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Search Results: 1 - 10 of 225127 matches for " Wayne R. Matson "
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Biological variability dominates and influences analytical variance in HPLC-ECD studies of the human plasma metabolome
Yevgeniya I Shurubor, Wayne R Matson, Walter C Willett, Susan E Hankinson, Bruce S Kristal
BMC Clinical Pathology , 2007, DOI: 10.1186/1472-6890-7-9
Abstract: Human plasma samples were biochemically analyzed using HPLC separations coupled with coulometric electrode array detection.We identified these markers/metabolites in human plasma, and then used them to determine which human samples represent blinded duplicates with 100% accuracy (N = 30 of 30). At least 47 of 61 metabolites tested were sufficiently stable for use even after 48 hours of exposure to shipping conditions. Stability of some metabolites differed between individuals (N = 10 at 0, 24, and 48 hours), suggesting the influence of some biological factors on parameters normally considered as analytical.Overall analytical precision (mean median CV, ~9%) and total between-person variation (median CV, ~50–70%) appear well suited to enable use of metabolomics markers in human clinical trials and epidemiological studies, including studies of the effect of caloric intake and balance on long-term cancer risk.After tobacco, over-nutrition is, arguably, the major cause of excess morbidity in developed countries, affecting a broad spectrum of diseases including cancer, cardio-/cerebrovascular disease, and type II diabetes. This association may be seen in both broad demographic groups, such as the American Cancer Society study group (900,000 U.S. adults)[1] and in more narrowly defined demographic groups, such as the Nurses' Health Study (NHS) group (122,000 U.S. female registered nurses) [2]. The difficulty of accurately assessing caloric intake and energy expenditure [3] has hampered studies relating to energy restriction, caloric balance, and caloric intake in both epidemiology and clinical nutrition. Several of the major hurdles in identifying biomarkers to address this and similar epidemiological problems are related to analytical (the lack of useful measurement standards) and methodological (the inability to distinguish individual physiology) issues [4-13]. Recent results have suggested the advantage of metabolomics approaches in clarifying these situations, at least
Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder – Possible Role for Methoxyindole Pathway
Hongjie Zhu, Mikhail B. Bogdanov, Stephen H. Boyle, Wayne Matson, Swati Sharma, Samantha Matson, Erik Churchill, Oliver Fiehn, John A. Rush, Ranga R. Krishnan, Eve Pickering, Marielle Delnomdedieu, Rima Kaddurah-Daouk, Pharmacometabolomics Research Network
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0068283
Abstract: Therapeutic response to selective serotonin (5-HT) reuptake inhibitors in Major Depressive Disorder (MDD) varies considerably among patients, and the onset of antidepressant therapeutic action is delayed until after 2 to 4 weeks of treatment. The objective of this study was to analyze changes within methoxyindole and kynurenine (KYN) branches of tryptophan pathway to determine whether differential regulation within these branches may contribute to mechanism of variation in response to treatment. Metabolomics approach was used to characterize early biochemical changes in tryptophan pathway and correlated biochemical changes with treatment outcome. Outpatients with MDD were randomly assigned to sertraline (n = 35) or placebo (n = 40) in a double-blind 4-week trial; response to treatment was measured using the 17-item Hamilton Rating Scale for Depression (HAMD17). Targeted electrochemistry based metabolomic platform (LCECA) was used to profile serum samples from MDD patients. The response rate was slightly higher for sertraline than for placebo (21/35 [60%] vs. 20/40 [50%], respectively, χ2(1) = 0.75, p = 0.39). Patients showing a good response to sertraline had higher pretreatment levels of 5-methoxytryptamine (5-MTPM), greater reduction in 5-MTPM levels after treatment, an increase in 5-Methoxytryptophol (5-MTPOL) and Melatonin (MEL) levels, and decreases in the (KYN)/MEL and 3-Hydroxykynurenine (3-OHKY)/MEL ratios post-treatment compared to pretreatment. These changes were not seen in the patients showing poor response to sertraline. In the placebo group, more favorable treatment outcome was associated with increases in 5-MTPOL and MEL levels and significant decreases in the KYN/MEL and 3-OHKY/MEL; changes in 5-MTPM levels were not associated with the 4-week response. These results suggest that recovery from a depressed state due to treatment with drug or with placebo could be associated with preferential utilization of serotonin for production of melatonin and 5-MTPOL.
Metabolomic Profiling in LRRK2-Related Parkinson's Disease
Krisztina K. Johansen,Lei Wang,Jan O. Aasly,Linda R. White,Wayne R. Matson,Claire Henchcliffe,M. Flint Beal,Mikhail Bogdanov
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007551
Abstract: Mutations in LRRK2 gene represent the most common known genetic cause of Parkinson's disease (PD).
Homeostatic Imbalance of Purine Catabolism in First-Episode Neuroleptic-Na?ve Patients with Schizophrenia
Jeffrey K. Yao,George G. Dougherty Jr.,Ravinder D. Reddy,Matcheri S. Keshavan,Debra M. Montrose,Wayne R. Matson,Joseph McEvoy,Rima Kaddurah-Daouk
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009508
Abstract: Purine catabolism may be an unappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. Accumulating evidence suggests a pivotal role of oxidative stress in schizophrenia pathology.
Associations between Purine Metabolites and Clinical Symptoms in Schizophrenia
Jeffrey K. Yao, Ruth Condray, George G. Dougherty, Matcheri S. Keshavan, Debra M. Montrose, Wayne R. Matson, Joseph McEvoy, Rima Kaddurah-Daouk, Ravinder D. Reddy
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042165
Abstract: Background The antioxidant defense system, which is known to be dysregulated in schizophrenia, is closely linked to the dynamics of purine pathway. Thus, alterations in the homeostatic balance in the purine pathway may be involved in the pathophysiology of schizophrenia. Methodology/Principal Findings Breakdown products in purine pathway were measured using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system for 25 first-episode neuroleptic-na?ve patients with schizophrenia at baseline and at 4-weeks following initiation of treatment with antipsychotic medication. Associations between these metabolites and clinical and neurological symptoms were examined at both time points. The ratio of uric acid and guanine measured at baseline predicted clinical improvement following four weeks of treatment with antipsychotic medication. Baseline levels of purine metabolites also predicted clinical and neurological symtpoms recorded at baseline; level of guanosine was associated with degree of clinical thought disturbance, and the ratio of xanthosine to guanosine at baseline predicted degree of impairment in the repetition and sequencing of actions. Conclusions/Significance Findings suggest an association between optimal levels of purine byproducts and dynamics in clinical symptoms and adjustment, as well as in the integrity of sensory and motor processing. Taken together, alterations in purine catabolism may have clinical relevance in schizophrenia pathology.
Obstetric Hemorrhage and Hypothermia: Chilling Facts  [PDF]
Wayne R. Cohen
Open Journal of Obstetrics and Gynecology (OJOG) , 2018, DOI: 10.4236/ojog.2018.813128
Abstract: Objective: This clinical perspective reviews the causes, prevention and treatment of accidental hypothermia in severe obstetric hemorrhage. Results: Hypothermia commonly accompanies hemorrhagic shock. Hypothermia can inhibit blood coagulation, reduce cardiac contractility, predispose to arrhythmias, contribute to acidosis, and suppress immune function. Several techniques for warming a patient or reducing heat loss are available. Keeping the patient dry, covering her with blankets, and raising the ambient temperature in the room are valuable. Methods to transmit heat actively are more effective. Forced warm air blowers are efficient. Heating intravenous fluids is important, and warm fluid lavage of the open abdomen can be effective. Conclusion: Monitoring core temperature in the operating room and choosing therapy is a shared responsibility of surgeon and anesthesiologist.
Hemofiltration, adsorption, sieving and the challenge of sepsis therapy design
Patrick M Honoré, James R Matson
Critical Care , 2002, DOI: 10.1186/cc1826
Abstract: Circulating inflammatory mediators (IM) spilling into the circulation from sites of active inflammation are considered the source of remote tissue injury and associated organ dysfunction in sepsis. Hemofiltration has been proposed as a therapy for sepsis based on its ability to remove circulating IM by sieving or by adsorption, or both. Designing devices and methods for sepsis therapy will require optimization of these two mechanisms. In the present issue of Critical Care Forum, Kellum and Dishart report the relative effects of sieving and adsorption on plasma IL-6 following cecal ligation and puncture in rats [1]. The authorsconclude that hemoadsorption is the main mechanism of removal, and discuss some possible implications for filter design. Hemoadsorption is dependent on membrane material and filtration operating parameters (e.g. filtration fraction: the so-called adsorption/synergistic effect).If hemofiltration is to be an effective therapy in the complexity of sepsis, then proper design of its material and operational characteristics must be pursued. Adsorption of proteins to membrane materials is well recognized in pharmaceutical manufacturing, food processing and medical filtration. The type and extent of feed solution proteins adsorbed depends on the membrane material, the pH, ionic strength and composition of the feed solution, the pore size, the membrane morphology and the presence of a polarization layer.Membrane materials vary in the extent and type of cytokines adsorbed. Data from in vitro studies reveal tumor necrosis factor adsorption of 30–32% for polyamide and AN69, and of 0% for cellulose acetate and polysulfone. IL-1 adsorption was 40% for polyacrylonitrile, 0–11% for polysulfone, 2% for AN69 and 0% for polyamide [2,3]. Birk et al. found an approximately sixfold difference in total plasma protein adsorption between different membrane materials. Total protein adsorption was negatively correlated with the adsorption of proteins with molecular weigh
Assessing Risks to Wildlife Populations from Multiple Stressors: Overview of the Problem and Research Needs.
Wayne R. Munns, Jr.
Ecology and Society , 2006,
Abstract: Wildlife populations are experiencing increasing pressure from human-induced changes in the landscape. Stressors including agricultural and urban land use, introduced invasive and exotic species, nutrient enrichment, direct human disturbance, and toxic chemicals directly or indirectly influence the quality and quantity of habitat used by terrestrial and aquatic wildlife. Governmental agencies such as the U.S. Environmental Protection Agency are required to assess risks to wildlife populations, in its broadest definition, that result from exposure to these stressors, yet considerable uncertainty exists with respect to how such assessments should be conducted. This uncertainty is compounded by questions concerning the interactive effects of co-occurring stressors, appropriate spatial scales of analysis, extrapolation of response data among species and from organisms to populations, and imperfect knowledge and use of limited data sets. Further, different risk problems require varying degrees of sophistication, methodological refinement, and data quality. These issues suggest a number of research needs to improve methods for wildlife risk assessments, including continued development of population dynamics models to evaluate the effects of multiple stressors at varying spatial scales, methods for extrapolating across endpoints and species with reasonable confidence, stressor-response relations and methods for combining them in predictive and diagnostic assessments, and accessible data sets describing the ecology of terrestrial and aquatic species. Case study application of models and methods for assessing wildlife risk will help to demonstrate their strengths and limitations for solving particular risk problems.
Topological Combinatorics of a Quantized String Gravitational Metric
Wayne R. Lundberg
Physics , 1997,
Abstract: A string-theoretic structure of the standard model is defined having a 4-D quantum gravity metric consistent with topological and algebraic first principles. Unique topological diagrams of string states, strong and weak interactions and quark families are evolved from this metric (but published separately). The theoretical structure includes known static and dynamic symmetries. A philosophical perspective on modern physics originates numerous opportunities for formal mathematical discussion.
A Cyclic Universe without Missing Mass: Implications of R->alpha'/R
Wayne R. Lundberg
Physics , 2000,
Abstract: Results from string theory conclude that a spatial dimension R is equivalent to *'/R. If R is considered as a four-space dimension, several interesting results emerge. In this paradigm, *'/R exists in a time-reversed, "anti- parallel" universe. Cosmological distances in our real-time universe are equivalent to the compact dimensions at the instant of a Big Bang in a time- inverted universe. This model agrees with standard black hole theory in that particles become frozen in time when they reach the 'singularity' (of dimension alpha'). A particle which enters a black hole in real time exits from the Big Bang or "white hole" in the time-inverted universe, leaving behind a trace of annihilation radiation. A diagram of this phenomenon is constructed, consistent with existing knowledge of the early universe. The primordeal black holes predicted by Hawking are required. A cyclic universe is described by M^2\p,n + T^2\n = 1. The "missing mass" proscribed by standard closed- universe theories is not required. This result is useful if experimental evidence in the search for dark matter continues to leave a significant "missing mass" - and particularly in light of more recent observations indicating that, in fact, inflation continues at a much reduced rate.
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