tbuckley/cabot-search huggingface dataset:
Personal Control and Disordered Eating in Female Adolescents With Type 1 Diabetes
Authors: Stefanie A. Schwartz, Jill Weissberg-Benchell, Lawrence C. Perlmuter
Journal: Diabetes Care (2002)

The onset and subsequent management of diabetes can challenge one's sense of control. Sense of control can also be affected by the biological changes accompanying normal pubertal development. The negative impact on one's sense of control may be further exacerbated when both events (i.e., diabetes and puberty) occur in relatively close temporal proximity.This study examined the relationship between sense of control and disordered eating and glycemic control in 45 female adolescents with type 1 diabetes.A lower sense of overall control and a lower sense of bodily control were both directly related to more severe eating-disordered symptoms. However, a lower sense of overall control and lower bodily control were related to poorer metabolic control primarily when the diagnosis of diabetes occurred closer to the onset of puberty.Clinicians should assess and monitor perceptions of control and also consider the temporal proximity of disease onset and onset of puberty when managing type 1 diabetes in female adolescents.
Predicting Impaired Glucose Tolerance Using Common Clinical Information
Authors: Karin M. Nelson, Edward J. Boyko
Journal: Diabetes Care (2003)

To develop a score to predict impaired glucose tolerance (IGT) using common clinical data.We analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III) for 2,746 individuals aged 40-74 years who completed an oral glucose tolerance test. IGT was defined as a 2-h postchallenge glucose > or =140 mg/dl (7.7 mmol/l). We performed bivariate and multivariate analyses to describe the association of IGT with commonly available clinical information. A numerical score to predict IGT was derived from the results of the multivariate logistic regression models.Fasting glucose levels between 101 and 109 mg/dl (5.6 and 6.0 mmol/l) or between 110 and 125 mg/dl (6.1 and 6.9 mmol/l) were associated with IGT (odds ratio 1.8 and 6.2, respectively; P < 0.05). BMI > or =25 kg/m(2), Mexican-American ethnicity, age between 60 and 74 years, hypertension, and triglyceride level > or =150 mg/dl (1.69 mmol/l) were also associated with IGT. The area under the receiver operating characteristic curve for an 8-point scale derived from the multivariate analysis was 0.74 (95% CI 0.72-0.76). Setting a low cut point of 2 on this scale resulted in high sensitivity (86%), whereas a high cut point of 6 yielded high specificity (97%) for the detection of IGT.A numerical score based on common clinical data can identify individuals with a low or high likelihood of having IGT.
Expression and Intracellular Localization of an <b> <i>SCN5A</i> </b> Double Mutant R1232W/T1620M Implicated in Brugada Syndrome
Authors: Ghayath Baroudi, Said Acharfi, Chantal Larouche, Mohamed Chahine
Journal: Circulation Research (2002)

Brugada syndrome is an inherited cardiac disorder caused by mutations in the cardiac sodium channel gene, SCN5A, that leads to ventricular fibrillation and sudden death. This study reports the changes in functional expression and cellular localization of an SCN5A double mutant (R1232W/T1620M) recently discovered in patients with Brugada syndrome. Mutant and wild-type (WT) human heart sodium channels (hNa(v)1.5) were expressed in tsA201 cells in the presence of the beta(1)-auxiliary subunit. Patch-clamp experiments in whole-cell configuration were conducted to assess functional expression. Immunohistochemistry and confocal microscopy were used to determine the spatial distribution of either WT or mutant cardiac sodium channels. The results show an abolition of functional sodium channel expression of the hNa(v)1.5/R1232W/T1620M mutant in the tsA201 cells. A conservative positively charged mutant, hNa(v)1.5/R1232K/T1620M, produced functional channels. Immunofluorescent staining showed that the FLAG-tagged hNa(v)1.5/WT transfected into tsA201 cells was localized on the cell surface, whereas the FLAG-tagged hNa(v)1.5/R1232W/T1620M mutant was colocalized with calnexin within the endoplasmic reticulum (ER). These results indicate that a positively charged arginine or lysine residue at position 1232 in the double mutant is required for the proper transport and functional expression of the hNa(v)1.5 protein. These results support the concept that loss of function of the cardiac Na(+) channel is responsible for the Brugada syndrome. The full text of this article is available at http://www.circresaha.org.
Axon Guidance Factor SLIT2 Inhibits Neural Invasion and Metastasis in Pancreatic Cancer
Authors: Andreas Göhrig, Katharina M. Detjen, Georg Hilfenhaus, Jan L. Körner, Martina Welzel, Ruza Arsenic, Rosa Schmuck, Marcus Bahra, Jane Y. Wu, Bertram Wiedenmann, Christian Fischer
Journal: Cancer Research (2014)

Pancreatic ductal adenocarcinoma (PDAC) metastasizes by neural, vascular, and local invasion routes, which limit patient survival. In nerves and vessels, SLIT2 and its ROBO receptors constitute repellent guidance cues that also direct epithelial branching. Thus, the SLIT2-ROBO system may represent a key pinch point to regulate PDAC spread. In this study, we examined the hypothesis that escaping from repellent SLIT2-ROBO signaling is essential to enable PDAC cells to appropriate their local stromal infrastructure for dissemination. Through immunohistochemical analysis, we detected SLIT2 receptors ROBO1 and ROBO4 on epithelia, nerves, and vessels in healthy pancreas and PDAC specimens, respectively. SLIT2 mRNA expression was reduced in PDAC compared with nontransformed pancreatic tissues and cell lines, suggesting a reduction in SLIT2-ROBO pathway activity in PDAC. In support of this interpretation, restoring the SLIT2 expression in SLIT2-deficient PDAC cells inhibited their bidirectional chemoattraction with neural cells, and more specifically, impaired unidirectional PDAC cell navigation along outgrowing neurites in models of neural invasion. Restoring autocrine/paracrine SLIT2 signaling was also sufficient to inhibit the directed motility of PDAC cells, but not their random movement. Conversely, RNA interference-mediated silencing of ROBO1 stimulated the motility of SLIT2-competent PDAC cells. Furthermore, culture supernatants from SLIT2-competent PDAC cells impaired migration of endothelial cells (human umbilical vein endothelial cells), whereas an N-terminal SLIT2 cleavage fragment stimulated such migration. In vivo investigations of pancreatic tumors with restored SLIT2 expression demonstrated reduced invasion, metastasis, and vascularization, with opposing effects produced by ROBO1 silencing in tumor cells or sequestration of endogenous SLIT2. Analysis of clinical specimens of PDAC showed that those with low SLIT2 mRNA expression exhibited a higher incidence and a higher fraction of tumor-infiltrated lymph nodes. Taken together, our findings argue that disrupting SLIT2-ROBO signaling in PDAC may enhance metastasis and predispose PDAC cells to neural invasion.
Characterization of the primary structure of T cell receptor beta chains in cells infiltrating the salivary gland in the sicca syndrome of HIV-1 infection. Evidence of antigen-driven clonal selection suggested by restricted combinations of V beta J beta gene segment usage and shared somatically encoded amino acid residues.
Authors: E Dwyer, S Itescu, R Winchester
Journal: Journal of Clinical Investigation (1993)

Infection with HIV-1 occasionally results in a sicca syndrome, termed the diffuse infiltrative lymphocytosis syndrome, characterized by infiltration of the salivary glands with a predominance of CD8 T cells. This response is strongly associated with certain MHC class I and class II alleles. To define the salivary gland T cell receptor (TCR) repertoire, the primary structure of the TCR beta-chains was determined using in situ cDNA synthesis followed by the "anchored" polymerase chain reaction. The sequences of 59 beta-chains from five individuals with diffuse infiltrative lymphocytosis syndrome shared structural features suggesting antigenic clonal selection. Certain combinations of V beta J beta gene segments were selectively overrepresented in the repertoire sample, demonstrating a common restricted usage of certain V beta and J beta gene segments. The beta-chains derived from these overrepresented V beta J beta combinations revealed a preference for specific amino acids at position 97 in the third complementarity-determining region, a residue postulated to contact peptide antigen. Moreover, the nucleotides encoding this position were not germline in origin. TCR beta-chains in nonoverrepresented V beta J beta combinations did not exhibit preferential usage of selected somatically encoded residues. The pattern of TCR beta-chains expressed in the salivary gland of a control person with primary Sjögren's syndrome was considerably more heterogeneous and different from that found in diffuse infiltrative lymphocytosis syndrome.
New, Tolerable γ-Secretase Inhibitor Takes Desmoid Down a Notch
Authors: Dennis P.M. Hughes, Shivaani Kummar, Alexander J. Lazar
Journal: Clinical Cancer Research (2014)

Abstract A phase I trial of PF-03084014, an oral reversible γ-secretase inhibitor, in solid tumor malignancies shows drug tolerability in patients. Evidence of Notch pathway inhibition was demonstrated in peripheral blood. A surprisingly high rate of response was seen in desmoid tumors, a rare but sometimes locally aggressive sarcoma. Clin Cancer Res; 21(1); 7–9. ©2014 AACR. See related article by Messersmith et al., p. 60
Phosphorus and Survival
Authors: Jorge B. Cannata-Andi[Combining Acute Accent]a, Manuel Naves-Di[Combining Acute Accent]az
Journal: Journal of the American Society of Nephrology (2009)

For more than forty years now, high serum phosphate levels, a highly prevalent condition in patients with chronic kidney disease (CKD), have been associated with the pathogenesis of secondary hyperparathyroidism, a common mineral and bone disorder (MBD).1 Recent epidemiologic and experimental studies have further amplified the role this condition plays in the larger story of CKD-MBD. Experimental studies have demonstrated that high phosphorus plays a key role in the development of vascular calcification2 and impairment of bone mass and strength, induces changes in the expression pattern of muscle and bone-related genes,3,4 and may also act as a pro-aging factor.5 In addition, clinical studies have demonstrated an association among hyperphosphatemia, vascular stiffness, and left ventricular hypertrophy.6 Taking all of the aforementioned findings together, it is reasonable to hypothesize all these untoward actions of phosphorus may ultimately affect mortality, as it has been suggested by several studies carried out in different dialysis cohorts.7,8

The increase in the importance of phosphorus in the spectrum of CKD-MBD also coincides with the description of the multiple actions of a new modulator, fibroblast growth factor 23 (FGF-23). This phosphatonin carries out some effects independent of phosphorus, such as its inhibitory effect on parathyroid hormone synthesis,9 but, so far, most of the biologic actions of FGF-23, including its recently described association with mortality,10 seem to be highly interdependent and related …
Prospective study of malabsorption induced risk of gall stone formation in relation to fall in plasma cholesterol.
Authors: T I Sorensen, B Andersen, E Hylander, L I Jensen, K Laursen, H C Klein
Journal: Gut (1988)

The relationship between cholesterol in plasma and risk of gall stone formation was investigated in 210 obese patients who underwent jejunoileal bypass surgery and were free of gall stone disease at the time. Among 185, successfully reexamined on average 19 months after surgery, 26 (14%) developed gall stones. The fall in plasma cholesterol after surgery exhibited a U-shaped relation to risk of gall stone formation with a minimum risk around the average fall (2.6 mmol/l). This was confirmed by multivariate logistic regression analysis (p less than 0.01) taking into account other possible determinants. The relation was not significantly dependent on weight loss or ratio between jejunum and ileum left in function. The study suggests that malabsorption induced fall in plasma cholesterol is related to risk of gall stone formation by two oppositely working mechanisms, one enhancing and one reducing the risk.
Enhanced virulence, airway inflammation and impaired lung function induced by respiratory syncytial virus deficient in secreted G protein
Authors: J Schwarze
Journal: Thorax (2004)

<b>Background:</b> Respiratory syncytial virus (RSV) infection can cause bronchial hyperresponsiveness and asthma exacerbations. In mice it results in airway inflammation and airway hyperresponsiveness. Since viral factors influencing these responses are not well defined, a study was undertaken to investigate the role of secreted G protein of human RSV in determining virulence, inflammatory responses, and changes in lung function. <b>Methods:</b> BALB/c mice were infected with a spontaneous mutant of RSV deficient in secreted G protein (RSV-ΔsG) or with wild type RSV (RSV-WT). Viral titres, numbers of pulmonary inflammatory cells, and concentrations of interferon (IFN)-γ, interleukin (IL)-4, IL-5 and IL-10 in bronchoalveolar lavage (BAL) fluid were determined. Airway function was assessed at baseline and following methacholine provocation using barometric whole body plethysmography. <b>Result:</b> Following infection with RSV-ΔsG, viral titres were increased 50-fold compared with RSV-WT. Influx of eosinophils and macrophages to the lung and concentrations of IFN-γ and IL-10 in BAL fluid were also significantly higher following infection with RSV-ΔsG. Airway function, both at baseline and after methacholine provocation, was significantly decreased following infection with RSV-ΔsG compared with RSV-WT. <b>Conclusion:</b> Secreted G protein is likely to be a regulatory factor in RSV infection limiting infectivity of the virus, inflammatory responses in the lungs, and reduction in lung function.
Crystals in arthritis: new age nonsense or novel therapeutic target?
Authors: G. M MCCARTHY;, P. DIEPPE
Journal: Annals of the Rheumatic Diseases (1999)

Apatite crystals are present in up to 70% of fluids from degenerated joints.1 Their presence correlates strongly with radiographic evidence of cartilage degeneration and is associated with larger joint effusions when compared with joints without crystals.2 3 Whether the presence of apatite crystals is a cause of cartilage damage or an effect of cartilage damage is unclear.4 Several lines of evidence suggest that apatite crystals cause joint destruction. For example, apatite crystals induce both mitogenesis and prostaglandin synthesis in synovial fibroblasts and chondrocytes in vitro.5 They also induce matrix metalloprotease (MMP) synthesis and secretion, thus promoting tissue damage.6 7 The cellular mechanisms whereby apatite crystals induce such responses are currently under investigation. Like many other growth promoting agents, apatite crystals induce a variety of transcription factors such as nuclear factor κB (NF-κB) and activator protein 1 (AP-1).8 They also …
Omalizumab for the Treatment of Chronic Idiopathic or Spontaneous Urticaria
Authors: Marcus Maurer, Karin Rosén, Hsin-Ju Hsieh, Sarbjit Saini, Clive Grattan, Ana Gimenéz-Arnau, Sunil Agarwal, Ramona Doyle, Janice Canvin, Allen Kaplan, Thomas Casale
Journal: New England Journal of Medicine (2013)

Many patients with chronic idiopathic urticaria (also called chronic spontaneous urticaria) do not have a response to therapy with H1-antihistamines, even at high doses. In phase 2 trials, omalizumab, an anti-IgE monoclonal antibody that targets IgE and affects mast-cell and basophil function, has shown efficacy in such patients.
Effect of breathing circuit resistance on the measurement of ventilatory function
Authors: D. P Johns, C. M Ingram, S. Khov, P. D Rochford, E H. Walters
Journal: Thorax (1998)

The American Thoracic Society (ATS) has set the acceptable resistance for spirometers at less than 1.5 cm H2O/l/s over the flow range 0-14 l/s and for monitoring devices at less than 2.5 cm H2O/l/s (0-14 l/s). The aims of this study were to determine the resistance characteristics of commonly used spirometers and monitoring devices and the effect of resistance on ventilatory function.The resistance of five spirometers (Vitalograph wedge bellows, Morgan rolling seal, Stead Wells water sealed, Fleisch pneumotachograph, Lilly pneumotachograph) and three monitoring devices (Spiro 1, Ferraris, mini-Wright) was measured from the back pressure developed over a range of known flows (1.6-13.1 l/s). Peak expiratory flow (PEF), forced expiratory flow in one second (FEV1), forced vital capacity (FVC), and mid forced expiratory flow (FEF25-75%) were measured on six subjects with normal lung function and 13 subjects with respiratory disorders using a pneumotachograph. Ventilatory function was then repeated with four different sized resistors (approximately 1-11 cmH2O/l/s) inserted between the mouthpiece and pneumotachograph.All five diagnostic spirometers and two of the three monitoring devices passed the ATS upper limit for resistance. PEF, FEV1 and FVC showed significant (p < 0.05) inverse correlations with added resistance with no significant difference between the normal and patient groups. At a resistance of 1.5 cm H2O/l/s the mean percentage falls (95% confidence interval) were: PEF 6.9% (5.4 to 8.3); FEV1 1.9% (1.0 to 2.8), and FVC 1.5% (0.8 to 2.3).The ATS resistance specification for diagnostic spirometers appears to be appropriate. However, the specification for monitoring devices may be too conservative. PEF was found to be the most sensitive index to added resistance.
Combination of interferon alpha therapy with non-steroidal anti-inflammatory drugs in chronic hepatitis C
Authors: S J HADZIYANNIS
Journal: Gut (2000)

See article on page 427 

Chronic infection with hepatitis C virus (HCV) affects 2–15 % of the world's population. In the USA there are more than 4 million chronically HCV infected people and the estimates for Europe are similar. In the European Community chronic hepatitis C is viewed as a major health problem and efforts are being made to develop both preventive and new therapeutic strategies (Key Action 2 of the 5th Framework Programme 1998–2002 of Quality of Life and Management of Living Resources ).

Treatment of chronic hepatitis C is currently based on interferon α (IFN-α) with limited efficacy, only achieving a sustained virological response in less than 25% of patients with a favourable profile treated for one year.1 To improve the response rate of standard IFN-α monotherapy, several regimens have been tried combining IFN-α three times weekly for six to 12 months with various other agents. These agents include those with antiviral activity like ribavirin, amantadine,2 and azidothymidine; others with immunomodulatory properties such as thymosin; those with liver enzyme lowering activity like ursodeoxycholic acid and ribavirin2; and others with miscellaneous properties such as ofloxacin, N-acetylcysteine, glycyrrhizin, and non-steroidal anti-inflammatory drugs (NSAIDs). The aim of all these efforts was to increase IFN efficacy by decreasing the number of non-responders and relapsed responders as well as to reduce the dose of IFN-α required for a sustained response and consequently its side effects. The most rewarding of all these combinations with IFN was that …
A phase II study of single agent abraxane as second-line therapy in patients with advanced urothelial carcinoma
Authors: S. S. Sridhar, C. M. Canil, A. Eisen, I. F. Tannock, J. J. Knox, N. Reaume, S. D. Mukherjee, E. Winquist, A. Chung, Y. J. Ko
Journal: Journal of Clinical Oncology (2009)

e16058 Background: Metastatic urothelial cancer progressing on or after first-line platinum-based chemotherapy is incurable and has a very poor prognosis. There is no standard second-line therapy, but the taxanes including paclitaxel, have previously shown activity. Abraxane (ABI-007) is a novel well tolerated albumin-bound nanoparticle formulation of paclitaxel. The goal of this study was to determine the efficacy and tolerability of single agent Abraxane in the second-line metastatic urothelial cancer setting. Methods: Patients with measureable metastatic urothelial cancer, who progressed on or after first-line cisplatin based chemotherapy were enrolled onto this phase II, two-stage multicenter trial. Patients received Abraxane 260 mg/m 2 intravenously every 3 weeks. Clinical evaluation, CBC and blood chemistries were performed every cycle and restaging CT scans every 2 cycles. Results: Fourteen patients have been enrolled to date. Patient demographics: M: F 12:2; mean age 64 (range 45–80); ECOG 0:1:2 4:5:5. A total of 57 cycles, avg 4 cycles/ patient (range 1–9) have been administered. There were three dose delays due to neuropathy, pain, and low neutrophil count respectively. There were two dose reductions due to fatigue and neuropathy. Most frequent adverse events (AE) were fatigue, alopecia, anorexia, cough and joint pain; the most frequent grade 3+ AE were fatigue, joint pain, hypertension, joint stiffness and back pain. Fourteen patients are currently evaluable for best response using RECIST criteria. There have been 5 partial responses (PR), 5 stable disease (SD) and 4 progressive disease (PD). Conclusions: Single agent Abraxane was well tolerated in the 2 nd line, cisplatin refractory/resistant metastatic urothelial cancer setting. Preliminary efficacy results are encouraging with a clinical benefit rate of 71% (10 out of 14 evaluable pts having either SD or PR). Stage 1 response criteria have been met and accrual is ongoing to a total of 48 patients. No significant financial relationships to disclose.
Cardiac high-energy phosphates adapt faster than oxygen consumption to changes in heart rate.
Authors: M H Eijgelshoven, J H van Beek, I Mottet, M G Nederhoff, C J van Echteld, N Westerhof
Journal: Circulation Research (1994)

To investigate the dynamic control of cardiac ATP synthesis, we simultaneously determined the time course of mitochondrial oxygen consumption with the time course of changes in high-energy phosphates following steps in cardiac energy demand. Isolated isovolumically contracting rabbit hearts were perfused with Tyrode's solution at 28 degrees C (n = 7) or at 37 degrees C (n = 7). Coronary arterial and venous oxygen tensions were monitored with fast-responding oxygen electrodes. A cyclic pacing protocol in which we applied 64 step changes between two different heart rates was used. This enabled nuclear magnetic resonance measurement of the phosphate metabolites with a time resolution of approximately 2 seconds. Oxygen consumption changed after heart-rate steps with time constants of 14 +/- 1 (mean +/- SEM) seconds at 28 degrees C and 11 +/- 1 seconds at 37 degrees C, which are already corrected for diffusion and vascular transport delays. Doubling of the heart rate resulted in a significant decrease in phosphocreatine (PCr) content (11% at 28 degrees C, 8% at 37 degrees C), which was matched by an increase in inorganic phosphate (P(i)) content, although oxygen supply was shown to be nonlimiting. The time constants for the change of both P(i) and PCr content, approximately 5 seconds at 28 degrees C and 2.5 seconds at 37 degrees C, are significantly smaller than the respective time constants for oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)