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Biomedical subjects

R C Beier

Publications and source records attributed to R C Beier.

At least 37 records · Page 2Linked to original sources

Phototoxic coumarins in limes.

Coumarins in the rind and pulp of Persian and Key limes were quantified. In the rind of Persian limes, coumarin concentrations were in the order: limettin > bergapten > isopimpinellin > xanthotoxin > psoralen. In the rind of Key limes, psoralen and xanthotoxin were analytically absent; limettin was 10 times more concentrated than either bergapten or isopimpinellin, which were equal in concentration. Coumarin content in Persian lime pulp was in the order: isopimpinellin > limettin > bergapten > xanthotoxin > psoralen. For Key lime pulp, the concentrations of limettin, isopimpinellin and bergapten were equal; psoralen and xanthotoxin were not detected. Coumarins in lime pulp were 13 to 182 times less concentrated than those in the peel. Based on the amounts and types of coumarins, Persian limes appear to be potentially more phototoxic than Key limes. Although bergapten may be the main component of limes responsible for phytophotodermatitis, dermatological interaction assays with psoralen, bergapten, xanthotoxin and limettin should be conducted.

Chromatography, High Pressure Liquid↗

Acyl, pseudotetra-, tri- and dipeptide active-core analogs of insect neuropeptides.

Pseudopeptides of the achetakinin insect neuropeptide family were synthesized by replacing the amino acid blocks Phe-, Phe-Tyr-, and Phe-Tyr-Pro- of the active-core pentapeptide Phe-Tyr-Pro-Trp-Gly-NH2 with hydrocinnamic acid, 6-phenylhexanoic acid, and both 9-phenylnonanoic and 6-phenylhexanoic acid, respectively. All four of these analogs retained myotropic activity, demonstrating that the active core could be reduced from a pentapeptide to a modified dipeptide. Most notable of these was the pseudotetrapeptide hydrocinnamyl-Tyr-Pro-Trp-Gly-NH2, which retained 70% of the potency and over 85% of the maximal activity of the parent pentapeptide. The N-terminal amino group, the phenol ring of the Tyr residue, the sulfate moiety and the Gly residue of the insect sulfakinin active core Tyr(SO3H)-Gly-His-Met-Arg-Phe-NH2 were all replaced by dodecanedioic acid. The resulting pseudotetrapeptide, dodecandioyl-His-Nle-Arg-Phe-NH2, elicited myostimulatory activity. Conversely, the related acyl pseudopentapeptide azelayl-Gly-His-Nle-Arg-Phe-NH2 proved myoinhibitory. A possible explanation for these disparate biological responses is discussed. These acyl pseudopeptides are important advances towards the eventual development of stable, potent mimetic agonists and antagonists of insect neuropeptides.

Amino Acid Sequence↗

In vitro metabolism of radiolabeled carbohydrates by protective cecal anaerobic bacteria.

Cecal anaerobic bacteria from adult broilers were cultured in media containing .25% glucose or .25% lactose. Media also contained either [14C]-labeled lactose, glucose, galactose, or lactic acid as metabolic tracers. Cultures were analyzed at 4, 8, and 12 h for pH, radiolabeled and unlabeled volatile fatty acids, and lactic acid. The pH values of cultures containing .25% lactose were significantly (P < .05) higher than the pH values of cultures containing .25% glucose. Lactose cultures reached their lowest pH more slowly than glucose cultures. Concentrations of unlabeled volatile fatty acids increased and lactic acid decreased during incubation of the cultures. Radiolabeled sugars and lactic acid were more readily metabolized to volatile fatty acids in media containing lactose than in media containing glucose. The preferred metabolism of [14C]substrates, independent of media carbohydrate, was in the following order: lactic acid > galactose, lactose > glucose. The volatile fatty acids in which radiolabel was most concentrated were acetic acid, propionic acid, or butyric acid.

Animals↗

Fermentation of [14C]lactose in broiler chicks by cecal anaerobes.

Volatile fatty acids and lactic acid were products of [14C]lactose metabolism in 10-day-old broiler chicks. The [14C]lactose and unlabeled lactose were given to chicks in combination with cultures of cecal anaerobes (direct fed microbials) from adult broiler chickens. Aliquots of these cecal anaerobes had been used previously to reduce Salmonella typhimurium colonization in broiler chicks. In the current study, chicks were treated with anaerobes and anaerobes plus lactose on the day of hatch. Chicks given lactose plus anaerobes also received unlabeled lactose in the drinking water. Chicks in all treatment groups received [14C]lactose on Day 10 posthatch. After 5 h, most of the radiolabel was detected in the foregut and intestine. Significantly lower concentrations of [14C]lactic acid were detected in the serum and foregut of chicks given anaerobes and anaerobes plus lactose than in the similar samples from control chicks. Additionally, significantly less [14C]lactic acid was detected in the feces of chicks treated with anaerobes plus lactose than in feces from control chicks and chicks receiving only anaerobes. Significant differences in the total content of volatile fatty acids and lactic acid were detected in the serum, liver, intestine, and ceca of chicks treated with anaerobes or anaerobes plus lactose. These data indicate that cecal flora utilize lactose to produce volatile fatty acids and lactic acid.

Animals↗

Colonization control of lactose-fermenting Salmonella typhimurium in young broiler chickens by use of dietary lactose.

Inclusion of lactose in the diets of chickens has been determined to reduce cecal colonization with Salmonella typhimurium. We hypothesized, therefore, that dietary lactose may be a practical means for reducing the prevalence of Salmonella contamination of chicken products. Because some strains of Salmonella are atypical and ferment lactose, we investigated the effects of dietary lactose on cecal colonization with lactose-fermenting S typhimurium. Broiler chicks were inoculated intracloacally with Lac+ S typhimurium selected for resistance to novobiocin and rifampicin. The chicks also were inoculated orally with certain anaerobes that do not effectively inhibit colonization by S typhimurium, but do appear essential for lactose mediated inhibition of cecal colonization. Control chicks were not given dietary lactose, and chicks in the experimental group were fed a diet containing 7% lactose. Enumeration of Lac+ S typhimurium in cecal contents revealed dietary lactose to be effective at controlling this organism. Control was correlated with changes in cecal pH and increases in undissociated volatile fatty acids, especially propionic acid.

Animals↗

Natural pesticides and bioactive components in foods.

In this review, some common food plants and their toxic or otherwise bioactive components and mycotoxin contaminants have been considered. Crucifers contain naturally occurring components that are goitrogenic, resulting from the combined action of allyl isothiocyanate, goitrin, and thiocyanate. Although crucifers may provide some protection from cancer when taken prior to a carcinogen, when taken after a carcinogen they act as promoters of carcinogenesis. The acid-condensed mixture of indole-3-carbinol (a component of crucifers) binds to the TCDD receptor and causes responses similar to those of TCDD. Herbs contain many biologically active components, with more than 20% of the commercially prepared human drugs coming from these plants. Onion and garlic juices can help to prevent the rise of serum cholesterol. Most herbs used in treatments may have many natural constituents that act oppositely from their intended use. Some herbs like Bishop's week seed contain carcinogens, and many contain pyrrolizidine alkaloids that can cause cirrhosis of the liver. The general phytoalexin response in plants (including potatoes, tomatoes, peppers, eggplant, celery, and sweet potatoes) induced by external stimuli can increase the concentrations of toxic chemical constituents in those plants. In potatoes, two major indigenous compounds are alpha-solanine and alpha-chaconine, which are human plasma cholinesterase inhibitors and teratogens in animals. Because of its toxicity, the potato variety Lenape was withdrawn from the market. Celery, parsley, and parsnips contain the linear furanocoumarin phytoalexins psoralen, bergapten, and xanthotoxin that can cause photosensitization and also are photomutagenic and photocarcinogenic. Celery field workers and handlers continually have photosensitization problems as a result of these indigenous celery furanocoumarins. A new celery cultivar (a result of plant breeding to produce a more pest-resistant variety) was responsible for significant incidences of phytophotodermatitis of grocery employees. Since there is no regulatory agency or body designated to oversee potential toxicological issues associated with naturally occurring toxicants, photodermatitis continues to occur from celery exposure. Sweet potatoes contain phytoalexins that can cause lung edema and are hepatotoxic to mice. At least one of these, 4-ipomeanol, can cause extensive lung clara cell necrosis and can increase the severity of pneumonia in mice. Some phytoalexins in sweet potatoes are hepatotoxic and nephrotoxic to mice. The common mushroom Agaricus bisporus contains benzyl alcohol as its most abundant volatile, and A. bisporus and Gyromitra esculenta both contain hydrazine analogues. Mycotoxins are found in corn, cottonseed, fruits, grains, grain sorghums, and nuts (especially peanuts); therefore, they also occur in apple juice, bread, peanut butter, and other products made from contaminated starting materials.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Stimulation and release of prostaglandins and thromboxane from macrophages by cotton dust associated lipopolysaccharides.

Decreases in the ventilation capacity of human lungs following the inspiration of cotton dust correlates more closely with the concentration of endotoxin in the dust than with any other parameter measured thus far. A lipopolysaccharide isolated from the endotoxin of Enterobacter agglomerans, a common bacterial contaminant of cotton fiber, stimulated isolated rat macrophages to produce and release prostaglandins 6 keto-PGF1 alpha, PGF2 alpha, PGE2, PGD2, PGA2, and PGB2 and thromboxane B2. If in vivo human pulmonary macrophages respond in a similar fashion by releasing these arachidonic acid metabolites or their immediate precursors in response to stimulation by cotton dust associated lipopolysaccharides, some of the acute pulmonary changes observed in humans following inspiration of cotton dust could be caused by increased release of these biologically active compounds. Daily release of arachidonic acid metabolites at concentrations significantly above normal homeostatic levels could produce some of the pathophysiologic pulmonary changes observed in byssinotics. This paper reports the results of an experiment to quantitate arachidonic acid metabolite production following macrophage stimulation by E. agglomerans lipopolysaccharide. Procedures are described for the stimulation of macrophages by cotton dust associated lipopolysaccharide, for the separation and identification of arachidonic acid and its metabolites by high-performance liquid chromatography, and for the quantification of those products by radioisotope techniques.

Animals↗

Host plant resistance and linear furanocoumarin content of Apium accessions.

Linear furanocoumarin contents and antibiotic resistance to Liriomyza trifolii (Burgess) were documented for Apium species being investigated in a celery breeding program. In no-choice tests, L. trifolii fed more, produced more offspring, and had the highest pupal and adult productivity on the widely planted cultivar 'Tall Utah' 52-70R (Apium graveolens L.). Antibiotic effects of the commercial cultivar 'Tall Utah' 52-70 HK and University of California families 87A-147 and 87A-338, derived from A. chilense Hook and Arn., were intermediate. Only A. nodiflorum (L.) Lag (accession 87A-236) did not allow survival beyond the larval stage. Concentrations of the carcinogenic and mutagenic linear furanocoumarins varied by location within plants (leaves usually greater than petioles), by specific compound (trend: psoralen less than xanthotoxin less than bergapten or isopimpinellin), and between accessions. A. nodiflorum had the lowest foliar levels of phototoxic furanocoumarins (11.8 micrograms/g fresh weight) and the best potential for use in the breeding program. Foliar levels of phototoxic furanocoumarins (psoralen, bergapten, and xanthotoxin) in plants 87A-147-3 (406 micrograms/g), 87A-147-2 (292.9 micrograms/g), and the family 87A-338 (265.9 micrograms/g) were 22.6, 16.3, and 14.8 times higher, respectively, than the concentration known to produce contact dermatitis (18 micrograms/g). Even with such variability in concentration, the foliar content of linear furanocoumarins (individually or total) and L. trifolii adult production were not correlated.

Animals↗

The toxic factor in white snakeroot: identity, analysis and prevention.

White snakeroot (Eupatorium rugosum Houtt) has been known to cause trembles in animals and milk sickness in humans since the American Revolution. It still continues to poison animals. Horses and goats are particularly sensitive to white snakeroot poisoning. Resurgence of livestock production on small farm units, and utilization of fresh raw milk may result in milk sickness; if the animals have white snakeroot exposure. The goat is the only animal with good toxicity threshold data. In other animals and humans the toxicity thresholds of white snakeroot are not known, and that until responsible toxic principles are identified and their fate in animals and milk studied, such an assessment will not be possible. The toxic component(s) in white snakeroot has not been identified. The mechanism of action of the toxin in animals or humans remains unknown. However, metabolic studies in chicks initially suggest that a specific metabolic enzyme may be the target of the toxic principle. Components of white snakeroot that are toxic after microsomal activation have been isolated. Cytochrome P-450 is responsible for this activation. Activation in vitro can be totally inhibited by the cytochrome P-450 specific autocatalytic inhibitor, 1-aminobenzotriazole. In view of the importance of white snakeroot in the history of the United States and the ongoing problems today, it would be most unfortunate if studies were not pursued expeditiously to identify the toxicant(s) responsible, and to understand the mechanism(s) of action and toxicity thresholds.

Animals↗

Phytophotodermatitis from celery among grocery store workers.

We detected 19 cases of phytophotodermatitis during a cross-sectional epidemiological investigation of two Oregon grocery stores that were part of the same supermarket chain. Outdoor sunlight exposure during the workshift and tanning salon use were identified as risk factors; the most severe cutaneous reactions tended to occur among tanning salon users. Although both stores carried the same brands and varieties of produce, all 19 cases occurred among employees of one store, which had held a celery sale coincident with the outbreak, resulting in a quadrupling of the usual volume of celery sold. We found elevated psoralen levels in two of three celery samples obtained from the affected store; cutaneous provocation tests with trimmed surfaces of these celery samples produced phototoxic reactions. Preliminary experiments with one brand of celery have demonstrated psoralen levels as high as 25 micrograms/cm2 of trimmed surface. These observations suggest that clinical phytophotodermatitis among grocery store workers may be caused by healthy celery and results from a complex interaction of exposure variables, including ultraviolet radiation from tanning salon use, frequency of handling celery, celery brand, and sporadic elevation of psoralen content from environmental stresses.

Cross-Sectional Studies↗

Microsomal activation of constituents of white snakeroot (Eupatorium rugosum Houtt) to form toxic products.

Components of white snakeroot, a plant toxic to livestock and human beings, were activated by Aroclor 1254-induced rat liver microsomes. The toxic products of microsomal activation were evaluated in murine melanoma (B16F1) cell cultures. Toxic products in white snakeroot were inactive in cell culture systems without microsomal activation. This activation system revealed that at least 2 fractions of white snakeroot were metabolically activated to cytotoxic agents. The autocatalytic inactivator of cytochrome P-450, 1-aminobenzotriazole, inhibited activation of white snakeroot constituents by rat liver microsomes.

Animals↗

Purification and measurement of abscisic Acid and indoleacetic Acid by high performance liquid chromatography.

A procedure was selected for the simultaneous extraction and purification of abscisic acid (ABA) and indoleacetic acid (IAA). Unnecessary steps were eliminated and an accumulation of aqueous phase was avoided. The superior performance of diethyl ether (compared to ethyl acetate) for bulk purification and the superior resolution provided by 250 millimeter columns packed with 5-micrometer spherical particles of strong anion exchanger and octadecylsilane (C18) greatly facilitated the purification of samples. A fixed-wavelength (254 nanometer) ultraviolet detector and a fluorescence detector connected in series on a high performance liquid chromatograph permitted nondestructive monitoring and measurement of ABA and IAA. Derivatization was not necessary for chromatography or for detection. Isocratic elution with simple mobile phases gave sharp peaks. A few simple precautions minimized losses. Recoveries through the entire procedure averaged about 75% for ABA and about 50% for IAA. Purified ABA and IAA fractions were usually free of interfering contaminants. Identities were confirmed by gas chromatography-mass spectrometry.

Journal Article↗

Dermatitis in grocery workers associated with high natural concentrations of furanocoumarins in celery.

A vesicular, peeling rash characteristic of a phytophototoxic dermatitis developed on the hands and arms of 30 of 127 grocery workers. The rash subsequently healed with residual hyperpigmentation. Produce workers had the highest attack rate, 100% (8 of 8, p less than 0.0001). Although contact with celery had the highest relative risk for disease (relative risk, 6.3; 95% confidence interval, 2.6, 19.2) and the strongest dose-response effect, an association with celery alone could not be shown because workers were also exposed to other produce. However, anecdotal evidence also suggested that celery might be involved. The disease-resistant, high-quality brand of celery carried by these stores had higher levels of furanocoumarins, potent photosensitizers and a known cause of phytophotodermatitis, than other brands (p = 0.01). A randomly selected nationwide sample of stores in this chain showed dermatitis in 13 of 17 states and 26% of produce workers surveyed. Plant breeding to produce a more disease-resistant celery stock may lead to increased levels of endogenous furanocoumarins, resulting in phytophotodermatitis in grocery workers.

Dermatitis, Occupational↗

Fate of [14C]xanthotoxin (8-methoxypsoralen) in a goat and in bovine ruminal fluid.

A lactating Nubian goat was treated with [14C]xanthotoxin, a photosensitizing psoralen that occurs naturally in some phototoxic range plants, as a single oral dose equivalent to 10.0 mg of xanthotoxin/kg of body weight. The radiochemical was rapidly absorbed, metabolized, and excreted. Although expired air was not monitored for the presence of volatile radiocarbon, the data indicated that greater than 50% of the administered [14C]xanthotoxin was metabolized by cleavage of the O-[14C]methyl moiety, with subsequent loss of the label as, presumably, [14C]CO2. Studies with bovine ruminal fluid in vitro indicated that cleavage of the O-methyl moiety of xanthotoxin could occur rapidly in the rumen. In the goat, nonmetabolized xanthotoxin was not excreted in urine, and of several metabolites in urine extracts, 3 were identified as resulting from opening of the furan or lactone ring. Only about 2% of the dose was recovered in the feces, and this consisted mainly of unmetabolized xanthotoxin. Although appreciable amounts of radiocarbon were secreted into milk, this radiocarbon was not in the form of xanthotoxin or any identifiable metabolites. The radiocarbon in milk likely resulted from the biosynthetic incorporation of [14C]CO2 into normal milk components.

Animals↗

HPLC analysis of linear furocoumarins (psoralens) in healthy celery (Apium graveolens).

Four linear furocoumarins (psoralen, bergapten, xanthotoxin, and isopimpinellin) were isolated from three varieties of healthy, commercially grown celery (Apium graveolens). Psoralen has not previously been reported to occur in celery. Combined levels of these photomutagenic and photocarcinogenic furocoumarins measured by normal-phase HPLC did not exceed 1.3 ppm in any of the celery varieties studied.

Chromatography, High Pressure Liquid↗

Structure-activity relationships for inhibitory insect myosuppressins: contrast with the stimulatory sulfakinins.

Unusual among insect neuropeptides, the decapeptide myosuppressins are capable of inhibiting contractions of visceral muscle, including the isolated cockroach hindgut. The C-terminal pentapeptide Val-Phe-Leu-Arg-Phe-NH2 has been identified as the myosuppressin active core, the minimum number of residues required to elicit hindgut myoinhibitory activity. Activity of the same magnitude as the parent neuropeptide requires the C-terminal heptapeptide fragment Asp-His-Val-Phe-Leu-Arg-Phe-NH2. Evaluation of a series of substitution analogs delineates structural features critical for myoinhibitory activity within this important fragment. The branched, hydrophobic residues in myosuppressin position 6 (Val) and particularly position 8 (Leu), their absence in the myostimulatory sulfakinins, and the different roles played by the shared Asp residue (myosuppressin position 4; leucosulfakinin position 5) in peptide-receptor interaction, account in large degree for the contrasting biological activities elicited by these otherwise structurally similar peptide families. The results may have broad significance for other invertebrate myotropic systems, such as the locust heart and the pharyngeal retractor muscle of the mollusc Helix aspersa.

Amino Acid Sequence↗