tbuckley/cabot-search huggingface dataset:
Misleading Information on the Properties of Vitamin C
Authors: Steve Hickey, Hilary Roberts
Journal: PLoS Medicine (2005)

Covering 60 years of research without mentioning a paper that highlights fl aws in the literature, in a review, should negate any conclusion.In the Cochrane review by Douglas et al. [1], which is referenced in the Best Practice article by Douglas and Hemilä [2], there was no mention of the revealing paper published last year by Padayatty et al. [3], which shows that three-times greater blood concentration can be achieved with an oral dose of vitamin C than previously thought possible.Since viruses increase the demand for ascorbic acid, the oral doses used in the reviewed studies appear trivial, and would not be expected to produce any positive effect.Compare human oral dose studies to what animals synthesize throughout the day.It is obvious that a single dose of a watersoluble vitamin, regardless of the number of milligrams consumed, will not elevate blood plasma levels enough to produce a preventive or therapeutic effect.
Importance of Blood Pressure Control in Chronic Kidney Disease
Authors: Maura Ravera, Michela Re, Luca Deferrari, Simone Vettoretti, Giacomo Deferrari
Journal: Journal of the American Society of Nephrology (2006)

Arterial hypertension together with proteinuria is one of the most important factors associated with the progression of both diabetic and nondiabetic chronic kidney disease. In this review, the role of hypertension and proteinuria in renal disease progression, the BP target that should be achieved to slow the progression of renal damage, and the influence of baseline and current proteinuria on the renoprotective effects of antihypertensive therapy are discussed thoroughly. The interaction between the renoprotective effects of specific antihypertensive agents—mostly angiotensin-converting enzyme inhibitors and angiotensin receptor blockers—and the level of achieved BP also are evaluated. The body of evidence provided by several studies emphasizes the importance of both lowering BP and inhibiting the renin-angiotensin system as specific goals for renal and cardiovascular protection in chronic kidney disease.
Cerebral edema associated with Gliadel wafers: Two case studies
Authors: Emil L. Weber, Eric A. Goebel
Journal: Neuro-Oncology (2005)

While the introduction of carmustine wafers (Gliadel wafers) into the tumor resection cavity has been shown to be a beneficial therapy for malignant glioma, it is recognized that clinically significant cerebral edema is a potential adverse effect. Following are two clinical case reports demonstrating profound cerebral edema associated with implantation of Gliadel wafers. As a result, one of these individuals had premature death. A brief literature review is provided to assist in explaining the mechanisms by which clinically significant cerebral edema may develop.
Mucopolysaccharides and Sodium Metabolism
Authors: SAUL J. FARBER
Journal: Circulation (1960)

This paper deals with the possible relationship between a native, negatively charged polyelectrolyte, chondroitin sulfate, and sodium metabolism. The physical chemical property of decreased activity of the cations Na, K and Ca in chondroitin sulfate is described. The data of experiments indicating an alteration in the mucoprotein metabolism of the cartilage of the rabbit's ear in response to the depletion of salt are presented.
The antimicrobial protein S100A7/psoriasin enhances the expression of keratinocyte differentiation markers and strengthens the skin's tight junction barrier
Authors: F. Hattori, C. Kiatsurayanon, K. Okumura, H. Ogawa, S. Ikeda, K. Okamoto, F. Niyonsaba
Journal: British Journal of Dermatology (2014)

S100A7/psoriasin is a member of the S100 protein family and is encoded in the epidermal differentiation complex, which contains genes for markers of epidermal differentiation. S100A7/psoriasin is overexpressed in hyperproliferative skin diseases, where it is believed not only to exhibit antimicrobial functions, but also to induce immunomodulatory activities, including chemotaxis and cytokine/chemokine production.To evaluate the effect of S100A7/psoriasin on keratinocyte differentiation and regulation of the tight junction (TJ) barrier.Expression of differentiation markers and TJ proteins in human keratinocytes was determined by real-time polymerase chain reaction and Western blot. The changes in TJ barrier function were assessed by transepithelial electrical resistance and paracellular permeability assays. Glycogen synthase kinase-3 (GSK-3) and mitogen-activated protein kinase (MAPK) activation was analysed by Western blot, whereas β-catenin and E-cadherin activation was evaluated by Western blot and immunofluorescence.S100A7/psoriasin enhanced the expression of several differentiation markers and selectively increased the expression of TJ proteins (e.g. claudins and occludin), which are known to strengthen the TJ barrier. Furthermore, S100A7/psoriasin increased β-catenin and E-cadherin accumulation at cell-cell contact, and enhanced transepithelial electrical resistance while reducing the paracellular permeability of keratinocyte layers. The data suggest that S100A7/psoriasin-mediated regulation of the TJ barrier was via both the GSK-3 and MAPK pathways, as evidenced by the inhibitory effects of inhibitors for GSK-3 and MAPKs.Our finding that S100A7/psoriasin regulates differentiation and strengthens TJ barrier function provides novel evidence that, in addition to antimicrobial and immunoregulatory activities, S100A7/psoriasin is involved in skin innate immunity.
Bacterial protein signals are associated with Crohn’s disease
Authors: Catherine Juste, David P Kreil, Christian Beauvallet, Alain Guillot, Sebastian Vaca, Christine Carapito, Stanislas Mondot, Peter Sykacek, Harry Sokol, Florence Blon, Pascale Lepercq, Florence Levenez, Benoît Valot, Wilfrid Carré, Valentin Loux, Nicolas Pons, Olivier David, Brigitte Schaeffer, Patricia Lepage, Patrice Martin, Véronique Monnet, Philippe Seksik, Laurent Beaugerie, S Dusko Ehrlich, Jean-François Gibrat, Alain Van Dorsselaer, Joël Doré
Journal: Gut (2014)

<h3>Objective</h3> No Crohn's disease (CD) molecular maker has advanced to clinical use, and independent lines of evidence support a central role of the gut microbial community in CD. Here we explore the feasibility of extracting bacterial protein signals relevant to CD, by interrogating myriads of intestinal bacterial proteomes from a small number of patients and healthy controls. <h3>Design</h3> We first developed and validated a workflow—including extraction of microbial communities, two-dimensional difference gel electrophoresis (2D-DIGE), and LC-MS/MS—to discover protein signals from CD-associated gut microbial communities. Then we used selected reaction monitoring (SRM) to confirm a set of candidates. In parallel, we used 16S rRNA gene sequencing for an integrated analysis of gut ecosystem structure and functions. <h3>Results</h3> Our 2D-DIGE-based discovery approach revealed an imbalance of intestinal bacterial functions in CD. Many proteins, largely derived from <i>Bacteroides</i> species, were over-represented, while under-represented proteins were mostly from Firmicutes and some <i>Prevotella</i> members. Most overabundant proteins could be confirmed using SRM. They correspond to functions allowing opportunistic pathogens to colonise the mucus layers, breach the host barriers and invade the mucosae, which could still be aggravated by decreased host-derived pancreatic zymogen granule membrane protein GP2 in CD patients. Moreover, although the abundance of most protein groups reflected that of related bacterial populations, we found a specific independent regulation of bacteria-derived cell envelope proteins. <h3>Conclusions</h3> This study provides the first evidence that quantifiable bacterial protein signals are associated with CD, which can have a profound impact on future molecular diagnosis.
The ITK-SYK Fusion Oncogene Induces a T-Cell Lymphoproliferative Disease in Mice Mimicking Human Disease
Authors: Christine Dierks, Francisco Adrian, Paul Fisch, Hong Ma, Helga Maurer, Dieter Herchenbach, Christine Ulrike Forster, Clara Sprissler, Guoxun Liu, Sabine Rottmann, Gui-Rong Guo, Zirlik Katja, Hendrik Veelken, Markus Warmuth
Journal: Cancer Research (2010)

Abstract Peripheral T-cell lymphomas (PTCL) constitute a major treatment problem with high mortality rates due to the minimal effectiveness of conventional chemotherapy. Recent findings identified ITK-SYK as the first recurrent translocation in 17% of unspecified PTCLs and showed the overexpression of SYK in more than 90% of PTCLs. Here, we show that the expression of ITK-SYK in the bone marrow of BALB/c mice causes a T-cell lymphoproliferative disease in all transplanted mice within 8 weeks after transplantation. The disease was characterized by the infiltration of spleen, lymph nodes, bone marrow, and skin with CD3+CD4+CD8− and CD3+CD4−CD8− ITK-SYK–positive T-cells accompanied by a systemic inflammatory reaction with upregulation of interleukin 5 and INF-γ. ITK-SYK–positive T-cells showed enhanced apoptosis resistance and INF-γ production in vitro. The disease was serially transplantable, inducing clonal T-cell expansion in secondary recipients. The action of ITK-SYK in vivo was dependent on SYK kinase activity and disease development could be inhibited by the treatment of mice with SYK inhibitors. Interestingly, the translocation of ITK-SYK from the membrane to the cytoplasm, using a point mutation in the pleckstrin homology domain (ITK-SYK R29C), did not abolish, but rather, enhanced disease development in transplanted mice. CBL binding was strongly enhanced in membrane-associated ITK-SYK E42K and was causative for delayed disease development. Our results show that ITK-SYK causes a T-cell lymphoproliferative disease in mice, supporting its role in T-cell lymphoma development in humans. Therefore, pharmacologic inhibition of SYK in patients with U-PTCLs carrying the ITK-SYK fusion protein might be an effective treatment strategy. Cancer Res; 70(15); 6193–204. ©2010 AACR.
Matuzumab Short-Term Therapy in Experimental Pancreatic Cancer: Prolonged Antitumor Activity in Combination with Gemcitabine
Authors: Axel Kleespies, Ivan Ischenko, Martin E. Eichhorn, Hendrik Seeliger, Christiane Amendt, Ole Mantell, Karl-Walter Jauch, Christiane J. Bruns
Journal: Clinical Cancer Research (2008)

The epidermal growth factor receptor ErbB-1 is commonly expressed in pancreatic cancer and ErbB-1 targeting has shown promising results. We wanted to evaluate matuzumab (EMD72000), a fully humanized ErbB-1-specific monoclonal antibody in combination with gemcitabine in experimental pancreatic cancer.Using the human pancreatic cancer cell line L3.6pl, we investigated matuzumab in vitro and in vivo. ErbB-1 phosphorylation and downstream pathway activation were evaluated by Western blot. Proliferation and migration assays and fluorescence-activated cell sorting analysis were done. For in vivo studies, we used an orthotopic nude mice model in which 40 mg/kg of matuzumab+/-100 mg/kg of gemcitabine were administered twice weekly. Different treatment durations (7, 14, 21, and 25 days) and varying time points of treatment initiation (days 8, 15, 22, and 29) were evaluated. Ki67, CD31, and phosphorylated p44/42 mitogen-activated protein kinase (MAPK) immunohistochemistry were done.ErbB-1 phosphorylation and downstream MAPK and AKT signaling were significantly reduced by matuzumab. Matuzumab significantly inhibited proliferation and migration in vitro, and induced tumor cell apoptosis in a dose-dependant manner. Matuzumab therapy significantly lowered tumor volume in vivo, reduced lymph node and liver metastases, and decreased microvessel density and tumor cell proliferation. These effects were significantly enhanced when gemcitabine was added. A significant and prolonged antitumor activity was even evident with short-term therapy (7 days) and with a late onset of therapy (day 22 after tumor cell injection).Matuzumab is an effective agent with long-lasting antiproliferative, proapoptotic, antiangiogenic, and antimetastatic activity in human pancreatic cancer models. These effects might be potentiated by gemcitabine.
Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients
Authors: R Gunnarsson, A Isaksson, M Mansouri, H Göransson, M Jansson, N Cahill, M Rasmussen, J Staaf, J Lundin, S Norin, A M Buhl, K E Smedby, H Hjalgrim, K Karlsson, J Jurlander, G Juliusson, R Rosenquist
Journal: Leukemia (2009)
Semaphorin 3F, a chemorepulsant for endothelial cells, induces a poorly vascularized, encapsulated, nonmetastatic tumor phenotype
Authors: Diane R. Bielenberg, Yasuhiro Hida, Akio Shimizu, Arja Kaipainen, Michael Kreuter, Caroline Choi Kim, Michael Klagsbrun
Journal: Journal of Clinical Investigation (2004)

Melanoma is the most lethal skin cancer. Most deaths from melanoma result from metastases. Semaphorins have been shown to inhibit neuronal and endothelial cell migration, but the effects of semaphorins on tumor metastasis have not been documented. We found that semaphorin 3F (SEMA3F) was markedly downregulated in highly metastatic human cell lines in vitro and in vivo, which suggested that it may be a metastasis inhibitor. Metastatic human melanoma cells were transfected with SEMA3F and implanted into mice; the resultant tumors did not metastasize. Rather, the primary tumors resembled benign nevi characterized by large areas of apoptosis, diminished vascularity, inhibition of hyperplasia in overlying epidermal cells, and encapsulated tumor borders delineated by thick layers of fibroblasts and collagen matrix. This phenotype is in stark contrast to highly invasive, vascular mock-transfected tumors. In vitro, tumor cells expressing SEMA3F had a diminished capacity to adhere and migrate on fibronectin. Consistent with semaphorin-mediated chemorepulsion of neurons, tumor cells expressing SEMA3F were chemorepulsive for vascular and lymphatic endothelial cells expressing neuropilin-2 (NRP2), a novel mechanism for a tumor angiogenesis inhibitor. The repulsive activity was abrogated by NRP2 RNA interference. Together these results indicate that SEMA3F is a potent metastasis inhibitor that targets both tumor and stromal cells and raise the possibility of SEMA3F having therapeutic potential.
A New Look at T Cells
Authors: Andrew J. McMichael, Christopher A. O'Callaghan
Journal: The Journal of Experimental Medicine (1998)

Recent technological advances have shed unexpected light on the CD8+ T cell responses to pathogens and have raised concerns that a familiar quantitative assay is wrong. The most exciting of the new advances is the MHC tetramer. Ever since T cells were first identified, there have been attempts to
Sexuality Among Middle-Aged and Older Adults With Diagnosed and Undiagnosed Diabetes
Authors: Stacy Tessler Lindau, Hui Tang, Ada Gomero, Anusha Vable, Elbert S. Huang, Melinda L. Drum, Dima M. Qato, Marshall H. Chin
Journal: Diabetes Care (2010)

To describe sexual activity, behavior, and problems among middle-age and older adults by diabetes status.This was a substudy of 1,993 community-residing adults, aged 57-85 years, from a cross-sectional, nationally representative sample (N = 3,005). In-home interviews, observed medications, and A1C were used to stratify by diagnosed diabetes, undiagnosed diabetes, or no diabetes. Logistic regression was used to model associations between diabetes conditions and sexual characteristics, separately by gender.The survey response rate was 75.5%. More than 60% of partnered individuals with diagnosed diabetes were sexually active. Women with diagnosed diabetes were less likely than men with diagnosed diabetes (adjusted odds ratio 0.28 [95% CI 0.16-0.49]) and other women (0.63 [0.45-0.87]) to be sexually active. Partnered sexual behaviors did not differ by gender or diabetes status. The prevalence of orgasm problems was similarly elevated among men with diagnosed and undiagnosed diabetes compared with that for other men, but erectile difficulties were elevated only among men with diagnosed diabetes (2.51 [1.53 to 4.14]). Women with undiagnosed diabetes were less likely to have discussed sex with a physician (11%) than women with diagnosed diabetes (19%) and men with undiagnosed (28%) or diagnosed (47%) diabetes.Many middle-age and older adults with diabetes are sexually active and engage in sexual behaviors similarly to individuals without diabetes. Women with diabetes were more likely than men to cease all sexual activity. Older women with diabetes are as likely to have sexual problems but are significantly less likely than men to discuss them.
Particle deposition and resistance in the noses of adults and children
Authors: MH Becquemin, DL Swift, A Bouchikhi, M Roy, A Teillac
Journal: European Respiratory Journal (1991)

Nasal filter efficiency for particles has been described by several authors as showing large individual variations, probably somehow related to airflow resistance. Twelve children, aged 5.5-11.5 yrs and 8 aged 12-15 yrs were compared to a group of ten adults. Deposition of polystyrene beads (1, 2.05, 2.8 microns mass median aerodynamic diameter (MMAD] was measured by comparing inhaled aerosols and exhaled air concentrations, for both nose and mouth breathing. Ventilation was controlled to scale breathing patterns appropriate for each age either at rest or during moderate exercise to allow comparison between subjects in similar physiological conditions. Anterior nasal resistance (as a function of flow rate) and standard lung function were measured for each subject. For the same inhalation flow rate of 0.300 l.s-1, children had much higher nasal resistances than the adults, 0.425 +/- 0.208 kPa.l.1.s under 12 yrs, 0.243 +/- 0.080 kPa.l.1.s over 12 yrs and 0.145 +/- 0.047 kPa.l.1.s in adults. Individually, nasal deposition increased with particle size, ventilation flow rate and nasal resistance, from rest to exercise. The average nasal deposition percentages were lower in children than in adults, in similar conditions: at rest, 12.9 and 11.7 versus 15.6 for 1 microns; 13.3 and 15.9 versus 21.6 for 2.05 microns; 11 and 17.7 versus 20 for 2.8 microns. This was even more significant during exercise, 17.8 and 15.9 versus 29.2 for 1 microns; 21.3 and 18.4 versus 34.7 for 2.05 microns; 16 and 16.1 versus 36.8 for 2.8 microns.(ABSTRACT TRUNCATED AT 250 WORDS)
The T cell receptor repertoire influences V beta element usage in response to myoglobin.
Authors: G Ruberti, A Gaur, C G Fathman, A M Livingstone
Journal: The Journal of Experimental Medicine (1991)

T cell clones recognizing the sperm whale myoglobin (SpWMb) epitope 110-121 in association with H-2d major histocompatibility complex class II molecules display a very limited heterogeneity of T cell receptor (TCR) V beta usage in DBA/2 mice. All clones previously tested used the same V beta 8.2 gene segment and very restricted junctional regions. To investigate the significance of this observation in vivo, we immunized DBA/2 mice with the intact SpW Mb protein or peptide 110-121. Only the V beta 8+ T cells showed any significant response to the 110-121 epitope. The response to peptide 110-121 was then analyzed in mice which, either as a consequence of antibody depletion or through genetic deletion of TCR V beta genes, lacked V beta 8+ peripheral T cells. DBA/2 mice depleted of V beta 8+ T cells by antibody treatment responded poorly to the 110-121 peptide, and only at high antigen concentrations. In contrast, DBA/2V beta a mice (homozygous for a deletion of multiple V beta gene segments including the V beta 8 family) made a response at least as great as that made by DBA/2 mice, even though the DBA/2V beta a mice had a very restricted TCR V beta repertoire compared with DBA/2 mice. Mechanisms which might determine differences in the 110-121 specific response of DBA/2, DBA/2V beta a and F23.1-treated DBA/2 mice are discussed.
Downregulation of Delayed Rectifier K <sup>+</sup> Currents in Dogs With Chronic Complete Atrioventricular Block and Acquired Torsades de Pointes
Authors: Paul G. A. Volders, Karin R. Sipido, Marc A. Vos, Roel L. H. M. G. Spätjens, Jet D. M. Leunissen, Edward Carmeliet, Hein J. J. Wellens
Journal: Circulation (1999)

Background —Acquired QT prolongation enhances the susceptibility to torsades de pointes (TdP). Clinical and experimental studies indicate ventricular action potential prolongation, increased regional dispersion of repolarization, and early afterdepolarizations as underlying factors. We examined whether K + -current alterations contribute to these proarrhythmic responses in an animal model of TdP: the dog with chronic complete atrioventricular block (AVB) and biventricular hypertrophy. Methods and Results —The whole-cell K + currents I TO1 , I K1 , I Kr , and I Ks were recorded in left (LV) and right (RV) ventricular midmyocardial cells from dogs with 9±1 weeks of AVB and controls with sinus rhythm. I TO1 density and kinetics and I K1 outward current were not different between chronic AVB and control cells. I Kr had a similar voltage dependence of activation and time course of deactivation in chronic AVB and control. I Kr density was similar in LV myocytes but smaller in RV myocytes (−45%) of chronic AVB versus control. For I Ks , voltage-dependence of activation and time course of deactivation were similar in chronic AVB and control. However, I Ks densities of LV (−50%) and RV (−55%) cells were significantly lower in chronic AVB than control. Conclusions —Significant downregulation of delayed rectifier K + current occurs in both ventricles of the dog with chronic AVB. Acquired TdP in this animal model with biventricular hypertrophy is thus related to intrinsic repolarization defects.
Emerging Applications of Metabolomic and Genomic Profiling in Diabetic Clinical Medicine
Authors: Aine M. McKillop, Peter R. Flatt
Journal: Diabetes Care (2011)

Clinical and epidemiological metabolomics provides a unique opportunity to look at genotype-phenotype relationships as well as the body\x{2019}s responses to environmental and lifestyle factors. Fundamentally, it provides information on the universal outcome of influencing factors on disease states and has great potential in the early diagnosis, therapy monitoring, and understanding of the pathogenesis of disease. Diseases, such as diabetes, with a complex set of interactions between genetic and environmental factors, produce changes in the body\x{2019}s biochemical profile, thereby providing potential markers for diagnosis and initiation of therapies. There is clearly a need to discover new ways to aid diagnosis and assessment of glycemic status to help reduce diabetes complications and improve the quality of life. Many factors, including peptides, proteins, metabolites, nucleic acids, and polymorphisms, have been proposed as putative biomarkers for diabetes. Metabolomics is an approach used to identify and assess metabolic characteristics, changes, and phenotypes in response to influencing factors, such as environment, diet, lifestyle, and pathophysiological states. The specificity and sensitivity using metabolomics to identify biomarkers of disease have become increasingly feasible because of advances in analytical and information technologies. Likewise, the emergence of high-throughput genotyping technologies and genome-wide association studies has prompted the search for genetic markers of diabetes predisposition or susceptibility. In this review, we consider the application of key metabolomic and genomic methodologies in diabetes and summarize the established, new, and emerging metabolomic and genomic biomarkers for the disease. We conclude by summarizing future insights into the search for improved biomarkers for diabetes research and human diagnostics.