tbuckley/cabot-search huggingface dataset:
Cystatin C and Mortality Risk in the Elderly
Authors: Michael G. Shlipak, Christina L. Wassel Fyr, Glenn M. Chertow, Tamara B. Harris, Stephen B. Kritchevsky, Frances A. Tylavsky, Suzanne Satterfield, Steven R. Cummings, Anne B. Newman, Linda F. Fried
Journal: Journal of the American Society of Nephrology (2005)

Kidney dysfunction is known to decrease life expectancy in the elderly. Cystatin C is a novel biomarker of kidney function that may have prognostic utility in older adults. The association of cystatin C with mortality was evaluated in a biracial cohort of black and white ambulatory elderly and compared with that of serum creatinine concentrations. The Health, Aging and Body Composition study is a cohort of well-functioning elderly that was designed to evaluate longitudinal changes in weight, body composition, and function. A total of 3075 participants who were aged 70 to 79 yr and had no disability were recruited at sites in Memphis, TN, and Pittsburgh, PA, between April 1997 and June 1998 with a follow-up of 6 yr. At entry, the mean cystatin C was 1.05 mg/L and the mean creatinine was 1.06 mg/dl. After 6 yr of follow-up, 557 participants had died. The mortality rates in each ascending cystatin C quintile were 1.7, 2.7, 2.9, 3.1, and 5.4%/yr. After adjustment for demographic risk factors, comorbid health conditions, and inflammatory biomarkers (C-reactive protein, IL-6. and TNF-alpha), each quintile of cystatin C was significantly associated with increased mortality risk compared with the lowest: Hazard ratios (HR; 95% confidence intervals) quintile 1, -1.0 (referent); quintile 2, -1.74 (1.21 to 2.50); quintile 3, -1.51 (1.05 to 2.18); quintile 4, -1.49 (1.04 to 2.13); and quintile 5, -2.18 (1.53 to 3.10). These associations did not differ by gender or race. Results were consistent for cardiovascular and other-cause mortality, but not cancer mortality. Creatinine quintiles were not associated with mortality after multivariate adjustment (HR: 1.0 [referent], 1.00 [0.72 to 1.39], 0.95 [0.68 to 1.32], 1.11 [0.79 to 1.57], 1.16 [0.86 to 1.58]). Cystatin C is a strong, independent risk factor for mortality in the elderly. Future studies should investigate whether cystatin C has a role in clinical medicine.
Myeloid marker S100A8/A9 and lymphocyte marker, soluble interleukin 2 receptor: biomarkers of hidradenitis suppurativa disease activity?
Authors: C.W. Wieland, T. Vogl, A. Ordelman, H.G.M. Vloedgraven, L.H.A. Verwoolde, J.M. Rensen, J. Roth, J. Boer, J. Hessels
Journal: British Journal of Dermatology (2013)

Background Hidradenitis suppurativa (HS) is a chronic inflammatory and debilitating disease of the skin. No biomarkers for this disease exist. Objectives We set out to test whether angiotensin-converting enzyme (ACE), lysozyme, soluble interleukin 2 receptor (sIL-2R) and S100A8/A9 (calprotectin) are elevated in patients with HS. Methods Serum was collected from 29 patients with HS at different stages of the disease, and from 51 controls. ACE, lysozyme, sIL-2R and S100A8/A9 levels were measured. Clinical observation of disease activity was scored according to the Hurley grading system and by a physician global score (PGS) of disease severity. Results Serum levels of lysozyme and ACE were not increased above the normal reference values in controls or patients with HS. Levels of sIL-2R and S100A8/A9 were significantly higher in patients with HS than in controls (P < 0·001 for both sIL-2R and S100A8/A9). Based on the receiver operating characteristic curves, the optimum sIL-2R and S100A8/A9 cut-off values were 375 U mL−1 and 680 ng mL−1, respectively, with a sensitivity of 0·79 and specificity of 0·78 for sIL-2R, and 0·86 and 0·88, respectively, for S100A8/A9. No correlations with Hurley classification scores were found. However, when using PGS of disease activity to categorize patients, levels of S100A8/A9, but not sIL-2R, tended to be higher in patients with more active disease. Conclusions Levels of S100A8/A9 and sIL-2R, but not ACE or lysozyme, are elevated in the serum of patients with HS. However, there is no correlation between S100A8/A9 or sIL-2R levels and disease stage according to the Hurley classification system. Further research is needed to study the potential of S100A8/A9 to score disease activity in larger cohorts of patients and to predict disease flares.
Perforation of Heart during Cardiac Catheterization and Selective Angiocardiography
Authors: P. G. KEATES, G. R. WAGNER
Journal: Circulation (1963)

A case is reported in which cardiac catheterization and selective angiocardiography led to perforation of the heart without any further complications. It is suggested that distortion of the pressure tracing indicates partial obstruction of the catheter holes and that it should serve as a warning sign not to proceed with the injection of contrast medium, but to re-position the catheter first. Furthermore, inspection of the electrocardiogram immediately after the injection may give an early indication of myocardial disturbance in the form of ST-segment depression.
Toe ulceration associated with compression bandaging: observational study
Authors: C. L H Chan, F. J Meyer, R. J Hay, K. G Burnand
Journal: BMJ (2001)

Foot ulcers can be caused by arterial insufficiency, diabetes mellitus, neuropathy, musculoskeletal disorders, or injury. 1 The clinical features of an ulcer-such as site, shape, edge, base, and state of the surrounding tissues-often give some indication of its aetiology and aid in further management and treatment.Ulceration of the foot is seen in some patients with venous disease but has not been observed in association with any particular treatment regimen. 2 We describe a previously unreported finding of ulceration of the toe and cleft, for which there was no demonstrable ischaemic or vasculitic cause, developing in patients treated with compression bandaging for venous ulcers.
Biologic discontinuation studies: a systematic review of methods
Authors: Kazuki Yoshida, Yoon-Kyoung Sung, Arthur Kavanaugh, Sang-Cheol Bae, Michael E Weinblatt, Mitsumasa Kishimoto, Kazuo Matsui, Shigeto Tohma, Daniel H Solomon
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> We conducted a systematic review to assess the design and 'failure definition' in studies of biologic discontinuation in rheumatoid arthritis (RA). <h3>Methods</h3> We found 403 studies on PubMed, and included nine published papers and five abstracts from scientific meetings. We used a structured extraction form to collect information regarding study design and outcome (failure) definition. <h3>Results</h3> Three types of studies were found: randomised controlled trials, long-term extension studies of clinical trials and prospective discontinuation studies. The largest study had 196 subjects in the discontinuation arm. Most studies allowed concomitant use of non-biologic drugs at biologic discontinuation. Heterogeneity was also found in the failure definition. Although all studies used measures of disease activity, the threshold for failure and the time point of assessment differed among studies. Few studies incorporated changing use of non-biologic drugs or glucocorticoids into the failure definition. <h3>Conclusions</h3> Although many studies have examined the outcome of biologic discontinuation, they have all been relatively small. Typical practice studies from registries may add important information but will likely need to rely on a broader failure definition.
Cognitive function and fatigue after diagnosis of colorectal cancer
Authors: J. Vardy, H.M. Dhillon, G.R. Pond, S.B. Rourke, W. Xu, A. Dodd, C. Renton, A. Park, T. Bekele, J. Ringash, H. Zhang, R. Burkes, S.J. Clarke, I.F. Tannock
Journal: Annals of Oncology (2014)
Endogenous Anti-HER2 Antibodies Block HER2 Phosphorylation and Signaling through Extracellular Signal-Regulated Kinase
Authors: R. Bruce Montgomery, Ekram Makary, Kathy Schiffman, Vivian Goodell, Mary L. Disis
Journal: Cancer Research (2005)

Abstract Immunologic targeting of the oncoprotein HER2/neu with monoclonal antibodies is an important component of current therapeutic strategies for patients with locally and systemically advanced breast cancer. Engineered antibodies targeting HER2 may have agonist or antagonist effects on HER2, but little is known about whether endogenous antibodies modulate HER2 activity. Vaccination of patients with HER2 peptides successfully induced antibodies in a minority of patients with HER2-expressing malignancy. A subset of antibodies specifically suppressed phosphorylation of HER2 on tyrosine Y1248, a residue critical for HER2 signaling through extracellular signal-regulated kinase. These antibodies also suppressed extracellular signal-regulated kinase phosphorylation and inhibited colony formation in soft agar. The majority of the antibodies that suppressed HER2 phosphorylation displayed specificity for amino acids 328 to 345 and 369 to 384. The isotype of anti-HER2 antibodies was predominantly IgG3 of low avidity, suggesting a Th1 response to peptide vaccine. Endogenous anti-HER2 antibodies can effectively suppress HER2 kinase activity and downstream signaling to inhibit the transformed phenotype of HER2-expressing tumor cells.
<i>De novo</i> Lipogenesis Protects Cancer Cells from Free Radicals and Chemotherapeutics by Promoting Membrane Lipid Saturation
Authors: Evelien Rysman, Koen Brusselmans, Katryn Scheys, Leen Timmermans, Rita Derua, Sebastian Munck, Paul P. Van Veldhoven, David Waltregny, Veerle W. Daniëls, Jelle Machiels, Frank Vanderhoydonc, Karine Smans, Etienne Waelkens, Guido Verhoeven, Johannes V. Swinnen
Journal: Cancer Research (2010)

Activation of de novo lipogenesis in cancer cells is increasingly recognized as a hallmark of aggressive cancers and has been implicated in the production of membranes for rapid cell proliferation. In the current report, we provide evidence that this activation has a more profound role. Using a mass spectrometry-based phospholipid analysis approach, we show that clinical tumor tissues that display the lipogenic phenotype show an increase in the degree of lipid saturation compared with nonlipogenic tumors. Reversal of the lipogenic switch in cancer cells by treatment with the lipogenesis inhibitor soraphen A or by targeting lipogenic enzymes with small interfering RNA leads to a marked decrease in saturated and mono-unsaturated phospholipid species and increases the relative degree of polyunsaturation. Because polyunsaturated acyl chains are more susceptible to peroxidation, inhibition of lipogenesis increases the levels of peroxidation end products and renders cells more susceptible to oxidative stress-induced cell death. As saturated lipids pack more densely, modulation of lipogenesis also alters lateral and transversal membrane dynamics as revealed by diffusion of membrane-targeted green fluorescent protein and by the uptake and response to doxorubicin. These data show that shifting lipid acquisition from lipid uptake toward de novo lipogenesis dramatically changes membrane properties and protects cells from both endogenous and exogenous insults. These findings provide important new insights into the role of de novo lipogenesis in cancer cells, and they provide a rationale for the use of lipogenesis inhibitors as antineoplastic agents and as chemotherapeutic sensitizers.
Deep Sequencing of the Human TCRγ and TCRβ Repertoires Suggests that TCRβ Rearranges After αβ and γδ T Cell Commitment
Authors: Anna M. Sherwood, Cindy Desmarais, Robert J. Livingston, Jessica Andriesen, Maximilian Haussler, Christopher S. Carlson, Harlan Robins
Journal: Science Translational Medicine (2011)

Deep sequencing provides new insights about T cell receptor rearrangement in humans.
Effect of classic preconditioning and diazoxide on endothelial function and O2− and NO generation in the post-ischemic guinea-pig heart
Authors: A BERSEWICZ, M MCZEWSKI, M DUDA
Journal: Cardiovascular Research (2004)

Objectives: A hypothesis was tested that a reaction product between superoxide (O2−) and nitric oxide (NO) mediates post-ischemic coronary endothelial dysfunction that ischemic preconditioning (IPC) protects the endothelium by preventing post-ischemic cardiac O2− and/or NO formation, and that the opening of the mitochondrial ATP-dependent potassium channel (mKATP) plays a role in the mechanism of IPC. Methods: Langendorff-perfused guinea-pig hearts were subjected either to 30 min global ischemia/30 min reperfusion (IR) or were preconditioned prior to IR with three cycles of either 5 min ischemia/5 min reperfusion or 5 min infusion/5 min wash-out of mKATP opener, diazoxide (0.5 μM). Coronary flow responses to acetylcholine (ACh) and nitroprusside were used as measures of endothelium-dependent and -independent vascular function, respectively. Myocardial outflow of O2− and NO, and functional recoveries were followed during reperfusion. Results: IR impaired the ACh response by approximately 60% and augmented cardiac O2− and NO outflow. Superoxide dismutase (150 U/ml) and NO synthase inhibitor, l-NMMA (100 μM) inhibited the burst of O2− and NO, respectively, and afforded partial preservation of the ACh response in IR hearts. NO scavenger, oxyhemoglobin (25 μM), afforded similar endothelial protection. IPC and diazoxide preconditioning attenuated post-ischemic burst of O2−, but not of NO, and afforded a complete endothelial protection. Diazoxide given after 30-min ischemia increased the O2− burst and was not protective. The effects of IPC and diazoxide preconditioning were not affected by HMR-1098 (25 μM), a selective blocker of plasmalemmal KATP, and were abolished by glibenclamide (0.6 μM) and 5-hydroxydecanoate (100 μM), a nonselective and selective mKATP blocker, respectively. 5-Hydroxydecanoate produced similar effects, whether it was given as a continuous treatment or was washed out prior to IR. Conclusion: The results suggest that in guinea-pig heart: (i) a reaction product between O2− and NO mediates the post-ischemic endothelial dysfunction; (ii) the mKATP opening serves as a trigger of the IPC and diazoxide protection; and (iii) the mKATP opening protects the endothelium in the mechanism that involves the attenuation of the O2− burst at reperfusion.
Dual AKT inhibition with perifosine and GCP enhances apoptosis in prostate cancer: Clinical implications
Authors: R. L. Vinall, K. Hwa, C. Pan, P. Ghosh, P. N. Lara, R. W. deVere White
Journal: Journal of Clinical Oncology (2007)

14096 Background: Genistein combined polysaccharide (GCP) has been shown to exhibit anti-cancer properties in both experimental and clinical models of prostate cancer (CaP). Perifosine is an alkylphospholipid with clinical anti-neoplastic activity. Both agents inhibit the AKT signaling pathway. Methods: Prostate cancer cell lines (LNCaP, LNCaP stably transfected with R273H or P151S p53 mutant allele, cds1, and PC3) were treated with GCP, perifosine, or both. IC50 values were established using the MTT assay. Apoptosis was assessed by flow cytometry, Western blot of PARP cleavage, and caspase activity. Clonogenic potential was assessed by colony assay. Status of AKT, p53, p21, AR and PSA was determined by Western blot. All experiments were performed in triplicate. Results: Perifosine inhibited AKT activity in all the cell lines. GCP had little or no effect on AKT activity but reduced AR and PSA levels. The combination of GCP and perifosine further increased the level of AKT inhibition and maintained inhibition for longer when compared to treatment with perifosine alone. Flow cytometric analysis of LNCaP revealed that combination treatment dramatically increased SubG1 levels (23-fold increase versus a 4.4-fold increase for GCP alone and a 6.5% increase for perifosine alone). Apoptosis was confirmed by PARP and caspase analysis. As single agents, the main effect of GCP or perifosine was to induce growth arrest as shown by a decrease in S-phase and increased p21. The cds1 cell line responded similarly to LNCaP, however, cell lines that expressed mutant p53 or were p53 null were not susceptible to GCP/perifosine-induced apoptosis. Combination treatment further decreased the clonogenic potential in all of the cell lines assessed when compared to treatment with the single agents alone. Conclusions: Treatment with a combination of the AKT inhibitors GCP and perifosine dramatically increases apoptosis and/or inhibits clonogenic potential in several CaP cell lines. The effect of the combination treatment on apoptosis appears to be dependent on p53 status. Clinical validation of these findings is warranted. A clinical trial of hormone therapy with or without GCP/perifosine is presently in development. No significant financial relationships to disclose.
Long-term efficacy of a single course of infliximab in hidradenitis suppurativa
Authors: J.R. Mekkes, J.D. Bos
Journal: British Journal of Dermatology (2007)

Background Hidradenitis suppurativa is a chronic inflammatory skin disease characterized by abscess formation, predominantly in the axillae and groins. The disease is difficult to treat and has a severe impact on quality of life. Recently, several case reports have been published describing successful treatment of hidradenitis suppurativa with infliximab and other tumour necrosis factor α inhibitors. Objectives To evaluate the long-term efficacy of a single course of infliximab. Methods Ten patients with severe, recalcitrant hidradenitis were treated with infliximab (three infusions of 5 mg kg−1 at weeks 0, 2 and 6) and followed up for at least 1 year. The disease activity was measured using laboratory parameters and a recently developed acne score. The patients rated the efficacy of infliximab on a 10-point scale at regular intervals. Quality of life was measured before and after treatment using the Dermatology Quality of Life Index (DQLI). Results All patients improved within 2–6 weeks. The average acne score diminished from 164 ± 50 (mean ± SD) before treatment to 89 ± 49 after 1 year (P = 0·002). The mean CRP (C-reactive protein) was reduced from 31·7 mg mL−1 to 5·5 mg mL−1 after 1 month (P = 0·015). Patients judged the efficacy with a score of 7·9. The mean DQLI was reduced from 18·4 ± 7·9 before treatment to 9·3 ± 9·1 after 1 year (P = 0·007). In three patients long-lasting improvement was observed, with no recurrence of lesions in a 2-year follow-up period. The other patients showed recurrence of lesions after 8·5 months (range 4·3–13·4 months). Conclusions Infliximab is an effective treatment in severe hidradenitis suppurativa, leading to reduction of symptoms for a prolonged period.
High Glucose Causes Upregulation of Cyclooxygenase-2 and Alters Prostanoid Profile in Human Endothelial Cells
Authors: Francesco Cosentino, Masato Eto, Paola De Paolis, Bernd van der Loo, Markus Bachschmid, Volker Ullrich, Alexei Kouroedov, Chiara Delli Gatti, Hana Joch, Massimo Volpe, Thomas F. Lüscher
Journal: Circulation (2003)

Background— Prostaglandins generated by cyclooxygenase (COX) have been implicated in hyperglycemia-induced endothelial dysfunction. However, the role of individual COX isoenzymes as well as the molecular mechanisms linking oxidative stress and endothelial dysfunction in diabetes remains to be clarified. Methods and Results— Human aortic endothelial cells were exposed to normal (5.5 mmol/L) and high (22.2 mmol/L) glucose. Glucose selectively increased mRNA and protein expression of COX-2. Its upregulation was associated with an increase of thromboxane A 2 and a reduction of prostacyclin (PGI 2 ) release. Glucose-induced activation of PKC resulted in the formation of peroxynitrite and tyrosine nitration of PGI 2 synthase. NO release was reduced despite 2-fold increase of endothelial NO synthase expression. Phorbol ester caused an increase of COX-2 and endothelial NO synthase expression similar to that elicited by glucose. These effects were prevented by the PKC inhibitor calphostin C. N-acetylcysteine, vitamin C, and calphostin C prevented ROS formation, restored NO release, and reduced colocalization of nitrotyrosine and PGI 2 synthase. Expression of p22 phox , a subunit of NAD(P)H oxidase, was increased, and diphenyleneiodonium inhibited ROS formation. By contrast, indomethacin did not affect glucose-induced ROS generation. Conclusions— Thus, high glucose, via PKC signaling, induces oxidative stress and upregulation of COX-2, resulting in reduced NO availability and altered prostanoid profile.
Molluscum contagiosum and the acquired immunodeficiency syndrome: clinical and immunological details of two cases
Authors: M. KATZMAN, J.T. CAREY, C.A. ELMETS, GRETTA H. JACOBS, M.M. LEDERMAN
Journal: British Journal of Dermatology (1987)

We report here the clinical and immunological findings in two patients with molluscum contagiosum poxvirus infection and the acquired immunodeficiency syndrome (AIDS). These cases support earlier evidence that the molluscum contagiosum virus may act as an opportunistic pathogen. There is now evidence that members of all five families of double stranded DNA‐containing human viruses have been associated with unusual clinical manifestations in AIDS patients, and the significance of DNA virus infections in patients with AIDS is discussed.
Comparison of spatially matched airways reveals thinner airway walls in COPD. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS)
Authors: Benjamin M Smith, Eric A Hoffman, Dan Rabinowitz, Eugene Bleecker, Stephanie Christenson, David Couper, Kathleen M Donohue, Meilan K Han, Nadia N Hansel, Richard E Kanner, Eric Kleerup, Stephen Rennard, R Graham Barr
Journal: Thorax (2014)

<h3>Background</h3> COPD is characterised by reduced airway lumen dimensions and fewer peripheral airways. Most studies of airway properties sample airways based upon lumen dimension or at random, which may bias comparisons given reduced airway lumen dimensions and number in COPD. We sought to compare central airway wall dimensions on CT in COPD and controls using spatially matched airways, thereby avoiding selection bias of airways in the lung. <h3>Methods</h3> The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) recruited smokers with COPD and controls aged 50–79 years and 40–80 years, respectively. COPD was defined by current guidelines. Using CT image data, airway dimensions were measured for all central airway segments (generations 0–6) following 5 standardised paths into the lungs. Case-control airway comparisons were spatially matched by generation and adjusted for demographics, body size, smoking, CT dose, per cent emphysema, airway length and lung volume. <h3>Results</h3> Among 311 MESA COPD participants, airway wall areas at generations 3–6 were smaller in COPD compared with controls (all p&lt;0.001). Among 1248 SPIROMICS participants, airway wall areas at generations 1–6 were smaller (all p&lt;0.001), and this reduction was monotonic with increasing COPD severity (p&lt;0.001). In both studies, sampling airways by lumen diameter or randomly resulted in a comparison of more proximal airways in COPD to more peripheral airways in controls (p&lt;0.001) resulting in the appearance of thicker walls in COPD (p&lt;0.02). <h3>Conclusions</h3> Airway walls are thinner in COPD when comparing spatially matched central airways. Other approaches to airway sampling result in comparisons of more proximal to more distal airways and potentially biased assessment of airway properties in COPD.
Response of rheumatoid arthritis to chemotherapy for Hodgkin's disease in a patient with IgA deficiency and overlap connective tissue disease.
Authors: M G Cohen, B Janssen, J Webb
Journal: Annals of the Rheumatic Diseases (1988)

A patient with IgA deficiency presented with classical rheumatoid arthritis (RA) and subsequently, features of multiple other connective tissue diseases (CTD). When Hodgkin9s disease later developed the patient received combination chemotherapy, which induced remission of both neoplastic and connective tissue diseases. As the RA remained in remission for three years this case may offer insight into a mode of use of cytotoxic agents in CTD.