tbuckley/cabot-search huggingface dataset:
Residual Viability Is a Predictor of the Perfusion Enhancement Obtained With the Cell Therapy of Chronic Myocardial Infarction
Authors: Pablo Maureira, Nguyen Tran, Wassila Djaballah, Michaël Angioï, Danièle Bensoussan, Nicolas Didot, Renaud Fay, Nicolas Sadoul, Jean-Pierre Villemot, Pierre-Yves Marie
Journal: Clinical Nuclear Medicine (2012)

Up to now, there has been limited investigation into cell therapy in the chronic phase of severe myocardial infarction (MI), and many questions remain concerning the contribution of the engrafted cells and especially their impact on the reperfusion of MI areas, when assessed by objective quantitative imaging techniques. This randomized pilot SPECT, PET, and MRI study was aimed at assessing the effects of bone marrow mononuclear cells (BMNCs) when implanted in areas of severe and chronic MI.Fourteen patients, who were referred for coronary artery bypass grafting (CABG) and in whom a screening MIBI-SPECT revealed severely damaged myocardium (<50% uptake under nitrate), were randomized between a cell therapy group (n = 7; CABG and injection of BMNCs within MI areas) and a control group (n = 7; CABG alone).The MI areas exhibited a posttherapeutic enhancement in the rest-uptake of MIBI in the cell therapy group [difference between 6-month control and baseline: +6.8% (5.4%), P = 0.03] but not in the control group [+1.0% (4.3%)]. However, in a per-patient analysis, this improvement was significant (> +9%) in only 3 cell therapy patients, whose MI areas before therapy had a higher FDG uptake [59% (9%) vs 38% (8%), P = 0.03] and a lower transmural extent at MRI [40% (6%) vs 73% (18%), P = 0.03] when compared with the other cell therapy patients.Perfusion enhancement, obtained with BMNCs in areas of chronic MI, might require an intermediate level of viability documented with FDG-PET and MRI and that totally necrotic MI seems refractory to this cell therapy technique.
Rates and dates of divergence between AIDS virus nucleotide sequences.
Authors: W H Li, M Tanimura, P M Sharp
Journal: Molecular Biology and Evolution (1988)

The acquired immune deficiency syndrome (AIDS), caused by a retrovirus called human immunodeficiency virus (HIV), has become a pandemic. A knowledge of the rate of nucleotide substitution in HIV and of the history and pattern of spread of the virus is important for understanding the epidemiology and pathogenesis of AIDS and for developing therapies and vaccine strategies. A new model has been developed and used to estimate the substitution rates in various regions in the HIV genome. The rate of nonsynonymous (amino acid-changing) substitution is lowest in the regions coding for the capsid proteins and the reverse transcriptase, being approximately 1.7 X 10(-3) nucleotide substitutions/site/year. The nonsynonymous rate is extremely high (14 X 10(-3] in the hypervariable regions of the envelope gene, suggesting extremely rapid change in viral antigenicity. The nonsynonymous rates in the other coding regions are between 3 X 10(-3) and 7 X 10(-3). The average synonymous rate for the HIV genome is 10 X 10(-3). These rates are 10(6) times greater than the rates in DNA genomes and at least as high as the rates in other RNA viruses. Evidence is provided for a case of recombination between different HIV strains. Our analysis suggests that the AIDS virus had existed in central Africa before 1960 and spread to North America before the mid 1970s. The evolutionary relationships among HIV isolates are inferred from nucleotide sequence data, and the result is consistent with the view that AIDS spread from Haiti to the United States.
Chemical extraction technique for tattoo removal: reply from authors
Authors: A.M.R. DOWNS
Journal: British Journal of Dermatology (2004)

Journal Article Chemical extraction technique for tattoo removal: reply from authors Get access A.M.R. DOWNS A.M.R. DOWNS Department of Dermatology, Royal Devon and Exeter Hospitals, Exeter EX2 5DW, U.K. E‐mail: Anthony.Downs@rdehc‐tr.swest.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 6, 1 December 2004, Pages 1283–1284, https://doi.org/10.1111/j.1365-2133.2004.06288.x Published: 01 December 2004
THE PRACTICE OF PATHOLOGY.
Authors: H.A. Cookson, J.B. Davey, S.C. Dyke, C.E. Jenkins, C.Powell White, A. Renshaw, A.G. Shera, A.F.S. Sladden, R.V. Solly, E. Wordley, A.F. Wright
Journal: The Lancet (1927)
Low-Frequency Positive-Pressure Ventilation With Extracorporeal CO2 Removal in Severe Acute Respiratory Failure
Authors: L Gattinoni, A Pesenti, D Mascheroni, R Marcolin, R Fumagalli, F Rossi, G Iapichino, G Romagnoli, L Uziel, A Agostoni
Journal: JAMA (1986)

Forty-three patients were entered in an uncontrolled study designed to evaluate extracorporeal membrane lung support in severe acute respiratory failure of parenchymal origin. Most of the metabolic carbon dioxide production was cleared through a low-flow venovenous bypass. To avoid lung injury from conventional mechanical ventilation, the lungs were kept "at rest" (three to five breaths per minute) at a low peak airway pressure of 35 to 45 cm H2O (3.4 to 4.4 kPa). The entry criteria were based on gas exchange under standard ventilatory conditions (expected mortality rate, greater than 90%). Lung function improved in thirty-one patients (72.8%), and 21 patients (48.8%) eventually survived. The mean time on bypass for the survivors was 5.4 +/- 3.5 days. Improvement in lung function, when present, always occurred within 48 hours. Blood loss averaged 1800 +/- 850 mL/d. No major technical accidents occurred in more than 8000 hours of perfusion. Extracorporeal carbon dioxide removal with low-frequency ventilation proved a safe technique, and we suggest it as a valuable tool and an alternative to treating severe acute respiratory failure by conventional means.
Safety and Efficacy of Oxaliplatin and Fluoropyrimidine Regimens With or Without Bevacizumab As First-Line Treatment of Metastatic Colorectal Cancer: Results of the TREE Study
Authors: Howard S. Hochster, Lowell L. Hart, Ramesh K. Ramanathan, Barrett H. Childs, John D. Hainsworth, Allen L. Cohn, Lucas Wong, Louis Fehrenbacher, Yousif Abubakr, M. Wasif Saif, Lee Schwartzberg, Eric Hedrick
Journal: Journal of Clinical Oncology (2008)

To evaluate the safety and efficacy of three oxaliplatin and fluoropyrimidine regimens, with or without bevacizumab, as first-line treatment for metastatic colorectal cancer (CRC).Patients with histologically documented metastatic or recurrent CRC and no prior treatment for advanced disease were randomly assigned to mFOLFOX6 (bolus and infusion fluorouracil [FU] and leucovorin [LV] with oxaliplatin), bFOL (bolus FU and low-dose LV with oxaliplatin), or CapeOx (capecitabine with oxaliplatin), respectively (Three Regimens of Eloxatin Evaluation [TREE-1]). The study was later modified such that subsequent patients were randomized to the same regimens plus bevacizumab (TREE-2).A total of 150 and 223 patients were randomly assigned in the TREE-1 and TREE-2 cohorts, respectively. Incidence of grade 3/4 treatment-related adverse events during the first 12 weeks of treatment were 59%, 36%, and 67% for mFOLFOX6, bFOL, and CapeOx, respectively, (TREE-1) and 59%, 51%, and 56% for the corresponding treatments plus bevacizumab (TREE-2; primary end point). CapeOx toxicity in TREE-1 included grade 3/4 diarrhea (31%) and dehydration (27%); capecitabine dose reduction to 1,700 mg/m(2)/d in TREE-2 resulted in improved tolerance. Overall response rates were 41%, 20%, and 27% (TREE-1) and 52%, 39%, and 46% (TREE-2); median overall survival (OS) was 19.2, 17.9, and 17.2 months (TREE-1) and 26.1, 20.4, and 24.6 months (TREE-2). For all treated patients, median OS was 18.2 months (95% CI, 14.5 to 21.6; TREE-1) and 23.7 months (95% CI, 21.3 to 26.8; TREE-2).The addition of bevacizumab to oxaliplatin and fluoropyrimidine regimens is well tolerated as first-line treatment of mCRC and does not markedly change overall toxicity. CapeOx tolerability and efficacy is improved with reduced-dose capecitabine. First-line oxaliplatin and fluoropyrimidine-based therapy plus bevacizumab resulted in a median OS of approximately 2 years.
Elimination of Haemophilus influenzae type b (Hib) disease from The Gambia after the introduction of routine immunisation with a Hib conjugate vaccine: a prospective study
Authors: Richard A Adegbola, Ousman Secka, George Lahai, Nellie Lloyd-Evans, Alpha Njie, Stanley Usen, Claire Oluwalana, Stephen Obaro, Martin Weber, Tumani Corrah, Kim Mulholland, Keith McAdam, Brian Greenwood, Paul JM Milligan
Journal: The Lancet (2005)
Transcriptome analyses of primitively eusocial wasps reveal novel insights into the evolution of sociality and the origin of alternative phenotypes
Authors: Pedro G Ferreira, Solenn Patalano, Ritika Chauhan, Richard Ffrench-Constant, Toni Gabaldón, Roderic Guigó, Seirian Sumner
Journal: Genome biology (2013)

Understanding how alternative phenotypes arise from the same genome is a major challenge in modern biology. Eusociality in insects requires the evolution of two alternative phenotypes - workers, who sacrifice personal reproduction, and queens, who realize that reproduction. Extensive work on honeybees and ants has revealed the molecular basis of derived queen and worker phenotypes in highly eusocial lineages, but we lack equivalent deep-level analyses of wasps and of primitively eusocial species, the latter of which can reveal how phenotypic decoupling first occurs in the early stages of eusocial evolution.We sequenced 20 Gbp of transcriptomes derived from brains of different behavioral castes of the primitively eusocial tropical paper wasp Polistes canadensis. Surprisingly, 75% of the 2,442 genes differentially expressed between phenotypes were novel, having no significant homology with described sequences. Moreover, 90% of these novel genes were significantly upregulated in workers relative to queens. Differential expression of novel genes in the early stages of sociality may be important in facilitating the evolution of worker behavioral complexity in eusocial evolution. We also found surprisingly low correlation in the identity and direction of expression of differentially expressed genes across similar phenotypes in different social lineages, supporting the idea that social evolution in different lineages requires substantial de novo rewiring of molecular pathways.These genomic resources for aculeate wasps and first transcriptome-wide insights into the origin of castes bring us closer to a more general understanding of eusocial evolution and how phenotypic diversity arises from the same genome.
The Intestinal T Cell Response to α-Gliadin in Adult Celiac Disease Is Focused on a Single Deamidated Glutamine Targeted by Tissue Transglutaminase
Authors: Helene Arentz-Hansen, Roman Körner, Øyvind Molberg, Hanne Quarsten, Willemijn Vader, Yvonne M.C. Kooy, Knut E.A. Lundin, Frits Koning, Peter Roepstorff, Ludvig M. Sollid, Stephen N. McAdam
Journal: The Journal of Experimental Medicine (2000)

The great majority of patients that are intolerant of wheat gluten protein due to celiac disease (CD) are human histocompatibility leukocyte antigen (HLA)-DQ2+, and the remaining few normally express HLA-DQ8. These two class II molecules are chiefly responsible for the presentation of gluten peptides to the gluten-specific T cells that are found only in the gut of CD patients but not of controls. Interestingly, tissue transglutaminase (tTG)-mediated deamidation of gliadin plays an important role in recognition of this food antigen by intestinal T cells. Here we have used recombinant antigens to demonstrate that the intestinal T cell response to α-gliadin in adult CD is focused on two immunodominant, DQ2-restricted peptides that overlap by a seven-residue fragment of gliadin. We show that tTG converts a glutamine residue within this fragment into glutamic acid and that this process is critical for T cell recognition. Gluten-specific T cell lines from 16 different adult patients all responded to one or both of these deamidated peptides, indicating that these epitopes are highly relevant to disease pathology. Binding studies showed that the deamidated peptides displayed an increased affinity for DQ2, a molecule known to preferentially bind peptides containing negatively charged residues. Interestingly, the modified glutamine is accommodated in different pockets of DQ2 for the different epitopes. These results suggest modifications of anchor residues that lead to an improved affinity for major histocompatibility complex (MHC), and altered conformation of the peptide–MHC complex may be a critical factor leading to T cell responses to gliadin and the oral intolerance of gluten found in CD.
Digital vasculitis after splenectomy in a patient with Felty's syndrome.
Authors: M Comer, R C Bucknall
Journal: Annals of the Rheumatic Diseases (1992)

The case is reported of a man with Felty9s syndrome in whom digital cutaneous vasculitis developed after a splenectomy. This may be a coincidental occurrence but a possible mechanism is suggested by which the splenectomy may have modified the immunopathology of the disease.
Depression of Endothelial Nitric Oxide Synthase but Increased Expression of Endothelin-1 Immunoreactivity in Rat Thoracic Aortic Endothelium Associated With Long-term, but Not Short-term, Sympathectomy
Authors: Gjumrakch Aliev, Vera Ralevic, Geoffrey Burnstock
Journal: Circulation Research (1996)

Recent pharmacological studies have shown that perivascular nerves can influence the development and function of vascular endothelial cells (ECs). However, morphological studies have not yet been carried out to investigate whether these functional changes are associated with changes in vasoactive substances in ECs. We used postembedding electron microscopy (EM) triple gold–labeling immunocytochemistry to study the effects of short-term sympathectomy (3 days after 6-hydroxydopamine [6-OHDA] treatment) and long-term sympathectomy (guanethidine and 8 days after 6-OHDA) on the distribution of vasoactive substances in ECs of the rat thoracic aorta. The postembedding immunocytochemistry, which can detect levels of label in individual cells, showed that there was a significant decrease in endothelial NO synthase (NOS3)–labeled, serotonin (5-HT)–labeled, and substance P (SP)–labeled, but a significant increase in endothelin-1 (ET-1)–labeled, gold particles in ECs after long-term, but not after short-term (3-day), sympathectomy. In conclusion, our results show that long-term sympathectomy causes an increase in ET-1 and decrease in NOS3, 5-HT, and SP immunoreactivity in ECs of the thoracic aorta. Our data also indicate that postembedding EM triple gold–labeling immunocytochemistry is a valuable technique for quantitative studies of the content of vasoactive substances in ECs.
Interferon-Alpha Is Effective in the Treatment of HIV-1–Related, Severe, Zidovudine-Resistant Thrombocytopenia: A Prospective, Placebo-controlled, Double-Blind Trial
Authors: Massimo Marroni
Journal: Annals of Internal Medicine (1994)

Objective: To determine the effect of interferon-α for severe, zidovudine-resistant, HIV-1–related thrombocytopenia. Design: Prospective, randomized, double-blind, placebo-controlled, multicenter, crossover trial. Setting: Outpatient clinics in Central Northern Italy. Patients: 15 sequential patients positive for HIV-1 with platelet counts less than 25 × 109/L who were refractory to 1 month of full-dose (1000 mg/d) zidovudine. Intervention: Interferon-α (3 million units) or placebo (1 mL saline) three times a week subcutaneously for 4 weeks, followed by a 4-week washout period. Patients were then switched to the alternative treatment for the next 4 weeks, followed by another 4 weeks of washout, and they were randomly assigned to either sequence of treatment. Patients received zidovudine (200 mg three times daily) throughout the study. Measurements: The primary end point was the platelet count (measured weekly). Secondary end points were qualitative assessment of the platelet response; bleeding time; p24 antigen in serum; CD4/CD8 counts; β2-microglobulin in serum; and platelet-associated IgG. Results: Interferon-α significantly increased platelet counts in the 12 patients who completed the study (baseline level, 15.6 ± 7.1 × 109/L; after 4 weeks of interferon-α therapy, 82.2 ± 52.2 × 109/L). The estimated increase in the platelet count after interferon-α compared with placebo was 60.0 × 109/L (95% CI, 23.2 to 96.8 × 109/L). The increase was already statistically significant after 3 weeks (66.6 ± 49.7 × 109/L) and remained significantly increased 1 week after discontinuing interferon-α therapy (58.2 ± 45.0 × 109/L). Placebo did not modify the platelet count. The bleeding time was significantly shortened by interferon-α. Four of 12 patients who had more serious alterations of some measures reflecting disease severity did not respond to interferon-α. No relevant side effects were observed. Conclusions: Interferon-α is a safe and effective treatment for zidovudine-resistant, HIV-related thrombocytopenia.
Risk of Fetal Death after Pandemic Influenza Virus Infection or Vaccination
Authors: Siri E. Håberg, Lill Trogstad, Nina Gunnes, Allen J. Wilcox, Håkon K. Gjessing, Sven Ove Samuelsen, Anders Skrondal, Inger Cappelen, Anders Engeland, Preben Aavitsland, Steinar Madsen, Ingebjørg Buajordet, Kari Furu, Per Nafstad, Stein Emil Vollset, Berit Feiring, Hanne Nøkleby, Per Magnus, Camilla Stoltenberg
Journal: New England Journal of Medicine (2013)

During the 2009 influenza A (H1N1) pandemic, pregnant women were at risk for severe influenza illness. This concern was complicated by questions about vaccine safety in pregnant women that were raised by anecdotal reports of fetal deaths after vaccination.We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios for fetal death, with the gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables.There were 117,347 eligible pregnancies in Norway from 2009 through 2010. Fetal mortality was 4.9 deaths per 1000 births. During the pandemic, 54% of pregnant women in their second or third trimester were vaccinated. Vaccination during pregnancy substantially reduced the risk of an influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). Among pregnant women with a clinical diagnosis of influenza, the risk of fetal death was increased (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). The risk of fetal death was reduced with vaccination during pregnancy, although this reduction was not significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17).Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis. Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.).
Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice.
Authors: B S Graham, L A Bunton, P F Wright, D T Karzon
Journal: Journal of Clinical Investigation (1991)

The role of CD4+ and CD8+ T lymphocytes in terminating respiratory syncytial virus (RSV) replication, causing disease, and protecting from reinfection was investigated using a BALB/c mouse model in which CD4+ or CD8+ lymphocytes or both were depleted by injections of Mab directed against the respective mouse lymphocyte determinants. Kinetics of RSV replication, illness, and pathology were assessed after primary infection and rechallenge. Both CD4+ and CD8+ lymphocyte subsets were involved in terminating RSV replication after primary infection. When both T lymphocyte subsets were depleted RSV replication was markedly prolonged, yet no illness was evident, suggesting that host immune response rather than viral cytocidal effect was the primary determinant of disease in mice. Both CD4+ and CD8+ lymphocytes contributed to illness, although CD8+ lymphocytes appeared to play the dominant role in this particular system. Analysis of histological responses suggested that CD4+ lymphocytes were required for the appearance of peribronchovascular lymphocytic aggregates seen in normal mice after rechallenge, and that the presence of alveolar lymphocytes was correlated with illness. It is postulated that antibody is an illness-sparing mechanism for protecting mice from RSV infection, and that T lymphocytes are an important determinant of illness. Further delineation of RSV-induced immunopathogenesis in primary infection and reinfection will provide important information for the development of vaccine strategies.
Specificity of the Methylation-Suppressed A Isoform of Candidate Tumor Suppressor RASSF1 for Microtubule Hyperstabilization Is Determined by Cell Death Inducer C19ORF5
Authors: Leyuan Liu, Amy Vo, Wallace L. McKeehan
Journal: Cancer Research (2005)

Abstract Isoform-specific epigenetic silencing of RASSF1A (3p21.3) by promoter-specific CpG island hypermethylation occurs at high frequency in human tumors, whereas the closely related product of the same gene, RASSF1C, continues to be expressed. Both isoforms in isolation exhibit tumor suppressor properties and we show here similar cellular locations on mitochondria and microtubules, paclitaxel-like microtubule hyperstabilization, disruption of mitosis, and interaction with C19ORF5. We show both have identical but distinct sequence domains for microtubule association and hyperstabilization. C19ORF5 is a hyperstabilized microtubule-specific binding protein of which accumulation causes mitochondrial aggregation and cell death. We report herein that when A or C isoforms of RASSF1 are coexpressed with C19ORF5, the unique N-terminal sequence of RASSF1C prevents it from hyperstabilizing microtubules. This confers specificity on RASSF1A in microtubule hyperstabilization and accumulation of C19ORF5 on microtubules and could underlie a specific effect of hypermethylation-suppressed RASSF1A in tumor suppression.
Tryptase in nasal lavage fluid after local allergen challenge: Relationship to histamine levels and TAME‐esterase activity
Authors: S. JULIUSSON, K. HOLMBERG, C. R. BAUMGARTEN, M. OLSSON, I. ENANDER, U. PIPKORN
Journal: Allergy (1991)

The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10‐fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME‐esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME‐esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME‐esterase levels and the tryptase levels (r = 0.71; P &lt; 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non‐allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.