therapy is likely to interrupt the synergistic effect between these two cytokines.
Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy
Authors: Aijing Shang, Karin Huwiler-Müntener, Linda Nartey, Peter Jüni, Stephan Dörig, Jonathan AC Sterne, Daniel Pewsner, Matthias Egger
Journal: The Lancet (2005)
Diabetic Ketoacidosis at Diagnosis Influences Complete Remission After Treatment With Hematopoietic Stem Cell Transplantation in Adolescents With Type 1 Diabetes
Authors: Weiqiong Gu, Jiong Hu, Weiqing Wang, Lirong Li, Wei Tang, Shouyue Sun, Weijuan Cui, Lei Ye, Yifei Zhang, Jie Hong, Dalong Zhu, Guang Ning
Journal: Diabetes Care (2012)

OBJECTIVE To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) was beneficial for type 1 diabetic adolescents with diabetic ketoacidosis (DKA) at diagnosis. RESEARCH DESIGN AND METHODS We enrolled 28 patients with type 1 diabetes, aged 14–30 years, in a prospective AHSCT phase II clinical trial. HSCs were harvested from the peripheral blood after pretreatment consisting of a combination of cyclophosphamide and antithymocyte globulin. Changes in the exogenous insulin requirement were observed and serum levels of HbA1c, C-peptide, and anti-glutamic acid decarboxylase antibody were measured before and after the AHSCT. RESULTS After transplantation, complete remission (CR), defined as insulin independence, was observed in 15 of 28 patients (53.6%) over a mean period of 19.3 months during a follow-up ranging from 4 to 42 months. The non-DKA patients achieved a greater CR rate than the DKA patients (70.6% in non-DKA vs. 27.3% in DKA, P = 0.051). In the non-DKA group, the levels of fasting C-peptide, peak value during oral glucose tolerance test (Cmax), and area under C-peptide release curve during oral glucose tolerance test were enhanced significantly 1 month after transplantation and remained high during the 24-month follow-up (all P &amp;lt; 0.05). In the DKA group, significant elevation of fasting C-peptide levels and Cmax levels was observed only at 18 and 6 months, respectively. There was no mortality. CONCLUSIONS We have performed AHSCT in 28 patients with type 1 diabetes. The data show AHSCT to be an effective long-term treatment for insulin dependence that achieved a greater efficacy in patients without DKA at diagnosis.
Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial
Authors: Matthew R Smith, Fred Saad, Robert Coleman, Neal Shore, Karim Fizazi, Bertrand Tombal, Kurt Miller, Paul Sieber, Lawrence Karsh, Ronaldo Damião, Teuvo L Tammela, Blair Egerdie, Hendrik Van Poppel, Joseph Chin, Juan Morote, Francisco Gómez-Veiga, Tomasz Borkowski, Zhishen Ye, Amy Kupic, Roger Dansey, Carsten Goessl
Journal: The Lancet (2011)
Identification of RNA Editing Sites in Chloroplast Transcripts from the Maternal and Paternal Progenitors of Tobacco (Nicotiana tabacum): Comparative Analysis Shows the Involvement of Distinct Trans-Factors for ndhB Editing
Authors: T. Sasaki
Journal: Molecular Biology and Evolution (2003)

RNA editing alters genomic nucleotide sequences at the transcript level. In higher plant chloroplasts, C-to-U conversion is known to occur at around 30 specific sites. The tobacco cultivar Nicotiana tabacum is an amphidiploid derived from ancestors of N. sylvestris (maternal) and N. tomentosiformis (paternal). The chloroplast genome of N. tabacum is believed to originate from an ancestor of N. sylvestris. To study the evolution of RNA editing in higher plant chloroplasts, editing sites in the two likely progenitors have first been identified based on those found in N. tabacum. Altogether 34, 33, and 32 editing sites have been found in the chloroplast transcripts from N. tabacum, N. sylvestris, and N. tomentosiformis, respectively. Thirty-one sites are conserved among the three species, whereas remarkable differences are observed in the editing of ndhB and ndhD transcripts. Sites 7 and 8 in ndhB mRNAs are separated only by five nt, and both are edited in N. tabacum and N. sylvestris. However, site 8 is not edited in N. tomentosiformis, indicating that distinct trans-factors are involved in the two editing events. The first site in ndhD mRNAs is edited to produce an AUG start codon in N. sylvestris as well as in N. tabacum but not in N. tomentosiformis, suggesting that a distinct mechanism operates for the translational initiation of N. tomentosiformisndhD mRNAs. Four to six sites are edited partially in green leaves. Some of these sites may represent evolutionary intermediates in the process of losing editing events.
Use of 5 -reductase inhibitors for lower urinary tract symptoms and risk of prostate cancer in Swedish men: nationwide, population based case-control study
Authors: D. Robinson, H. Garmo, A. Bill-Axelson, L. Mucci, L. Holmberg, P. Stattin
Journal: BMJ (2013)

<b>Objective</b> To assess the association between 5α-reductase inhibitor (5-ARI) use in men with lower urinary tract symptoms and prostate cancer risk. <b>Design</b> Nationwide, population based case-control study for men diagnosed with prostate cancer in 2007-09 within the Prostate Cancer data Base Sweden 2.0. <b>Setting</b> The National Prostate Cancer Register, National Patient Register, census, and Prescribed Drug Register in Sweden, from which we obtained data on 5-ARI use before date of prostate cancer diagnosis. <b>Participants</b> 26 735 cases and 133 671 matched controls; five controls per case were randomly selected from matched men in the background population. 7815 men (1499 cases and 6316 controls) had been exposed to 5-ARI. 412 men had been exposed to 5-ARI before the diagnosis of a cancer with Gleason score 8-10. <b>Main outcome measures</b> Risk of prostate cancer calculated as odds ratios and 95% confidence intervals by conditional logistic regression analyses. <b>Results</b> Risk of prostate cancer overall decreased with an increasing duration of exposure; men on 5-ARI treatment for more than three years had an odds ratio of 0.72 (95% confidence interval 0.59 to 0.89; P&lt;0.001 for trend). The same pattern was seen for cancers with Gleason scores 2-6 and score 7 (both P&lt;0.001 for trend). By contrast, the risk of tumours with Gleason scores 8-10 did not decrease with increasing exposure time to 5-ARI (for 0-1 year of exposure, odds ratio 0.96 (95% confidence interval 0.83 to 1.11); for 1-2 years, 1.07 (0.88 to 1.31); for 2-3 years, 0.96 (0.72 to 1.27); for &gt;3 years, 1.23 (0.90 to 1.68); P=0.46 for trend). <b>Conclusions</b> Men treated with 5-ARI for lower urinary tract symptoms had a decreased risk of cancer with Gleason scores 2-7, and showed no evidence of an increased risk of cancer with Gleason scores 8-10 after up to four years' treatment.
Duodenal mucosa and extracellular cyclic nucleotide pattern in coeliac disease.
Authors: M Peracchi, F Bamonti-Catena, P Faggioli, N Molteni, M T Bardella, B Bareggi, P A Bianchi
Journal: Gut (1993)

This study measured the values of cyclic nucleotides and adenylate and guanylate cyclase activities in duodenal mucosa homogenates to verify if they played a part in coeliac disease. Nine controls, 13 patients who did not receive treatment and nine patients who received treatment were studied. Cyclase activity assays were performed under basal conditions and in the presence of gliadin derived peptides. Duodenal mucosa cyclic nucleotide values and adenylate cyclase activity were significantly higher in patients who did not receive treatment than in those who did and in controls, whereas guanylate cyclase activity was similar in all groups. Gliadin derived peptides did not affect guanylate cyclase activity, but significantly increased adenylate cyclase activity in homogenates from patients who did not receive treatment. As extracellular cyclic nucleotide concentrations could reflect changes in their intracellular metabolism, plasma and urine cyclic nucleotide values were also measured in 25 controls and in 55 patients studied at different stages of their disease. Extracellular cyclic nucleotides were considerably high in patients who were not healed and became normal after about one year of treatment. These data suggest that cyclic nucleotides may participate in the pathophysiological processes of coeliac disease.
Dissociation of electromyogram and mechanical response in sleep apnoea during propofol anaesthesia
Authors: Yaniv Dotan, Giora Pillar, Nave Tov, Ron Oliven, Uri Steinfeld, Luis Gaitini, Majed Odeh, Alan R. Schwartz, Arie Oliven
Journal: European Respiratory Journal (2012)

Pharyngeal collapsibility during sleep is believed to increase due to a decline in dilator muscle activity. However, genioglossus electromyogram (EMG) often increases during apnoeas and hypopnoeas, often without mechanical effect. 17 patients with obstructive sleep apnoea were anaesthetised and evaluated from termination of propofol administration to awakening. Genioglossus EMG, flow and pharyngeal area (pharyngoscopy) were monitored. Prolonged hypopnoeas enabled evaluation of the relationships between genioglossus EMG and mechanical events, before and after awakening. Additional dilator muscle EMGs were recorded and compared to the genioglossus. Electrical stimulation of the genioglossus was used to evaluate possible mechanical dysfunction. Prolonged hypopnoeas during inspiration before arousal triggered an increase in genioglossus EMG, reaching mean ± SD 62.2 ± 32.7% of maximum. This augmented activity failed to increase flow and pharyngeal area. Awakening resulted in fast pharyngeal enlargement and restoration of unobstructed flow, with marked reduction in genioglossus EMG. Electrical stimulation of the genioglossus under propofol anaesthesia increased the inspiratory pharyngeal area (from 25.1 ± 28 to 66.3 ± 75.5 mm(2); p<0.01) and flow (from 11.5 ± 6.5 to 18.6 ± 9.2 L · min(-1); p<0.001), indicating adequate mechanical response. All additional dilators increased their inspiratory activity during hypopnoeas. During propofol anaesthesia, pharyngeal occlusion persists despite large increases in genioglossus EMG, in the presence of a preserved mechanical response to electrical stimulation.
A disease-associated PTPN22 variant promotes systemic autoimmunity in murine models
Authors: Xuezhi Dai, Richard G. James, Tania Habib, Swati Singh, Shaun Jackson, Socheath Khim, Randall T. Moon, Denny Liggitt, Alejandro Wolf-Yadlin, Jane H. Buckner, David J. Rawlings
Journal: Journal of Clinical Investigation (2013)

Multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, Graves disease, and systemic lupus erythematosus, are associated with an allelic variant of protein tyrosine phosphatase nonreceptor 22 (PTPN22), which encodes the protein LYP. To model the human disease-linked variant LYP-R620W, we generated knockin mice expressing the analogous mutation, R619W, in the murine ortholog PEST domain phosphatase (PEP). In contrast with a previous report, we found that this variant exhibits normal protein stability, but significantly alters lymphocyte function. Aged knockin mice exhibited effector T cell expansion and transitional, germinal center, and age-related B cell expansion as well as the development of autoantibodies and systemic autoimmunity. Further, PEP-R619W affected B cell selection and B lineage-restricted variant expression and was sufficient to promote autoimmunity. Consistent with these features, PEP-R619W lymphocytes were hyperresponsive to antigen-receptor engagement with a distinct profile of tyrosine-phosphorylated substrates. Thus, PEP-R619W uniquely modulates T and B cell homeostasis, leading to a loss in tolerance and autoimmunity.
THE OXIDATION OF p-AMINOBENZOIC ACID AND ANTHRANILIC ACID BY SPECIFICALLY ADAPTED ENZYMES OF A SOIL BACILLUS
Authors: G. S. Mirick
Journal: The Journal of Experimental Medicine (1943)

1. A soil bacillus has been isolated capable of developing specific adaptive enzymes which oxidize PABA apparently to carbon dioxide, water, and ammonia. A few related compounds which, however, do not give the diazo reaction are similarly attacked. 2. This bacillus is also capable of developing analogous but apparently independent adaptive enzymes specifically directed against anthranilic acid, the ortho isomer of PABA. 3. Sulfapyridine is bacteriostatic for this bacillus and this effect is inhibited as in the case of other bacterial species by PABA. Other effects of the sulfonamide drugs and sulfanilic acid upon the specific oxidative enzymes have been described. 4. The specific adaptive enzymes of this soil bacillus may be used for the identification of as little as 10 gamma of either PABA or OABA. A method is described for carrying out these determinations. 5. The possible advantages of this enzymatic method as compared with the more sensitive but less specific techniques which measure the activity of PABA as a growth factor for certain bacterial species have been discussed.
Translating Glutamate: From Pathophysiology to Treatment
Authors: Daniel C. Javitt, Darryle Schoepp, Peter W. Kalivas, Nora D. Volkow, Carlos Zarate, Kalpana Merchant, Mark F. Bear, Daniel Umbricht, Mihaly Hajos, William Z. Potter, Chi-Ming Lee
Journal: Science Translational Medicine (2011)

On 21 to 22 June 2010, the Institute of Medicine Forum on Neuroscience and Nervous System Disorders, Board on Health Sciences Policy, discussed the role of glutamate in neuropsychiatric disease at the meeting “Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System.”
Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis
Authors: R. Z. Pinto, C. G. Maher, M. L. Ferreira, P. H. Ferreira, M. Hancock, V. C. Oliveira, A. J. McLachlan, B. Koes
Journal: BMJ (2012)

<b>Objective</b> To investigate the efficacy and tolerability of analgesic and adjuvant pain drugs typically administered in primary care for the management of patients with sciatica. <b>Design</b> Systematic review. <b>Data source</b> International Pharmaceutical Abstracts, PsycINFO, Medline, Embase, Cochrane Central Register of Clinical Trials (CENTRAL), CINAHL, and LILACS. <b>Study selection</b> Randomised controlled trials assessing the efficacy and tolerability of drugs versus placebo or other treatment for sciatica. <b>Data extraction</b> Two independent reviewers extracted data and assessed methodological quality using the PEDro scale. Pain and disability outcomes were converted to a common 0 to 100 scale. Data were pooled with a random effects model, and the GRADE approach was used in summary conclusions. <b>Results</b> Twenty three published reports met the inclusion criteria. The evidence to judge the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antidepressants, anticonvulsants, muscle relaxants, and opioid analgesics ranged from moderate to low quality. Most of the pooled estimates did not favour the active treatment over placebo. The pooled results of two trials of corticosteroids (mean difference in overall and leg pain −12.2, 95% confidence interval −20.9 to −3.4) and a single trial of the anticonvulsant gabapentin for chronic sciatica (mean difference in overall pain relief −26.6, −38.3 to −14.9) showed some benefits but only in the short term. The median rate of adverse events was 17% (interquartile range 10-30%) for the active drugs and 11% (3-23%) for placebo. Trial limitations included failure to use validated outcome measures, lack of long term follow-up, and small sample size. <b>Conclusions</b> As the existing evidence from clinical trials is of low quality, the efficacy and tolerability of drugs commonly prescribed for the management of sciatica in primary care is unclear.
Cytokine Therapy With Interleukin-2/Anti–Interleukin-2 Monoclonal Antibody Complexes Expands CD4+CD25+Foxp3+ Regulatory T Cells and Attenuates Development and Progression of Atherosclerosis
Authors: Tam Nguyen Dinh, Tin Soe Kyaw, Peter Kanellakis, Kelly To, Peter Tipping, Ban-Hock Toh, Alexander Bobik, Alex Agrotis
Journal: Circulation (2012)

CD4+CD25+Foxp3+ regulatory T cells (Tregs) attenuate atherosclerosis, but their therapeutic application by adoptive transfer is limited by the need for their expansion in vitro and limited purity. Recently, an interleukin (IL)-2/anti-IL-2 neutralizing monoclonal antibody (IL-2/anti-IL-2 mAb) complex has been shown to expand these Tregs. We examined the capacity of a modified IL-2/anti-IL-2 mAb treatment to expand Tregs and inhibit both the progression and development of developed atherosclerosis.Six-week old apolipoprotein E-deficient mice fed a high-fat diet for 8 weeks were administered IL-2/anti-IL-2 mAb commencing 2 weeks after starting the diet. Tregs in the spleen, lymph node, and liver were selectively expanded without affecting CD4+, CD8+, or natural killer cells. Tregs were increased in lesions and lesion size reduced. CD4+ T-cells, macrophages, mature dendritic cells, proliferating cell nuclear antigen+ cells, and monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 were reduced. In anti-CD3-stimulated splenocytes, proliferation and secretion of Th1, Th2, and Th17 (IL-17) cytokines and IL-1β were reduced. To determine whether treatment attenuated progression of developed atherosclerosis, 6-week-old apolipoprotein E-deficient mice were fed a high-fat diet for 6 weeks, followed by IL-2/anti-IL-2 mAb treatment for 6 weeks while continuing the high-fat diet. Treatment also increased Tregs without affecting CD4+, CD8+, or natural killer cells, suppressed inflammation, and greatly attenuated progression of atherosclerosis.IL-2/anti-IL-2 mAb treatment in vivo attenuates atherosclerosis via selective Tregs expansion. The findings suggest that cytokine-based IL-2/anti-IL-2 mAb complex therapy could represent an attractive approach for treating atherosclerosis, because it markedly attenuates progression as well as development, by modulating its immunoinflammatory component.