tbuckley/cabot-search huggingface dataset:
The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer
Authors: Elliott Middleton, Chithan Kandaswami, Theoharis C. Theoharides
Journal: Pharmacological Reviews (2000)

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.
Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis
Authors: Rebecca N. Bauer, Luisa E. Brighton, Loretta Mueller, Zhidan Xiang, Julia E. Rager, Rebecca C. Fry, David B. Peden, Ilona Jaspers
Journal: Journal of Allergy and Clinical Immunology (2012)
Hypermethylator Phenotype in Sporadic Colon Cancer: Study on a Population-Based Series of 582 Cases
Authors: Ludovic Barault, Céline Charon-Barra, Valérie Jooste, Mathilde Funes de la Vega, Laurent Martin, Patrick Roignot, Patrick Rat, Anne-Marie Bouvier, Pierre Laurent-Puig, Jean Faivre, Caroline Chapusot, Francoise Piard
Journal: Cancer Research (2008)

The CpG island methylator phenotype (CIMP) is a distinct phenotype in colorectal cancer, associated with specific clinical, pathologic, and molecular features. However, most of the studies stratified methylation according to two subgroups (CIMP-High versus No-CIMP/CIMP-Low). In our study, we defined three different subgroups of methylation (No-CIMP, CIMP-Low, and CIMP-High) and evaluated the prognostic significance of methylation status on a population-based series of sporadic colon cancers. A total of 582 colon adenocarcinomas were evaluated using methylation-specific PCR for 5 markers (hMLH1, P16, MINT1, MINT2, and MINT31). No-CIMP status was defined as no methylated locus, CIMP-Low status as one to three methylated loci, and CIMP-High status as four or five methylated loci. Clinicopathologic and molecular characteristics were correlated to the methylation status. Crude and relative survival was compared according to methylation status. In the microsatellite-stable (MSS) group, CIMP-High was significantly associated with proximal location (P = 0.011) and BRAF mutation (P < 0.001). KRAS mutations were more associated with CIMP-High and CIMP-Low status (P = 0.008). A shorter 5-year survival was observed in MSS cancer patients with CIMP-Low or CIMP-High status. These results remained significant in multivariate analysis adjusted for age, stage, and BRAF and KRAS mutational status [CIMP-Low: hazard ratio (HR), 1.85; 95% confidence interval (95% CI), 1.37-2.51; CIMP-High, HR, 2.90; 95% CI, 1.53-5.49 compared with No-CIMP]. Within the high-level microsatellite instability group, no difference in survival was observed between the different CIMP groups. Our results show the interest of defining three subgroups of patients according to their methylation status (No-CIMP/CIMP-Low/CIMP-High). Methylation is an independent prognostic factor in MSS colon cancer.
Are dynamical systems the answer?
Authors: Arthur B. Markman
Journal: Behavioral and Brain Sciences (2001)

The proposed model is put forward as a template for the dynamical systems approach to embodied cognition. In order to extend this view to cognitive processing in general, however, two limitations must be overcome. First, it must be demonstrated that sensorimotor coordination of the type evident in the A-not-B error is typical of other aspects of cognition. Second, the explanatory utility of dynamical systems models must be clarified.
Revisiting interactions between hypoxaemia and beta2 agonists in asthma
Authors: B J LIPWORTH
Journal: Thorax (2001)

The excessive use of β2 agonists has been associated with increased asthma mortality, although this seems to be due to confounding by disease severity rather than direct drug toxicity.1 2 Dose-response studies in stable asthmatics have shown the potential for high doses of salbutamol to produce direct or indirect cardiovascular sequelae mediated by extrapulmonary β2 adrenoceptor stimulation including chronotropic and inotropic activity, peripheral vasodilatation, electrocardiographic changes, as well as hypokalaemia and hypomagnesaemia.3 4 

The potential for cardiovascular toxicity with high doses of inhaled β2 agonists may be considered in the context of “the seed and the soil”. In terms of the “seed”, there are conflicting reports as to whether a full agonist such as fenoterol produces greater dose related systemic β2 mediated systemic effects than a partial agonist such as salbutamol in asthmatic patients when comparing microgram equivalent doses with the same bronchodilator potency.4-6 In terms of the “soil” for salbutamol mediated adverse effects, concomitant diuretic therapy may augment hypokalaemic and electrocardiographic sequelae, concomitant corticosteroid may sensitise cardiac β2 adrenoceptors, while the elderly exhibit increased chronotropy and peripheral vasodilatation.7-9 Patients with more severe asthma have reduced systemic effects of salbutamol due to reduced lung absorption so they may, in effect, be protecting themselves from adverse effects.10 The lung absorption of salbutamol may …
IMMUNE CYTOLYSIS: ELECTRON MICROSCOPIC LOCALIZATION OF CELLULAR ANTIGENS WITH FERRITIN-ANTIBODY CONJUGATES
Authors: John M. Easton, Burton Goldberg, Howard Green
Journal: The Journal of Experimental Medicine (1962)

Immune gamma globulin has been coupled to ferritin by the diisocyanate method of Singer. The final product ("ferroglobulin") had approximately 13 per cent of its gamma globulin coupled to ferritin, and roughly half of its ferritin coupled to gamma globulin. The uncoupled gamma globulin could be removed by ultracentrifugal sedimentation of the free ferritin and the ferritin-antibody conjugates. The characteristics of the native antibody were retained by the ferritin-antibody conjugates, for they could be precipitated by anti-gamma globulin antisera, and when used as antibodies, they reacted specifically with soluble and cellular antigens. Ferroglobulin preparations made from rabbit antisera against whole ascites tumor cells were incubated with the cells, and the location of ferritin determined by electron microscopy of thin-sectioned material. It was found that the immune ferroglobulins localized specifically on antigens of the cell membrane. Some of the ferritin label entered the cells by pinocytosis, but the ferritin-antibody units did not appear able to pass directly through the cell membrane into the cytoplasmic matrix. When cells were incubated with ferritin-labeled antibody and complement, antibody could be located in the cytoplasmic matrix, and it therefore appeared that complement action was required before antibody could pass directly through the cell membrane. This finding was consistent with previous observations that the plasma membrane of an antibody-complement treated cell becomes permeable to large molecules. In broken cell preparations incubated with ferroglobulin, antibody combined with amorphous material and with structures derived from cell membranes and from smooth membranes of the endoplasmic reticulum. The data favor the concept that antigens contained within the membranous structures are most important in the formation of cytotoxic antibodies. The reported experiments support the view that cytotoxic antibodies fix primarily to surface antigens of the cell membrane. The subsequent action of complement establishes the permeability defect that induces the osmotic lysis of the cell and permits antibody to pass into the cell where it may act in a similar fashion on intracellular organelles.
Cartilage issues in football—today's problems and tomorrow's solutions
Authors: Kai Mithoefer, Lars Peterson, Marcy Zenobi-Wong, Bert R Mandelbaum
Journal: British Journal of Sports Medicine (2015)

Articular cartilage injury is prevalent in football players and results from chronic joint stress or acute traumatic injuries. Articular cartilage injury can often result in progressive painful impairment of joint function and limit sports participation. Management of articular cartilage injury in athletes aims to return the player to competition, and requires effective and durable joint surface restoration that resembles normal hyaline articular cartilage that can withstand the high joint stresses of football. Existing articular cartilage repair techniques can return the athlete with articular cartilage injury to high-impact sports, but treatment does not produce normal articular cartilage, and this limits the success rate and durability of current cartilage repair in athletes. Novel scientific concepts and treatment techniques that apply modern tissue engineering technologies promise further advancement in the treatment of these challenging injuries in the high demand athletic population. We review the current knowledge of cartilage injury pathophysiology, epidemiology and aetiology, and outline existing management algorithms, developing treatment options and future strategies to manage articular cartilage injuries in football players.
Detection of <i>Mycoplasma pneumoniae</i> in the Airways of Adults with Chronic Asthma
Authors: MONICA KRAFT, GAIL H. CASSELL, JAN E. HENSON, HAROLD WATSON, JAN WILLIAMSON, B. P. MARMION, CHARLOTTE A. GAYDOS, RICHARD J. MARTIN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Infection with Mycoplasma pneumoniae has been shown to exacerbate asthma in humans. However, the role of M. pneumoniae in the pathogenesis of chronic asthma has not been defined. Eighteen asthmatics with chronic, stable asthma and 11 nonasthmatic control subjects underwent evaluation of the upper and lower airways and serologic analysis to determine the presence of M. pneumoniae, Chlamydia pneumoniae, and seven respiratory viruses through culture, enzyme-linked immunoassay (EIA) and polymerase chain reaction (PCR). M. pneumoniae was detected by PCR in 10 of 18 asthmatics and one of 11 control subjects (p = 0.02). In nine of the 10 patients, the organism was detected in bronchoalveolar lavage or bronchial biopsies. Seven of 18 asthmatics and one of 11 control subjects were also positive for M. fermentans and M. genitalium by PCR. All patients' cultures, EIAs, and serology were negative for M. pneumoniae. All PCR and cultures were negative for C. pneumoniae, and all EIAs for respiratory viruses were negative in all subjects. Nine asthmatics and one control subject exhibited positive serology for C. pneumoniae (p = 0.05). M. pneumoniae was present in the lower airways of chronic, stable asthmatics with greater frequency than control subjects, and may play a role in the pathogenesis of chronic asthma.
Disposition and bioavailability of ceftazidime after intraperitoneal administration in patients receiving continuous ambulatory peritoneal dialysis.
Authors: S Stea, T Bachelor, M Cooper, P de Souza, K Koenig, W K Bolton
Journal: Journal of the American Society of Nephrology (1996)

This study investigated the disposition and bioavailability of ceftazidime when it was given intraperitoneally. Seven patients were given 1 gm of ceftazidime intravenously, and 1 wk later, the same dose was given intraperitoneally. After both intravenous and intraperitoneal dosing, serum and peritoneal dialysate samples were obtained at set time intervals over a 24-h period. High-performance liquid chromatography was used to determine the ceftazidime concentrations in the serum and dialysate samples. Inspection of the concentration versus time data after intraperitoneal dosing demonstrated that serum ceftazidime concentrations reached therapeutic (> 8 micrograms/mL) levels within 30 min and remained in the therapeutic range for the entire 24-h period. Simulation of a variety of ceftazidime dosing regimens using the mean pharmacokinetic parameters from this population of patients suggests that a regimen of 1.5 gm administered intraperitoneally every 24 h produces trough serum drug concentrations (approximately 40 micrograms/mL) similar to those achieved with a standard regimen of 1.0 gm given intravenously every 24 h in patients undergoing continuous ambulatory peritoneal dialysis. It was concluded that the intraperitoneal dosing of ceftazidime in these patients is an equally effective and a more convenient alternative to its administration.
Antibody‐Functionalized Porous Silicon Nanoparticles for Vectorization of Hydrophobic Drugs
Authors: Emilie Secret, Kevin Smith, Valentina Dubljevic, Eli Moore, Peter Macardle, Bahman Delalat, Mary‐Louise Rogers, Terrance G. Johns, Jean‐Olivier Durand, Frédérique Cunin, Nicolas H. Voelcker
Journal: Advanced Healthcare Materials (2012)

Abstract We describe the preparation of biodegradable porous silicon nanoparticles (pSiNP) functionalized with cancer cell targeting antibodies and loaded with the hydrophobic anti‐cancer drug camptothecin. Orientated immobilization of the antibody on the pSiNP is achieved using novel semicarbazide based bioconjugate chemistry. To demonstrate the generality of this targeting approach, the three antibodies MLR2, mAb528 and Rituximab are used, which target neuroblastoma, glioblastoma and B lymphoma cells, respectively. Successful targeting is demonstrated by means of flow cytometry and immunocytochemistry both with cell lines and primary cells. Cell viability assays after incubation with pSiNPs show selective killing of cells expressing the receptor corresponding to the antibody attached on the pSiNP.
osr1 Is Required for Podocyte Development Downstream of wt1a
Authors: Ritu Tomar, Sudha P. Mudumana, Narendra Pathak, Neil A. Hukriede, Iain A. Drummond
Journal: Journal of the American Society of Nephrology (2014)

Odd-skipped related 1 (Osr1) encodes a zinc finger transcription factor required for kidney development. Osr1 deficiency in mice results in metanephric kidney agenesis, whereas knockdown or mutation studies in zebrafish revealed that pronephric nephrons require osr1 for proximal tubule and podocyte development. osr1-deficient pronephric podocyte progenitors express the Wilms' tumor suppressor wt1a but do not undergo glomerular morphogenesis or express the foot process junctional markers nephrin and podocin. The function of osr1 in podocyte differentiation remains unclear, however. Here, we found by double fluorescence in situ hybridization that podocyte progenitors coexpress osr1 and wt1a. Knockdown of wt1a disrupted podocyte differentiation and prevented expression of osr1. Blocking retinoic acid signaling, which regulates wt1a, also prevented osr1 expression in podocyte progenitors. Furthermore, unlike the osr1-deficient proximal tubule phenotype, which can be rescued by manipulation of endoderm development, podocyte differentiation was not affected by altered endoderm development, as assessed by nephrin and podocin expression in double osr1/sox32-deficient embryos. These results suggest a different, possibly cell- autonomous requirement for osr1 in podocyte differentiation downstream of wt1a. Indeed, osr1-deficient embryos did not exhibit podocyte progenitor expression of the transcription factor lhx1a, and forced expression of activated forms of the lhx1a gene product rescued nephrin expression in osr1-deficient podocytes. Our results place osr1 in a framework of transcriptional regulators that control the expression of podocin and nephrin and thereby mediate podocyte differentiation.
Relation Between Alkaline Phosphatase, Serum Phosphate, and All-Cause or Cardiovascular Mortality
Authors: Marcello Tonelli, Gary Curhan, Marc Pfeffer, Frank Sacks, Ravi Thadhani, Michal L. Melamed, Natasha Wiebe, Paul Muntner
Journal: Circulation (2009)

Background— Higher levels of serum alkaline phosphatase (AlkP) are associated with excess mortality in dialysis patients, but whether AlkP is associated with adverse outcomes among people without kidney failure is unknown. Methods and Results— We first analyzed the association between AlkP and cardiovascular outcomes among 4115 participants with a previous myocardial infarction (the Cholesterol And Recurrent Events [CARE] study). Results were validated by analyzing the association between AlkP and mortality in an independent sample of 14 716 adults from the general US population (the Third National Health and Nutrition Examination Survey). A graded, independent association was noted between baseline tertile of AlkP and the adjusted hazard ratio of all-cause mortality in CARE participants ( P trend =0.02). After adjustment for serum phosphate, hepatic enzymes, and other potential confounders, participants with AlkP in the highest tertile had an adjusted hazard ratio of 1.43 (95% confidence interval 1.08 to 1.89) compared with those in the lowest tertile. Multivariable-adjusted associations between higher AlkP and all-cause and cardiovascular mortality were present in the Third National Health and Nutrition Examination Survey ( P trend across tertiles of AlkP=0.006 and 0.038, respectively). Findings from both CARE and the Third National Health and Nutrition Examination Survey were similar among individuals with and without evidence of kidney disease, defined by estimated glomerular filtration rate &lt;60 mL · min −1 · 1.73 m −2 . Conclusions— We found an independent relation between higher levels of AlkP and adverse outcomes among survivors of myocardial infarction and in a general population sample. The excess risk of death was present in people without evidence of kidney disease and was particularly high among people with higher levels of both AlkP and serum phosphate.
The effect of acute alterations in left ventricular afterload and beta-adrenergic tone on indices of early diastolic filling rate.
Authors: M R Zile, A S Blaustein, W H Gaasch
Journal: Circulation Research (1989)

The effects of an acute increase in left ventricular systolic pressure and the effects of an intravenous isoproterenol infusion on myocardial (segment) lengthening rate and chamber (minor axis dimension) filling rate were examined in 12 anesthetized dogs. Measurements of left ventricular systolic pressure (by micromanometer) and of segment length and chamber dimension transients (by ultrasonic crystals) were made in variably afterloaded beats (three-beat descending aortic cross-clamp) before and during an isoproterenol infusion that raised (+)dP/dt by 40%. During the baseline state, we found an inverse relation between the peak rate of increase in minor axis dimension [(+)dD/dt] and systolic pressure over a wide range of systolic pressures (110-160 mm Hg) and end-systolic dimensions (25-40 mm); peak (+)dD/dt and end-systolic dimension were also inversely related. During isoproterenol infusion, end-systolic dimension fell from 29.7 +/- 3.1 to 28.0 +/- 3.1 mm and (+)dD/dt increased from 79.6 +/- 8.0 to 90.1 +/- 8.7 mm/sec; however, the slope and y intercept of the relation between (+)dD/dt and end-systolic dimension were unchanged. Peak (+)dD/dt at a common end-systolic dimension of 31 mm was nearly equal during baseline and isoproterenol states (64.2 +/- 6.3 vs. 65.1 +/- 6.6 mm/sec). Similar results were found using segment length transients. We interpret these data to indicate that (+)dD/dt is strongly influenced by changes in systolic pressure and dimension and that isoproterenol-induced changes in (+)dD/dt are mediated, at least in part, through changes in systolic pressure and dimension.
Randomized Study of the Dopamine Receptor Agonist Piribedil in the Treatment of Mild Cognitive Impairment
Authors: Dindagur Nagaraja, Sivaramakrishnan Jayashree
Journal: American Journal of Psychiatry (2001)

Age-related decrease in dopamine D(2) receptors is associated with cognitive decline in healthy elderly individuals. This study was an investigation of whether the dopamine receptor agonist piribedil improves global cognitive function in patients with mild cognitive impairment.In a 90-day randomized double-blind study, treatment with piribedil was compared to placebo in 60 patients with clinically diagnosed mild cognitive impairment and a Mini-Mental State Examination (MMSE) score of 21 to 25. The primary outcome was change in MMSE score.Of the 30 patients randomly assigned to each treatment group, 19 (63.3%) of those taking piribedil and eight (26.7%) of those treated with placebo had increases in MMSE scores, to 26 or more. The response rate and the mean increase in MMSE scores were significantly greater with piribedil.Patients with mild cognitive impairment had improvement in global cognitive function when treated with the dopamine receptor agonist piribedil. The results support the role of age-related dopamine decline in cognitive impairment of the elderly.
The economic impact of smoking in Germany
Authors: L.K. Ruff, T. Volmer, D Nowak, A Meyer
Journal: European Respiratory Journal (2000)

Smoking is a high-risk behaviour affecting health and economic welfare of society. Thus it is important to quantify the economic burden smoking places on social institutions in Germany. Approximately 33.4% of the male and 20.4% of the female population are current smokers. This study investigates the health care costs of smoking based on 1996 figures, focusing on the seven most frequent diseases associated with the inhalation of tobacco smoke: chronic obstructive pulmonary disease (COPD, international classification of diseases (ICD) 490-491); lung cancer (ICD 162); stroke (ICD 434-438); coronary artery disease (ICD 410-414); cancer of the mouth and larynx (ICD 140-149, 161) and artherosclerotic occlusive disease (ICD 440). A data search was carried out on MEDLINE, the German Institute for Medical Documentation and Information, and the Internet as well as in databases of health insurance companies and the German Federal institute of statistics. Direct and indirect costs were calculated separately. The results estimate the total smoking related health care costs (attributable fraction due to smoking) for COPD to be 5.471 billion EURO (73%), for lung cancer 2.593 billion EURO (89%), for cancer of the mouth and larynx 0.996 billion EURO (65%), for stroke 1.774 billion EURO (28%), for coronary artery disease 4.963 billion EURO (35%) and for atherosclerotic occlusive disease 0.761 billion EURO (28%). The economic burden of smoking related health care costs for Germany is 16.6 billion EURO. Smoking is therefore responsible for 47% of the overall costs of these diseases (35.2 billion EURO). In the view of the high costs for smoking, of which almost 50% are due to respiratory disease, pneumologists should enhance their effort in primary, secondary and tertiary prevention.
Flow cytometry imaging identifies rare TH2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu
Authors: Amanda J. Reefer, Kathryn E. Hulse, Josephine A. Lannigan, Michael D. Solga, Paul W. Wright, Libby A. Kelly, James Patrie, Martin D. Chapman, Judith A. Woodfolk
Journal: Journal of Allergy and Clinical Immunology (2010)