tbuckley/cabot-search huggingface dataset:
Cytometric profiling in various clinical forms of multiple sclerosis with respect to CD21+, CD32+, and CD35+ B and T cells
Authors: Ali Zandieh, Maryam Izad, Mohammad Fakhri, Hamed Amirifard, Zahra Khazaeipour, Mohammad Hosein Harirchian
Journal: Translational Neurodegeneration (2013)

We aimed to evaluate the frequency of various types of B and T cells expressing CD21, CD32, and CD35 in multiple sclerosis (MS) clinical courses.Peripheral blood mononuclear cell from 30 MS patients (17 relapsing remitting [RRMS], six secondary progressive [SPMS], and seven primary progressive MS [PPMS]) and 18 healthy subjects were analyzed. All patients were in acute attack. Healthy controls were matched for age and gender ratio. The frequencies of various subsets of B and T cells were determined using flow cytometry.The frequency of CD4+T cells was lower in MS patients compared to control subjects (41.14 ± 9.45% vs. 46.88 ± 6.98%, respectively, P < 0.05). The CD32+ fraction of CD4+T cells and the CD21+ fraction of CD8+T cells were higher in MS patients (2.85 ± 3.72% vs. 1.06 ± 0.62% for CD32+CD4+T cells, 2.71 ± 1.86% vs. 1.16 ± 0.99% for CD21+CD8+T cells in MS patients and control subjects, respectively, P < 0.05). After dividing subjects by type of MS course, higher values of these two T cell subsets were found in SPMS patients compared to control subjects (P < 0.05). Further, RRMS patients had lower levels of CD32+CD4+T cells than SPMS patients and also they had lower levels of CD32+CD8+T cells than PPMS patients (P < 0.05). However, neither the expression of CD35 on T cells nor the various B cell subsets were statistically different between the compared groups.Our findings demonstrate that T cell subsets expressing CD21 and CD32 may differ with respect to the presence or clinical forms of MS disease. By contrast, CD35+T cells and different subsets of B cells are not altered in various MS clinical courses.
The Roles of Growth Arrest DNA Damage-Inducible Gene 45Γ (GADD45Γ) Expression in Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma (HCC) Cells
Authors: C. Hsu, D.-L. Ou, C.-W. Shiau, H.-H. Fan, S.-C. Liao, Y.-Y. Lin, C.-H. Hsu, A.-L. Cheng, L.-C. Lu, Y.-Y. Shao, M.-S. Hsieh, C.-C. Huang, M. Ikeda, Y. Arai, S. J. Park, Y. Takeuchi, H. Anai, J. K. Kim, Y. Inaba, T. Aramaki, S. H. Kwon, S. Yamamoto, T. Okusaka, H. J. Lee, J.-K. Min, K. Lee, D. G. Lee, Z. L. Liang, S. M. Huang, Y. S. Oh, H. Y. Kim, D. Y. Jo, J.-M. Kim, K. Ikezawa, M. Kanai, T. Ajiki, T. Tsukamoto, H. Toyokawa, H. Terajima, H. Furuyama, H. Nagano, I. Ikai, N. Kuroda, M. Awane, T. Ochiai, S. Takemura, A. Miyamoto, T. Ioka, S. H. Lee, B. S. Lee, S. E. Jang, D.-W. Ahn, J.-H. Hwang, D. W. Hwang, J. Y. Cho, Y.-S. Yoon, H.-S. Han, S. Ahn
Journal: Annals of Oncology (2012)
Variations in the functional electrical coupling between the subendocardial Purkinje and ventricular layers of the canine left ventricle.
Authors: D A Rawling, R W Joyner, E D Overholt
Journal: Circulation Research (1985)

Action potential propagation from the subendocardial Purkinje network into the ventricular muscle is an essential link in cardiac activation. Studies of papillary muscles have indicated that ventricular muscle activation by the Purkinje network occurs only at discrete, localized regions near the papillary muscle base. Over the rest of the endocardial surface, however, the spatial distribution of these subendocardial Purkinje to ventricular muscle connections has been less well defined. We therefore studied in vitro 12 canine left ventricular preparations (eight from the septum, four from the lateral wall), using a high-density (1-mm spacings), high-resolution extracellular mapping technique to determine the subendocardial Purkinje and ventricular muscle activation sequences. These studies show that the distribution of subendocardial Purkinje to ventricular muscle electrical coupling is spatially inhomogeneous, and that the junctional regions themselves have variable degrees of electrical coupling. We also attempted to determine whether ventricular muscle coupling to the Purkinje network might influence Purkinje network conduction velocity. We found that on the papillary muscle apex, a region without direct Purkinje to ventricular muscle propagation, Purkinje network conduction velocity was slowed, suggesting that the Purkinje network might be electrically loaded by the underlying ventricular muscle. Finally, we performed numerical simulations using a model consisting of two layers of excitable cells to evaluate the effects that different electrical coupling patterns and/or different coupling resistivities between the two layers might have on activation of each layer. These simulation studies suggest that a coupling pattern having discrete junctional sites between the two layers (similar to our findings for subendocardial Purkinje to ventricular muscle coupling) is beneficial, as this arrangement allows more rapid activation of both layers by minimizing electrical loading of the thin Purkinje layer by the thicker ventricular muscle layer.
Enhancement of Folate Receptor α Expression in Tumor Cells Through the Glucocorticoid Receptor: A Promising Means to Improved Tumor Detection and Targeting
Authors: Thuyet Tran, Aymen Shatnawi, Xuan Zheng, Karen M.M. Kelley, Manohar Ratnam
Journal: Cancer Research (2005)

Abstract The utility of the folate receptor (FR) type α, in a broad range of targeted therapies and as a diagnostic serum marker in cancer, is confounded by its variable tumor expression levels. FR-α, its mRNA and its promoter activity were coordinately up-regulated by the glucocorticoid receptor (GR) agonist, dexamethasone. Optimal promoter activation which occurred at &amp;lt;50 nmol/L dexamethasone was inhibited by the GR antagonist, RU486, and was enhanced by coactivators, supporting GR mediation of the dexamethasone effect. The dexamethasone response of the FR-α promoter progressed even after dexamethasone was withdrawn, but this delayed effect required prior de novo protein synthesis indicating an indirect regulation. The dexamethasone effect was mediated by the G/C-rich (Sp1 binding) element in the core P4 promoter and was optimal in the proper initiator context without associated changes in the complement of major Sp family proteins. Histone deacetylase (HDAC) inhibitors potentiated dexamethasone induction of FR-α independent of changes in GR levels. Dexamethasone/HDAC inhibitor treatment did not cause de novo FR-α expression in a variety of receptor-negative cells. In a murine HeLa cell tumor xenograft model, dexamethasone treatment increased both tumor-associated and serum FR-α. The results support the concept of increasing FR-α expression selectively in the receptor-positive tumors by brief treatment with a nontoxic dose of a GR agonist, alone or in combination with a well-tolerated HDAC inhibitor, to increase the efficacy of various FR-α–dependent therapeutic and diagnostic applications. They also offer a new paradigm for cancer diagnosis and combination therapy that includes altering a marker or a target protein expression using general transcription modulators.
External pancreatic secretion after bombesin infusion in man.
Authors: N Basso, S Giri, G Improta, E Lezoche, P Melchiorri, M Percoco, V Speranza
Journal: Gut (1975)

The effect of bombesin on external pancreatic secretion was studied in seven healthy volunteers and intwo patients with a two-thirds gastrectomy and a pancreatic fistula. After bombesin infusion (15 ng/kg/min), gastrin levels were significantly raised in all volunteers, but remained at basal levels in the gastrectomized patients. Bombesin was effective in stimulating pancreatic secretion in all patients. The volume of secretion increased tow-fold when compared with basal volume. Amylase and trypsin concentrations and outputs in the duodenal juice were greatly agumented (amylase concentration: basal, 70 dye U/ml; post-bombesin, 620 dye U/ml. Amylase output: basal, 1000 dye U/15 min; post-bombesin, 15,800 dye U/15 min). Secretin, when administered in conjunction with bombesin, partially inhibited its secretory effect. Bicarbonate secretion was slightly stimulated by bombesin, but at a very low level. A similar pattern of results was obtained in the two gastrectomized patients. In man, bombesin exerts an effect on pancreatic secretion that mimics the effect of CCK-PZ, thus confirming the results obtained in the experimental animal. Gastrin does not play a fundamental role in this phenomenon.
Hydrolysis of pyridoxal-5'-phosphate in plasma in conditions with raised alkaline phosphate.
Authors: B B Anderson, H O'Brien, G E Griffin, D L Mollin
Journal: Gut (1980)

Hydrolysis of pyridoxal phosphate in plasma was demonstrated in patients with liver disease and other conditions with raised alkaline phosphatase, and this usually closely paralleled the alkaline phosphatase level, whether of liver or bone origin. The endogenous plasma pyridoxal phosphate was inversely related to the alkaline phosphatase, and plasma hydrolysis of pyridoxal phosphate may at least in part be responsible. Very large doses of vitamin B6 may be necessary to compensate for this hydrolysis.
S52 The role of the Receptor for Advanced End Products (RAGE) in Acute Lung Injury (ALI)
Authors: B. A. Thompson, C. W. Stitt, D. F. McAuley, C. M. O'Kane
Journal: Thorax (2010)

<h3>Introduction</h3> RAGE is expressed by both alveolar epithelial and endothelial cells. The receptor can bind to pro-inflammatory ligands, including HMGB1 which is elevated in ALI. RAGE negative mice show a reduced inflammatory response when challenged with LPS. We hypothesised that RAGE activation in the pulmonary circulation propagates inflammation in ALI and that soluble RAGE (sRAGE) can act as a scavenger receptor, reducing RAGE-mediated inflammation. <h3>Aim</h3> To investigate HMGB1 RAGE-dependent activation of pulmonary microvascular endothelial cells, and resultant production of inflammatory cytokines and tissue-destructive proteases in a model of ALI. <h3>Methods</h3> Primary HPMECs (human pulmonary microvascular endothelial cells) were stimulated with clinically relevant concentrations of HMGB1. MAPK phosphorylation was assessed by Western Blot. Supernatants collected at 72 h were analysed by ELISA for IL-8, Tissue Inhibitors of Metalloproteinases (TIMPs)-1 and -2. Experiments were repeated both with a RAGE-blocking antibody and in the presence of sRAGE. <h3>Results</h3> HMGB1 increased phosphorylation of ERK1/2 at 15 min and p38 at 30 min after stimulation HMGB1 increased IL-8 secretion (from 6.46 ng/ml to 8.75 ng/ml, p&lt;0.01) and significant decrease in TIMP-1 secretion (from 19.79 ng/ml to 16.9 ng/ml, p&lt;0.05) at 72 h. MAPK activation, IL-8 increase and TIMP-1 decrease was significantly reversed in the presence of sRAGE (p&lt;0.05) (Abstract S52 Figure 1). Incubating cells with a RAGE blocking antibody inhibited MAPK phosphorylation by HMGB1. <h3>Conclusions</h3> Data suggest that RAGE ligation leads to an increase in pulmonary endothelial cell activation and IL-8 release. <i>In vivo</i> this would increase inflammatory cell influx into the pulmonary environment, propagating inflammation. This is combined with a decrease in TIMP protection potentially increasing degradation of the basement membrane by functionally unopposed proteinases. That these changes can be partially rescued using sRAGE shows that it could potentially decrease inflammatory damage in ALI.
Impact of IL-6 receptor inhibition on human memory B cells in vivo: impaired somatic hypermutation in preswitch memory B cells and modulation of mutational targeting in memory B cells
Authors: K. Muhammad, P. Roll, T. Seibold, S. Kleinert, H. Einsele, T. Dorner, H.-P. Tony
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> Interleukin 6 (IL-6) receptor (IL-6R) inhibition by tocilizumab is a novel anti-inflammatory therapy for rheumatoid arthritis (RA) patients. As IL-6 is a late differentiation factor of B cells the authors asked if IL-6R inhibition impacts on the mutational differentiation of human memory B-cell antigen receptors in vivo. <h3>Methods</h3> 1733 immunoglobulin receptors (IgR) of single cell sorted preswitch and postswitch memory B cells were prospectively analysed from 11 RA patients under IL-6R inhibition (7 patients) or tumour necrosis factor (TNF) inhibition (4 patients). <h3>Results</h3> The results show a reduced mutational frequency in IgR of preswitch memory B cells (p=0.0001) during week 12, week 24 and 1 year of tocilizumab therapy. Mutational hotspot RGYW/WRCY motifs indicated significantly decreased targeting (p&lt;0.05) in preswitch and postswitch memory B cells. Anti-TNFα therapy had no effect on mutational frequency and mutational hotspot targeting motifs in memory B-cell subsets. <h3>Conclusions</h3> These data suggest that preswitch and postswitch memory B cells are susceptible to IL-6R inhibition in vivo. Acquisition of mutations was substantially altered in preswitch memory B cells, while targeting of mutational hotspots affected preswitch and postswitch memory B cells. The results indicate that preswitch and postswitch memory B cells have a differential dependence on the IL-6/IL-6R system for differentiation, which can be influenced by tocilizumab in vivo.
Topical spermine and putrescine stimulated DNA synthesis in the hairless mouse epidermis
Authors: RICHARD W. GANGE, PETER R. DEQUOY
Journal: British Journal of Dermatology (1980)

Polyamines were applied topically to the skin of the hairless mouse. Putrescine stimulated the incorporation of thymidine after a 24-h application period. The effect of polyamines upon skin pretreated with a potent topical steroid was also examined; in this model thymidine incorporation was stimulated by both spermine and putrescine. Pretreatment was performed in order to reduce endogenous polyamine biosynthesis and increase the sensitivity of the epidermis to exogenous polyamines. Depletion of the activity of ornithine decarboxylase, the rate-limiting polyamine biosynthetic enzyme, by topical steroids was confirmed in the hairless mouse following induction of the enzyme by UV-B. The results are consistent with those of in vitro studies suggesting a role for polyamines in the control of DNA synthesis; the effect of corticosteroids upon proliferative skin disorders may be mediated through this mechanism.
Will recording of lung function fluctuation open the door to internet-guided treatment of asthma?
Authors: M. Kupczyk, S.-E. Dahlen
Journal: Thorax (2011)

Asthma is a heterogeneous and variable chronic disease. Although it is very common, affecting more than 5% of adults and 10% of children in most parts of the world, asthma remains a great challenge both with respect to proper diagnosis and the means proactively to adjust treatment in a disease that is characterised by periods of worsening and remissions. The diagnostic difficulties are mirrored in the complex definition of asthma which comprises four domains: airway obstruction, symptoms, airway inflammation and airway hyper-responsiveness.1 None of these domains alone is sufficient for diagnosis but together they describe the clinical and pathophysiological face of the syndrome of asthma. Nowadays it is widely accepted that the main goal of asthma treatment is to reach and maintain good control of the disease and, in particular, to prevent and limit periods of flare-ups. In order to improve treatment there is a great need to provide the doctor with a better objective understanding of the level of disease control over time during the patient's daily activities rather than only judging from history and examinations at a visit to the clinic. There is also a desire to find ways to give patients more effective support for self-management, as asthma is a disease where environmental triggers and lifestyle factors play a significant part. Taken together, asthma is the perfect case for internet-governed personalised medicine. It remains, however, to implement this vision because sufficiently sensitive and specific measures have not been established.

In previous editions of the Global Initiative for Asthma (GINA) recommendations for asthma treatment, strong emphasis was placed on lung function measurement. Recording of forced expiratory volume in 1 s (FEV1) and peak expiratory flow …
Exercise and associated dietary extremes impact on gut microbial diversity
Authors: Siobhan F Clarke, Eileen F Murphy, Orla O'Sullivan, Alice J Lucey, Margaret Humphreys, Aileen Hogan, Paula Hayes, Maeve O'Reilly, Ian B Jeffery, Ruth Wood-Martin, David M Kerins, Eamonn Quigley, R Paul Ross, Paul W O'Toole, Michael G Molloy, Eanna Falvey, Fergus Shanahan, Paul D Cotter
Journal: Gut (2014)

The commensal microbiota, host immunity and metabolism participate in a signalling network, with diet influencing each component of this triad. In addition to diet, many elements of a modern lifestyle influence the gut microbiota but the degree to which exercise affects this population is unclear. Therefore, we explored exercise and diet for their impact on the gut microbiota.Since extremes of exercise often accompany extremes of diet, we addressed the issue by studying professional athletes from an international rugby union squad. Two groups were included to control for physical size, age and gender. Compositional analysis of the microbiota was explored by 16S rRNA amplicon sequencing. Each participant completed a detailed food frequency questionnaire.As expected, athletes and controls differed significantly with respect to plasma creatine kinase (a marker of extreme exercise), and inflammatory and metabolic markers. More importantly, athletes had a higher diversity of gut micro-organisms, representing 22 distinct phyla, which in turn positively correlated with protein consumption and creatine kinase.The results provide evidence for a beneficial impact of exercise on gut microbiota diversity but also indicate that the relationship is complex and is related to accompanying dietary extremes.
WHO-EORTC classification for cutaneous lymphomas
Authors: Rein Willemze, Elaine S. Jaffe, Günter Burg, Lorenzo Cerroni, Emilio Berti, Steven H. Swerdlow, Elisabeth Ralfkiaer, Sergio Chimenti, José L. Diaz-Perez, Lyn M. Duncan, Florent Grange, Nancy Lee Harris, Werner Kempf, Helmut Kerl, Michael Kurrer, Robert Knobler, Nicola Pimpinelli, Christian Sander, Marco Santucci, Wolfram Sterry, Maarten H. Vermeer, Janine Wechsler, Sean Whittaker, Chris J.L.M. Meijer
Journal: Blood (2005)
Effect of protriptyline on ventilatory responses to hypercapnia and asphyxia in normal subjects
Authors: AK Simonds, N Carroll, MA Branthwaite, NA Saunders
Journal: European Respiratory Journal (1989)

A double-blind crossover study was undertaken to assess the effect of protriptyline on ventilatory responses in normal subjects. Seven subjects received in random order placebo, 10 mg and 20 mg protriptyline daily for 2 weeks. Measurements of hypercapnic ventilatory response (HCVR) and asphyxial hypoxic ventilatory response (HVR) were made before treatment, 6-8 h after the first dose, and after 2 weeks treatment. Mean HCVR and HVR following 10 mg and 20 mg protriptyline did not differ significantly from measurements on placebo, neither for the single dose study or after 2 weeks.
The Enamelin Genes in Lizard, Crocodile, and Frog and the Pseudogene in the Chicken Provide New Insights on Enamelin Evolution in Tetrapods
Authors: N. Al-Hashimi, A.-G. Lafont, S. Delgado, K. Kawasaki, J.-Y. Sire
Journal: Molecular Biology and Evolution (2010)

Enamelin (ENAM) has been shown to be a crucial protein for enamel formation and mineralization. Previous molecular analyses have indicated a probable origin early in vertebrate evolution, which is supported by the presence of enamel/enameloid tissues in early vertebrates. In contrast to these hypotheses, ENAM was only characterized in mammals. Our aims were to 1) look for ENAM in representatives of nonmammalian tetrapods, 2) search for a pseudogene in the chicken genome, and 3) see whether the new sequences could bring new information on ENAM evolution. Using in silico approach and polymerase chain reaction, we obtained and characterized the messenger RNA sequences of ENAM in a frog, a lizard, and a crocodile; the genomic DNA sequences of ENAM in a frog and a lizard; and the putative sequence of chicken ENAM pseudogene. The comparison with mammalian ENAM sequences has revealed 1) the presence of an additional coding exon, named exon 8b, in sauropsids and marsupials, 2) a simpler 5'-untranslated region in nonmammalian ENAMs, 3) many sequence variations in the large exons while there are a few conserved regions in small exons, and 4) 25 amino acids that have been conserved during 350 million years of tetrapod evolution and hence of crucial biological importance. The chicken pseudogene was identified in a region that was not expected when considering the gene synteny in mammals. Together with the location of lizard ENAM in a homologous region, this result indicates that enamel genes were probably translocated in an ancestor of the sauropsid lineage. This study supports the origin of ENAM earlier in vertebrate evolution, confirms that tooth loss in modern birds led to the invalidation of enamel genes, and adds information on the important role played by, for example, the phosphorylated serines and the glycosylated asparagines for correct ENAM functions.
Regulation of Akt Signaling by Sirtuins
Authors: Vinodkumar B. Pillai, Nagalingam R. Sundaresan, Mahesh P. Gupta
Journal: Circulation Research (2014)

Cardiac hypertrophy is a multifactorial disease characterized by multiple molecular alterations. One of these alterations is change in the activity of Akt, which plays a central role in regulating a variety of cellular processes ranging from cell survival to aging. Akt activation is mainly achieved by its binding to phosphatidylinositol (3,4,5)-triphosphate. This results in a conformational change that exposes the kinase domain of Akt for phosphorylation and activation by its upstream kinase, 3-phosphoinositide-dependent protein kinase 1, in the cell membrane. Recent studies have shown that sirtuin isoforms, silent information regulator (SIRT) 1, SIRT3, and SIRT6, play an essential role in the regulation of Akt activation. Although SIRT1 deacetylates Akt to promote phosphatidylinositol (3,4,5)-triphosphate binding and activation, SIRT3 controls reactive oxygen species-mediated Akt activation, and SIRT6 transcriptionally represses Akt at the level of chromatin. In the first part of this review, we discuss the mechanisms by which sirtuins regulate Akt activation and how they influence other post-translational modifications of Akt. In the latter part of the review, we summarize the implications of sirtuin-dependent regulation of Akt signaling in the control of major cellular processes such as cellular growth, angiogenesis, apoptosis, autophagy, and aging, which are involved in the initiation and progression of several diseases.
A rare cause of bloody diarrhoea
Authors: Emma L Culver, Christopher Winearls, Ian Roberts, Satish Keshav
Journal: Gut (2011)

A 67-year-old woman presented with a 6-week history of progressive abdominal distension. Her clinical examination revealed a palpable pelvic mass. She underwent total abdominal hysterectomy, salpingo-oophorectomy and removal of a 3 kg ovarian cystadenoma. Postoperatively she had renal impairment; urine microscopy revealed red cell casts and renal biopsy demonstrated a segmental crescentic necrotising glomerulonephritis. This was successfully treated with pulsed steroids and cyclophosphamide. Three weeks later, she developed breathlessness, with fleeting pulmonary infiltrates on chest radiography, and was treated with plasmaphaeresis with resolution of symptoms.

She was referred to the gastroenterology department with a 2-week history of lower abdominal pain and bloody diarrhoea with urgency and frequency of eight times a day, preceded by 2 months of non-bloody loose stools. Physical examination revealed a sinus tachycardia, low-grade fever and lower abdominal tenderness without guarding. …