tbuckley/cabot-search huggingface dataset:
Effects of Long-Term Fenofibrate Treatment on Markers of Renal Function in Type 2 Diabetes
Authors: Carol Forsblom, Anne Hiukka, Eeva S. Leinonen, Jouko Sundvall, Per-Henrik Groop, Marja-Riitta Taskinen
Journal: Diabetes Care (2009)

OBJECTIVE Although fenofibrate was associated with less progression of albuminuria in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, it is unknown if it has any effect on renal function. We explored if there were changes in commonly available markers of renal function during fenofibrate treatment in the FIELD Helsinki cohort excluding statin users. RESEARCH DESIGN AND METHODS One hundred and seventy subjects with type 2 diabetes were randomly assigned to micronized fenofibrate (200 mg/day) or placebo for 5 years. In this substudy, we measured several markers of albumin excretion and renal function. RESULTS After intensified treatment, blood pressure and fasting glucose decreased in both groups while A1C remained at 7.2%. Plasma creatinine increased with fenofibrate while urine creatinine remained comparable between the groups, resulting in significant decreases in both creatinine clearance and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD)-4 and Cockroft-Gault equations in the fenofibrate group. Cystatin C increased during fenofibrate treatment. Urinary albumin-to-creatinine ratio and diurnal urine protein remained unchanged, whereas overnight urinary albumin excretion rate showed minor decreases in both groups. CONCLUSIONS We report concomitant decreases in creatinine clearance and eGFR by fenofibrate. These changes complicate the clinical surveillance during fenofibrate treatment. We could not demonstrate the beneficial effects of fenofibrate on albumin excretion. A novel finding is the increase of cystatin C in type 2 diabetic patients during fenofibrate treatment. The clinical relevance of the changes needs to be assessed in a long-term outcome study of renal function.
Diabetes Risk Assessment in Mexicans and Mexican Americans
Authors: Hector E. Velasco Mondragon, R. William Charlton, Tasha Peart, Ana I. Burguete-Garcia, Mauricio Hernandez-Avila, Wen-Chi Hsueh
Journal: Diabetes Care (2010)

OBJECTIVE Parental diabetes history is a well-known risk factor for type 2 diabetes and considered strong evidence for a genetic basis of type 2 diabetes. Whether this relationship is affected by other known risk factors, specifically obesity, remains unclear, possibly due to a relative paucity of lean diabetic patients. RESEARCH DESIGN AND METHODS This issue was investigated using data from a high-risk population from Mexico (National Health Survey 2000, n = 27,349), with observations replicated using U.S. citizens of Mexican descent from the National Health and Nutrition Examination Survey 2001–2002 and 2003–2004 (n = 1,568). RESULTS As expected, positive parental diabetes was a significant risk factor for type 2 diabetes, regardless of age, sex, or adiposity level. However, positive parental diabetes conferred greater risk in leaner individuals than in their overweight peers (P = 0.001). In other words, the effect of BMI on type 2 diabetes risk was smaller in the presence of parental diabetes history. CONCLUSIONS These findings suggest that parental diabetes is a stronger risk factor for type 2 diabetes in the absence of obesity. Thus, studies in lean diabetic patients could help identify type 2 diabetes susceptibility genes. This study reinforces the concept that parental diabetes and BMI are independent type 2 diabetes risk factors and suggests that glycemic screening may be helpful in assessing type 2 diabetes risk in individuals with parental diabetes history, regardless of their overweight status.
STUDIES OF PHAGOCYTOSIS OF GROUP A STREPTOCOCCI BY POLYMORPHONUCLEAR LEUCOCYTES IN VITRO
Authors: James G. Hirsch, Alice B. Church
Journal: The Journal of Experimental Medicine (1960)

Studies have been made on phagocytosis and killing of Group A streptococci during mixing with suspensions of leucocytes in vitro. Under appropriate test conditions an anti-phagocytic effect can be demonstrated for the streptococcal hyaluronic acid capsule as well as for its M protein. The results obtained suggest an explanation for the suitability of human, but not rabbit, blood for opsonophagocytic tests designed to measure type-specific streptococcal antibodies. Human sera contain a factor which counteracts the anti-phagocytic effects of streptococcal hyaluronic acid capsules, and hence human blood serves well for detection of antibodies which combine with the only other phagocytosis-resisting component of this microorganism, namely M protein. In contrast, rabbit sera contain none of this factor, and addition of antibody to M protein to phagocytic test systems employing rabbit serum does not necessarily render the streptococci susceptible to engulfment by white cells, since the hyaluronic acid capsule may continue to interfere with phagocytosis. The nature of the human serum factor which opsonizes encapsulated streptococci is unknown. It does not appear to be an antibody or an enzyme capable of depolymerizing hyaluronic acid.
Temporal Dissection of Tumorigenesis in Primary Cancers
Authors: Steffen Durinck, Christine Ho, Nicholas J. Wang, Wilson Liao, Lakshmi R. Jakkula, Eric A. Collisson, Jennifer Pons, Sai-Wing Chan, Ernest T. Lam, Catherine Chu, Kyunghee Park, Sung-woo Hong, Joe S. Hur, Nam Huh, Isaac M. Neuhaus, Siegrid S. Yu, Roy C. Grekin, Theodora M. Mauro, James E. Cleaver, Pui-Yan Kwok, Philip E. LeBoit, Gad Getz, Kristian Cibulskis, Jon C. Aster, Haiyan Huang, Elizabeth Purdom, Jian Li, Lars Bolund, Sarah T. Arron, Joe W. Gray, Paul T. Spellman, Raymond J. Cho
Journal: Cancer Discovery (2011)

Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.
Human Airway Eosinophils Exhibit Differential Regulation of ERK and STAT5-Associated Signaling Responses to Interleukin-5 (IL-5) and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF)
Authors: C.J. Koziol, M. Bates, P.J. Bertics
Journal: Journal of Allergy and Clinical Immunology (2007)
Peak flow rate records in surveys: reproducibility of observers' reports.
Authors: K M Venables, P S Burge, A G Davison, A J Newman Taylor
Journal: Thorax (1984)

Records of peak expiratory flow rate (PEFR), commonly used in hospital in the management of asthma, have not been evaluated as a method of identifying cases of asthma in population surveys. Four observers were asked to report on whether asthma was present or absent in 61 graphs of PEFR recorded two hourly for four weeks during surveys of working population. Agreement within individual observers was measured using a subset of 29 graphs which had been copied and distributed at random among the set of 61; agreement was good, from 90% in one observer to 100% in two. Agreement between observers was measured on the basis of all 61 graphs. Agreement occurred between all four observers in 69% of graphs, between at least three out of four in 97%, and, when pairs of observers were examined, between 72% and 93% of graphs. Graphs assessed as showing asthma demonstrated more within day PEFR variability (expressed as the number of days in which the difference between maximum and minimum readings was at least 15%) than graphs assessed as not showing asthma. Some graphs with little within day variability were assessed as showing asthma, apparently because they demonstrated between day PEFR variability.
Exercise Capacity and Body Mass as Predictors of Mortality Among Male Veterans With Type 2 Diabetes
Authors: Paul A. McAuley, Jonathan N. Myers, Joshua P. Abella, Swee Y. Tan, Victor F. Froelicher
Journal: Diabetes Care (2007)

To demonstrate the relation of exercise capacity and BMI to mortality in a population of male veterans with type 2 diabetes.After excluding two underweight patients (BMI <18.5 kg/m2), the study population comprised 831 consecutive patients with type 2 diabetes (mean age 61 +/- 9 years) referred for exercise testing for clinical reasons between 1995 and 2006. Exercise capacity was determined from a maximal exercise test and measured in metabolic equivalents (METs). Patients were classified both according to BMI category (18.5-24.9, 25.0-29.9, and > or =30 kg/m2) and by exercise capacity (<5.0 or > or =5.0 maximal METs). The association among exercise capacity, BMI, other clinical variables, and all-cause mortality was assessed by Cox proportional hazards. Study participants were followed for mortality up to 30 June 2006.During a mean follow-up of 4.8 +/- 3.0 years, 112 patients died, for an average annual mortality rate of 2.2%. Each 1-MET increase in exercise capacity conferred a 10% survival benefit (hazard ratio 0.90 [95% CI 0.82-0.98]; P = 0.01), but BMI was not significantly associated with mortality. After adjustment for age, ethnicity, examination year, BMI, presence of cardiovascular disease (CVD), and CVD risk factors, diabetic patients achieving <5 maximal METs were 70% more likely to die (1.70 [1.13-2.54]) than those achieving > or =5 maximal METs.There was a strong inverse association between exercise capacity and mortality in this cohort of men with documented diabetes, and this relationship was independent of BMI.
Validation of a Novel Point-of-Care Nerve Conduction Device for the Detection of Diabetic Sensorimotor Polyneuropathy
Authors: Bruce A. Perkins, Jaspreet Grewal, Eduardo Ng, Mylan Ngo, Vera Bril
Journal: Diabetes Care (2006)

OBJECTIVE—The diagnosis of diabetic sensorimotor polyneuropathy using objective electrophysiological tests is hindered by limited access to the specialized laboratories and technicians that perform and interpret them. We evaluated the performance characteristics of a novel portable and automated point-of-care nerve conduction study device, which can be operated by nontechnical personnel, and compared it with conventional nerve conduction studies performed in a specialist setting. RESEARCH DESIGN AND METHODS—Seventy-two consecutive patients with diabetes (8 type 1, 64 type 2) from a diabetes and a neuropathy outpatient clinic were evaluated concurrently with conventional nerve conduction studies (the reference standard) and the point-of-care device for sural nerve function (sural nerve amplitude potentials in microvolts [μV]). RESULTS—Sural nerve amplitude potentials measured by the point-of-care device shared very strong correlation with the reference standard (Spearman’s correlation coefficient 0.95, P &amp;lt; 0.001). The Bland and Altman method yielded agreement despite a small systematic underestimation by the point-of-care device of 1.2 ± 3.4 μV. Despite this small systematic bias, the sensitivity and specificity of normal and abnormal sural nerve amplitude potentials measured by the point-of-care device for the detection of diabetic sensorimotor polyneuropathy defined by standard clinical and electrophysiological criteria were 92 and 82%, respectively. CONCLUSIONS—A novel point-of-care device has excellent diagnostic accuracy for detecting electrophysiological abnormality in the sural nerve of patients who have diabetes. This automated device represents an alternative to conventional nerve conduction studies for the diagnosis of diabetic sensorimotor polyneuropathy.
Spontaneous and induced immunoglobulin secretion by synovial fluid B lymphocytes in rheumatoid arthritis.
Authors: J Petersen, T Ingemann-Hansen, J.S Halkjaer-Kristensen
Journal: Annals of the Rheumatic Diseases (1984)

The functional properties of B lymphocytes in synovial fluid (SF) from patients with rheumatoid arthritis (RA) were analysed by means of a reverse haemolytic plaque forming cell (PFC) assay. SF mononuclear cells spontaneously secreted IgG, but little IgM or IgA. The SF cells failed to respond to the polyclonal B cell activators pokeweed mitogen (PWM) and Epstein-Barr virus. However, SF B cells cocultured with autologous T lymphocytes from the blood and stimulated with PWM secreted IgG but little IgM or IgA. The PFC responses of blood B cells cocultured with autologous SF T cells in the presence of PWM were low; irradiation of the T cells increased the blood B lymphocyte responses, but the differences were not statistically significant. It is concluded that suppressor SF T cells may be partly responsible for the poor response of SF B cells to PWM.
Blood Loss Associated with Ring Uncemented Total Knee Replacement: Comparison between Continuous and Intermittent Suction Drainage
Authors: F W Wittmann, P A Ring
Journal: Journal of the Royal Society of Medicine (1984)

In a retrospective comparison of blood loss following uncemented total knee replacement, in which either continuous or intermittent suction drainage was used, measured blood loss was significantly greater with continuous drainage. However, a method of calculating actual blood loss demonstrated no significant difference. With intermittent drainage, more blood remains undetected around the knee joint; this technique should therefore be abandoned in favour of continuous suction drainage.
Increased excretion of soluble interleukin 2 receptors and free light chain immunoglobulins in the urine of patients with active lupus nephritis.
Authors: C.Y Tsai, T.H Wu, K.H Sun, W.M Lin, C.L Yu
Journal: Annals of the Rheumatic Diseases (1992)

Samples of protein from the urine of 23 patients with lupus nephropathy and 15 patients with proteinuria who did not have systemic lupus erythematosus (SLE) were studied for the presence of cytokines, soluble interleukin 2 receptors (sIL-2R), and free light chain immunoglobulins. The patients with lupus nephropathy were divided into two groups with active (nephritis) and inactive inflammation (nephrosis) based on the results of the analysis of urine samples and renal histology. The crude urine proteins (5 mg/ml) after precipitation by 80% ammonium sulphate from 14 patients with lupus nephritis contained higher concentrations of sIL-2R (4.88 (SEM 1.27 ng/ml) than those from nine patients with nephrosis (1.11 (0.52) ng/ml) or 15 patients without SLE (1.31 (0.87) ng/ml). The concentration of sIL-2R in protein from urine samples was not correlated with the concentration in plasma and was inversely correlated with the excretion of protein in urine over 24 hours in patients with SLE. It is suggested that, in addition to leakage from the circulation, the local production of sIL-2R by inflamed kidneys is possible. The crude proteins in urine were further fractionated by gel filtration on Sephacryl S-200. Arbitrarily, four fractions could be obtained from urine from patients with SLE but only three fractions were found in the urine of patients without SLE. Fraction IV derived from patients with nephritis or nephrosis augmented the pokeweed mitogen induced [3H]thymidine uptake of mononuclear cells. In addition, the positive rates of free kappa (kappa) (35.7%) and lambda (lambda) (42.9%) chains in proteins in urine from nephritic patients were higher than those in the other two groups. These results suggest that the severity of inflammation in the kidneys of patients with lupus can be reflected by the increased excretion of sIL-2R, free light chain immunoglobulins, and cytokine-like molecules in urine.
Nuclear factor-kappa B interacts functionally with the platelet-derived growth factor B-chain shear-stress response element in vascular endothelial cells exposed to fluid shear stress.
Authors: L M Khachigian, N Resnick, M A Gimbrone, T Collins
Journal: Journal of Clinical Investigation (1995)

Hemodynamic forces, such as fluid shear stress, that act on the endothelial lining of the cardiovascular system can modulate the expression of an expanding number of genes crucial for homeostasis and the pathogenesis of vascular disease. A 6-bp core element (5'-GAGACC-3'), defined previously as a shear-stress response element is present in the promoters of many genes, including the PDGF B-chain, whose expression is modulated by shear stress. The identity of the nuclear protein(s) binding to this element has not yet been elucidated. Using electrophoretic mobility shift assays and in vitro DNase I footprinting, we demonstrate that nuclear factor-kappa B p50-p65 heterodimers, which accumulate in the nuclei of cultured vascular endothelial cells exposed to fluid shear stress, bind to the PDGF-B shear-stress response element in a specific manner. Mutation of this binding motif abrogated its interaction with p50-p65 and abolished the ability of the promoter to mediate increased gene expression in endothelial cells exposed to shear stress. Transient cotransfection studies indicate that p50-p65 is able to activate PDGF-B shear-stress response element-dependent reporter gene expression in these cells. These findings thus implicate nuclear factor-kappa B in the transactivation of an endothelial gene responding to a defined fluid mechanical force.
Comparison of Epoxide and Free-Radical Mechanisms for Activation of Benzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene by Sprague-Dawley Rat Liver Microsomes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: James K. Selkirk
Journal: JNCI Journal of the National Cancer Institute (1980)

Coincubation of [6-3H]benzo[a]pyrene ([6-3H]BP) and [14C]BP with SD rat liver microsomes produced metabolic profiles that showed that the C-6 of BP was not affected by formation of 4,5-dihydro-4,5-dihydroxy-BP, 7,8-dihydro-7,8-dihydroxy-BP, and 9,10-dihydro-9,10-dihydroxy-BP nor the 3- and 9-phenols of BP. Complete retention of tritium at C-6, except in the three quinones, confirmed the radical-cation model for formation of the 6-oxo-radical followed by oxidation to quinones. Epoxide formation at the carcinogenically active regions of BP appeared to biochemically isolate from 6-position activation and suggested that the microsomal epoxide pathway is unrelated to the radicalcation scheme. These molar ratios derived from double-label experiments reinforced the current literature that indicates the epoxide mechanism as the major pathway toward carcinogenic forms of BP.
Venous thromboembolism and survival in patients with high-grade glioma
Authors: Ralph Simanek, Rainer Vormittag, Marco Hassler, Karl Roessler, Martin Schwarz, Christoph Zielinski, Ingrid Pabinger, Christine Marosi
Journal: Neuro-Oncology (2007)

Patients with malignancy, particularly patients with high-grade glioma (HGG; WHO grade III/IV), have an increased risk of venous thromboembolism (VTE). It has been suggested that VTE predicts survival in cancer patients. The aim of our study was to investigate the occurrence of symptomatic VTE and its impact on survival in patients with HGG. Consecutive patients (n = 63; 36 female, 27 male; median age, 58 years) who had neurosurgical intervention between October 2003 and December 2004 were followed after surgery until October 2005. Objectively confirmed VTE was recorded as an event. All patients had received thrombosis prophylaxis with low-molecular-weight heparin (LMWH) during the immediate postoperative period. Subsequently, 56 patients received radiochemotherapy, 6 radiotherapy, and 1 chemotherapy only. Patients were followed over a median time period of 348 days. Fifteen patients (24%) developed VTE. Pulmonary embolism was diagnosed in nine patients (60%) and was fatal twice. The cumulative probability of VTE was 21% after three months and 26% after 12 months. The highest frequency of VTE was observed in patients with biopsy and subtotal tumor resection (n = 37; multivariate hazard ratio, 3.58; 95% CI = 0.98-13.13; P = 0.054) compared with patients with total resection. Survival did not significantly differ among patients with and without VTE and was 53% after 12 months in both groups. Patients with HGG, particularly those with biopsy and subtotal resection, are at high risk to develop VTE postoperatively. Thrombosis was not associated with a significant reduction of survival.
Tumor-Expressed B7-H1 and B7-DC in Relation to PD-1+ T-Cell Infiltration and Survival of Patients with Cervical Carcinoma
Authors: Rezaul Karim, Ekaterina S. Jordanova, Sytse J. Piersma, Gemma G. Kenter, Lieping Chen, Judith M. Boer, Cornelis J. M. Melief, Sjoerd H. van der Burg
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The interaction between programmed cell death 1 (PD-1), expressed by activated effector or regulatory T cells, and B7-H1 (PD-L1) and B7-DC (PD-L2) results in the inhibition of T-cell function. The aim of this study was to determine B7-H1, B7-DC, and PD-1 expression in cervical carcinoma. Experimental Design: A tissue microarray of a well-defined group of 115 patients was stained with antibodies against B7-H1 and B7-DC. Three-color fluorescent immunohistochemistry was used to study the number and phenotype of tumor-infiltrating T cells expressing PD-1. Additional analyses consisted of in vitro T-cell suppression assays. Results: B7-H1 was expressed in 19%, and B7-DC was expressed by 29% of the 115 tumors. PD-1 was expressed by more than half of both the infiltrating CD8+ T cells and CD4+Foxp3+ T cells, irrespective of B7-H1 or B7-DC expression by tumors. The expression of B7-H1 did not show a direct impact on patient survival. However, subgroup analysis revealed that patients with a relative excess of infiltrating regulatory T cells displayed a better survival when the tumor was B7-H1 positive (P = 0.033). Additional studies showed that the presence of B7-H1 during the activation of CD4+Foxp3+ regulatory T cells impaired their suppressive function in a functional in vitro assay. Conclusions: B7-H1 is expressed on only a minority of cervical cancers and does not influence the survival of patients with cervical cancer. PD-1 is expressed by a vast number of infiltrating CD8 T cells, suggesting that blocking of PD-1 could have therapeutic potential in cervical cancer patients. (Clin Cancer Res 2009;15(20):6341–7)