tbuckley/cabot-search huggingface dataset:
Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury
Authors: Prabal K. Chatterjee, Nimesh S.A. Patel, Espen O. Kvale, Salvatore Cuzzocrea, Paul A.J. Brown, Keith N. Stewart, Helder Mota-Filipe, Christoph Thiemermann
Journal: Kidney International (2002)
Gene Expression of Parathyroid Tumors
Authors: Carola J. Haven, Viive M. Howell, Paul H. C. Eilers, Robert Dunne, Masayuki Takahashi, Marjo van Puijenbroek, Kyle Furge, Job Kievit, Min-Han Tan, Gert Jan Fleuren, Bruce G. Robinson, Leigh W. Delbridge, Jeanette Philips, Anne E. Nelson, Ulf Krause, Henning Dralle, Cuong Hoang-Vu, Oliver Gimm, Hans Morreau, Deborah J. Marsh, Bin T. Teh
Journal: Cancer Research (2004)

Abstract Parathyroid tumors are heterogeneous, and diagnosis is often difficult using histologic and clinical features. We have undertaken expression profiling of 53 hereditary and sporadic parathyroid tumors to better define the molecular genetics of parathyroid tumors. A class discovery approach identified three distinct groups: (1) predominantly hyperplasia cluster, (2) HRPT2/carcinoma cluster consisting of sporadic carcinomas and benign and malignant tumors from Hyperparathyroidism-Jaw Tumor Syndrome patients, and (3) adenoma cluster consisting mainly of primary adenoma and MEN 1 tumors. Gene sets able to distinguish between the groups were identified and may serve as diagnostic biomarkers. We demonstrated, by both gene and protein expression, that Histone 1 Family 2, amyloid β precursor protein, and E-cadherin are useful markers for parathyroid carcinoma and suggest that the presence of a HRPT2 mutation, whether germ-line or somatic, strongly influences the expression pattern of these 3 genes. Cluster 2, characterized by HRPT2 mutations, was the most striking, suggesting that parathyroid tumors with somatic HRPT2 mutation or tumors developing on a background of germ-line HRPT2 mutation follow pathways distinct from those involved in mutant MEN 1-related parathyroid tumors. Furthermore, our findings likely preclude an adenoma to carcinoma progression model for parathyroid tumorigenesis outside of the presence of either a germ-line or somatic HRPT2 mutation. These findings provide insights into the molecular pathways involved in parathyroid tumorigenesis and will contribute to a better understanding, diagnosis, and treatment of parathyroid tumors.
Metabolic health in families enriched for longevity is associated with low prevalence of hand osteoarthritis and influences OA biomarker profiles
Authors: Steffan Daniël Bos, Marian Beekman, Andrea B Maier, Morton A Karsdal, Wing-Yee Kwok, Anne Christine Bay-Jensen, Margreet Kloppenburg, P Eline Slagboom, Ingrid Meulenbelt
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Individual metabolic characteristics and age-related changes may affect osteoarthritis (OA) risk as well as levels of potential OA biomarkers such as serum cartilage oligomeric protein (sCOMP) and urinary cross-linked C-telopeptide of type 2 collagen (uCTX2). We investigated hand OA and these putative OA biomarker characteristics at different ages in individuals with a propensity for healthy ageing, in controls, and in patients with OA. <h3>Methods</h3> We investigated hand radiological OA (ROA) and levels of sCOMP and uCTX2 in the Leiden Longevity Study, which consisted of the middle-aged offspring of long-lived sibling pairs as metabolically healthy agers and their partners as controls, and for ROA we compared patients with OA at multiple joint sites from the Genetics, osteoARthritis and Progression Study with the healthy agers and controls. <h3>Results</h3> Hand ROA mean scores were lower in the healthy agers than in controls. Lower hand ROA scores at higher ages were observed in healthy agers with low glucose levels. Furthermore, in healthy agers, a higher mean sCOMP level was observed than in controls. All study groups had higher sCOMP levels at higher chronological age. Likewise, uCTX2 levels were higher at higher chronological age in the controls and patients with OA, which was not observed in the healthy agers. <h3>Conclusions</h3> Metabolic health in middle age is associated with less ROA and influences putative OA marker profiles, independently of chronological age. When used as OA biomarkers, it is relevant that independently of hand ROA status, uCTX2 is influenced by healthy metabolism and sCOMP is higher at higher chronological age.
Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy
Authors: Changhan Lee, Lizzia Raffaghello, Sebastian Brandhorst, Fernando M. Safdie, Giovanna Bianchi, Alejandro Martin-Montalvo, Vito Pistoia, Min Wei, Saewon Hwang, Annalisa Merlino, Laura Emionite, Rafael de Cabo, Valter D. Longo
Journal: Science Translational Medicine (2012)

Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2(val19) to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs--but not either treatment alone--resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress-sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers.
Kidney Dendritic Cells Induce Innate Immunity against Bacterial Pyelonephritis
Authors: André P. Tittel, Christoph Heuser, Christina Ohliger, Percy A. Knolle, Daniel R. Engel, Christian Kurts
Journal: Journal of the American Society of Nephrology (2011)

Dendritic cells (DCs) are the most abundant immune cells in the kidney and form an intricate network in the tubulointerstitium, suggesting that they may play an important role in interstitial infections such as pyelonephritis. Here, we optimized a murine pyelonephritis model by instilling uropathogenic Escherichia coli two times at a 3-hour interval, which produced an infection rate of 84%. By 3 hours after the second instillation, resident kidney DCs began secreting the chemokine CXCL2, which recruits neutrophilic granulocytes. During the time studied, DCs remained responsible for most of the CXCL2 production. Neutrophils began infiltrating the kidney 3 hours after the second instillation and phagocytozed bacteria. Macrophages followed 3 hours later and contributed much less to both CXCL2 production and bacterial phagocytosis. To investigate whether DCs recruit neutrophils into the kidney for antibacterial defense, we used CD11c.DTR mice allowing conditional depletion of CD11c(+) dendritic cells. The absence of CD11c(+) DCs markedly delayed neutrophil recruitment and bacterial clearance. In conclusion, these findings suggest that the tubulointerstitial dendritic cell network serves an innate immune sentinel function against bacterial pyelonephritis.
Cardiac Rehabilitation and Secondary Prevention of Coronary Heart Disease
Authors: Arthur S. Leon, Barry A. Franklin, Fernando Costa, Gary J. Balady, Kathy A. Berra, Kerry J. Stewart, Paul D. Thompson, Mark A. Williams, Michael S. Lauer
Journal: Circulation (2005)

This article updates the 1994 American Heart Association scientific statement on cardiac rehabilitation. It provides a review of recommended components for an effective cardiac rehabilitation/secondary prevention program, alternative ways to deliver these services, recommended future research directions, and the rationale for each component of the rehabilitation/secondary prevention program, with emphasis on the exercise training component.
Multicenter evaluation of the Glucometer Elite XL meter, an instrument specifically designed for use with neonates.
Authors: J Girouard, J C Forest, J Massé, M Leroux, N C Bradburn, T C Noblet, J O Joynes, J Baum
Journal: Diabetes Care (2000)

OBJECTIVE: To evaluate the clinical performance of the Glucometer Elite XL Diabetes Care System in neonatal settings using a multicenter study RESEARCH DESIGN AND METHODS: A total of 388 blood specimens from 333 neonates were included in the study. A capillary or arterial sample was analyzed for determination of glucose with the Glucometer Elite XL system by an attending trained nurse. Through the same sampling site, a specimen was collected and sent to the laboratory for measurement of plasma glucose, bilirubin, and hematocrit. RESULTS: The regression analysis between the results of the Glucometer Elite XL system and comparative methods resulted in the following: Glucometer Elite XL meter = 1.01 x laboratory method + 0.02 mmol/l (n = 388). For the 1.1-4.0 mmol/l plasma glucose range, the regression was Glucometer Elite XL meter = 1.07 x laboratory method + 0.12 mmol/l (n = 150). A difference plot indicated a mean bias of 0.04 mmol/l (95% CI -0.01 to 0.10). No relationship was found between meter glucose biases and hematocrit levels (r = 0.10, P = 0.14). Although a statistically significant correlation existed between bilirubin levels and the glucose meter biases (r = 0.14, P = 0.005), the predicted mean biases were of little clinical significance. CONCLUSIONS: The Glucometer Elite XL system showed a good performance when used in neonatal settings.
Fitness and health of children through sport: the context for action
Authors: Lyle Micheli, Margo Mountjoy, Lars Engebretsen, Ken Hardman, Sonja Kahlmeier, Estelle Lambert, Arne Ljungqvist, Victor Matsudo, Heather McKay, Carl Johan Sundberg
Journal: British Journal of Sports Medicine (2011)

A growing body of scientific evidence indicates that the declining levels of physical activity and fitness in children and youth are associated with adverse impacts on their health, including rising levels of obesity, diabetes, heart disease, metabolic syndrome and increased risk of sports injury. In response, a number of governmental and non-governmental organisations have instituted programmes to promote health in children and youth through sports and physical activity. Many of these programmes have achieved success in increasing participation in sports and other forms of physical activity and, by extension, improving the health of these young people. These programmes have also been used successfully to enhance the lives of the young participants by means other than improving physical health.
Finding a Panacea among Combination Cancer Therapies
Authors: Ryuji Yamaguchi, Guy Perkins
Journal: Cancer Research (2011)

Because each cancer is a heterogeneous mix of cancer cells at different stages of development, we are faced with trying to treat many different diseased cells all at once. An authentic approach is to build a genomic and proteomic profile of a patient, identify the target oncogenes, and prescribe the combination of targeted drugs tailored for that patient. However, there are many practical problems with this personalized medicine approach: (i) cancers often generate treatment-resistant phenotypes, (ii) the treatment could be enormously expensive, and (iii) most of the targeted drugs have not been developed yet. We propose a different approach: therapies that combine 2-deoxyglucose (2DG) with Bcl-2 antagonist such as ABT-263/737 (ABT). Proapoptotic protein Bak is normally sequestered by Mcl-1 and Bcl-xL. Only when Bak is released from both Mcl-1 and Bcl-xL can it induce apoptosis. 2DG can prime highly glycolytic cells by dissociating Bak-Mcl-1 complex. Some brain cells and most cancer cells are primed by 2DG. ABT can bind to Bcl-xL, dissociating Bak-Bcl-xL complex, freeing Bak and inducing apoptosis. Because ABT cannot cross blood-brain barrier, the only cells exposed to both agents are highly glycolytic cancer cells located outside the brain. Because ABT directly triggers apoptosis at the step very near the terminal point of apoptosis, 2DG-ABT combination therapies are applicable to many types of cancer at all stages of development, with little side effect.
Salivary flow rates and iodide trapping capacity in patients with Sjogren's syndrome.
Authors: D K Mason, R M Harden, J A Boyle, M K Jasani, J Williamson, W W Buchanan
Journal: Annals of the Rheumatic Diseases (1967)

Sjogren's syndrome (Sjogren, 1933) in its severer forms presents a relatively simple clinical diagnosis.In many patients, however, the condition may be mild and it may be difficult for the clinician to find c on July 13,
Targeting melanoma growth and viability reveals dualistic functionality of the phosphonothionate analogue of carba cyclic phosphatidic acid
Authors: Molly K Altman, Vashisht Gopal, Wei Jia, Shuangxing Yu, Hassan Hall, Gordon B Mills, A Cary McGinnis, Michael G Bartlett, Guowei Jiang, Damian Madan, Glenn D Prestwich, Yong Xu, Michael A Davies, Mandi M Murph
Journal: Molecular Cancer (2010)

Abstract Background Although the incidence of melanoma in the U.S. is rising faster than any other cancer, the FDA-approved chemotherapies lack efficacy for advanced disease, which results in poor overall survival. Lysophosphatidic acid (LPA), autotaxin (ATX), the enzyme that produces LPA, and the LPA receptors represent an emerging group of therapeutic targets in cancer, although it is not known which of these is most effective. Results Herein we demonstrate that thio-ccPA 18:1, a stabilized phosphonothionate analogue of carba cyclic phosphatidic acid, ATX inhibitor and LPA1/3 receptor antagonist, induced a marked reduction in the viability of B16F10 metastatic melanoma cells compared with PBS-treated control by 80-100%. Exogenous LPA 18:1 or D-sn-1-O-oleoyl-2-O-methylglyceryl-3-phosphothioate did not reverse the effect of thio-ccPA 18:1. The reduction in viability mediated by thio-ccPA 18:1 was also observed in A375 and MeWo melanoma cell lines, suggesting that the effects are generalizable. Interestingly, siRNA to LPA3 (siLPA3) but not other LPA receptors recapitulated the effects of thio-ccPA 18:1 on viability, suggesting that inhibition of the LPA3 receptor is an important dualistic function of the compound. In addition, siLPA3 reduced proliferation, plasma membrane integrity and altered morphology of A375 cells. Another experimental compound designed to antagonize the LPA1/3 receptors significantly reduced viability in MeWo cells, which predominantly express the LPA3 receptor. Conclusions Thus the ability of thio-ccPA 18:1 to inhibit the LPA3 receptor and ATX are key to its molecular mechanism, particularly in melanoma cells that predominantly express the LPA3 receptor. These observations necessitate further exploration and exploitation of these targets in melanoma.
Expression Profiles of Osteosarcoma That Can Predict Response to Chemotherapy
Authors: Tsz-Kwong Man, Murali Chintagumpala, Jaya Visvanathan, Jianhe Shen, Laszlo Perlaky, John Hicks, Mark Johnson, Nelson Davino, Jeffrey Murray, Lee Helman, William Meyer, Timothy Triche, Kwong-Kwok Wong, Ching C. Lau
Journal: Cancer Research (2005)

Osteosarcoma is the most common malignant bone tumor in children. After initial diagnosis is made with a biopsy, treatment consists of preoperative chemotherapy followed by definitive surgery and postoperative chemotherapy. The degree of tumor necrosis in response to preoperative chemotherapy is a reliable prognostic factor and is used to guide the choice of postoperative chemotherapy. Patients with tumors, which reveal > or = 90% necrosis (good responders), have a much better prognosis than those with < 90% necrosis (poor responders). Despite previous attempts to improve the outcome of poor responders by modifying the postoperative chemotherapy, their prognosis remains poor. Therefore, there is a need to predict at the time of diagnosis patients' response to preoperative chemotherapy. This will provide the basis for developing potentially effective therapy that can be given at the outset for those who are likely to have a poor response. Here, we report the analysis of 34 pediatric osteosarcoma samples by expression profiling. Using parametric two-sample t test, we identified 45 genes that discriminate between good and poor responders (P < 0.005) in 20 definitive surgery samples. A support vector machine classifier was built using these predictor genes and was tested for its ability to classify initial biopsy samples. Five of six initial biopsy samples that had corresponding definitive surgery samples in the training set were classified correctly (83%; confidence interval, 36%, 100%). When this classifier was used to predict eight independent initial biopsy samples, there was 100% accuracy (confidence interval, 63%, 100%). Many of the predictor genes are implicated in bone development, drug resistance, and tumorigenesis.
The importance of erythroid expansion in determining the extent of apoptosis in erythroid precursors in patients with β-thalassemia major
Authors: Filippo Centis, Laura Tabellini, Guido Lucarelli, Ornella Buffi, Paola Tonucci, Barbara Persini, Mauro Annibali, Roberto Emiliani, Anca Iliescu, Simona Rapa, Raffaella Rossi, Lisa Ma, Emanuele Angelucci, Stanley L. Schrier
Journal: Blood (2000)
Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate
Authors: G Wells, J-C Becker, J Teng, M Dougados, M Schiff, J Smolen, D Aletaha, P L C M van Riel
Journal: Annals of the Rheumatic Diseases (2008)

Objective: To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR). Methods: Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 <2.6) based on the two DAS28 definitions were examined. Trends in radiographic progression (erosion score, joint space narrowing score and total score) and physical function (Health Assessment Questionnaire Disability Index (HAQ-DI)) across the EULAR responder states (none, moderate and good) were analysed. Results: There was general agreement in determining the EULAR responder state using both DAS28 definitions (κ = 0.80, 95% CI 0.76 to 0.83). Overall, there was 82.4% agreement on the EULAR response criteria; when disagreements occurred, the DAS28 (CRP) yielded a better EULAR response more often then DAS28 (ESR) (12.6% vs 4.9%, respectively). There was also agreement in determining remission: κ = 0.69 (95% CI 0.60 to 0.78). Radiographic progression decreased in patients treated with abatacept across EULAR states (from none to moderate to good) based on both definitions. For patients treated with placebo, the trend was not as pronounced, with radiographic scores higher for moderate vs non-responders. For physical function, similar trends were observed across the EULAR states for both DAS28 definitions. Conclusions: The DAS28 (CRP) has been validated against radiographic progression and physical function. While the DAS28 (CRP) yielded a better EULAR response more often than the DAS28 (ESR), the validation profile was similar to the DAS28 (ESR), indicating that both measures are useful for assessing disease activity in patients with rheumatoid arthritis.
Effect of variation in dietary NaCl intake on total and fractional renal blood flow in the normal and mercury-intoxicated rat.
Authors: N Lameire, S Ringoir, I Leusen
Journal: Circulation Research (1976)

We studied the effect of different chronic (3-4 weeks) dietary salt intakes on intrarenal hemodynamics of normal and mercury-intoxicated rats. Cardiac output (CO), total renal blood flow (RBF), and the zonal perfusion rate in the outer cortex (OC) and inner cortex (IC) were measured by the radioactive microsphere method. The distribution of cortical blood flow was calculated as the distribution index (DI), which reflects the ratio OC/IC. Rats were placed on a high salt diet (group I), intermediate salt diet (group II), or low salt diet (group III). For each group control rats (subgroup A) and mercury-intoxicated rats (subgroup B) were studied. No effect of the different salt intakes on the DI could be detected. The DI in group IA was 2.35 +/- 0.14; in IIA, 2.40 +/- 0.16; and in IIIA, 2.38 +/- 0.09 (P greater than 0.05). After mercury injection RBF changed from 5.32 +/- 0.36 ml/g.min(-1) (IIA) to 3.31 +/- 0.20 ml/g.min(-1), IIB and from 4.32 +/- 0.11ml/g.min(-1) (IIIA) to 1.98 +/- 0.10 ml/g.min(-1) (IIIB) P less than 0.01). The DI was lowered to 1.53 +/- 0.06 (IIB) (P less than 0.05) and to 1.16 +/- 0.10 (IIIB) (P less than 0.01). In both IIB and IIIB a marked elevation of the blood urea was noted (IIB = 97 +/- 9 MG/100 ML AND IIIB = 182 +/- 25 mg/100 ml). In group IB no effect on RBF, OC, IC, or DI could be observed (for all values, P greater than 0.05) despite similar histological renal lesions. Group IB rats also had normal blood urea levels (31 +/- 6 mg/100 ml;P greater than 0.05). We conclude (1) that variations in dietary salt intake appear to have no detectable effect on the intracortical blood flow distribution; and furthermore (2) that the mercury-induced acute renal failure (ARF) is characterized hemodynamically by a total renal and preferential outer cortical ischemia and that chronic salt loading prevents the ARF while preserving normal renal perfusion.
Decreased pulmonary distensibility in fibrosing alveolitis and its relation to decreased lung volume.
Authors: M J Thompson, H J Colebatch
Journal: Thorax (1989)

The relation between pulmonary distensibility, lung volume, and elastic recoil pressure was examined in 45 patients (38 men) with cryptogenic fibrosing alveolitis (mean age 61 (SD 14) years). Exponential analysis of static pressure-volume data obtained during deflation of the lungs gave the exponent K, an index of the distensibility of the remaining inflatable lung tissue. Total lung capacity (TLC) was measured in a body plethysmograph or by nitrogen washout. The results were compared with values obtained in 147 healthy subjects (95 men), of mean age 39 (SD 16) years. Fibrosing alveolitis decreased K by 0.62 (SEM 0.04) kPa-1. This decrease was approximately equal to 2 SD of the regression of log K on age in healthy subjects. TLC was decreased to a mean of 70% (SD 14%) predicted in the patients with fibrosing alveolitis. Lung recoil pressure at maximum inspiration was about twice the expected value and regression analysis showed that most of this increase was related to the decreased K rather than to the decreased TLC. In the men with fibrosing alveolitis the regression of height standardised TLC (TLC/Ht3) on K was significant (p less than 0.02); the regression slope was similar to that for 95 healthy men, but was displaced to a smaller lung volume. The dependence of TLC/Ht3 on K is consistent with the close relation between K and peripheral airspace size found in normal lungs. In fibrosing alveolitis decreased pulmonary distensibility probably reflects a decrease in airspace size, whereas most of the decrease in lung volume reflects the loss of inflatable tissue in the fibrotic process.