Nancy Higley - Academia.edu (original) (raw)

Papers by Nancy Higley

Nutrition Reviews, May 1, 2009

There has been significant public debate about the susceptibility of research to biases of variou... more There has been significant public debate about the susceptibility of research to biases of various kinds. The dialogue has extended to the peer-reviewed literature, scientific conferences, the mass media, government advisory bodies, and beyond. While biases can come from myriad sources, the overwhelming focus of the discussion, to date, has been on industry-funded science. Given the critical role that industry has played and will continue to play in the research process, the International Life Sciences Institute (ILSI) North America Working Group on Guiding Principles has, in this paper, set out proposed conflict-of-interest guidelines, regarding industry funding, for protecting the integrity and credibility of the scientific record, particularly with respect to health, nutrition, and food-safety science. Eight principles are enumerated, specifying ground rules for industry-sponsored research. The paper, which issues a challenge to the broader scientific community to address all bias issues, is only a first step; the document is intended to be dynamic, prompting ongoing discussion and refinement. The Guiding Principles are as follows. In the conduct of public/private research relationships, all relevant parties shall: 1) conduct or sponsor research that is factual, transparent, and designed objectively; according to accepted principles of scientific inquiry, the research design will generate an appropriately phrased hypothesis and the research will answer the appropriate questions, rather than favor a particular outcome; 2) require control of both study design and research itself to remain with scientific investigators; 3) not offer or accept remuneration geared to the outcome of a research project; 4) prior to the commencement of studies, ensure that there is a written agreement that the investigative team has the freedom and obligation to attempt to publish the findings within some specified time-frame; 5) require, in publications and conference presentations, full signed disclosure of all financial interests; 6) not participate in undisclosed paid authorship arrangements in industry-sponsored publications or presentations; 7) guarantee accessibility to all data and control of statistical analysis by investigators and appropriate auditors/ reviewers; and 8) require that academic researchers, when they work in contract research organizations (CRO) or act as contract researchers, make clear statements of their affiliation; require that such researchers publish only under the auspices of the CRO.

Food flavors are complex mixtures of individual flavor ingredients which are often natural consti... more Food flavors are complex mixtures of individual flavor ingredients which are often natural constituents of food, and can be produced through physical means from traditional plant and animal sources, chemical synthesis, and processes incorporating the techniques of modern biotechnology. Plant cell and tissue culture provide alternative methods for the production of food flavors and food flavor ingredients. The use of plant cell and tissue culture presents new issues related to the safety assessment of flavors. A safety assessment scheme has been developed to address these issues, particularly issues associated with plant cell and tissue culture methods, with and without the incorporation of genetic modification. A key issue associated with plant cell and tissue culture also addressed in the new scheme is the safety assessment of complex mixtures that may be produced through plant cell and tissue culture.

Food and Chemical Toxicology, 2021

Food and Chemical Toxicology, Dec 1, 1984

Abstraet-Monolayers of L-cell cultures were incubated with oxygenated cholesterols and cellular p... more Abstraet-Monolayers of L-cell cultures were incubated with oxygenated cholesterols and cellular protein was subsequently measured to assess the cytotoxicity of the cholesterol oxides. The site of oxidation of the cholesterol molecule was not reflected in the degree of cytotoxicity. Of the 12 cholesterol oxides tested, cholestan-3fl,5~,6fl-triol and cholestan-3,5-diene-7-one exhibited the greatest cytotoxicity, approximately 45% inhibition (reduction) in protein compared to the control at concentrations of 10/~ g/ml, after 1 day of incubation with the compounds. 5-Cholesten-3B,25-diol and 5-cholesten-3fl-ol-7-one were the most cytotoxic after 5 days' exposure with concentrations of 10pg/ml reducing the protein content to approximately 10% of the control. Lipid accumulation in the L cells (steatosis), as measured by Oil Red O-stainable droplets formed in response to cholesterol oxides was also investigated. Grade 3 steatosis (an increase in lipid droplets so that more than 75% of the L-cell cytoplasm was occupied by lipid droplets) after 1 day of exposure to cholesterol oxides generally reflected the cytotoxic effect of the same cholesterol oxides after 5 days' exposure. However some of the steatotic cholesterol oxides, such as the c~ and fl epimers of cholestan-5,6-epoxy-3fl-ol were highly active with respect to steatosis, increasing the grade 3 value to 209 and 390% of control, respectively, but were not cytotoxic. This has led to the suggestion that the cholesterol oxides have more than one mode of action in L cells.

Journal of Food Protection, Feb 1, 1985

Potato chips and french fries were analyzed by high performance liquid chromatography and thin la... more Potato chips and french fries were analyzed by high performance liquid chromatography and thin layer chromatography for cholesterol and (3-sitosterol oxidation products. Chips stored for 150 d at 23°C in unopened foil bags contained no detectable sitosterol oxidation products, but those held at 40°C contained 7a-hydroxysitosterol, 7p-hydroxysitosterol, and sitosterol (3epoxide only after an extended storage of 95 d. French fries as purchased contained sterol a-and (3-epoxides, and la-and 7(3-hydroxysterols. These sterol oxidation products were present in repeat samples from five different fast food restaurants. Ingestion of sterol oxides from potato chips is unlikely, whereas ingestion of sterol oxides from french fries is possible.

Meat Science, 1986

Methods for the extraction of cholesterol oxides from meats were studied. A dry column technique ... more Methods for the extraction of cholesterol oxides from meats were studied. A dry column technique for the extraction of sterols was found to be more rapid and convenient than conventional chloroform-methanol extraction. An overall yield of 32·0% and 23·6% for radiolabelled cholesterol and cholesterol oxides, respectively, was obtained after dry column extraction, saponification and chromatography on a silica arrestant column, Florisil®-AgNO(3) column and silica Sep-Pak® column. The overall extraction efficiency of ten meat samples was 22·3 ± 1·7 %. Cholesterol oxides present in measurable amounts included 5-cholesten-3β, 19-diol, 5-cholesten-3β-ol-22-one, the α and β epimers of 5-cholesten-3β, 7-diol and cholestan-3 β, 5α, 6β-triol in some of the meat samples analyzed, but, for the majority of samples, no detectable amounts of known cholesterol oxides were found. Most of the meats, however, contained unidentified components that are non-polar with respect to cholesterol.

Atherosclerosis, Nov 1, 1986

Previous findings indicating that the oxidation products of cholesterol are associated with ather... more Previous findings indicating that the oxidation products of cholesterol are associated with atherogenicity have led to a comparative study of the subchronic effects of feeding rabbits purified cholesterol, oxidized cholesterols free of cholesterol and cholesterol esters, or a mixture of cholesterol and oxidized cholesterols. Macroscopically, the cholesterol-fed animals exhibited 6-fold more arterial lesions than the animals fed cholesterol-free oxidized cholesterols. Microscopically, there was no statistically significant difference from the control in the number of histochemically-defined lesions in any of the groups. However, the lesions in the cholesterol-fed group were more severe, as indicated by a statistically significant increase in the magnitude of the lesions. This increased severity was also characterized by greater frequency and intensity of Azure A/Thionin, VonKossa, and Horseradish Peroxidase-Wheat Germ Agglutinin staining. Electronmicroscopic studies of normal appearing arterial tissues showed an increased density of viable smooth muscle cells and an increase in vacuolar extracellular debris in the cholesterol-fed group. Oxidized cholesterols in the concentrations and relative compositions administered here are markedly less atherogenie to rabbits than highly purified cholesterol.

Elsevier eBooks, 1986

... f William S. Middlelon Memorial Veterans Hospital, Madison, Wisconsin 53705 ^ Department of M... more ... f William S. Middlelon Memorial Veterans Hospital, Madison, Wisconsin 53705 ^ Department of Medicine, University of Wisconsin, Madison, Wisconsin 53706 I ... years regarding the possibility that many consumers may be exceeding the Acceptable Daily Intake (ADI) for sulfites ...

Food and Chemical Toxicology, 1989

A subchronic oral toxicity study of sodium metabisulphite and acetaldehyde hydroxysulphonate was ... more A subchronic oral toxicity study of sodium metabisulphite and acetaldehyde hydroxysulphonate was conducted in normal and sulphite oxidase-deficient rats. At the highest dose level (350 mg SO2 equiv./kg body weight/day for 3 wk followed by 175 mg SO2 equiv./kg body weight/day for 5 wk of either compound), gastric lesions were noted histologically in both normal and sulphite oxidase-deficient rats. The lesions were more severe and more frequently encountered in the sulphite oxidase-deficient rats. The no-effect level for Na2S2O5 was 70 mg SO2 equiv./kg body weight/day in both normal and sulphite oxidase-deficient rats. Liver lesions were noted in rats treated with acetaldehyde hydroxysulphonate. These lesions may possibly be attributable to the effects of free acetaldehyde. The no-effect level for acetaldehyde hydroxysulphonate was 7 mg SO2 equiv./kg body weight/day for sulphite oxidase-deficient rats and 70 mg SO2 equiv./kg body weight/day for normal rats. Increased urinary excretion of sulphite was noted in sulphite oxidase-deficient rats whether or not they were given exogenous sulphites. An increase in urinary sulphite levels in sulphite oxidase-deficient rats was observed after dosing with acetaldehyde hydroxy-sulphonate. These findings suggest that acetaldehyde hydroxysulphonate is metabolized to acetaldehyde and free sulphite.

... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to... more ... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to epithelia of the stomach, small intestine, and colon but not to the kidneys, and this damage was observed only in mice ... O'Brien, AD, Lively, TA, Chen, ME, Rothman, SW, Formal, SB 1983. ...

Current Microbiology, Nov 1, 1984

... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to... more ... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to epithelia of the stomach, small intestine, and colon but not to the kidneys, and this damage was observed only in mice ... O'Brien, AD, Lively, TA, Chen, ME, Rothman, SW, Formal, SB 1983. ...

Food and Chemical Toxicology, 2005

A scientifically-based guide has been developed to evaluate the safety of naturally occurring mix... more A scientifically-based guide has been developed to evaluate the safety of naturally occurring mixtures, particularly essential oils, for their intended use as flavor ingredients. The approach relies on the complete chemical characterization of the essential oil and the variability of the composition of the oil in the product intended for commerce. Being products of common plant biochemical pathways, the chemically-identified constituents are organized according to a limited number of well-established chemical groups called congeneric groups. The safety of the intake of the each congeneric group from consumption of the essential oil is evaluated in the context of data on absorption, metabolism, and toxicology of members of the congeneric group. The intake of the group of unidentified constituents is evaluated in the context of the consumption of the essential oil as a food, a highly conservative toxicologic threshold, and toxicity data on the essential oil or an essential oil of similar chemotaxonomy. The flexibility of the guide is reflected in the fact that high intake of major congeneric groups of low toxicologic concern will be evaluated along with low intake of minor congeneric groups of significant toxicological concern (i.e., higher structural class). The guide also provides a comprehensive evaluation of all congeneric groups and constituents that account for the majority of the composition of the essential oil. The overall objective of the guide is to organize and prioritize the chemical constituents of an essential oil in order that no reasonably possible significant risk associated with the intake of essential oil goes unevaluated. The guide is, however, not intended to be a rigid checklist. The Panel will continue to evaluate each essential oil on a case by case basis applying their scientific judgment to insure that each NFC is exhaustively evaluated.

Journal of Food Protection, 1985

Potato chips and french fries were analyzed by high performance liquid chromatography and thin la... more Potato chips and french fries were analyzed by high performance liquid chromatography and thin layer chromatography for cholesterol and (β-sitosterol oxidation products. Chips stored for 150 d at 23°C in unopened foil bags contained no detectable sitosterol oxidation products, but those held at 40°C contained 7α-hydroxysitosterol, 7β-hydroxysitosterol, and sitosterol (β-epoxide only after an extended storage of 95 d. French fries as purchased contained sterol α- and β-epoxides, and 7α- and 7β-hydroxysterols. These sterol oxidation products were present in repeat samples from five different fast food restaurants. Ingestion of sterol oxides from potato chips is unlikely, whereas ingestion of sterol oxides from french fries is possible.

ACS Symposium Series, 2008

Multinational companies continually seek that one "global" formula that would allow the... more Multinational companies continually seek that one "global" formula that would allow them to do business internationally while taking advantage of economies of scale. Country variability of the legality and specifications for color additives often necessitates the design of different product formulae for different markets, making the "global" formula elusive. The use of different coloring agents can dramatically impact a product's appearance, taste, stability, cost and consumer perception. Examples of how internationally marketed beverages are impacted by the variability of color regulations will be presented.

Advances in Food Research, 1986

... f William S. Middlelon Memorial Veterans Hospital, Madison, Wisconsin 53705 ^ Department of M... more ... f William S. Middlelon Memorial Veterans Hospital, Madison, Wisconsin 53705 ^ Department of Medicine, University of Wisconsin, Madison, Wisconsin 53706 I ... years regarding the possibility that many consumers may be exceeding the Acceptable Daily Intake (ADI) for sulfites ...

Food and Chemical Toxicology, 1984

Abstraet-Monolayers of L-cell cultures were incubated with oxygenated cholesterols and cellular p... more Abstraet-Monolayers of L-cell cultures were incubated with oxygenated cholesterols and cellular protein was subsequently measured to assess the cytotoxicity of the cholesterol oxides. The site of oxidation of the cholesterol molecule was not reflected in the degree of cytotoxicity. Of the 12 cholesterol oxides tested, cholestan-3fl,5~,6fl-triol and cholestan-3,5-diene-7-one exhibited the greatest cytotoxicity, approximately 45% inhibition (reduction) in protein compared to the control at concentrations of 10/~ g/ml, after 1 day of incubation with the compounds. 5-Cholesten-3B,25-diol and 5-cholesten-3fl-ol-7-one were the most cytotoxic after 5 days' exposure with concentrations of 10pg/ml reducing the protein content to approximately 10% of the control. Lipid accumulation in the L cells (steatosis), as measured by Oil Red O-stainable droplets formed in response to cholesterol oxides was also investigated. Grade 3 steatosis (an increase in lipid droplets so that more than 75% of the L-cell cytoplasm was occupied by lipid droplets) after 1 day of exposure to cholesterol oxides generally reflected the cytotoxic effect of the same cholesterol oxides after 5 days' exposure. However some of the steatotic cholesterol oxides, such as the c~ and fl epimers of cholestan-5,6-epoxy-3fl-ol were highly active with respect to steatosis, increasing the grade 3 value to 209 and 390% of control, respectively, but were not cytotoxic. This has led to the suggestion that the cholesterol oxides have more than one mode of action in L cells.

Food and Chemical Toxicology, 1989

A subchronic oral toxicity study of sodium metabisulphite and acetaldehyde hydroxysulphonate was ... more A subchronic oral toxicity study of sodium metabisulphite and acetaldehyde hydroxysulphonate was conducted in normal and sulphite oxidase-deficient rats. At the highest dose level (350 mg SO2 equiv./kg body weight/day for 3 wk followed by 175 mg SO2 equiv./kg body weight/day for 5 wk of either compound), gastric lesions were noted histologically in both normal and sulphite oxidase-deficient rats. The lesions were more severe and more frequently encountered in the sulphite oxidase-deficient rats. The no-effect level for Na2S2O5 was 70 mg SO2 equiv./kg body weight/day in both normal and sulphite oxidase-deficient rats. Liver lesions were noted in rats treated with acetaldehyde hydroxysulphonate. These lesions may possibly be attributable to the effects of free acetaldehyde. The no-effect level for acetaldehyde hydroxysulphonate was 7 mg SO2 equiv./kg body weight/day for sulphite oxidase-deficient rats and 70 mg SO2 equiv./kg body weight/day for normal rats. Increased urinary excretion of sulphite was noted in sulphite oxidase-deficient rats whether or not they were given exogenous sulphites. An increase in urinary sulphite levels in sulphite oxidase-deficient rats was observed after dosing with acetaldehyde hydroxy-sulphonate. These findings suggest that acetaldehyde hydroxysulphonate is metabolized to acetaldehyde and free sulphite.

Current Microbiology, 1984

... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to... more ... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to epithelia of the stomach, small intestine, and colon but not to the kidneys, and this damage was observed only in mice ... O'Brien, AD, Lively, TA, Chen, ME, Rothman, SW, Formal, SB 1983. ...

Atherosclerosis, 1986

Previous findings indicating that the oxidation products of cholesterol are associated with ather... more Previous findings indicating that the oxidation products of cholesterol are associated with atherogenicity have led to a comparative study of the subchronic effects of feeding rabbits purified cholesterol, oxidized cholesterols free of cholesterol and cholesterol esters, or a mixture of cholesterol and oxidized cholesterols. Macroscopically, the cholesterol-fed animals exhibited 6-fold more arterial lesions than the animals fed cholesterol-free oxidized cholesterols. Microscopically, there was no statistically significant difference from the control in the number of histochemically-defined lesions in any of the groups. However, the lesions in the cholesterol-fed group were more severe, as indicated by a statistically significant increase in the magnitude of the lesions. This increased severity was also characterized by greater frequency and intensity of Azure A/Thionin, VonKossa, and Horseradish Peroxidase-Wheat Germ Agglutinin staining. Electronmicroscopic studies of normal appearing arterial tissues showed an increased density of viable smooth muscle cells and an increase in vacuolar extracellular debris in the cholesterol-fed group. Oxidized cholesterols in the concentrations and relative compositions administered here are markedly less atherogenie to rabbits than highly purified cholesterol.

Nutrition Reviews, May 1, 2009

There has been significant public debate about the susceptibility of research to biases of variou... more There has been significant public debate about the susceptibility of research to biases of various kinds. The dialogue has extended to the peer-reviewed literature, scientific conferences, the mass media, government advisory bodies, and beyond. While biases can come from myriad sources, the overwhelming focus of the discussion, to date, has been on industry-funded science. Given the critical role that industry has played and will continue to play in the research process, the International Life Sciences Institute (ILSI) North America Working Group on Guiding Principles has, in this paper, set out proposed conflict-of-interest guidelines, regarding industry funding, for protecting the integrity and credibility of the scientific record, particularly with respect to health, nutrition, and food-safety science. Eight principles are enumerated, specifying ground rules for industry-sponsored research. The paper, which issues a challenge to the broader scientific community to address all bias issues, is only a first step; the document is intended to be dynamic, prompting ongoing discussion and refinement. The Guiding Principles are as follows. In the conduct of public/private research relationships, all relevant parties shall: 1) conduct or sponsor research that is factual, transparent, and designed objectively; according to accepted principles of scientific inquiry, the research design will generate an appropriately phrased hypothesis and the research will answer the appropriate questions, rather than favor a particular outcome; 2) require control of both study design and research itself to remain with scientific investigators; 3) not offer or accept remuneration geared to the outcome of a research project; 4) prior to the commencement of studies, ensure that there is a written agreement that the investigative team has the freedom and obligation to attempt to publish the findings within some specified time-frame; 5) require, in publications and conference presentations, full signed disclosure of all financial interests; 6) not participate in undisclosed paid authorship arrangements in industry-sponsored publications or presentations; 7) guarantee accessibility to all data and control of statistical analysis by investigators and appropriate auditors/ reviewers; and 8) require that academic researchers, when they work in contract research organizations (CRO) or act as contract researchers, make clear statements of their affiliation; require that such researchers publish only under the auspices of the CRO.

Food flavors are complex mixtures of individual flavor ingredients which are often natural consti... more Food flavors are complex mixtures of individual flavor ingredients which are often natural constituents of food, and can be produced through physical means from traditional plant and animal sources, chemical synthesis, and processes incorporating the techniques of modern biotechnology. Plant cell and tissue culture provide alternative methods for the production of food flavors and food flavor ingredients. The use of plant cell and tissue culture presents new issues related to the safety assessment of flavors. A safety assessment scheme has been developed to address these issues, particularly issues associated with plant cell and tissue culture methods, with and without the incorporation of genetic modification. A key issue associated with plant cell and tissue culture also addressed in the new scheme is the safety assessment of complex mixtures that may be produced through plant cell and tissue culture.

Food and Chemical Toxicology, 2021

Food and Chemical Toxicology, Dec 1, 1984

Abstraet-Monolayers of L-cell cultures were incubated with oxygenated cholesterols and cellular p... more Abstraet-Monolayers of L-cell cultures were incubated with oxygenated cholesterols and cellular protein was subsequently measured to assess the cytotoxicity of the cholesterol oxides. The site of oxidation of the cholesterol molecule was not reflected in the degree of cytotoxicity. Of the 12 cholesterol oxides tested, cholestan-3fl,5~,6fl-triol and cholestan-3,5-diene-7-one exhibited the greatest cytotoxicity, approximately 45% inhibition (reduction) in protein compared to the control at concentrations of 10/~ g/ml, after 1 day of incubation with the compounds. 5-Cholesten-3B,25-diol and 5-cholesten-3fl-ol-7-one were the most cytotoxic after 5 days' exposure with concentrations of 10pg/ml reducing the protein content to approximately 10% of the control. Lipid accumulation in the L cells (steatosis), as measured by Oil Red O-stainable droplets formed in response to cholesterol oxides was also investigated. Grade 3 steatosis (an increase in lipid droplets so that more than 75% of the L-cell cytoplasm was occupied by lipid droplets) after 1 day of exposure to cholesterol oxides generally reflected the cytotoxic effect of the same cholesterol oxides after 5 days' exposure. However some of the steatotic cholesterol oxides, such as the c~ and fl epimers of cholestan-5,6-epoxy-3fl-ol were highly active with respect to steatosis, increasing the grade 3 value to 209 and 390% of control, respectively, but were not cytotoxic. This has led to the suggestion that the cholesterol oxides have more than one mode of action in L cells.

Journal of Food Protection, Feb 1, 1985

Potato chips and french fries were analyzed by high performance liquid chromatography and thin la... more Potato chips and french fries were analyzed by high performance liquid chromatography and thin layer chromatography for cholesterol and (3-sitosterol oxidation products. Chips stored for 150 d at 23°C in unopened foil bags contained no detectable sitosterol oxidation products, but those held at 40°C contained 7a-hydroxysitosterol, 7p-hydroxysitosterol, and sitosterol (3epoxide only after an extended storage of 95 d. French fries as purchased contained sterol a-and (3-epoxides, and la-and 7(3-hydroxysterols. These sterol oxidation products were present in repeat samples from five different fast food restaurants. Ingestion of sterol oxides from potato chips is unlikely, whereas ingestion of sterol oxides from french fries is possible.

Meat Science, 1986

Methods for the extraction of cholesterol oxides from meats were studied. A dry column technique ... more Methods for the extraction of cholesterol oxides from meats were studied. A dry column technique for the extraction of sterols was found to be more rapid and convenient than conventional chloroform-methanol extraction. An overall yield of 32·0% and 23·6% for radiolabelled cholesterol and cholesterol oxides, respectively, was obtained after dry column extraction, saponification and chromatography on a silica arrestant column, Florisil®-AgNO(3) column and silica Sep-Pak® column. The overall extraction efficiency of ten meat samples was 22·3 ± 1·7 %. Cholesterol oxides present in measurable amounts included 5-cholesten-3β, 19-diol, 5-cholesten-3β-ol-22-one, the α and β epimers of 5-cholesten-3β, 7-diol and cholestan-3 β, 5α, 6β-triol in some of the meat samples analyzed, but, for the majority of samples, no detectable amounts of known cholesterol oxides were found. Most of the meats, however, contained unidentified components that are non-polar with respect to cholesterol.

Atherosclerosis, Nov 1, 1986

Previous findings indicating that the oxidation products of cholesterol are associated with ather... more Previous findings indicating that the oxidation products of cholesterol are associated with atherogenicity have led to a comparative study of the subchronic effects of feeding rabbits purified cholesterol, oxidized cholesterols free of cholesterol and cholesterol esters, or a mixture of cholesterol and oxidized cholesterols. Macroscopically, the cholesterol-fed animals exhibited 6-fold more arterial lesions than the animals fed cholesterol-free oxidized cholesterols. Microscopically, there was no statistically significant difference from the control in the number of histochemically-defined lesions in any of the groups. However, the lesions in the cholesterol-fed group were more severe, as indicated by a statistically significant increase in the magnitude of the lesions. This increased severity was also characterized by greater frequency and intensity of Azure A/Thionin, VonKossa, and Horseradish Peroxidase-Wheat Germ Agglutinin staining. Electronmicroscopic studies of normal appearing arterial tissues showed an increased density of viable smooth muscle cells and an increase in vacuolar extracellular debris in the cholesterol-fed group. Oxidized cholesterols in the concentrations and relative compositions administered here are markedly less atherogenie to rabbits than highly purified cholesterol.

Elsevier eBooks, 1986

... f William S. Middlelon Memorial Veterans Hospital, Madison, Wisconsin 53705 ^ Department of M... more ... f William S. Middlelon Memorial Veterans Hospital, Madison, Wisconsin 53705 ^ Department of Medicine, University of Wisconsin, Madison, Wisconsin 53706 I ... years regarding the possibility that many consumers may be exceeding the Acceptable Daily Intake (ADI) for sulfites ...

Food and Chemical Toxicology, 1989

A subchronic oral toxicity study of sodium metabisulphite and acetaldehyde hydroxysulphonate was ... more A subchronic oral toxicity study of sodium metabisulphite and acetaldehyde hydroxysulphonate was conducted in normal and sulphite oxidase-deficient rats. At the highest dose level (350 mg SO2 equiv./kg body weight/day for 3 wk followed by 175 mg SO2 equiv./kg body weight/day for 5 wk of either compound), gastric lesions were noted histologically in both normal and sulphite oxidase-deficient rats. The lesions were more severe and more frequently encountered in the sulphite oxidase-deficient rats. The no-effect level for Na2S2O5 was 70 mg SO2 equiv./kg body weight/day in both normal and sulphite oxidase-deficient rats. Liver lesions were noted in rats treated with acetaldehyde hydroxysulphonate. These lesions may possibly be attributable to the effects of free acetaldehyde. The no-effect level for acetaldehyde hydroxysulphonate was 7 mg SO2 equiv./kg body weight/day for sulphite oxidase-deficient rats and 70 mg SO2 equiv./kg body weight/day for normal rats. Increased urinary excretion of sulphite was noted in sulphite oxidase-deficient rats whether or not they were given exogenous sulphites. An increase in urinary sulphite levels in sulphite oxidase-deficient rats was observed after dosing with acetaldehyde hydroxy-sulphonate. These findings suggest that acetaldehyde hydroxysulphonate is metabolized to acetaldehyde and free sulphite.

... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to... more ... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to epithelia of the stomach, small intestine, and colon but not to the kidneys, and this damage was observed only in mice ... O'Brien, AD, Lively, TA, Chen, ME, Rothman, SW, Formal, SB 1983. ...

Current Microbiology, Nov 1, 1984

... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to... more ... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to epithelia of the stomach, small intestine, and colon but not to the kidneys, and this damage was observed only in mice ... O'Brien, AD, Lively, TA, Chen, ME, Rothman, SW, Formal, SB 1983. ...

Food and Chemical Toxicology, 2005

A scientifically-based guide has been developed to evaluate the safety of naturally occurring mix... more A scientifically-based guide has been developed to evaluate the safety of naturally occurring mixtures, particularly essential oils, for their intended use as flavor ingredients. The approach relies on the complete chemical characterization of the essential oil and the variability of the composition of the oil in the product intended for commerce. Being products of common plant biochemical pathways, the chemically-identified constituents are organized according to a limited number of well-established chemical groups called congeneric groups. The safety of the intake of the each congeneric group from consumption of the essential oil is evaluated in the context of data on absorption, metabolism, and toxicology of members of the congeneric group. The intake of the group of unidentified constituents is evaluated in the context of the consumption of the essential oil as a food, a highly conservative toxicologic threshold, and toxicity data on the essential oil or an essential oil of similar chemotaxonomy. The flexibility of the guide is reflected in the fact that high intake of major congeneric groups of low toxicologic concern will be evaluated along with low intake of minor congeneric groups of significant toxicological concern (i.e., higher structural class). The guide also provides a comprehensive evaluation of all congeneric groups and constituents that account for the majority of the composition of the essential oil. The overall objective of the guide is to organize and prioritize the chemical constituents of an essential oil in order that no reasonably possible significant risk associated with the intake of essential oil goes unevaluated. The guide is, however, not intended to be a rigid checklist. The Panel will continue to evaluate each essential oil on a case by case basis applying their scientific judgment to insure that each NFC is exhaustively evaluated.

Journal of Food Protection, 1985

Potato chips and french fries were analyzed by high performance liquid chromatography and thin la... more Potato chips and french fries were analyzed by high performance liquid chromatography and thin layer chromatography for cholesterol and (β-sitosterol oxidation products. Chips stored for 150 d at 23°C in unopened foil bags contained no detectable sitosterol oxidation products, but those held at 40°C contained 7α-hydroxysitosterol, 7β-hydroxysitosterol, and sitosterol (β-epoxide only after an extended storage of 95 d. French fries as purchased contained sterol α- and β-epoxides, and 7α- and 7β-hydroxysterols. These sterol oxidation products were present in repeat samples from five different fast food restaurants. Ingestion of sterol oxides from potato chips is unlikely, whereas ingestion of sterol oxides from french fries is possible.

ACS Symposium Series, 2008

Multinational companies continually seek that one "global" formula that would allow the... more Multinational companies continually seek that one "global" formula that would allow them to do business internationally while taking advantage of economies of scale. Country variability of the legality and specifications for color additives often necessitates the design of different product formulae for different markets, making the "global" formula elusive. The use of different coloring agents can dramatically impact a product's appearance, taste, stability, cost and consumer perception. Examples of how internationally marketed beverages are impacted by the variability of color regulations will be presented.

Advances in Food Research, 1986

... f William S. Middlelon Memorial Veterans Hospital, Madison, Wisconsin 53705 ^ Department of M... more ... f William S. Middlelon Memorial Veterans Hospital, Madison, Wisconsin 53705 ^ Department of Medicine, University of Wisconsin, Madison, Wisconsin 53706 I ... years regarding the possibility that many consumers may be exceeding the Acceptable Daily Intake (ADI) for sulfites ...

Food and Chemical Toxicology, 1984

Abstraet-Monolayers of L-cell cultures were incubated with oxygenated cholesterols and cellular p... more Abstraet-Monolayers of L-cell cultures were incubated with oxygenated cholesterols and cellular protein was subsequently measured to assess the cytotoxicity of the cholesterol oxides. The site of oxidation of the cholesterol molecule was not reflected in the degree of cytotoxicity. Of the 12 cholesterol oxides tested, cholestan-3fl,5~,6fl-triol and cholestan-3,5-diene-7-one exhibited the greatest cytotoxicity, approximately 45% inhibition (reduction) in protein compared to the control at concentrations of 10/~ g/ml, after 1 day of incubation with the compounds. 5-Cholesten-3B,25-diol and 5-cholesten-3fl-ol-7-one were the most cytotoxic after 5 days' exposure with concentrations of 10pg/ml reducing the protein content to approximately 10% of the control. Lipid accumulation in the L cells (steatosis), as measured by Oil Red O-stainable droplets formed in response to cholesterol oxides was also investigated. Grade 3 steatosis (an increase in lipid droplets so that more than 75% of the L-cell cytoplasm was occupied by lipid droplets) after 1 day of exposure to cholesterol oxides generally reflected the cytotoxic effect of the same cholesterol oxides after 5 days' exposure. However some of the steatotic cholesterol oxides, such as the c~ and fl epimers of cholestan-5,6-epoxy-3fl-ol were highly active with respect to steatosis, increasing the grade 3 value to 209 and 390% of control, respectively, but were not cytotoxic. This has led to the suggestion that the cholesterol oxides have more than one mode of action in L cells.

Food and Chemical Toxicology, 1989

A subchronic oral toxicity study of sodium metabisulphite and acetaldehyde hydroxysulphonate was ... more A subchronic oral toxicity study of sodium metabisulphite and acetaldehyde hydroxysulphonate was conducted in normal and sulphite oxidase-deficient rats. At the highest dose level (350 mg SO2 equiv./kg body weight/day for 3 wk followed by 175 mg SO2 equiv./kg body weight/day for 5 wk of either compound), gastric lesions were noted histologically in both normal and sulphite oxidase-deficient rats. The lesions were more severe and more frequently encountered in the sulphite oxidase-deficient rats. The no-effect level for Na2S2O5 was 70 mg SO2 equiv./kg body weight/day in both normal and sulphite oxidase-deficient rats. Liver lesions were noted in rats treated with acetaldehyde hydroxysulphonate. These lesions may possibly be attributable to the effects of free acetaldehyde. The no-effect level for acetaldehyde hydroxysulphonate was 7 mg SO2 equiv./kg body weight/day for sulphite oxidase-deficient rats and 70 mg SO2 equiv./kg body weight/day for normal rats. Increased urinary excretion of sulphite was noted in sulphite oxidase-deficient rats whether or not they were given exogenous sulphites. An increase in urinary sulphite levels in sulphite oxidase-deficient rats was observed after dosing with acetaldehyde hydroxy-sulphonate. These findings suggest that acetaldehyde hydroxysulphonate is metabolized to acetaldehyde and free sulphite.

Current Microbiology, 1984

... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to... more ... John T. Beery, Michael P. Doyle, and Nancy A. Higley ... In contrast, O157HT was cytotoxic to epithelia of the stomach, small intestine, and colon but not to the kidneys, and this damage was observed only in mice ... O'Brien, AD, Lively, TA, Chen, ME, Rothman, SW, Formal, SB 1983. ...

Atherosclerosis, 1986

Previous findings indicating that the oxidation products of cholesterol are associated with ather... more Previous findings indicating that the oxidation products of cholesterol are associated with atherogenicity have led to a comparative study of the subchronic effects of feeding rabbits purified cholesterol, oxidized cholesterols free of cholesterol and cholesterol esters, or a mixture of cholesterol and oxidized cholesterols. Macroscopically, the cholesterol-fed animals exhibited 6-fold more arterial lesions than the animals fed cholesterol-free oxidized cholesterols. Microscopically, there was no statistically significant difference from the control in the number of histochemically-defined lesions in any of the groups. However, the lesions in the cholesterol-fed group were more severe, as indicated by a statistically significant increase in the magnitude of the lesions. This increased severity was also characterized by greater frequency and intensity of Azure A/Thionin, VonKossa, and Horseradish Peroxidase-Wheat Germ Agglutinin staining. Electronmicroscopic studies of normal appearing arterial tissues showed an increased density of viable smooth muscle cells and an increase in vacuolar extracellular debris in the cholesterol-fed group. Oxidized cholesterols in the concentrations and relative compositions administered here are markedly less atherogenie to rabbits than highly purified cholesterol.