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D Winters

Publications and source records attributed to D Winters.

10 recordsLinked to original sources
PubMed2000

Current risk assessment approaches in different countries.

Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) exist as complex mixtures in environmental and biological samples. There is sufficient evidence that the toxic congeners share a common mode of action, involving binding to the Ah-receptor. Toxic equivalency factors (TEFs) and chemical residue data are used to calculate toxic equivalent (TEQ) concentrations in environmental samples, foods, animal and human tissues. Two different approaches have been used in the risk assessments of PCDDs, PCDFs and dioxin-like PCBs. WHO and most countries outside the USA have derived Tolerable Daily (or weekly) Intakes (TDI) in the order of 1-10 pg per kg of body weight for TCDD or TEQs based on data from rodent carcinogenicity studies. These countries have assumed the existence of a threshold dose for the carcinogenicity of dioxins, while US EPA and USFDA have used probabilistic estimates of cancer potency, treating cancer as a non-threshold effect and using a descriptor that addresses upper bound risk, the Risk Specific Dose (RsD). In the USA and other countries there is a growing concern over the non-cancer effects of dioxin-like compounds. In general, the various risk assessments have identified groups of the population that are at particular high risks and all have stressed the urgent need to reduce the sources of the environmental contamination with these compounds to the lowest possible.

Benzofurans↗
PubMed1998

Efficacy of exogenous recombinant murine leptin in lean and obese 10- to 12-mo-old female CD-1 mice.

Leptin efficacy was compared in obese and lean female CD-1 mice. Body weights in these 10- to 12-mo-old mice ranged from 29.7 to 62.0 g, and leptin levels correlated with body weight. Mice from the lean and obese ends of the weight distribution were treated with daily peripheral leptin injections (1-100 mg/kg) for a 33-day period. The half-maximal effective doses for weight loss and fat reduction were shifted 0.5-0.7 log to the right for obese mice. Leptin was less efficacious at low doses (1-3 mg/kg) in obese mice but equal to or more efficacious in obese than lean mice at high doses (30-100 mg/kg). Leptin's initial effects on weight loss could be explained by appetite suppression in both groups, but its effects on fat reduction were greater in leptin-treated than pair-fed mice, particularly in the lean group. Leptin also prevented the elevations in serum corticosterone and ketones found in pair-fed lean mice. These data allow a quantitative comparison of leptin sensitivity in obese vs. lean CD-1 mice and suggest that in mice where obesity is a function of outbreeding and age, leptin sensitivity is moderately reduced. Furthermore, although appetite suppression has a clear role in leptin's effects on body weight, leptin may also have specific effects on lipid metabolism and mobilization that are different from the metabolic compensations that normally occur with food deprivation.

Adipose Tissue↗
PubMed1998

Pharmacoeconomic analysis of 3 treatment strategies for cytomegalovirus retinitis in patients with AIDS.

A decision-analytical simulation model was constructed to perform a pharmacoeconomic analysis of the following 3 treatment strategies for previously untreated cytomegalovirus (CMV) retinitis in patients with AIDS: (i) intravenous foscarnet (IVF) for induction and maintenance therapy; (ii) intravenous ganciclovir (IVG) for induction and maintenance therapy; and (iii) intravenous ganciclovir for induction therapy, followed by oral ganciclovir for maintenance therapy (IVG-ORG). Patients who experienced significant adverse effects during, or who failed, initial therapy were switched once to one of the other 2 treatments. The model was used to estimate the direct medical cost (from the perspective of a public payer), survival, and survival adjusted for disutility because of lost vision, for each strategy in the first year following treatment initiation. The expected first-year costs of treatment initiated with IVF, IVG and IVG-ORG were $US47,918, $US38,817 and $US32,036 (1994 values), respectively, while expected first-year survival was 41 weeks, 35 weeks and 35 weeks, respectively. The incremental cost per incremental year of survival using IVF was $US78,000 versus IVG and $US138,000 versus IVG-ORG before adjustment for lost vision, and $US93,000 versus IVG and $US166,000 versus IVG-ORG after adjustment for lost vision. About 23% of the cost of the IVG treatment strategy was attributable to treatment-related adverse events, compared with 14% of the cost of IVF and 16% of the cost of IVG-ORG. Because of the high failure rate with IVG-ORG, initial treatment with IVG-ORG frequently led to switching to another treatment. Only 27% of the costs associated with the IVG-ORG treatment strategy were in fact attributable to the cost of induction and maintenance therapy prior to a switch to alternative treatment. In this analysis, initial treatment with IVG-ORG was the least costly approach for treating CMV retinitis in patients with AIDS. Initial treatment with IVF resulted in slightly longer survival adjusted for vision-related quality of life. New treatments for AIDS may reduce the survival benefit of initial treatment with IVF.

Acquired Immunodeficiency Syndrome↗
PubMed1996

A statistical survey of dioxin-like compounds in United States beef: a progress report.

The USEPA and the USDA have completed the first statistically designed survey of the occurrence and concentration of CDDs and CDFs in the fat of beef animals raised for human consumption in the United States. Back fat was sampled from 63 carcasses at federally inspected slaughter establishments nationwide. The sample design called for sampling beef animal classes in proportion to national annual slaughter statistics. All samples were analyzed using a modification of EPA method 1613, using isotope dilution, High Resolution GC/MS to determine the rate of occurrence of 2,3,7,8-substituted CDDs/CDFS. The whole weight method detection limits ranged from 0.05 ng kg-1 for TCDD to 3 ng kg-1 for OCDD. The results of this survey showed a mean concentration (reported as I-TEQ, lipid adjusted) in U.S. beef animals of 0.35 ng kg-1 and 0.89 ng kg-1 when either non-detects are treated as 0 value or assigned a value of 1/2 the detection limit, respectively.

Animals↗
PubMed1995

Pegylated megakaryocyte growth and development factor abrogates the lethal thrombocytopenia associated with carboplatin and irradiation in mice.

Megakaryocyte growth and development factor (MGDF) is a potent inducer of megakaryopoiesis in vitro and thrombopoiesis in vivo. The effects of MGDF appear to be lineage-selective, making this cytokine an ideal candidate for use in alleviating clinically relevant thrombocytopenias. This report describes a murine model of life-threatening thrombocytopenia that results from the combination treatment of carboplatin and sublethal irradiation. Mortality of this regimen is 94% and is associated with widespread internal bleeding. The daily administration of pegylated recombinant human MGDF (PEG-rMGDF) significantly reduced mortality (to < 15%) and ameliorated the depth and duration of thrombocytopenia. The severity of leucopenia and anemia was also reduced, although it was not clear whether these effects were direct. Platelets generated in response to PEG-rMGDF were morphologically indistinguishable from normal platelets. PEG-rMGDF administered in combination with murine granulocyte colony-stimulating factor completely prevented mortality and further reduced leukopenia and thrombocytopenia. These data support the concept that PEG-rMGDF may be useful to treat iatrogenic thrombocytopenias.

Animals↗
PubMed1995

Effects of the obese gene product on body weight regulation in ob/ob mice.

C57BL/6J mice with a mutation in the obese (ob) gene are obese, diabetic, and exhibit reduced activity, metabolism, and body temperature. Daily intraperitoneal injection of these mice with recombinant OB protein lowered their body weight, percent body fat, food intake, and serum concentrations of glucose and insulin. In addition, metabolic rate, body temperature, and activity levels were increased by this treatment. None of these parameters was altered beyond the level observed in lean controls, suggesting that the OB protein normalized the metabolic status of the ob/ob mice. Lean animals injected with OB protein maintained a smaller weight loss throughout the 28-day study and showed no changes in any of the metabolic parameters. These data suggest that the OB protein regulates body weight and fat deposition through effects on metabolism and appetite.

Adipose Tissue↗
PubMed1993

Diabetes in pregnancy in Zuni Indian women. Prevalence and subsequent development of clinical diabetes after gestational diabetes.

OBJECTIVE: To determine the prevalence of gestational diabetes mellitus in Zuni Indian women and the subsequent rate of diabetes among Zuni women with GDM. RESEARCH DESIGN AND METHODS: A retrospective analysis of 809 deliveries over a 4-yr period among Zuni Indian women was conducted to determine the prevalence of GDM and diabetes antedating pregnancy. A prospective case-control study of 47 full-blooded Zuni Indian women with GDM and 47 control subjects was performed to determine the progression to clinical diabetes in women with a first-time diagnosis of GDM. Cases with GDM delivered during a defined 8-yr period. The control group of Zuni women delivered during the same time period but had plasma glucose values < 7.8 mM on the 1-h glucose screening test. Cases with GDM and control subjects were matched for age, body mass index, gravidity, and length of follow-up. All women were re-evaluated for diabetes up to 9 yr after the index pregnancy. RESULTS: Between 1987-1990, 116 cases of GDM and 8 cases of pre-existing diabetes were identified, giving a prevalence of maternal diabetes in pregnancy of 15.3%. At the time of follow-up, 14 of 47 (30%) women with GDM had developed diabetes after a mean of 4.8 yr compared with only 3 of 47 (6%) from the control group with an average of 5.5 yr follow-up. CONCLUSIONS: GDM is prevalent among Zuni Indians and is associated with an increased risk of diabetes. Glucose tolerance after GDM may deteriorate at a greater rate in Native Americans than in other populations.

Adult↗
PubMedDate not supplied

Relationships between dioxins in soil, air, ash, and emissions from a municipal solid waste incinerator emitting large amounts of dioxins.

The Columbus Municipal Waste-to-Energy (Columbus WTE) facility in Columbus, Ohio, began operation in June, 1983 and ceased operation in December, 1994. During its operation, it was estimated to have released nearly 1,000 grams of dioxin Toxic Equivalents (TEQs) per year. This compares to a 1994 estimate of 9,300 g TEQ/yr from all sources emitting dioxins into the air in the United States (EPA, 1994), and to total releases of dioxins near or below 1,000 grams TEQ/Yr for England (Eduljee and Keyke, 1996), Belgium (Wevers and De Fre, 1995), and West Germany (Fiedler and Hutzinger, 1992). Because of the magnitude of emissions from this single source, studies were undertaken to evaluate the impacts to air and soil near the incinerator. This paper presents analyses evaluating dioxin concentrations and profiles in four media: stack gas, ambient air within 3 km of the incinerator, soil samples up to 8 km from the incinerator, and incinerator ash. Principal findings include: 1) an "incinerator signature" profile, as defined by stack gas emissions, was found in the ash and in subsets of the air and soil matrices, 2) soil concentrations declined from directly outside the incinerator property to the city at large, 3) an urban background soil concentration of dioxin Toxic Equivalents (TEQs) was estimated at 4 pg/g, while concentrations generally within 2 km of the incinerator ranged from 4-60 pg TEQ/g, 4) an urban background air concentration was estimated at 0.05 pg TEQ/m3, while air concentrations at a specific location about 2 km in the downwind direction of the incinerator had concentrations of 0.17 and 0.35 pg TEQ/m3 during two sampling dates, 5) analysis of the soil monitoring data in combination with the stack test data suggests that less than 2% of emitted dioxins can be found in the soil near the incinerator, and 6) principal component analysis suggests that the fraction of total concentration of OCDD is the single feature explaining most of the variation of all concentration profiles. This paper discusses these and other findings, and their implications.

Air Pollution↗
PubMedDate not supplied

Preparative electrofocusing for industrial applications.

This paper presents a case study of using a multicompartment isoelectric focusing apparatus to determine the isoelectric points and focus preparative quantities of brain derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT3). A separation of PEGylated from unPEGylated forms of granulocyte colony stimulating factor (G-CSF) is described as well. Both BDNF and NT3 have substantially higher pI values in this system than is predicted from sequenced based modeling. Although PEGylated forms of G-CSF can be separated from the unPEGylated forms, separation of protein with differing degrees of PEGylation was not achieved. The paper additionally demonstrates that this technique can be used simultaneously as an analytical and preparative tool, eliminating the need for analytical IEF gels.

Brain-Derived Neurotrophic Factor↗