tbuckley/cabot-search huggingface dataset:
Fas Signaling in Thyroid Carcinomas Is Diverted from Apoptosis to Proliferation
Authors: Constantine S. Mitsiades, Vassiliki Poulaki, Galinos Fanourakis, Elias Sozopoulos, Douglas McMillin, Zhaoqin Wen, Gerassimos Voutsinas, Sophia Tseleni-Balafouta, Nicholas Mitsiades
Journal: Clinical Cancer Research (2006)

The death receptor Fas is present in thyroid carcinomas, yet fails to trigger apoptosis. Interestingly, Fas has been reported to be actually overexpressed in papillary thyroid carcinomas, suggesting that it may confer a survival advantage.We investigated the expression and activation status of Fas pathway mediators in thyroid carcinoma cell lines and tumor specimens.All cell lines tested express Fas-associated death domain, procaspase-8, procaspase-9, and procaspase-3; resistance to Fas-mediated apoptosis could not be attributed to lack of any of these apoptosis mediators. Moreover, Fas death domain mutations were not found in our study. The proteasome inhibitors MG132 and PS-341 (bortezomib, Velcade), which lead to accumulation of the nuclear factor kappaB (NF-kappaB) inhibitor IkappaB, did not sensitize SW579 cells to Fas-mediated apoptosis, suggesting that resistance to Fas-mediated apoptosis is not due to proteasome or NF-kappaB activity. Cross-linking of Fas in vitro induced recruitment of Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (FLIP) instead of procaspase-8. Inhibition of FLIP expression with a FLIP antisense oligonucleotide resulted in significant sensitization to Fas-mediated apoptosis. Fas cross-linking promoted BrdUrd incorporation; activated the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase, NF-kappaB, and activator protein-1 pathways in thyroid carcinoma cells in vitro; and protected cells from tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. We also found that good prognosis papillary thyroid carcinoma specimens exhibited higher immunoreactivity for cleaved (activated) caspase-8 than poor prognosis tumors.In thyroid carcinomas, the proteolytic cleavage and activation of caspase-8 depends on the balance between expression levels for procaspase-8 and FLIP and correlates with favorable clinical prognosis. Fas may actually stimulate proliferation and confer a survival advantage to thyroid cancer cells.
Recommendations for Management of Diabetes During Ramadan
Authors: Mayer B. Davidson
Journal: Diabetes Care (2006)

In their otherwise fine article concerning recommendations for the management of diabetes during Ramadan, Al-Arouj et al. (1) perpetuate an ingrained, but mistaken, view of the glycemic response to different kinds of ingested carbohydrates. Their recommendations of eating foods containing complex carbohydrates at the predawn meal and simple carbohydrates at the sunset meal is based on their stated assumption that digestion and absorption of the former is delayed and faster for the latter. These …
Cutaneous mycoses in children
Authors: B.E. ELEWSKI
Journal: British Journal of Dermatology (1996)

This article describes common cutaneous mycoses in children: mucocutaneous candidiasis, pityriasis versicolor, tinea corporis, tinea pedis, onychomycosis and tinea capitis. Topical therapy is effective in tinea corporis and pedis, pityriasis versicolor and cutaneous candidiasis. It is ineffective in tinea capitis, in immunocompromised children and onychomycosis. Griseofulvin has been the main treatment until now in children, but it is only fungistatic, may cause interactions and has to be given for long periods. Ketoconazole has not been widely accepted for use in children because of hepatotoxicity and it is not as effective as griseofulvin. There are few data on paediatric use of fluconazole, although it is available in liquid form, has an excellent safety profile and may become important for treating paediatric mycoses. Similarly, there are only limited data on itraconazole in this area, with most experience in tinea capitis. There is only a 100–mg capsule available, which is not easy to administer in paediatric dosages. All azoles have the potential for drug interaction. Most experience in the treatment of children with the allylamine, terbinafine, has been in tinea capitis. A treatment time of 4 weeks with terbinafine and 8 weeks with griseofulvin has produced similar results at 12 weeks. There are also limited data on the use of terbinafine in paediatric onychomycosis. Terbinafine has the best safety profile, least risk of drug interactions and may be the most suitable alternative to griseofulvin in children. The lack of a liquid formulation may preclude its use. Itraconazole and fluconazole are also potential replacement drugs for griseofulvin.
Association Between Arterial Hyperoxia Following Resuscitation From Cardiac Arrest and In-Hospital Mortality
Authors: J Hope Kilgannon, Alan E Jones, Nathan I Shapiro, Mark G Angelos, Barry Milcarek, Krystal Hunter, Joseph E Parrillo, Stephen Trzeciak
Journal: JAMA (2010)

Laboratory investigations suggest that exposure to hyperoxia after resuscitation from cardiac arrest may worsen anoxic brain injury; however, clinical data are lacking.To test the hypothesis that postresuscitation hyperoxia is associated with increased mortality.Multicenter cohort study using the Project IMPACT critical care database of intensive care units (ICUs) at 120 US hospitals between 2001 and 2005. Patient inclusion criteria were age older than 17 years, nontraumatic cardiac arrest, cardiopulmonary resuscitation within 24 hours prior to ICU arrival, and arterial blood gas analysis performed within 24 hours following ICU arrival. Patients were divided into 3 groups defined a priori based on PaO(2) on the first arterial blood gas values obtained in the ICU. Hyperoxia was defined as PaO(2) of 300 mm Hg or greater; hypoxia, PaO(2) of less than 60 mm Hg (or ratio of PaO(2) to fraction of inspired oxygen <300); and normoxia, not classified as hyperoxia or hypoxia.In-hospital mortality.Of 6326 patients, 1156 had hyperoxia (18%), 3999 had hypoxia (63%), and 1171 had normoxia (19%). The hyperoxia group had significantly higher in-hospital mortality (732/1156 [63%; 95% confidence interval {CI}, 60%-66%]) compared with the normoxia group (532/1171 [45%; 95% CI, 43%-48%]; proportion difference, 18% [95% CI, 14%-22%]) and the hypoxia group (2297/3999 [57%; 95% CI, 56%-59%]; proportion difference, 6% [95% CI, 3%-9%]). In a model controlling for potential confounders (eg, age, preadmission functional status, comorbid conditions, vital signs, and other physiological indices), hyperoxia exposure had an odds ratio for death of 1.8 (95% CI, 1.5-2.2).Among patients admitted to the ICU following resuscitation from cardiac arrest, arterial hyperoxia was independently associated with increased in-hospital mortality compared with either hypoxia or normoxia.
Left Ventricular Eccentric Remodeling and Matrix Loss Are Mediated by Bradykinin and Precede Cardiomyocyte Elongation in Rats With Volume Overload
Authors: Thomas D. Ryan, Emily C. Rothstein, Inmaculada Aban, Jose A. Tallaj, Ahsan Husain, Pamela A. Lucchesi, Louis J. Dell’Italia
Journal: Journal of the American College of Cardiology (2007)
Halogenase Genes in Nonribosomal Peptide Synthetase Gene Clusters of Microcystis (Cyanobacteria): Sporadic Distribution and Evolution
Authors: S. Cadel-Six, C. Dauga, A. M. Castets, R. Rippka, C. Bouchier, N. Tandeau de Marsac, M. Welker
Journal: Molecular Biology and Evolution (2008)

Cyanobacteria of the genus Microcystis are known to produce secondary metabolites of large structural diversity by nonribosomal peptide synthetase (NRPS) pathways. For a number of such compounds, halogenated congeners have been reported along with nonhalogenated ones. In the present study, chlorinated cyanopeptolin- and/or aeruginosin-type peptides were detected by mass spectrometry in 17 out of 28 axenic strains of Microcystis. In these strains, a halogenase gene was identified between 2 genes coding for NRPS modules in respective gene clusters, whereas it was consistently absent when the strains produced only nonchlorinated corresponding congeners. Nucleotide sequences were obtained for 12 complete halogenase genes and 14 intermodule regions of gene clusters lacking a halogenase gene or containing only fragments of it. When a halogenase gene was found absent, a specific, identical excision pattern was observed for both synthetase gene clusters in most strains. A phylogenetic analysis including other bacterial halogenases showed that the NRPS-related halogenases of Microcystis form a monophyletic group divided into 2 subgroups, corresponding to either the cyanopeptolin or the aeruginosin peptide synthetases. The distribution of these peptide synthetase gene clusters, among the tested Microcystis strains, was found in relative agreement with their phylogeny reconstructed from 16S–23S rDNA intergenic spacer sequences, whereas the distribution of the associated halogenase genes appears to be sporadic. The presented data suggest that in cyanobacteria these prevalent halogenase genes originated from an ancient horizontal gene transfer followed by duplication in the cyanobacterial lineage. We propose an evolutionary scenario implying repeated gene losses to explain the distribution of halogenase genes in 2 NRPS gene clusters that subsequently defines the seemingly erratic production of halogenated and nonhalogenated aeruginosins and cyanopeptolins among Microcystis strains.
Characterization of an epibody. An antiidiotype that reacts with both the idiotype of rheumatoid factors (RF) and the antigen recognized by RF.
Authors: P P Chen, S Fong, R A Houghten, D A Carson
Journal: The Journal of Experimental Medicine (1985)

Recently, an antiidiotype to human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors) was found to react also with human IgG. This peculiar antiidiotype was called an 'epibody'. We describe the induction of a similar epibody by immunization with a synthetic peptide (corresponding to one hypervariable region of the IgM-RF Glo). The results confirm the existence of epibodies, and provide the possible molecular basis of the epibody phenomenon.
Relative Clinical Usefulness of Glycosylated Serum Albumin and Fructosamine During Short-Term Changes In Glycemic Control in IDDM
Authors: Peter H Winocour, Deepak Bhatnagar, Paramjeet Kalsi, Valerie F Hillier, David C Anderson
Journal: Diabetes Care (1989)

Serial changes in glycosylated blood proteins and direct measures of glycemia were studied in 100 subjects with insulin-dependent diabetes mellitus (IDDM) over a 6-wk period while attempts were made to improve glycemic control. All measures of glycemic control improved significantly (P &amp;lt; .001). Mean ± SE glycosylated hemoglobin (HbA,) fell from 9.1 ± 0.2 to 8.0 ± 0.1%, glycosylated serum albumin (GSA) from 9.8 ± 0.4 to 7.3 ± 0.3%, and fructosamine from 3.92 ± 0.08 to 3.42 ± 0.07 mM. Fasting blood glucose levels fell from 11.1 ± 0.6 to 8.1 ± 0.7 mM, mean blood glucose levels from 12.5 ± 0.3 to 8.8 ± 0.3 mM, and the M value from 118 ± 7 to 40 ± 3 U. Mean percentage changes in direct measures of glycemia (32–66%) and GSA (29%) were greater than for fructosamine (11%) or HbA, (12%) levels (P &amp;lt; .001). Furthermore, the correlation between the change in GSA and changes in direct measures of glycemia over the initial 2-wk period was significantly different from the corresponding correlations between direct measures of glycemia and fructosamine over this period (P &amp;lt; .05-.01). Changes in GSA also correlated more closely than HbA, or fructosamine did with direct measures of glycemia after 4 and 6 wk. The Spearman rank-correlation coefficient (rs) of absolute changes in GSA, fructosamine, and HbA1 after 2–6 wk ranged from 0.27 to 0.57, confirming that the three measures responded differently to changing glycemic control. Cross-sectional analysis between different measures of glycemia demonstrated considerable variation in the degree of association at different times, with the closest correlations observed after 6 wk when glycemic control was relatively stable. GSA and fructosamine levels correlated with levels of mean blood glucose and M values estimated 2–4 wk earlier. GSA appears to be a more sensitive indicator of short-term improvement in glycemic control and glycemic instability in IDDM than fructosamine or HbA1.
Cooperation across the histocompatibility barrier: H2d T cells primed to antigen in an H-2d environment can cooperate with H-2k B cells.
Authors: H Waldmann, H Pope, A J Munro
Journal: The Journal of Experimental Medicine (1976)

H-2d spleen cells derived from either tetraparental or semiallogeneic radiation bone marrow chimeras can be primed to antigen within H-2d recipients to generate helper T cells capable of cooperating in a secondary response with equal efficiency with H-2d or H-2k B cells. Thus it would seem that the cooperative act between T and B cells does not require that the T cell interacts with its target B cells by either cell interaction genes or via an altered self mechanism involving both antigen and the target B-cell I-region products. This does not preclude a requirement for associative recognition or altered self in the interaction of helper T cells with accessory cells.
A Phase 1 Dose Escalation, Pharmacokinetic, and Pharmacodynamic Evaluation of eIF-4E Antisense Oligonucleotide LY2275796 in Patients with Advanced Cancer
Authors: David S. Hong, Razelle Kurzrock, Yun Oh, Jennifer Wheler, Aung Naing, Les Brail, Sophie Callies, Valérie André, Sunil K. Kadam, Aejaz Nasir, Timothy R. Holzer, Funda Meric-Bernstam, Mayer Fishman, George Simon
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The antisense oligonucleotide LY2275796 blocks expression of cap-binding protein eukaryotic initiation factor 4E (eIF-4E), an mRNA translation regulator upregulated in tumors. This phase I study sought an appropriate LY2275796 dose in patients with advanced tumors. Experimental Design: A 3-day loading dose, then weekly maintenance doses, were given to 1 to 3 patient cohorts, beginning with 100 mg and escalating. Plasma samples were collected to determine LY2275796 concentrations and tumor biopsies to quantify eIF-4E mRNA/protein. Results: Thirty patients with stage 4 disease received 1 or more LY2275796 dose. A dose-limiting toxicity was observed at 1,200 mg, with 1,000 mg the maximum-tolerated dose. Across all dose levels, most patients (87%) had only grade 1 to 2 toxicities. LY2275796 pharmacokinetics supported the dosing regimen. Comparison of pre- and postdose biopsies showed eIF-4E decreased in most patients. Fifteen patients had progressive disease, and 7 patients achieved stable disease (minimum of 6 weeks) as best response, with 2 patients on therapy for more than 3 months (one with melanoma, one with cystadenocarcinoma of the head/neck). Conclusions: LY2275796 was well tolerated up to 1,000 mg. Because tumor eIF-4E expression was decreased, but no tumor response observed, LY2275796 should be studied combined with other treatment modalities. Clin Cancer Res; 17(20); 6582–91. ©2011 AACR.
Multiple Pain Complaints in Amputees
Authors: J E B Lindesay
Journal: Journal of the Royal Society of Medicine (1985)

A group of amputees complaining of longstanding phantom pain was compared with another comparable group of non-complainers. It was found that those with phantom pain made significantly more complaints of other painful conditions, both related and unrelated to the amputation; they were also more depressed. It is suggested that this association is due to a lowered pain tolerance in the group with phantom pain complaints, and that depression is one factor contributing to this lowered tolerance.
Ras Transformation of RIE-1 Cells Activates Cap-Independent Translation of Ornithine Decarboxylase: Regulation by the Raf/MEK/ERK and Phosphatidylinositol 3-Kinase Pathways
Authors: Sofia Origanti, Lisa M. Shantz
Journal: Cancer Research (2007)

Abstract Ornithine decarboxylase (ODC) is the first and generally rate-limiting enzyme in polyamine biosynthesis. Deregulation of ODC is critical for oncogenic growth, and ODC is a target of Ras. These experiments examine translational regulation of ODC in RIE-1 cells, comparing untransformed cells with those transformed by an activated Ras12V mutant. Analysis of the ODC 5′ untranslated region (5′UTR) revealed four splice variants with the presence or absence of two intronic sequences. All four 5′UTR species were found in both cell lines; however, variants containing intronic sequences were more abundant in Ras-transformed cells. All splice variants support internal ribosome entry site (IRES)–mediated translation, and IRES activity is markedly elevated in cells transformed by Ras. Inhibition of Ras effector targets indicated that the ODC IRES element is regulated by the phosphorylation status of the translation factor eIF4E. Dephosphorylation of eIF4E by inhibition of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK) or the eIF4E kinase Mnk1/2 increases ODC IRES activity in both cell lines. When both the Raf/MEK/ERK and phosphatidylinositol 3-kinase/mammalian target of rapamycin pathways are inhibited in normal cells, ODC IRES activity is very low and cells arrest in G1. When these pathways are inhibited in Ras-transformed cells, cell cycle arrest does not occur and ODC IRES activity increases, helping to maintain high ODC activity. [Cancer Res 2007;67(10):4834–42]
Final Results and Biomarker Correlation of a Phase II Study of the MTOR Inhibitor Everolimus in Patients with Pre-Treated Metastatic Esophagus, Gastro-Esophageal Junction and Gastric Adenocarcinoma
Authors: Wainberg Zev, Patel Ravi, Park David, Liem Andre, Yonemoto Lisa, DiCarlo Brian, Wang He-Jing, Martinez Diego, J. Hecht
Journal: Annals of Oncology (2014)
HEREDITARY ANGIOMATA (TELANGIECTASES) WITH EPISTAXIS
Authors: S. NORMAN PAUL
Journal: British Journal of Dermatology (1918)

Journal Article HEREDITARY ANGIOMATA (TELANGIECTASES) WITH EPISTAXIS Get access S. NORMAN PAUL, M.B., Ch.M. S. NORMAN PAUL, M.B., Ch.M. Hon. Assistant Physician for Diseases of the Skin, Sydney Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 30, Issue 1, 1 January 1918, Pages 27–32, https://doi.org/10.1111/j.1365-2133.1918.tb12371.x Published: 01 January 1918
Protecting the Microvasculature
Authors: Jill T. Norman
Journal: Journal of the American Society of Nephrology (2006)

Chronic kidney disease (CKD) results from diverse etiologies, including glomerulonephritis, diabetes, and hypertension ([1][1]). The incidence of CKD is increasing worldwide and is predicted to reach epidemic proportions over the next decade ([1][1]). Current therapeutic strategies are based on the
Depression and cognitive decline after coronary artery bypass grafting
Authors: Guy M McKhann, Louis M Borowicz, Maura A Goldsborough, Cheryl Enger, Ola A Selnes
Journal: The Lancet (1997)

BackgroundDepression is commonly reported after coronary artery bypass grafting (CABG), and after cardiac surgery in general. Many earlier reports relied on non-standard assessments of depression, which may have overestimated its frequency. Cognitive decline has also been reported after CABG. We assessed the frequency of depression after CABG by a validated depression measure (Center for Epidemiological Study of Depression, CES-D), and examined the relation between depression and cognitive decline.MethodsPatients were tested before CABG and 1 month and 1 year after surgery with a series of neuropsychological tests that assessed a range of cognitive areas. Depressed mood was measured by the CES-D scale, and defined as a score above 16.Findings90 (73%) of the 124 patients were not depressed before surgery, and 34 were depressed at that time. Only 12 (13%) of patients not depressed before surgery were depressed at 1 month afterwards, whereas 18 (53%) of those who were depressed before surgery were depressed at 1 month (p<0–001). 8 (9%) patients not depressed before surgery were depressed at 1 year; 16 (47%) of patients who were depressed before CABG were depressed at 1 year (p<0–001). Statistical analysis showed only minimal correlation–or none at all–between depression and eight areas of cognitive outcome, or between changes in depressed status and cognitive scores.InterpretationOf those patients who were depressed after CABG, the large majority were depressed before surgery. There was no correlation, moreover, between depressed mood and cognitive decline after CABG, which suggests that depression alone cannot account for cognitive decline
DUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase
Authors: Mathieu Amand, Charlotte Erpicum, Khalid Bajou, Fabio Cerignoli, Silvia Blacher, Maud Martin, Franck Dequiedt, Pierre Drion, Pratibha Singh, Tinatin Zurashvili, Maud Vandereyken, Lucia Musumeci, Tomas Mustelin, Michel Moutschen, Christine Gilles, Agnes Noel, Souad Rahmouni
Journal: Molecular Cancer (2014)

DUSP3 phosphatase, also known as Vaccinia-H1 Related (VHR) phosphatase, encoded by DUSP3/Dusp3 gene, is a relatively small member of the dual-specificity protein phosphatases. In vitro studies showed that DUSP3 is a negative regulator of ERK and JNK pathways in several cell lines. On the other hand, DUSP3 is implicated in human cancer. It has been alternatively described as having tumor suppressive and oncogenic properties. Thus, the available data suggest that DUSP3 plays complex and contradictory roles in tumorigenesis that could be cell type-dependent. Since most of these studies were performed using recombinant proteins or in cell-transfection based assays, the physiological function of DUSP3 has remained elusive.Using immunohistochemistry on human cervical sections, we observed a strong expression of DUSP3 in endothelial cells (EC) suggesting a contribution for this phosphatase to EC functions. DUSP3 downregulation, using RNA interference, in human EC reduced significantly in vitro tube formation on Matrigel and spheroid angiogenic sprouting. However, this defect was not associated with an altered phosphorylation of the documented in vitro DUSP3 substrates, ERK1/2, JNK1/2 and EGFR but was associated with an increased PKC phosphorylation. To investigate the physiological function of DUSP3, we generated Dusp3-deficient mice by homologous recombination. The obtained DUSP3-/- mice were healthy, fertile, with no spontaneous phenotype and no vascular defect. However, DUSP3 deficiency prevented neo-vascularization of transplanted b-FGF containing Matrigel and LLC xenograft tumors as evidenced by hemoglobin (Hb) and FITC-dextran quantifications. Furthermore, we found that DUSP3 is required for b-FGF-induced microvessel outgrowth in the aortic ring assay.All together, our data identify DUSP3 as a new important player in angiogenesis.