tbuckley/cabot-search huggingface dataset:
The multi-faceted behavior of nitric oxide in vascular “inflammation”: catchy terminology or true phenomenon?
Authors: I TRITTO, G AMBROSIO
Journal: Cardiovascular Research (2004)

See article by Hattori et al. [11] (pages 31–40) in this issue .

Over the last 20 years, our understanding of the role of nitric oxide (NO) in biological systems has evolved enormously. Once considered merely a vasodilator (albeit a very powerful one), NO has subsequently attracted attention for its ability to modulate a number of intracellular pathways at the vascular and extravascular level. This is, however, when the headache began. The flurry of studies investigating a variety of possible cellular targets soon led to the discovery that, under different conditions, several pathophysiological events could be affected by NO by seemingly divergent mechanisms.

Initial studies pointed towards a protective effect of NO on cellular activities, indicating that NO would prevent development of the pro-atherogenic phenotype in endothelial cells and vascular smooth muscle cells, reduce leukocyte adhesion and recruitment from the blood stream into the vessel wall, prevent apoptosis, and reduce tissue injury during ischemia–reperfusion [1]. However, it has become evident that the issue is more complicated than this simplified view would predict, since conflicting data have been reported about the effects of nitric oxide on several conditions, such as myocardial contractile function [2], atherosclerosis [3], and ischemia/reperfusion injury [4]. These controversies were only partly explained by differences in experimental models and in the source and amount of NO formed.

Describing the opposite effects of nitric oxide on various aspect of vascular pathophysiology has thus become fuel for an extensive literature centered around the apparently double-faceted nature of this molecule. Accordingly, NO behavior has been at times described as “friend or foe”, a “double-edge sword”, “yin-yang”, or as having a “Janus face”. … 

*Corresponding author. Tel.: +39-75-527-1509; fax: +39-75-527-1244. Email address: giuseppe.ambrosio{at}ospedale.perugia.it
The gut microbiota and host health: a new clinical frontier
Authors: Julian R Marchesi, David H Adams, Francesca Fava, Gerben D A Hermes, Gideon M Hirschfield, Georgina Hold, Mohammed Nabil Quraishi, James Kinross, Hauke Smidt, Kieran M Tuohy, Linda V Thomas, Erwin G Zoetendal, Ailsa Hart
Journal: Gut (2015)

Over the last 10-15 years, our understanding of the composition and functions of the human gut microbiota has increased exponentially. To a large extent, this has been due to new 'omic' technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.
Continuous Infusion High-Dose Leucovorin with 5-Fluorouracil and Cisplatin for Untreated Stage IV Carcinoma of the Head and Neck
Authors: Arnon I. Dreyfuss
Journal: Annals of Internal Medicine (1990)

Study Objective: To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck. Design: Nonrandomized, prospective trial. Setting: A comprehensive cancer center. Patients: Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity. Interventions: Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/ m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy. Results: A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (± SD) was 34.3 ± 1.5 μmol/L, of which only 8.0 ± 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 ± 0.6 ¼mol/L. Conclusions: Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.
Efficient gene transduction of adipose tissue-derived mesenchymal stem cells (MSCs) for asthma research
Authors: Luis Antonio Mariñas-Pardo, Óscar Amor-Carro, Laura Núñez-Naveira, Beatriz Lema-Costa, Javier García-Castro, David Ramos-Barbόn
Journal: European Respiratory Journal (2011)

Background: MSCs may offer therapeutic potential for asthma due to their immunomodulatory properties and host tolerability. MSCs may however be involved in airway remodeling. Solid preclinical development is therefore indispensable prior to clinical trial attempts. We aimed at establishing a technique for MSC genetic engineering and in vivo tracking in experimental asthma.

Methods: A gene transfer retroviral vector to induce permanent green fluorescent protein (GFP) expression on MSCs was generated. MSC cultures were produced from abdominal adipose tissue of adult mice, as per established procedures (MesenCult Kit, StemCell Technologies). GFP expression was assessed by flow cytometry and fluorescent microscopy. The MSC phenotype was verified by cell surface marker analysis, and by differentiation in adipogenic and osteogenic commercial media followed by oil-red and alizarin-red staining.

Results: Passage-4 cells targeted with a single retroviral hit at a multiplicity of infection of 1 preserved 99.4% cell viability and yielded 82.6% transduced cells highly expressing GFP. The cells showed a Sca-1+CD44+CD14-CD45-CD11b- MSC phenotype, and differentiated into adipocyte and osteocyte lineages in conditioned media.

Conclusions: Adipose tissue derived MSCs can be efficiently transduced with retroviral vectors for permanent gene expression. This provides a tool for in vivo MSC tracking to remodeling airways, and for exploring pathogenic mechanisms and therapeutic avenues through MSC genetic modifications.

Funded by the Fondo de Investigaciόn Sanitaria of Spain & European Regional Development Fund, a GlaxoSmithKline Collaborative Research Trial and SEPAR.
MALIGNANT ATROPHIC PAPULOSIS: A FATAL CUTANEO-INTESTINAL SYNDROME.
Authors: R. DEGOS
Journal: British Journal of Dermatology (1954)

Journal Article MALIGNANT ATROPHIC PAPULOSIS: A FATAL CUTANEO‐INTESTINAL SYNDROME. Get access R. DEGOS R. DEGOS Professeur de Clinique des Maladies Cutanées et Syphilitiques à la Faculté de Médecine: Médecin de l'Hopital Saint‐Louis, Paris Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 66, Issue 8-9, 1 August 1954, Pages 304–307, https://doi.org/10.1111/j.1365-2133.1954.tb12639.x Published: 01 August 1954
Response of mature unprimed CD8+ T cells to Mlsa determinants.
Authors: S R Webb, J Sprent
Journal: The Journal of Experimental Medicine (1990)

Contrary to existing dogma, evidence is presented that proliferative responses of mature unprimed T cells to Mlsa antigens involve CD8+ cells as well as CD4+ cells. The response of CD8+ cells to Mlsa antigens proved to be heavily dependent on help from CD4+ cells, and responses were stronger in three I-E+ strain combinations than in an I-E- combination. In I-E+ combinations, CD8+ blast cells accounted for 20-25% of the blasts generated from unseparated T cells responding to Mlsa-bearing stimulator cells in vitro; similar findings applied to blast cells generated in vivo. The observation that the majority (greater than or equal to 50%) of Mlsa-stimulated CD8+ cells (and CD4+ cells) were V beta 6+ indicated that CD8+ cells respond to Mlsa antigens, per se, rather than to nonspecific stimuli. Whether CD4+ and CD8+ cells use the same or different H-2-restricting elements to respond to Mlsa antigens has yet to be resolved.
The influence of age on the intestinal absorption of 47-Ca absorption in post-menopausal osteoporosis.
Authors: L V Avioli, J E McDonald, S W Lee
Journal: Journal of Clinical Investigation (1965)

The literature is still controversial regarding the intestinal absorption of calcium in osteoporosis, with conflicting reports of decreased absorption (1-4), increased absorption (5-7), and normal absorption (8-10).The apparent discrepancies in these reports may stem from a) the absence of a common isotopic absorption test wherein oral "7Ca doses of uniform specific activity are adminis- tered in the fasting state, b) wide variations in the amount and chemical form of the administered stable calcium carrier, c) inadequate identification of the osteoporotic disease process and its differ- entiation from osteomalacia, d) the lack of suffi- cient age-matched nonosteoporotic controls for comparison, and e) wide variations in dietary cal- cium intakes, which prohibit adequate comparison between individual reports.The lack of reported investigations in humans relating the absorptive capacity of the intestine to age and to osteoporosis and the availability of a simplied oral isotopic test of calcium absorption (11) prompted an evaluation of calcium absorp- tion in 59 normal women of various ages and in 16 women with severe osteoporosis. MethodsThe normal population consisted of 59 women with an average age of 40 years (range, 12 to 85 years).This
Paracrine Signaling between Carcinoma Cells and Mesenchymal Stem Cells Generates Cancer Stem Cell Niche via Epithelial–Mesenchymal Transition
Authors: Kati Räsänen, Meenhard Herlyn
Journal: Cancer Discovery (2012)

Li and colleagues present data that cancer cell-derived interleukin-1 induces prostaglandin E(2) and cytokine secretion in mesenchymal stem cells (MSC) to activate β-catenin signaling in the cancer cell. This paracrine signaling between carcinoma cells and MSC leads to the creation of a cancer stem cell niche via epithelial-mesenchymal transition.
Epidemiology of seasonal and perennial rhinitis: clinical presentation and medical history.
Authors: B Sibbald, E Rink
Journal: Thorax (1991)

BACKGROUND: Little is known about the epidemiology of rhinitis, particularly the perennial and non-allergic forms. The aim of this study was to compare the symptoms, atopic state, and medical history of individuals with seasonal and perennial rhinitis. DESIGN: Of 7702 adults aged 16-65 years registered with a London general practice, 2969 (30%) were screened by postal questionnaire. Samples of 113 subjects without rhinitis, 51 with seasonal symptoms alone, 128 with perennial symptoms and seasonal exacerbations were then interviewed. Atopic and non-atopic subjects were distinguished by skinprick testing with five common allergens. RESULTS: The estimated minimum prevalence of rhinitis was 24%: 3% had seasonal symptoms only, of whom 78% were atopic; 13% had perennial symptoms only, of whom 50% were atopic; and 8% had perennial symptoms with seasonal exacerbations, of whom 68% were atopic. Seasonal rhinitis was characterised by sneezing, itching, and a high prevalence of diurnal variation in symptoms. The most common provoking factors were dust, pollens, and infections. By comparison, perennial rhinitis was characterised by a higher prevalence of nasal blockage and catarrh, and a lower prevalence of diurnal variation and provocation by pollen. There were no significant differences among the groups in the sociodemographic characteristics examined. Subjects with seasonal rhinitis were more likely to be atopic and to have eczema and a family history of hayfever than those without rhinitis. Those with perennial rhinitis were more likely to have past or current eczema or migraine, be wheezy or labelled asthmatic, or have a family history of nose trouble other than hayfever. Subjects with both seasonal and perennial symptoms presented an intermediate clinical picture. CONCLUSIONS: Seasonal and perennial rhinitis differ in their atopic state, clinical presentation, and medical history. The extent to which these differences are genetically or environmentally determined requires further investigation.
P167 Characterisation of tuberculous mediastinal lymphadenopathy on CT and correlation with biomarkers and chest radiograph findings
Authors: A. Singanayagam, P. George, D. Connell, S. Kaneria, J. Dhariwal, P. Molyneaux, M. Wickremasinghe, A. Lalvani, A. Wright, O. M. Kon
Journal: Thorax (2010)

<h3>Introduction</h3> The aim of this study was to characterise the anatomical pattern of mediastinal lymphadenopathy on CT in active tuberculosis (TB) and assess correlation with biomarkers and chest radiograph (CXR) findings. <h3>Methods</h3> We conducted a retrospective analysis of patients treated for active TB with mediastinal lymphadenopathy at a tertiary centre between January 2007 and May 2009. CT scans performed prior to commencement of therapy were reviewed by two radiologists to assess for pathologically enlarged lymph nodes (LN) (short axis diameter &gt;1.0 cm) at each of the LN stations defined by the International Association for the Study of Lung Cancer (IASLC). <h3>Results</h3> 55 patients were included in the study. 56.3% of enlarged LNs were right sided, 32.9% were in central LN groups and 10.8% were left sided. 40.0% of patients had evidence of necrosis within LNs. The most frequently occurring enlarged LNs were in the subcarinal (level 7; 81.8% of patients), right lower paratracheal (level 4R; 58.2%) and right hilar (level 10R; 52.7%) stations. The Abstract P167 Table 1 shows correlation of biomarkers and CXR abnormalities with extent of LN involvement on CT. Results are displayed as % group or median (IQR). There were 49.1% with a normal CXR. In this subgroup, ESR and Globulin levels also correlated with extent of LN involvement on CT. The median (IQR) LN involvement stratified by ESR levels was: 2 (1–2), 2 (1–2.8) and 5 (4–5) for ESR ≤15, ESR 16–49 and ESR &gt;49 mm/h, respectively (p=0.039). The median (IQR) LN involvement stratified by Globulin levels was: 2 (1–3), 2 (2–4.8) and 5 (2.8–5.3) for Globulin ≤35, Globulin 36–45 and Globulin&gt;45 g/l, respectively (p=0.048). <h3>Conclusion</h3> Tuberculous mediastinal lymphadenopathy on CT is characterised by a specific anatomical pattern with predominance of right sided LNs and more frequent involvement of particular LN stations. A large proportion of patients with pathologically enlarged LNs on CT have normal CXRs. Biomarkers such as ESR and globulin levels correlate with extent of LN involvement on CT.
Novel Point Mutation in the Extracellular Domain of the Granulocyte Colony-Stimulating Factor (G-Csf) Receptor in a Case of Severe Congenital Neutropenia Hyporesponsive to G-Csf Treatment
Authors: Alister C. Ward, Yvette M. van Aesch, Judith Gits, Anita M. Schelen, John P. de Koning, Daphne van Leeuwen, Melvin H. Freedman, Ivo P. Touw
Journal: The Journal of Experimental Medicine (1999)

Severe congenital neutropenia (SCN) is a heterogeneous condition characterized by a drastic reduction in circulating neutrophils and a maturation arrest of myeloid progenitor cells in the bone marrow. Usually this condition can be successfully treated with granulocyte colony-stimulating factor (G-CSF). Here we describe the identification of a novel point mutation in the extracellular domain of the G-CSF receptor (G-CSF-R) in an SCN patient who failed to respond to G-CSF treatment. When this mutant G-CSF-R was expressed in myeloid cells, it was defective in both proliferation and survival signaling. This correlated with diminished activation of the receptor complex as determined by signal transducer and activator of transcription (STAT) activation, although activation of STAT5 was more affected than STAT3. Interestingly, the mutant receptor showed normal affinity for ligand, but a reduced number of ligand binding sites compared with the wild-type receptor. This suggests that the mutation in the extracellular domain affects ligand–receptor complex formation with severe consequences for intracellular signal transduction. Together these data add to our understanding of the mechanisms of cytokine receptor signaling, emphasize the role of GCSFR mutations in the etiology of SCN, and implicate such mutations in G-CSF hyporesponsiveness.
Oral Mesalamine (Asacol) for Mildly to Moderately Active Ulcerative Colitis
Authors: C A Sninsky, D H Cort, F Shanahan, B J Powers, J T Sessions, R E Pruitt, W H Jacobs, S K Lo, S R Targan, J J Cerda
Journal: Annals of Internal Medicine (1991)

Objective: To evaluate the efficacy and safety of a pH-sensitive, polymer-coated oral preparation of mesalamine in patients with mildly to moderately active ulcerative colitis. Design: A multicenter, double-blind, placebo-controlled randomized trial. Setting: Five university-based medical centers, one inflammatory bowel disease center, and three private practice sites. Patients: A total of 158 patients with newly or previously diagnosed active ulcerative colitis. Intervention: A pH-sensitive, polymer-coated oral preparation of mesalamine (5-aminosalicylic acid) was used at 1.6 and 2.4 g/d for 6 weeks. Measurements: Efficacy was measured by scores for stool frequency, rectal bleeding, patient's functional assessment, sigmoidoscopic findings, and physician's global assessment. Stringent criteria for disease activity were established prospectively. Results: The analysis of protocol-compliant patients showed a significant improvement at 3 weeks in patients taking 2.4 g/d of mesalamine compared with patients taking placebo (32% versus 9%; P = 0.003). At 6 weeks, both the 1.6 g/d (43%) and 2.4 g/d (49%) doses were significantly superior to placebo (23%) (P = 0.03 and P = 0.003, respectively). In addition, more patients worsened in the placebo group compared with the 2.4 g/d group (50% versus 19%; P= 0.003); however, there was no statistically significant difference in worsening between the 1.6 g/d mesalamine group and the placebo group. The oral mesalamine tablet was well tolerated, and no clinically significant changes were observed in hematologic, hepatic, or renal laboratory profiles. Conclusion: Colon-targeted oral mesalamine at 2.4 g/d is effective therapy for mildly to moderately active ulcerative colitis. It is well tolerated and should provide a viable therapeutic alternative to sulfasalazine.
Survival Benefits Associated With Provision of Psychotherapeutic Support to Patients With Gastrointestinal Cancer: Lots of Bang for a Few Bucks?
Authors: Michael A. Andrykowski
Journal: Journal of Clinical Oncology (2007)

In this issue of the Journal of Clinical Oncology ,K uchler et al 1 report 10-year survival data for participants in a randomized, controlled trial of psychotherapeutic support for patients with gastrointestinal cancers. Relative to patients who received routine standard of care, they found better 10-year survival rates for pa- tientswhoreceivedapsychotherapeuticsupportinterventiondur- ing their hospitalization for surgery for a gastrointestinal cancer. Specifically, 21.3% of patients (29 of 136) in the intervention arm were alive 10 years postdiagnosis compared with 9.6% of patients (13 of 135) in the control arm. Results of this 10-year follow-up mirror those of a 2-year follow-up of this same intervention study
Insulin Metabolism and Degradation*
Authors: WILLIAM C. DUCKWORTH, ABBAS E. KITABCHI
Journal: Endocrine Reviews (1981)

INSULIN degradation is a complex and incompletely, understood process at present. In terms of overall clearance and metabolism, the liver is responsible for more than half of the total insulin degradation, with kidney responsible for most of the rest. The peripheral tissues, fat and muscle, probably degrade the remainder of the insulin in the body, but the absolute contribution of these tissues to insulin turnover is uncertain. It now appears that peripheral tissues can serve as a reservoir for insulin, presumably by the hormone binding reversibly to membrane receptors. The function of this remains to be established. At a cellular level in most tissues, insulin degradation is initiated by the hormone binding to specific receptors. The hormone-receptor complex is processed, including internalization and degradation of at least some of the hormone-receptor complexes. The enzyme or enzymes involved in the degradative process have not been established, but three systems have been implicated: insulin protease, glutathione insulin transhydrogenase (GIT), and lysosomal enzymes.
Factors associated with surgical management following neoadjuvant therapy in patients with primary HER2-positive breast cancer: results from the NeoALTTO phase III trial
Authors: C. Criscitiello, H.A. Azim, D. Agbor-tarh, E. de Azambuja, M. Piccart, J. Baselga, H. Eidtmann, S. Di Cosimo, I. Bradbury, I.T. Rubio
Journal: Annals of Oncology (2013)