Benedict Green - Academia.edu (original) (raw)

Papers by Benedict Green

Rangelands, Feb 1, 2009

appropriate tests can be used to confi rm the cause of the clinical syndrome. The next step is to... more appropriate tests can be used to confi rm the cause of the clinical syndrome. The next step is to use the list of differential diagnoses to formulate a plan to rule out or confi rm possible causes. The plan will probably include fi eld investigations, physical examinations, biochemical or serologic evaluations of the blood, possible postmortem evaluations, and, at times, chemical or microscopic evaluations of plants or animal tissues.

Poisonous plants affecting cattle in the Brazilian Central-Western region are reviewed. The most ... more Poisonous plants affecting cattle in the Brazilian Central-Western region are reviewed. The most important poisonous plants in the region are Brachiaria spp., which cause hepatogenous photosensitization, and Palicourea marcgravii and Mascagnia pubiflora, which cause sudden death precipitated by exercise. Enterolobium contortisiliquum, Stryphnodendron obovatum, and Stryphnodendron fissuratum are trees whose pods cause digestive signs, photosensitization, and abortion. Vernonia mollissima and V. rubricaulis cause acute liver necrosis, but V. rubricaulis is much more important than V. mollisima as a cause of cattle losses. Other less important plants are Solanum glaucophyllum, which causes soft tissue calcification; Ipomoea carnea subsp. fistulosa, which causes nervous signs; Senna occidentalis and Senna obtusifolia, which cause segmental muscular necrosis; Tetrapterys multiglandulosa, which causes cardiac fibrosis, abortion, and neonatal mortality; Polygala klotzschii, which causes ly...

Israel Journal of Chemistry, 2019

Plants produce a multiplicity of chemical compounds which have a variety of uses including flavor... more Plants produce a multiplicity of chemical compounds which have a variety of uses including flavors, fragrances, insecticides, dyes, poisons, and pharmaceutical agents. In this review, we focus on plant alkaloids from the genera Delphinium, Lupinus, Conium, Nicotiana, Veratrum, and selected plant endophyte derived alkaloids. Alkaloids discussed include norditerpenoid alkaloids which act as antagonists to block the ligand binding sites of nicotinic acetylcholine receptors and cause acute toxicosis in adult animals which can result in death. The inhibition of fetal movement and resulting fetal defects caused by quinolizidine and piperidine alkaloids, the inhibition of the hedgehog (Hh) signaling pathway by Veratrum alkaloids, and compounds derived from fungal endophytes that form symbioses with plant hosts will be also be discussed. The bioactivity of these alkaloids makes them useful tools for research and in human and veterinary medicine or potentially harmful toxins.

The Faseb Journal, Apr 1, 2011

Mammalian Genome, Nov 1, 2006

Single nucleotide polymorphisms (SNPs) and haplotype alleles within the prion gene (PRNP) coding ... more Single nucleotide polymorphisms (SNPs) and haplotype alleles within the prion gene (PRNP) coding sequence of domestic sheep (Ovis aries) are associated with genetic predisposition to scrapie, a transmissible spongiform encephalopathy disease of sheep. This report describes regions of linkage disequilibrium (LD) throughout the PRNP gene region in U.S. sheep and provides a genetic framework for identifying additional PRNP determinants associated with scrapie resistance. Four sequence tagged sites (i.e., STS or amplicons) totaling 3869 bp and spanning 20 kbp of genomic PRNP sequence were sequenced in a diverse panel of 90 sires representing ten popular U.S. breeds of sheep. Analysis of these sequences identified 36 previously unreported polymorphisms. In combination with two previously characterized STS, 62 polymorphisms were analyzed in a 20-kbp PRNP region in this panel of U.S. sheep. Two regions of strong LD and ten common haplotypes were identified. The haplotype encoding amino acid residues A, R, and Q at codons 136, 154, and 171, respectively, was observed on nine larger haplotypes spanning PRNP from the promoter region to the 3¢ untranslated region. The haplotype encoding VRQ was observed on two larger haplotypes, whereas ARR, ARH, and AHQ were each present on a single haplotype. The existence of multiple haplotypes encoding ARQ raises the question of whether sheep bearing these different haplotypes are equally susceptible to scrapie. The haplotype structure within the 20-kbp region of PRNP identified in this study is important for higher-resolution analysis of genetics contributions to scrapie susceptibility. Nucleotide sequence data reported are available in the DDBJ/ EMBL/GenBank databases under the accession number DQ077504.

The FASEB Journal

The exposure of a developing fetus to certain plant alkaloids has the potential to inhibit fetal ... more The exposure of a developing fetus to certain plant alkaloids has the potential to inhibit fetal movement which can then result in developmental defects. The putative mechanism of movement inhibition is the desensitization of fetal muscle‐type nicotinic acetylcholine receptors (nAChR) which is affected by agonist chemical structure. In this study, we tested the hypothesis that a 1,2‐dehydropiperidine alkaloid agonist is more effective at desensitizing nAChR than a saturated analogue. Agonists were evaluated in TE‐671 cells which express fetal muscle‐type nAChR, and SHSY‐5Y cells which express autonomic‐type nAChRs using a membrane potential sensing dye system. Anabaseine, a 1,2‐dehydropiperidine alkaloid, was more effective at desensitizing TE‐671 cells than anabasine which is fully saturated at the 1,2 position. The neurotransmitter acetylcholine which was included as a control was more effective than the pyridine alkaloid nicotine at desensitizing the agonist response in TE‐671 ce...

Journal of Agricultural and Food Chemistry, Feb 25, 2009

Lupines are common plants on the rangelands in the western United States. Lupines contain alkaloi... more Lupines are common plants on the rangelands in the western United States. Lupines contain alkaloids that can be toxic and teratogenic causing congenital birth defects (crooked calf disease). One such lupine, Lupinus sulphureus, occurs in parts of Oregon, Washington, and British Columbia. Specimens of L. sulphureus from field collections and herbaria were evaluated taxonomically and by chemical means. A total of seven distinct alkaloid profiles and the individual alkaloids associated with each profile were identified. Each alkaloid profile was unique in its geographical distribution and its potential risk to livestock. In conclusion, taxonomic classification is not sufficient to determine risk, as chemical characterization of the alkaloids must also be performed.

Journal of Veterinary Diagnostic Investigation, Jul 1, 2010

Rayless goldenrod (Isocoma pluriflora) sporadically poisons livestock in the southwestern United ... more Rayless goldenrod (Isocoma pluriflora) sporadically poisons livestock in the southwestern United States. Similarities with white snakeroot (Ageratina altissima) poisoning and nearly identical chemical analyses led early researchers to conclude that tremetol, a mixture of benzofuran ketones, is the rayless goldenrod toxin. The toxicity of these ketone toxins have not been fully characterized nor are the pathogenesis and sequelae of poisoning completely understood. The objective of the current study was to characterize and describe the clinical and pathologic changes of rayless goldenrod toxicity in goats. Fifteen goats were gavaged with rayless goldenrod to obtain benzofuran ketone doses of 0, 10, 20, 40, and 60 mg/kg/day. After 7 treatment days, the goats were euthanized, necropsied, and tissues were processed for microscopic studies. After 5 or 6 days of treatment, the 40-mg/kg and 60-mg/kg goats were reluctant to move, stood with an erect stance, and became exercise intolerant. They had increased resting heart rate, prolonged recovery following exercise, and increased serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatinine kinase activities. All treated animals developed skeletal myopathy with dose-related distribution and severity. The goats dosed with 20 mg/kg and higher also developed myocardial degeneration and necrosis. Although skeletal myonecrosis was patchy and widely distributed, the quadriceps femoris was consistently damaged, even in low-dosed animals. Myocardial lesions were most severe in the papillary muscles of 60-mg/kg-dosed animals. This indicates that goats are highly susceptible to rayless goldenrod poisoning, and that the characteristic lesion of poisoning is skeletal and cardiac myonecrosis.

Frontiers in Veterinary Science, Feb 22, 2023

defines a biomarker as: "A biological molecule found in blood, other body fluids, or tissues that... more defines a biomarker as: "A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease." In Veterinary Medicine, biomarkers associated with plant poisonings of livestock have great utility. Since grazing livestock poisoned by toxic plants are often found dead, biomarkers of plant poisoning allow for a more rapid postmortem diagnosis and response to prevent further deaths. The presence and concentration of toxins in poisonous plants are biomarkers of risk for livestock poisoning that can be measured by the chemical analysis of plant material. More di cult is, the detection of plant toxins or biomarkers in biological samples from intoxicated or deceased animals. The purpose of this article is to review potential biomarkers of plant poisoning in grazing livestock in the Western North America including recently investigated non-invasive sampling techniques. Plants discussed include larkspur, lupine, water hemlock, swainsonine-containing plants, selenium-containing plants, and pyrrolizidine alkaloid containing plants. Other factors such as animal age and sex that a ect plant biomarker concentrations in vivo are also discussed.

Frontiers in Veterinary Science

The United States National Cancer Institute defines a biomarker as: “A biological molecule found ... more The United States National Cancer Institute defines a biomarker as: “A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease.” In Veterinary Medicine, biomarkers associated with plant poisonings of livestock have great utility. Since grazing livestock poisoned by toxic plants are often found dead, biomarkers of plant poisoning allow for a more rapid postmortem diagnosis and response to prevent further deaths. The presence and concentration of toxins in poisonous plants are biomarkers of risk for livestock poisoning that can be measured by the chemical analysis of plant material. More difficult is, the detection of plant toxins or biomarkers in biological samples from intoxicated or deceased animals. The purpose of this article is to review potential biomarkers of plant poisoning in grazing livestock in the Western North America including recently investigated non-invasive sampling techniques. Pl...

Fetal-muscle type nicotinic acetylcholine receptor activation in TE-671 cells, and inhibition of ... more Fetal-muscle type nicotinic acetylcholine receptor activation in TE-671 cells, and inhibition of fetal movement in a day 40 pregnant goat model by optical isomers of the piperidine alkaloid coniine.

Larkspurs (Delphinium spp.) are toxic native plants on foothill and mountain rangelands in wester... more Larkspurs (Delphinium spp.) are toxic native plants on foothill and mountain rangelands in western North America, which poison cattle grazing on those rangelands. The purpose of this study was to examine in a laboratory setting, the subclinical effects of larkspur intake and toxicosis, by allowing larkspur susceptible and resistant cattle to self-select the amount of larkspur consumed in pellet form. We hypothesized that there would be differences in short term (9-11 day) pellet consumption between susceptible and resistant animals. Two trials were completed, each with larkspur resistant and susceptible Angus steers, and larkspuralfalfa pellets at a 12% and 6% larkspur for trial 1 and trial 2, respectively. There were no differences in pellet consumption between the two groups in either trial. The cattle were averted to the 12% larkspur-containing pellet in trial 1. During trial 2, the susceptible and resistant steers differed in serum concentrations of methyllycaconitine (MLA) on days 9 to 12 but did not have significantly different exercise times (38.0 ± 3 min and 27.2 ± 6.5 min for resistant and susceptible steers, respectively). Larkspur alkaloids were potent aversive agents in cattle when fed as a 12% larkspur-containing pellet. The lack of differences in responses between susceptible and resistant cattle were attributed to the development of pharmacodynamic tolerance to larkspur alkaloids by the actions of larkspur alkaloids at nicotinic acetylcholine receptors.

Larkspurs (Delphinium spp.) are a major cause of cattle losses in western North America, whereas ... more Larkspurs (Delphinium spp.) are a major cause of cattle losses in western North America, whereas sheep have been shown to be resistant to larkspur toxicosis. Goats are often used as a small ruminant model to study poisonous plants, even though they can be more resistant to some poisonous plants. It is not known how susceptible goats are to the adverse effects of larkspurs. In this study, we evaluated the susceptibility of goats to larkspur toxicosis by performing a dose-response study. We dosed goats with D. barbeyi collected near Cedar City, Utah at 3.3, 4.4, 6.6, 8.8 and 10.0 g plant material per kg body weight. None of the goats, at any of the doses, exhibited clinical signs typical of larkspur poisoning, including no observable muscle weakness. We conclude that goats are resistant to larkspur toxicosis, and thus it is very unlikely that goats would be poisoned by larkspur.

The FASEB Journal, 2014

The exposure of a developing embryo or fetus to teratogenic alkaloids from plants has the potenti... more The exposure of a developing embryo or fetus to teratogenic alkaloids from plants has the potential to cause developmental defects in humans and animals due to the inhibition of fetal movement. The...

The FASEB Journal, 2020

This research compared the cytotoxic actions of the benzofuran ketone tremetone in B16 murine mel... more This research compared the cytotoxic actions of the benzofuran ketone tremetone in B16 murine melanoma cells, TE‐671 human rhabdomyosarcoma cells, and SH‐SY5Y human neuroblastoma cells using a MTT assay, with and without exposure to rat liver microsomes (RLM). Tremetone is of interest because it is a putative toxin in white snakeroot and rayless goldenrod. Identifying the toxic principal(s) of white snakeroot is important because in addition to poisoning livestock by causing “trembles,” it also causes “milk sickness” in humans that drink the milk from dairy animals that have eaten these toxic plants. Tremetone was not cytotoxic in B16 cells. In TE‐671 and SH‐SY5Y cells, concentration‐dependent tremetone cytotoxicity occurred without microsomal activation. In SH‐SY5Y cells the best fit values were; tremetone IC50 = 490 μM, tremetone and RLM IC50 = 505 μM. In TE‐671 cells the best fit values were; tremetone IC50 = 2.5 μM, tremetone and RLM IC50 = 2.2 μM. These results suggest that in ...

Toxicon: X, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Toxicon: X, 2019

This research compared the cytotoxic actions of the benzofuran ketone, tremetone in B16 murine me... more This research compared the cytotoxic actions of the benzofuran ketone, tremetone in B16 murine melanoma cells to SH-SY5Y human neuroblastoma cells with an MTT assay. Tremetone was not cytotoxic in B16 cells. In SH-SY5Y cells, concentration-dependent tremetone cytotoxicity occurred without microsomal activation. No cytotoxicity was observed with 6-hydroxytremetone. This suggests that SH-SY5Y cells are a better model for the cytotoxic actions of tremetone and that tremetone is toxic without microsomal activation.

Marine Drugs, 2019

Three major forms of the nicotinic agonist toxin anabaseine (cyclic iminium, cyclic imine and the... more Three major forms of the nicotinic agonist toxin anabaseine (cyclic iminium, cyclic imine and the monocationic open-chain ammonium-ketone) co-exist in almost equal concentrations at physiological pH. We asked the question: Which of these forms is pharmacologically active? First, we investigated the pH dependence of anabaseine inhibition of [3H]-methylcarbamylcholine binding at rat brain α4β2 nicotinic acetylcholine receptors (nAChRs). These experiments indicated that one or both monocationic forms interact with the orthosteric binding site for ACh. However, since they occur at equal concentrations near physiological pH, we employed another approach, preparing a stable analog of each form and examining its agonist activities and binding affinities at several vertebrate brain and neuromuscular nAChRs. Only 2-(3-pyridyl)-1,4,5,6-tetrahydropyrimidine monohydrogen chloride (PTHP), the cyclic iminium analog, displayed nAChR potencies and binding affinities similar to anabaseine. The cycli...