tbuckley/cabot-search huggingface dataset:
Impaired Skin Microvascular Reactivity in Painful Diabetic Neuropathy
Authors: Cristian Quattrini, Nigel D. Harris, Rayaz A. Malik, Solomon Tesfaye
Journal: Diabetes Care (2007)

The pathogenesis of painful diabetic neuropathy (PDN) is not clear. Following our in vivo observations of increased sural nerve epineurial blood flow in patients with PDN, we investigated the cutaneous microcirculation of the foot by laser Doppler flowmetry to determine if the epineurial findings were just confined to the nerve or more widespread in other vascular beds.We measured foot skin vasodilator responses to acetylcholine (Ach) and sodium nitroprusside (SNP) and vasoconstrictor responses to sympathetic (deepest possible gasp) stimulation in 5 healthy control subjects, 10 non-neuropathic diabetic (NND) patients, 10 diabetic patients with painless neuropathy (PLDN), and 8 diabetic patients with PDN.In PDN, there were significantly reduced responses to Ach (ANOVA P = 0.003) and vasoconstrictor inspiratory gasp (ANOVA P < 0.001) but not to SNP (NS). Post hoc analysis showed significant differences in Ach-induced vasodilation between PDN and nondiabetic control subjects (P < 0.05) as well as between PDN and NND (P < 0.05) but not PDN and PLDN (NS). There were no significant differences for SNP-induced vasodilation. However, there were significant differences in the vasoconstrictor response between PDN and control, NND, and PLDN (P < 0.01).We found an impairment of cutaneous endothelium-related vasodilation and C-fiber-mediated vasoconstriction in PDN. Inappropriate local blood flow regulation may have a role in the pathogenesis of pain in diabetic neuropathy. Prospective studies are required to determine the temporal relationship of these changes in relation to the emergence of neuropathic pain.
Hydrolytically activated etoposide prodrugs inhibit MDR-1 function and eradicate established MDR-1 multidrug-resistant T-cell leukemia
Authors: Ulrike Schroeder, Kathrin M. Bernt, Björn Lange, Jens Wenkel, Jiang Jikai, Doron Shabat, Roey Amir, Nicole Huebener, Andreas G. Niethammer, Christian Hagemeier, Lüder Wiebusch, Gerhard Gaedicke, Wolfgang Wrasidlo, Ralph A. Reisfeld, Holger N. Lode
Journal: Blood (2003)
Oxaliplatin and protracted continuous 5-fluorouracil infusion in patients with pretreated advanced colorectal carcinoma
Authors: A. Martoni, E. Mini, C. Pinto, S. Nobili, A.L. Gentile, P. Dentico, B. Angelelli, S. Scicolone, E. Piana, T. Mazzei
Journal: Annals of Oncology (2001)
Measuring tidal volume and functional residual capacity change in sleeping infants using a volume displacement plethysmograph
Authors: SJ Wilson, C O'Brien, MA Harris, IB Masters
Journal: European Respiratory Journal (1998)

The noninvasive measurement of infant lung function during unsedated sleep in infants has been a long-standing objective in paediatric respiratory medicine. This note reports on the design and performance of a head-out volume-displacement plethysmograph (VDP) that overcomes some of the limitations of traditional lung function apparatus. The VDP comprises a rigid acrylic box with an integral water-sealed spirometer and a novel neck seal. The bilayer neck seal is of variable compliance and is comfortable and simple to use. The spirometer permits volume resolution of 1.5 mL and a dynamic range in excess of 100 mL. The frequency response extends from 0-7 Hz. Spirometer inertance was measured as 0.0015 kPa.L(-1).s(-2), resistance 0.021 kPa.L(-1).s(-1) and box capacitance 0.18L.kPa(-1). Tidal volume, respiratory rate and changes in functional residual capacity can be recorded during unsedated rapid eye movement and nonrapid eye movement whilst monitoring with conventional polysomnographic methods. The head-out configuration allows additional instrumentation to be implemented with ease, avoids facial stimulation and allows unimpeded access to the upper airway. A polysomnograph illustrating the limitations of respiratory inductance plethysmography signals and typical changes in functional residual capacity are shown.
Validation Microsatellite Path Score in a Population-Based Cohort of Patients With Colorectal Cancer
Authors: Xavier Bessa, Cristina Alenda, Artemio Paya, Cristina Álvarez, Mar Iglesias, Agustín Seoane, Josep Maria Dedeu, Anna Abulí, Lucas Ilzarbe, Gemma Navarro, Maria Pellise, Francesc Balaguer, Sergi Castellvi-Bel, Xavier LLor, Antoni Castells, Rodrigo Jover, Montserrat Andreu
Journal: Journal of Clinical Oncology (2011)

Bethesda guidelines are used to recognize patients at risk for Lynch syndrome. However, obtaining personal and familial tumor data can sometimes be difficult. The Microsatellite Path Score (MsPath), a pathological score, based on age, tumor location, and pathologic features, has been developed to effectively predict colorectal cancer with DNA mismatch repair (MMR) deficiencies. However, the MsPath model's performance in an unselected, population-based colorectal cancer (CRC) population is unknown.We analyzed all patients with CRC regardless of age, personal or family history, and tumor characteristics from the EPICOLON study, an independent, prospective, multicenter, population-based cohort (N = 1,222). All patients underwent tumor microsatellite instability (MSI) analysis and immunostaining for MLH1/MSH2, and those with MMR underwent tumor BRAF mutation analysis and MLH1/MSH2 germline testing. All the pathologic features were centralized and evaluated blinded to the MMR status.MsPath score for prediction of having MSI high, with the recommended MsPath cutoff score ≥1.0, had a sensitivity, specificity, and positive predictive value (PPV) of 92.8% (95% CI, 86.9 to 98.3), 64.1% (95% CI, 61.1 to 66.8), and 15.8% (95% CI, 12.2 to 18.6), respectively. MsPath score had a sensitivity, specificity, and PPV of 81.8% (95% CI, 59.0 to 99.8), 60.6% (95% CI, 57.8 to 63.4), and 1.9% (95% CI, 0.7 to 3.1), respectively, for the identification of MLH1/MSH2 gene carriers. Application of the MsPath score, resulted in two (18%) of 11 mutation carriers being missed, both pathogenic germline MSH2 mutations.In the general nonselected population, the MsPath score accurately predicted the probability of bearing a MSI high CRC, but it was insufficiently accurate to use for the selection of patients warranting MLH1/MSH2 mutation testing in the setting of Lynch syndrome.
Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice.
Authors: C Pászty, N Maeda, J Verstuyft, E M Rubin
Journal: Journal of Clinical Investigation (1994)

Apolipoprotein E (apo E)-deficient mice are severely hypercholesterolemic and develop advanced atheromas independent of diet. The C57BL/6 strain differs from most inbred strains by having lower HDL concentrations and a high risk of developing early atherosclerotic lesions when fed an atherogenic diet. The relative HDL deficiency and atherosclerosis susceptibility of the C57BL/6 strain are corrected with the expression of a human apolipoprotein AI (apo AI) transgene in this genetic background. To examine if increases in apo AI and HDL are also effective in minimizing apo E deficiency--induced atherosclerosis, we introduced the human apo AI transgene into the hypercholesterolemic apo E knockout background. Similar elevations of total plasma cholesterol occurred in both the apo E knockout and apo E knockout mice also expressing the human apo AI transgene. The latter animals, however, also showed a two- to threefold increase in HDL and a sixfold decrease in susceptibility to atherosclerosis. This study demonstrates that elevating the concentration of apo AI reduces atherosclerosis in apo E deficient-mice and suggests that elevation of apo AI and HDL may prove to be a useful approach for treating unrelated causes of heightened atherosclerosis susceptibility.
Stable SET knockdown in head and neck squamous cell carcinoma promotes cell invasion and the mesenchymal-like phenotype in vitro, as well as necrosis, cisplatin sensitivity and lymph node metastasis in xenograft tumor models
Authors: Lays M Sobral, Lucas O Sousa, Ricardo D Coletta, Hamilton Cabral, Lewis J Greene, Eloiza H Tajara, J Silvio Gutkind, Carlos Curti, Andréia M Leopoldino
Journal: Molecular Cancer (2014)

SET/I2PP2A is a multifunctional protein that is up-regulated in head and neck squamous cell carcinoma (HNSCC). The action of SET in HNSCC tumorigenicity is unknown. Stable SET knockdown by shRNA (shSET) was established in three HNSCC cell lines: HN12, HN13, and Cal27. Protein expression and phosphorylated protein levels were determined by Western blotting and immunofluorescence, cell migration and invasion were measured by functional analysis, and PP2A activity was determined using a serine/threonine phosphatase assay. A real-time PCR array was used to quantify 84 genes associated with cell motility. Metalloproteinase (MMP) activity was assessed by zymographic and fluorometric assays. HN12shSET xenograft tumors (flank and tongue models) were established in Balb/c nude mice; the xenograft characteristics and cisplatin sensitivity were demonstrated by macroscopic, immunohistochemical, and histological analyses, as well as lymph node metastasis by histology. The HN12shSET cells displayed reduced ERK1/2 and p53 phosphorylation compared with control. ShSET reduced HN12 cell proliferation and increased the sub-G1 population of HN12 and Cal27 cells. Increased PP2A activity was also associated with shSET. The PCR array indicated up-regulation of three mRNAs in HN12 cells: vimentin, matrix metalloproteinase-9 (MMP9) and non-muscle myosin heavy chain IIB. Reduced E-cadherin and pan-cytokeratin, as well as increased vimentin, were also demonstrated as the result of SET knockdown. These changes were accompanied by an increase in MMP-9 and MMP-2 activities, migration and invasion. The HN12shSET subcutaneous xenograft tumors presented a poorly differentiated phenotype, reduced cell proliferation, and cisplatin sensitivity. An orthotopic xenograft tumor model using the HN12shSET cells displayed increased metastatic potential. SET accumulation has important actions in HNSCC. As an oncogene, SET promotes cell proliferation, survival, and resistance to cell death by cisplatin in vivo. As a metastasis suppressor, SET regulates invasion, the epithelial mesenchymal transition, and metastasis.
Nitric oxide-mediated effects of interleukin-6 on [Ca2+]i and cell contraction in cultured chick ventricular myocytes.
Authors: K Kinugawa, T Takahashi, O Kohmoto, A Yao, T Aoyagi, S Momomura, Y Hirata, T Serizawa
Journal: Circulation Research (1994)

Cytokines have significant roles in some cardiovascular disorders, but direct myocardial effects of cytokines remain to be elucidated. In the present study, we examined both the early and delayed effects of interleukin-6 (IL-6) on cultured chick embryo ventricular myocytes. Exposure of these cells to human recombinant IL-6 significantly decreased peak systolic [Ca2+]i (71.0 +/- 0.6% of the control value) and the amplitude of cell contraction (66.0 +/- 7.4% of the control value) within a few minutes. Pretreatment with NG-monomethyl-L-arginine (L-NMMA) or methylene blue completely inhibited the IL-6-induced early changes. Subsequent addition of L-arginine reversed the effects of L-NMMA. The levels of cGMP were significantly increased after 30 minutes of exposure to IL-6 (134.4 +/- 9.1% of the control value). Pretreatment with L-NMMA or EGTA significantly inhibited the IL-6-induced early elevation of cGMP. These results suggest that IL-6 acutely decreases intracellular Ca2+ transients and depresses cell contraction by nitric oxide (NO)-cGMP-mediated pathway. Therefore, IL-6 may enhance the Ca(2+)-dependent constitutive NO synthase activity in cardiac myocytes. On the other hand, 24-hour exposure to IL-6 also increased the levels of cGMP (159.0 +/- 22.8% of the control value) regardless of pretreatment with EGTA. These delayed increases in cGMP were also shown to be coupled with decreases in intracellular Ca2+ transients and the amplitude of cell contraction. Thus, IL-6 may induce Ca(2+)-independent NO synthase in cardiac myocytes. Together with the previous reports that have suggested the possible roles of IL-6 in myocardial stunning or endotoxic shock, this negative inotropic effect of IL-6 may contribute to these clinical settings.
Sarcoidosis with Arthritis
Authors: F. A. Bianchi, M. K. Keech
Journal: Annals of the Rheumatic Diseases (1964)

Sarcoidosis is a systemic granulomatous disease of undetermined aetiology and pathogenesis.Mediastinal and peripheral lymph nodes, lungs, liver, spleen, skin, eyes, phalangeal bones, and parotid glands are most often involved, but other organs or tissues may be affected.The Kveim reaction is frequently positive, and tuber- culin-type hypersensitivities are frequently depressed.Other important laboratory findings are hypercaluria and increased serum globulins.The characteristic histologic appearance of epithelioid tubercles with little or no necrosis is not pathognomonic, and tuberculosis, fungal infections, beryllium disease, and local sarcoid reactions must be excluded.The diagnosis should be regarded as established for clinical purposes in patients who have consistent clinical features, together with biopsy evidence of epithelioid tubercles or a positive Kveim test."(Definition prepared by the 1960 International Conference on Sarcoidosis, held in Washington, D.C.)The twelve patients (all Negroes), who are discussed below, were seen in a rheumatology clinic within a period of 18 months.At least nine of the twelve were first diagnosed as cases of arthritis, so that a detailed report of the tests carried out and * U.S.
Descriptions of spinal MRI lesions and definition of a positive MRI of the spine in axial spondyloarthritis: a consensual approach by the ASAS/OMERACT MRI study group
Authors: Kay-Geert A Hermann, Xenofon Baraliakos, Désirée MFM van der Heijde, Anne-Grethe Jurik, Robert Landewé, Helena Marzo-Ortega, Mikkel Østergaard, Martin Rudwaleit, Joachim Sieper, Jürgen Braun
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> The aim of this study was to define characteristic MRI findings in the spine of patients with axial spondyloarthritis (SpA) and provide a definition of a positive spinal MRI for inflammation and structural changes. <h3>Methods</h3> Technical details of spinal MRI and the description of spinal lesions of both inflammation and structural changes were discussed in consecutive meetings of 10 experts of the Assessment in SpondyloArthritis international Society (ASAS). The discussions aimed at a broad consensus on definitions of 'a positive spinal MRI' for both types of lesions and were backed up by a systematic literature search. <h3>Results</h3> A total of six different types of lesions were described for inflammation—anterior/posterior spondylitis, spondylodiscitis, arthritis of costovertebral joints, arthritis of zygoapophyseal joints and enthesitis of spinal ligaments—and another four for structural changes—fatty deposition, erosions, syndesmophytes and ankylosis. In the literature review, four relevant papers were identified. Anterior/posterior spondylitis and fat depositions at vertebral edges were considered as the most typical findings in SpA. Based on expert consensus and taking the literature review into consideration, a positive spinal MRI for inflammation was defined as the presence of anterior/posterior spondylitis in ≥3 sites. Evidence of fatty deposition at several vertebral corners was found to be suggestive of axial SpA, especially in younger adults. ASAS members (n=56) approved these definitions by voting in January 2010. <h3>Conclusions</h3> This consensus statement gives clear descriptions of disease-related spinal lesions and of definitions of a positive spinal MRI for inflammatory lesions (spondylitis) and structural changes (fat deposition). These definitions can be used to describe findings of spinal MRI in patients with SpA in daily practice and clinical studies.
Selective Cumulative Inhibition of Platelet Thromboxane Production by Low-dose Aspirin in Healthy Subjects
Authors: Paola Patrignani, Paola Filabozzi, Carlo Patrono
Journal: Journal of Clinical Investigation (1982)

Acetylation of platelet cyclooxygenase by oral aspirin is dose dependent and cumulative with repeated administration. However, no single dose of aspirin has been found to be completely selective of platelet thromboxane (TX) synthesis inhibition in man. We determined the dose dependence, cumulative nature and selectivity of aspirin effects on platelet TXB2 and renal prostaglandin (PG) and prostacyclin (PGI2) production. We measured, by radioimmunoassay, serum TXB2 levels after whole blood clotting and urinary excretion of PGE2, PGF2α, and 6-keto-PGF1α, before and after single or repeated oral aspirin doses given to 46 healthy subjects. Single doses of 6-100 mg aspirin resulted in a linear (r = 0.92, P < 0.01) inhibition of platelet TXB2 production, ranging from 12 to 95% after 24 h. A daily dose of 0.45 mg/kg given for 7 d produced a cumulative and virtually complete inhibition of platelet TXB2 production, without significantly reducing the urinary excretion of PGE2, PGF2α, and 6-keto-PGF1α in both healthy men and women. The platelet inhibitory effect of this regimen was maintained unaltered throughout 1 mo of therapy, with no evidence of cumulative inhibition of renal PG-synthesis. Moreover, furosemide-induced renal PGI2 synthesis and renin release were unaffected by chronic low-dose aspirin. Following cessation of aspirin therapy, platelet TXB2 production returned toward control values at a similar rate as after a single higher dose.
Immunogenicity, adalimumab levels and clinical response in ankylosing spondylitis patients during 24 weeks of follow-up
Authors: Eva L Kneepkens, James Cheng-Chung Wei, Michael T Nurmohamed, Kai-Jieh Yeo, C Y Chen, Irene E van der Horst-Bruinsma, Desiree van der Kleij, Theo Rispens, Gertjan Wolbink, Charlotte L M Krieckaert
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Immunogenicity influences adalimumab levels and therefore clinical response in patients with rheumatic diseases. <h3>Objectives</h3> To study the relationship between clinical response, adalimumab levels and antidrug antibodies (ADAb) in ankylosing spondylitis (AS). <h3>Methods</h3> Observational cohort study of 115 consecutive AS patients treated with adalimumab in the Netherlands (n=85) and Taiwan (n=30), monitored during 24 weeks. Adalimumab levels and ADAb titres were determined using an ELISA and an antigen binding test (ABT), respectively, designed by Sanquin Research, Amsterdam. Response to adalimumab treatment was defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) response, and disease activity was measured using the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (CRP) (ASDAS). <h3>Results</h3> At baseline, median BASDAI (IQR) was 6.4 (4.5–7.6) and mean ASDAS (SD) was 3.5 (1.0). After 24 weeks, 49 (42.6%) patients were BASDAI50 responders and mean ASDAS (SD) for responders was 1.5 (1.0) vs 2.6 (1.0) for non-responders (p&lt;0.001). Thirty-one (27.0%) patients had detectable ADAb. After 24 weeks, adalimumab levels (mg/L) (IQR) were significantly higher in ADAb-negative patients than in ADAb-positive patients (12.7 (8.2–18.0) vs 1.2 (0.0–2.0), (p&lt;0.001)). A significant association was demonstrated between adalimumab levels and ASDAS (p=0.02; RC −1.1; 95% CI −2.0 to −0.2). Eleven (9.6%) patients had no detectable adalimumab levels and high detectable ADAb titres (&gt;100 AU/mL). In these patients, CRP and erythrocyte sedimentation rate remained elevated during treatment. <h3>Conclusions</h3> Adalimumab levels are related to clinical response in AS patients measured with ASDAS and are influenced by ADAb detectable with an ABT.
Effects of a Functional COMT Polymorphism on Prefrontal Cognitive Function in Patients With 22q11.2 Deletion Syndrome
Authors: Carrie E. Bearden, Abbas F. Jawad, David R. Lynch, Set Sokol, Steven J. Kanes, Donna M. McDonald-McGinn, Sulagna C. Saitta, Stacy E. Harris, Edward Moss, Paul P. Wang, Elaine Zackai, Beverly S. Emanuel, Tony J. Simon
Journal: American Journal of Psychiatry (2004)

The 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) is associated with attentional problems and executive dysfunction, and is one of the highest known risk factors for schizophrenia. These behavioral manifestations of 22q11.2 deletion syndrome could result from haploinsufficiency of the catechol O-methyltransferase (COMT) gene, located within the 22q11 region. The goal of the present study was to examine COMT genotype as a predictor of prefrontal cognitive function in patients with 22q11.2 deletion syndrome.Patients with confirmed 22q11.2 deletions (N=44) underwent neurocognitive testing following Val(158)Met genotyping (Met hemizygous: N=16; Val hemizygous: N=28).Analyses of covariance revealed that Met-hemizygous patients performed significantly better on a composite measure of executive function (comprising set-shifting, verbal fluency, attention, and working memory) than did Val-hemizygous patients.These data are consistent with those of previous studies in normal individuals, suggesting that a functional genetic polymorphism in the 22q11 region may influence prefrontal cognition in individuals with COMT haploinsufficiency.
Chronic thromboembolic pulmonary hypertension: clinical picture and surgical treatment
Authors: KM Moser, WR Auger, PF Fedullo, SW Jamieson
Journal: European Respiratory Journal (1992)

Chronic, major vessel thromboembolic pulmonary hypertension (CTEPH), is an uncommon condition which, in the past, was an autopsy curiosity. Advances in diagnostic approaches, surgical techniques and postoperative management have transformed this disorder into a potentially curable form of pulmonary hypertension. The predominant symptom is unexplained dyspnoea on exertion. In patients with this complaint, CTEPH should be considered. Numerous pitfalls exist along the diagnostic path. Perfusion lung scans point toward the diagnosis, but often underestimate the extent of central arterial obstruction. Pulmonary angiography is the key diagnostic procedure, but the many patterns of thrombus organization-recanalization require a base of experience for proper interpretation. Criteria for selection of patients for surgery are evolving, but assurance of thrombus accessibility to surgery is critical. Surgical thromboendarterectomy bears no resemblance to acute pulmonary embolectomy. Recognition of thrombus (versus normal intima), meticulous dissection and a bloodless surgical field are essential for adequate restoration of pulmonary vascular patency. Multiple complications may arise postoperatively, and detailed attention to these is required for patient survival. With a co-ordinated, multi-specialty team effort, however, haemodynamic and clinical outcomes have been rewarding and persist long-term. Surgical mortality should steadily decline with such a co-ordinated effort, as well as earlier diagnosis and advances in surgical and postoperative management techniques.