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Biomedical subjects

Stephen H Schneider

Publications and source records attributed to Stephen H Schneider.

18 recordsLinked to original sources
PubMed2006

Tumor necrosis factor alpha and glucocorticoid synergistically increase leptin production in human adipose tissue: role for p38 mitogen-activated protein kinase.

CONTEXT: TNF increases plasma leptin in humans in vivo, but previous studies showed it decreases leptin in vitro. OBJECTIVE AND PARTICIPANTS: The objective of this study was to determine the effect of TNF on leptin release from human adipose tissue (AT) from healthy subjects undergoing elective surgery or needle aspirations of AT at a university hospital. DESIGN: Human omental and abdominal sc AT fragments from non- obese and obese subjects were placed in organ culture without or with TNF added in the presence or absence of insulin and/or dexamethasone (dex; a synthetic glucocorticoid) for up to 2 d. RESULTS: In the absence of hormones, culture with TNF decreased leptin release. In contrast, when added in the presence of dex, TNF increased secreted leptin and leptin mRNA abundance in AT from nonobese and obese subjects. The TNF + dex-stimulated increase in leptin was associated with an increase in p38 MAPK activity and was totally blocked by p38 MAPK inhibitors. In contrast, inhibition of p38 MAPK only partially blocked the effect of TNF on IL-6 production. Culture of obese AT with either p38 or p44/42 MAPK inhibitors also blunted the spontaneous increase in media leptin that occurred from d 1-2 of culture in omental AT of obese subjects. CONCLUSION: Synergistic effects of increased local or systemic TNF in combination with glucocorticoids may contribute to increased leptin expression in response to stress, including infection and obesity.

Adipocytes↗
PubMed2006

Climate change: do we know enough for policy action?

The climate change problem must be thought of in terms of risk, not certainty. There are many well-established elements of the problem that carry considerable confidence whereas some aspects are speculative. Therefore, the climate problem emerges not simply as a normal science research issue, but as a risk management policy debate as well. Descriptive science entails using empirical and theoretical methods to quantify the two factors that go into risk assessment: "What can happen?" and "What are the odds?" (Probability x Consequences). Policymakers should, in turn, take that information and use it to make value judgments about what is safe, what is dangerous, what is fair. To make these judgments, policymakers need to know the probabilities that experts assign to various possible outcomes in order to make risk management decisions to hedge against unsafe, dangerous and unfair outcomes. The climate debate needs to be reframed away from absolute costs--or benefits--into relative delay times to achieve specific caps or to avoid crossing specific agreed 'dangerous' climate change thresholds. Even in most optimistic scenarios, CO2 will stabilize at a much higher concentration than it has reached today, and temperature will rise accordingly. It will take even longer for sea level rise from thermal expansion and the melting of polar ice to occur, but what is most problematic is that how we handle our emissions now and in the next five decades preconditions the sustainability of the next millennium.

Climate↗
PubMed2005

Probabilistic assessment of "dangerous" climate change and emissions pathways.

Climate policy decisions driving future greenhouse gas mitigation efforts will strongly influence the success of compliance with Article 2 of the United Nations Framework Convention on Climate Change, the prevention of "dangerous anthropogenic interference (DAI) with the climate system." However, success will be measured in very different ways by different stakeholders, suggesting a spectrum of possible definitions for DAI. The likelihood of avoiding a given threshold for DAI depends in part on uncertainty in the climate system, notably, the range of uncertainty in climate sensitivity. We combine a set of probabilistic global average temperature metrics for DAI with probability distributions of future climate change produced from a combination of several published climate sensitivity distributions and a range of proposed concentration stabilization profiles differing in both stabilization level and approach trajectory, including overshoot profiles. These analyses present a "likelihood framework" to differentiate future emissions pathways with regard to their potential for preventing DAI. Our analysis of overshoot profiles in comparison with non-overshoot profiles demonstrates that overshoot of a given stabilization target can significantly increase the likelihood of exceeding "dangerous" climate impact thresholds, even though equilibrium warming in our model is identical for non-overshoot concentration stabilization profiles having the same target.

Climate↗
PubMed2005

Human-modified temperatures induce species changes: Joint attribution.

Average global surface-air temperature is increasing. Contention exists over relative contributions by natural and anthropogenic forcings. Ecological studies attribute plant and animal changes to observed warming. Until now, temperature-species connections have not been statistically attributed directly to anthropogenic climatic change. Using modeled climatic variables and observed species data, which are independent of thermometer records and paleoclimatic proxies, we demonstrate statistically significant "joint attribution," a two-step linkage: human activities contribute significantly to temperature changes and human-changed temperatures are associated with discernible changes in plant and animal traits. Additionally, our analyses provide independent testing of grid-box-scale temperature projections from a general circulation model (HadCM3).

Computer Simulation↗
PubMed2004

Isoproterenol decreases leptin release from rat and human adipose tissue through posttranscriptional mechanisms.

In vivo and in vitro studies indicate that beta-adrenergic receptor agonists decrease leptin release from fat cells in as little as 30 min. Our objective was to determine whether alterations in leptin biosynthesis or secretion were involved in the short-term adrenergic regulation of leptin in human and rat adipose tissue. Isoproterenol (Iso) decreased leptin release from incubated adipose tissue of both nonobese and obese subjects to similar extent (-28 vs. -21% after 3 h). Inhibition of protein synthesis with cycloheximide did not block the effect of Iso on leptin release from human adipose tissue, suggesting that the Iso effect is independent of leptin synthesis. Iso also tended to increase tissue leptin content at the end of the 3-h incubation, as expected from the observed inhibition of release. Consistent with a posttranslational mechanism, Iso treatment did not affect leptin mRNA levels or relative rate of leptin biosynthesis as directly assessed by [35S]methionine incorporation into immunoprecipitable leptin. In contrast to these results in human adipose tissues, Iso did not decrease basal leptin release from rat adipose tissue. However, Iso did decrease insulin-stimulated leptin release by inhibiting the ability of insulin to increase leptin biosynthesis without detectably affecting leptin mRNA levels. Thus, in both human and rat, adrenergic regulation of posttranscriptional events (secretion in humans, translation in rats) may contribute to the rapid decline in circulating leptin that occurs when the sympathetic nervous system is activated, such as during fasting and cold exposure. Furthermore, the rat does not provide an ideal model to study mechanisms of cellular leptin regulation in humans.

Adipose Tissue↗
PubMed2004

Emissions pathways, climate change, and impacts on California.

The magnitude of future climate change depends substantially on the greenhouse gas emission pathways we choose. Here we explore the implications of the highest and lowest Intergovernmental Panel on Climate Change emissions pathways for climate change and associated impacts in California. Based on climate projections from two state-of-the-art climate models with low and medium sensitivity (Parallel Climate Model and Hadley Centre Climate Model, version 3, respectively), we find that annual temperature increases nearly double from the lower B1 to the higher A1fi emissions scenario before 2100. Three of four simulations also show greater increases in summer temperatures as compared with winter. Extreme heat and the associated impacts on a range of temperature-sensitive sectors are substantially greater under the higher emissions scenario, with some interscenario differences apparent before midcentury. By the end of the century under the B1 scenario, heatwaves and extreme heat in Los Angeles quadruple in frequency while heat-related mortality increases two to three times; alpine/subalpine forests are reduced by 50-75%; and Sierra snowpack is reduced 30-70%. Under A1fi, heatwaves in Los Angeles are six to eight times more frequent, with heat-related excess mortality increasing five to seven times; alpine/subalpine forests are reduced by 75-90%; and snowpack declines 73-90%, with cascading impacts on runoff and streamflow that, combined with projected modest declines in winter precipitation, could fundamentally disrupt California's water rights system. Although interscenario differences in climate impacts and costs of adaptation emerge mainly in the second half of the century, they are strongly dependent on emissions from preceding decades.

Agriculture↗
PubMed2004

Probabilistic integrated assessment of "dangerous" climate change.

Climate policy decisions are being made despite layers of uncertainty. Such decisions directly influence the potential for "dangerous anthropogenic interference with the climate system." We mapped a metric for this concept, based on Intergovernmental Panel on Climate Change assessment of climate impacts, onto probability distributions of future climate change produced from uncertainty in key parameters of the coupled social-natural system-climate sensitivity, climate damages, and discount rate. Analyses with a simple integrated assessment model found that, under midrange assumptions, endogenously calculated, optimal climate policy controls can reduce the probability of dangerous anthropogenic interference from approximately 45% under minimal controls to near zero.

Journal Article↗
PubMed2004

Interleukin-6 regulates human adipose tissue lipid metabolism and leptin production in vitro.

Adipose tissue IL-6 expression is increased in obesity and is a strong predictor of abnormalities in adipocyte and systemic metabolism. We used adipose tissue organ culture to test the direct effects of IL-6 on leptin expression, lipolysis, and lipoprotein lipase activity. To assess possible interactions with the hormonal milieu, IL-6 effects were tested in the presence or absence of insulin and/or glucocorticoid [dexamethasone (dex)]. Because omental (Om) and abdominal sc depots differ in IL-6 expression, their responses to exogenous IL-6 were compared. Although IL-6 had no significant effects under basal conditions, culture with the combination of IL-6 and dex, compared with dex alone, for 2 d increased leptin in both depots [+95 +/- 30% (sc) and +67 +/- 19% (Om), P < 0.01]; IL-6 did not affect leptin production when added in the presence of insulin. Culture with IL-6 in the absence of hormones moderately increased lipolysis during culture in both sc and Om [+79 +/- 23% (sc) and +26 +/- 9% (Om), each P < 0.01]. IL-6 markedly reduced the high levels of lipoprotein lipase activity in tissue cultured with insulin plus dex. We conclude that high local concentrations of IL-6 can modulate leptin production and lipid metabolism in human adipose tissue.

Adipose Tissue↗
PubMed2003

Fingerprints of global warming on wild animals and plants.

Over the past 100 years, the global average temperature has increased by approximately 0.6 degrees C and is projected to continue to rise at a rapid rate. Although species have responded to climatic changes throughout their evolutionary history, a primary concern for wild species and their ecosystems is this rapid rate of change. We gathered information on species and global warming from 143 studies for our meta-analyses. These analyses reveal a consistent temperature-related shift, or 'fingerprint', in species ranging from molluscs to mammals and from grasses to trees. Indeed, more than 80% of the species that show changes are shifting in the direction expected on the basis of known physiological constraints of species. Consequently, the balance of evidence from these studies strongly suggests that a significant impact of global warming is already discernible in animal and plant populations. The synergism of rapid temperature rise and other stresses, in particular habitat destruction, could easily disrupt the connectedness among species and lead to a reformulation of species communities, reflecting differential changes in species, and to numerous extirpations and possibly extinctions.

Animals↗
PubMed2003

Perilipin expression in human adipose tissues: effects of severe obesity, gender, and depot.

OBJECTIVE: Perilipins are phosphoproteins that are localized to the surface of triacylglycerol droplets within adipocytes where they regulate the rate of lipolysis. We sought to determine the effects of severe obesity and depot [omental (Om) vs. subcutaneous (Sc)] on perilipin expression in the adipose tissue of individuals. RESEARCH METHODS AND PROCEDURES: Samples of Om and Sc adipose tissues obtained at surgery from severely obese subjects and fat aspirations from nonobese subjects were analyzed for perilipin protein and mRNA levels by Northern and Western analysis. RESULTS: Perilipin A (periA) was the major perilipin expressed in adipose tissues. periA mRNA relative abundance was significantly lower in Sc adipose tissue from severely obese compared to that from nonobese subjects. Western blotting of adipose tissue extracts showed that periA protein levels expressed relative to tissue protein or fat cell surface area were significantly lower ( approximately -40%) in abdominal Sc adipose tissue from severely obese compared to that from nonobese subjects. However, the calculated mass of perilipin per fat cell did not differ between the two groups. Perilipin mRNA levels were higher in Sc compared to Om adipose tissue from obese individuals (p < 0.025; n = 26; 17 women, 9 men); however, periA protein levels did not differ. In addition, perilipin protein, but not mRNA, levels were higher in Sc adipose tissue from obese men than from women (p < 0.025). DISCUSSION: Variations in perilipin expression may contribute to the higher basal lipolytic rates observed in obese compared to nonobese individuals and in obese women compared to obese men.

Adipocytes↗
PubMed2003

Coping with uncertainty: a call for a new science-policy forum.

The scientific and policy worlds have different goals, which can lead to different standards for what constitutes "proof" of a change or phenomena, and different approaches for characterizing and conveying uncertainty and risk. These differences can compromise effective communication among scientists, policymakers, and the public, and constrain the types of socially compelling questions scientists are willing to address. In this paper, we review a set of approaches for dealing with uncertainty, and illustrate some of the errors that arise when science and policy fail to coordinate correctly. We offer a set of recommendations, including restructuring of science curricula and establishment of science-policy forums populated by leaders in both arenas, and specifically constituted to address problems of uncertainty.

Curriculum↗
PubMed2002

Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery.

OBJECTIVES: The aim of this study was to determine the impact of diabetes mellitus (DM) on short-term mortality and morbidity in patients undergoing coronary artery bypass surgery (CABG). BACKGROUND: Diabetes mellitus is present in approximately 20% to 30% of patients undergoing CABG, and the impact of diabetes on short-term outcome is unclear. METHODS: We performed a retrospective cohort study in 434 hospitals from North America. The study population included 146,786 patients undergoing CABG during 1997: 41,663 patients with DM and 105,123 without DM. The primary outcome was 30-day mortality. Secondary outcomes were in-hospital morbidity, infections and composite outcomes of mortality or morbidity and mortality or infection. RESULTS: The 30-day mortality was 3.7% in patients with DM and 2.7% in those without DM; the unadjusted odds ratio was 1.40 (95% confidence interval [CI], 1.31 to 1.49). After adjusting for other baseline risk factors, the overall adjusted odds ratio for diabetics was 1.23 (95% CI, 1.15 to 1.32). Patients treated with oral hypoglycemic medications had adjusted odds ratio 1.13; 95% CI, 1.04 to 1.23, whereas those on insulin had an adjusted odds ratio 1.39; 95% CI, 1.27 to 1.52. Morbidity, infections and the composite outcomes occurred more commonly in diabetic patients and were associated with an adjusted risk about 35% higher in diabetics than nondiabetics, particularly among insulin-treated diabetics (adjusted risk between 1.5 to 1.61). CONCLUSIONS: Diabetes mellitus is an important risk factor for mortality and morbidity among those undergoing CABG. Research is needed to determine if good control of glucose levels during the perioperative time period improves outcome.

Aged↗
PubMed2002

Dynamics of climate and ecosystem coupling: abrupt changes and multiple equilibria.

Interactions between subunits of the global climate-biosphere system (e.g. atmosphere, ocean, biosphere and cryosphere) often lead to behaviour that is not evident when each subunit is viewed in isolation. This newly evident behaviour is an emergent property of the coupled subsystems. Interactions between thermohaline circulation and climate illustrate one emergent property of coupling ocean and atmospheric circulation. The multiple thermohaline circulation equilibria that result caused abrupt climate changes in the past and may cause abrupt climate changes in the future. Similarly, coupling between the climate system and ecosystem structure and function produces complex behaviour in certain regions. For example, atmosphere-biosphere interactions in the Sahel region of West Africa lead to multiple stable equilibria. Either wet or dry climate equilibria can occur under otherwise identical forcing conditions. The equilibrium reached is dependent on past history (i.e. initial conditions), and relatively small perturbations to either climate or vegetation can cause switching between the two equilibria. Both thermohaline circulation and the climate-vegetation system in the Sahel are prone to abrupt changes that may be irreversible. This complicates the relatively linear view of global changes held in many scientific and policy communities. Emergent properties of coupled socio-natural systems add yet another layer of complexity to the policy debate. As a result, the social and economic consequences of possible global changes are likely to be underestimated in most conventional analyses because these nonlinear, abrupt and irreversible responses are insufficiently considered.

Climate↗
PubMed2002

Lipoprotein oxidation mediated by J774 murine macrophages is inhibited by individual red wine polyphenols but not by ethanol.

The in vitro capacities of individual polyphenols in red wine to inhibit the cell-mediated oxidation of lipoproteins and their effects on cell viability were determined. LDL and HDL were incubated with J774.A1 macrophages and 2 and 4 micro mol/L copper, respectively, in the absence and presence of polyphenols in ethanol at concentrations found in red wine. A mixture of polyphenols in amounts found in red wine equivalent to 0.2 g/L ethanol and 0.05 g/L ethanol inhibited thiobarbituric acid-reactive substance production from LDL by 91.7 and 45.9%, respectively, compared with ethanol controls (P < 0.01). HDL oxidation was inhibited 85 and 82.4% by the polyphenols at 0.2 and 0.05 g/L ethanol (P < 0.01). The effects of the polyphenol mixture on LDL oxidation were confirmed by measuring production of conjugated dienes and lipid peroxides, and trinitrobenzene sulfonic acid reactivity. Catechin at the concentration found in red wine (1.32 micro mol/L) at an ethanol concentration equivalent to 0.2 g/L inhibited LDL oxidation by 83.2%, while epicatechin (0.56 micro mol/L) and gallic acid (1.02 micro mol/L) inhibited by 60.6 and 26.9%, respectively (P < 0.05). At 1 micro mol/L, LDL oxidation was inhibited by epicatechin, catechin and quercetin by 86.2, 79.9 and 69.4%, respectively (P < 0.05). Incubation of macrophages with ethanol alone and with polyphenols in ethanol did not affect cell viability. Our results indicate that catechin and epicatechin are the major contributors to the antioxidant activity of red wine.

Adult↗
PubMedDate not supplied

Patient perception and use of an insulin injector/glucose monitor combined device.

PURPOSE: This clinical trial assessed patient preference, satisfaction, and use of an insulin injector/glucose monitor combination device versus syringes and a separate glucose monitor. METHODS: In a randomized, multicenter, 2-period crossover study, 15 patients with type 1 diabetes were randomized to use either a combined injector/monitor device or syringes, a vial, and a separate glucose monitor, then switched to the alternate treatment. Efficacy, safety, preference, satisfaction, and actual use (via meter download) of the 2 systems were compared. RESULTS: Most of the patients preferred using the combination device to syringes and a separate meter. Results from the Handling of Delivery Systems questionnaire given at the end of the study indicated that 49% of patients felt they tested their blood glucose more often with the combination device than with a separate meter. A higher frequency of daily monitoring was reported with the combination device in patients overall (approximately 1 more reading per week). However, a large subset of patients (32%) showed substantial increases in their frequency of daily glucose monitoring (an average of 1 additional reading per day). CONCLUSIONS: Use of the combination device was associated with significant improvements in patient treatment satisfaction.

Adult↗