The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform
Kip E. Panter - One of the best experts on this subject based on the ideXlab platform.
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Cyclopamine: from cyclops lambs to cancer treatment.
Journal of agricultural and food chemistry, 2014Co-Authors: Stephen T. Lee, Dale R Gardner, Kip E. Panter, Kevin D. Welch, Massoud Garrossian, Cheng-wei Tom ChangAbstract:In the late 1960s, the steroidal alkaloid cyclopamine was isolated from the plant Veratrum Californicum and identified as the teratogen responsible for craniofacial birth defects including cyclops in the offspring of sheep grazing on mountain ranges in the western United States. Cyclopamine was found to inhibit the hedgehog (Hh) signaling pathway, which plays a critical role in embryonic development. More recently, aberrant Hh signaling has been implicated in several types of cancer. Thus, inhibitors of the Hh signaling pathway, including cyclopamine derivatives, have been targeted as potential treatments for certain cancers and other diseases associated with the Hh signaling pathway. A brief history of cyclopamine and cyclopamine derivatives investigated for the treatment of cancer is presented.
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biomedical applications of poisonous plant research
Journal of Agricultural and Food Chemistry, 2004Co-Authors: L F James, Kip E. Panter, William Gaffield, Russell J. MolyneuxAbstract:Research designed to isolate and identify the bioactive compounds responsible for the toxicity of plants to livestock that graze them has been extremely successful. The knowledge gained has been used to design management techniques to prevent economic losses, predict potential outbreaks of poisoning, and treat affected animals. The availability of these compounds in pure form has now provided scientists with tools to develop animal models for human diseases, study modes of action at the molecular level, and apply such knowledge to the development of potential drug candidates for the treatment of a number of genetic and infectious conditions. These advances are illustrated by specific examples of biomedical applications of the toxins of Veratrum Californicum (western false hellebore), Lupinus species (lupines), and Astragalus and Oxytropis species (locoweeds).
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Development of an Enzyme-Linked Immunosorbent Assay for the Veratrum Plant Teratogens: Cyclopamine and Jervine
Journal of agricultural and food chemistry, 2003Co-Authors: Stephen T. Lee, William Gaffield, Kip E. Panter, Bryan L. StegelmeierAbstract:Veratrum Californicum was responsible for large losses of sheep grazing high mountain ranges in central Idaho in the 1950s. Veratrum induces various birth defects including the cyclopic-type craniofacial defect (monkey-faced lambs) that is specifically induced in lambs after pregnant ewes grazed the plant on the 14th day of gestation. The steroidal alkaloids cyclopamine (1) and jervine (2) were isolated from Veratrum and shown to be primarily responsible for the malformations. Cyclopamine (1) and jervine (2) are potent teratogens that inhibit Sonic hedgehog (Shh) signaling during gastrulation-stage embryonic development, producing cyclopia and holoprosencephaly. Although losses to the sheep industry from Veratrum are now relatively infrequent, occasional incidents of toxicoses and craniofacial malformations are still reported in sheep and other species. However, the benefits to biomedical research using cyclopamine (1) as a tool to study human diseases have greatly expanded. A competitive inhibition enzyme-linked immunosorbent assay (ELISA) to detect and measure cyclopamine (1) and jervine (2) was developed using polyclonal antibodies produced in ewes. The limits of detection of the assay were 90.0 and 22.7 pg for cyclopamine (1) and jervine (2), respectively. This assay was used for the detection and measurement of cyclopamine (1) spiked into sheep blood. The simple extraction-ELISA methods developed in this study demonstrate the potential of using these techniques for the rapid screening of biological samples to detect the presence and concentration of cyclopamine (1) and jervine (2) and will be beneficial to pharmacological studies and livestock diagnostics.
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development of an enzyme linked immunosorbent assay for the Veratrum plant teratogens cyclopamine and jervine
Journal of Agricultural and Food Chemistry, 2003Co-Authors: Kip E. Panter, William Gaffield, Bryan L. StegelmeierAbstract:Veratrum Californicum was responsible for large losses of sheep grazing high mountain ranges in central Idaho in the 1950s. Veratrum induces various birth defects including the cyclopic-type craniofacial defect (monkey-faced lambs) that is specifically induced in lambs after pregnant ewes grazed the plant on the 14th day of gestation. The steroidal alkaloids cyclopamine (1) and jervine (2) were isolated from Veratrum and shown to be primarily responsible for the malformations. Cyclopamine (1) and jervine (2) are potent teratogens that inhibit Sonic hedgehog (Shh) signaling during gastrulation-stage embryonic development, producing cyclopia and holoprosencephaly. Although losses to the sheep industry from Veratrum are now relatively infrequent, occasional incidents of toxicoses and craniofacial malformations are still reported in sheep and other species. However, the benefits to biomedical research using cyclopamine (1) as a tool to study human diseases have greatly expanded. A competitive inhibition enzym...
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Reproductive losses to poisonous plants: influence of management strategies.
Journal of Range Management, 2002Co-Authors: Kip E. Panter, Dale R Gardner, James A Pfister, Michael H Ralphs, L F James, Bryan L. StegelmeierAbstract:Poisonous plants that impair normal reproductive functions in livestock include Veratrum Californicum Durand, lupines, ponderosa pine (Pinus ponderosa Dougl.), broom snakeweed (Gutierrezia sarothrae (Pursh) Britt. R (2) know what poisonous plants grow on ranges and understand their effects; (3) develop a management plan to provide for alternate grazing in poisonous plant-free pastures during critical times; (4) provide for balanced nutrition, including protein, energy, minerals and vitamins; (5) maintain a good herd health program; (6) integrate an herbicide treatment program to reduce poisonous plant populations or to maintain clean pastures for alternate grazing; and, (7) manage the range for maximum forage production. DOI:10.2458/azu_jrm_v55i3_panter
Bryan L. Stegelmeier - One of the best experts on this subject based on the ideXlab platform.
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development of an enzyme linked immunosorbent assay for the Veratrum plant teratogens cyclopamine and jervine
Journal of Agricultural and Food Chemistry, 2003Co-Authors: Kip E. Panter, William Gaffield, Bryan L. StegelmeierAbstract:Veratrum Californicum was responsible for large losses of sheep grazing high mountain ranges in central Idaho in the 1950s. Veratrum induces various birth defects including the cyclopic-type craniofacial defect (monkey-faced lambs) that is specifically induced in lambs after pregnant ewes grazed the plant on the 14th day of gestation. The steroidal alkaloids cyclopamine (1) and jervine (2) were isolated from Veratrum and shown to be primarily responsible for the malformations. Cyclopamine (1) and jervine (2) are potent teratogens that inhibit Sonic hedgehog (Shh) signaling during gastrulation-stage embryonic development, producing cyclopia and holoprosencephaly. Although losses to the sheep industry from Veratrum are now relatively infrequent, occasional incidents of toxicoses and craniofacial malformations are still reported in sheep and other species. However, the benefits to biomedical research using cyclopamine (1) as a tool to study human diseases have greatly expanded. A competitive inhibition enzym...
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Development of an Enzyme-Linked Immunosorbent Assay for the Veratrum Plant Teratogens: Cyclopamine and Jervine
Journal of agricultural and food chemistry, 2003Co-Authors: Stephen T. Lee, William Gaffield, Kip E. Panter, Bryan L. StegelmeierAbstract:Veratrum Californicum was responsible for large losses of sheep grazing high mountain ranges in central Idaho in the 1950s. Veratrum induces various birth defects including the cyclopic-type craniofacial defect (monkey-faced lambs) that is specifically induced in lambs after pregnant ewes grazed the plant on the 14th day of gestation. The steroidal alkaloids cyclopamine (1) and jervine (2) were isolated from Veratrum and shown to be primarily responsible for the malformations. Cyclopamine (1) and jervine (2) are potent teratogens that inhibit Sonic hedgehog (Shh) signaling during gastrulation-stage embryonic development, producing cyclopia and holoprosencephaly. Although losses to the sheep industry from Veratrum are now relatively infrequent, occasional incidents of toxicoses and craniofacial malformations are still reported in sheep and other species. However, the benefits to biomedical research using cyclopamine (1) as a tool to study human diseases have greatly expanded. A competitive inhibition enzyme-linked immunosorbent assay (ELISA) to detect and measure cyclopamine (1) and jervine (2) was developed using polyclonal antibodies produced in ewes. The limits of detection of the assay were 90.0 and 22.7 pg for cyclopamine (1) and jervine (2), respectively. This assay was used for the detection and measurement of cyclopamine (1) spiked into sheep blood. The simple extraction-ELISA methods developed in this study demonstrate the potential of using these techniques for the rapid screening of biological samples to detect the presence and concentration of cyclopamine (1) and jervine (2) and will be beneficial to pharmacological studies and livestock diagnostics.
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Reproductive losses to poisonous plants: influence of management strategies.
Journal of Range Management, 2002Co-Authors: Kip E. Panter, Dale R Gardner, James A Pfister, Michael H Ralphs, L F James, Bryan L. StegelmeierAbstract:Poisonous plants that impair normal reproductive functions in livestock include Veratrum Californicum Durand, lupines, ponderosa pine (Pinus ponderosa Dougl.), broom snakeweed (Gutierrezia sarothrae (Pursh) Britt. R (2) know what poisonous plants grow on ranges and understand their effects; (3) develop a management plan to provide for alternate grazing in poisonous plant-free pastures during critical times; (4) provide for balanced nutrition, including protein, energy, minerals and vitamins; (5) maintain a good herd health program; (6) integrate an herbicide treatment program to reduce poisonous plant populations or to maintain clean pastures for alternate grazing; and, (7) manage the range for maximum forage production. DOI:10.2458/azu_jrm_v55i3_panter
Owen M. Mcdougal - One of the best experts on this subject based on the ideXlab platform.
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review Veratrum Californicum alkaloids
Molecules, 2021Co-Authors: Madison Dirks, Jared T Seale, Joseph Collins, Owen M. McdougalAbstract:Veratrum spp. grow throughout the world and are especially prevalent in high mountain meadows of North America. All parts of Veratrum plants have been used for the treatment of ailments including injuries, hypertension, and rheumatic pain since as far back as the 1600s. Of the 17-45 Veratrum spp., Veratrum Californicum alkaloids have been proven to possess favorable medicinal properties associated with inhibition of hedgehog (Hh) pathway signaling. Aberrant Hh signaling leads to proliferation of over 20 cancers, including basal cell carcinoma, prostate and colon among others. Six of the most well-studied V. Californicum alkaloids are cyclopamine (1), veratramine (2), isorubijervine (3), muldamine (4), cycloposine (5), and veratrosine (6). Recent inspection of the ethanolic extract from V. Californicum root and rhizome via liquid chromatography-mass spectrometry has detected up to five additional alkaloids that are proposed to be verazine (7), etioline (8), tetrahydrojervine (9), dihydrojervine (10), 22-keto-26-aminocholesterol (11). For each alkaloid identified or proposed in V. Californicum, this review surveys literature precedents for extraction methods, isolation, identification, characterization and bioactivity to guide natural product drug discovery associated with this medicinal plant.
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steroidal alkaloid variation in Veratrum Californicum as determined by modern methods of analytical analysis
Fitoterapia, 2019Co-Authors: Matthew W. Turner, John French, Meagan Rossi, Vannessa D Campfield, Ellie I Hunt, Emily Wade, Owen M. McdougalAbstract:Veratrum Californicum is a rich source of steroidal alkaloids, many of which have proven to be antagonists of the Hedgehog (Hh) signaling pathway that becomes aberrant in over twenty types of cancer. These alkaloids first became known in the 1950's due to their teratogenic properties, which resulted in newborn and fetal lambs developing cyclopia as a result of pregnant ewes consuming Veratrum Californicum. It was discovered that the alkaloids in V. Californicum were concentrated in the root and rhizome of the plant with much lower amounts of the most active alkaloid, cyclopamine, present in the aerial plant, especially in the late growth season. Inspired by the limitations in analytical instrumentation and methods available to researchers at the time of the original investigation, we have used state-of-the-art instrumentation and modern analytical methods to quantitate four steroidal alkaloids based on study parameters including plant part, harvest location, and growth stage. The results of the current inquiry detail differences in alkaloid composition based on the study parameters, provide a detailed assessment for alkaloids that have been characterized previously (cyclopamine, veratramine, muldamine and isorubijervine), and identify at least six alkaloids that have not been previously characterized. This study provides insight into optimal harvest time, plant growth stage, harvest location, and plant part required to isolate, yet to be characterized, alkaloids of interest for exploration as Hh pathway antagonists with desirable medicinal properties.
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Native V. Californicum Alkaloid Combinations Induce Differential Inhibition of Sonic Hedgehog Signaling
MDPI AG, 2018Co-Authors: Matthew W. Turner, Roberto Cruz, Jared Mattos, Jordan Elwell, John French, Owen M. McdougalAbstract:Veratrum Californicum is a rich source of steroidal alkaloids such as cyclopamine, a known inhibitor of the Hedgehog (Hh) signaling pathway. Here we provide a detailed analysis of the alkaloid composition of V. Californicum by plant part through quantitative analysis of cyclopamine, veratramine, muldamine and isorubijervine in the leaf, stem and root/rhizome of the plant. To determine whether additional alkaloids in the extracts contribute to Hh signaling inhibition, the concentrations of these four alkaloids present in extracts were replicated using commercially available standards, followed by comparison of extracts to alkaloid standard mixtures for inhibition of Hh signaling using Shh-Light II cells. Alkaloid combinations enhanced Hh signaling pathway antagonism compared to cyclopamine alone, and significant differences were observed in the Hh pathway inhibition between the stem and root/rhizome extracts and their corresponding alkaloid standard mixtures, indicating that additional alkaloids present in these extracts are capable of inhibiting Hh signaling
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Improved extraction and complete mass spectral characterization of steroidal alkaloids from Veratrum Californicum.
Natural product communications, 2013Co-Authors: Christopher M. Chandler, Jeffrey W. Habig, Ashley A. Fisher, Katherine V. Ambrose, Susana T. Jiménez, Owen M. McdougalAbstract:Four steroidal alkaloids extracted from the roots and rhizomes of Veratrum Californicum were separated by high performance liquid chromatography (HPLC) and identified using high resolution electrospray ionization time of flight tandem mass spectrometry (ESI-TOF-MS/MS) as veratrosine, cycloposine, veratramine, and cyclopamine. This paper compares ethanol and benzene as extraction solvents, HPLC solvent conditions leading to good separation of steroidal alkaloids, and MS/MS fragmentation patterns for the four steroidal alkaloids which have been released to the public database MassBank.jp. The reported Soxhlet extraction method nearly triples the recovery of steroidal alkaloids from V. Californicum.
William Gaffield - One of the best experts on this subject based on the ideXlab platform.
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biomedical applications of poisonous plant research
Journal of Agricultural and Food Chemistry, 2004Co-Authors: L F James, Kip E. Panter, William Gaffield, Russell J. MolyneuxAbstract:Research designed to isolate and identify the bioactive compounds responsible for the toxicity of plants to livestock that graze them has been extremely successful. The knowledge gained has been used to design management techniques to prevent economic losses, predict potential outbreaks of poisoning, and treat affected animals. The availability of these compounds in pure form has now provided scientists with tools to develop animal models for human diseases, study modes of action at the molecular level, and apply such knowledge to the development of potential drug candidates for the treatment of a number of genetic and infectious conditions. These advances are illustrated by specific examples of biomedical applications of the toxins of Veratrum Californicum (western false hellebore), Lupinus species (lupines), and Astragalus and Oxytropis species (locoweeds).
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Development of an Enzyme-Linked Immunosorbent Assay for the Veratrum Plant Teratogens: Cyclopamine and Jervine
Journal of agricultural and food chemistry, 2003Co-Authors: Stephen T. Lee, William Gaffield, Kip E. Panter, Bryan L. StegelmeierAbstract:Veratrum Californicum was responsible for large losses of sheep grazing high mountain ranges in central Idaho in the 1950s. Veratrum induces various birth defects including the cyclopic-type craniofacial defect (monkey-faced lambs) that is specifically induced in lambs after pregnant ewes grazed the plant on the 14th day of gestation. The steroidal alkaloids cyclopamine (1) and jervine (2) were isolated from Veratrum and shown to be primarily responsible for the malformations. Cyclopamine (1) and jervine (2) are potent teratogens that inhibit Sonic hedgehog (Shh) signaling during gastrulation-stage embryonic development, producing cyclopia and holoprosencephaly. Although losses to the sheep industry from Veratrum are now relatively infrequent, occasional incidents of toxicoses and craniofacial malformations are still reported in sheep and other species. However, the benefits to biomedical research using cyclopamine (1) as a tool to study human diseases have greatly expanded. A competitive inhibition enzyme-linked immunosorbent assay (ELISA) to detect and measure cyclopamine (1) and jervine (2) was developed using polyclonal antibodies produced in ewes. The limits of detection of the assay were 90.0 and 22.7 pg for cyclopamine (1) and jervine (2), respectively. This assay was used for the detection and measurement of cyclopamine (1) spiked into sheep blood. The simple extraction-ELISA methods developed in this study demonstrate the potential of using these techniques for the rapid screening of biological samples to detect the presence and concentration of cyclopamine (1) and jervine (2) and will be beneficial to pharmacological studies and livestock diagnostics.
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development of an enzyme linked immunosorbent assay for the Veratrum plant teratogens cyclopamine and jervine
Journal of Agricultural and Food Chemistry, 2003Co-Authors: Kip E. Panter, William Gaffield, Bryan L. StegelmeierAbstract:Veratrum Californicum was responsible for large losses of sheep grazing high mountain ranges in central Idaho in the 1950s. Veratrum induces various birth defects including the cyclopic-type craniofacial defect (monkey-faced lambs) that is specifically induced in lambs after pregnant ewes grazed the plant on the 14th day of gestation. The steroidal alkaloids cyclopamine (1) and jervine (2) were isolated from Veratrum and shown to be primarily responsible for the malformations. Cyclopamine (1) and jervine (2) are potent teratogens that inhibit Sonic hedgehog (Shh) signaling during gastrulation-stage embryonic development, producing cyclopia and holoprosencephaly. Although losses to the sheep industry from Veratrum are now relatively infrequent, occasional incidents of toxicoses and craniofacial malformations are still reported in sheep and other species. However, the benefits to biomedical research using cyclopamine (1) as a tool to study human diseases have greatly expanded. A competitive inhibition enzym...
Stephen T. Lee - One of the best experts on this subject based on the ideXlab platform.
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Cyclopamine: from cyclops lambs to cancer treatment.
Journal of agricultural and food chemistry, 2014Co-Authors: Stephen T. Lee, Dale R Gardner, Kip E. Panter, Kevin D. Welch, Massoud Garrossian, Cheng-wei Tom ChangAbstract:In the late 1960s, the steroidal alkaloid cyclopamine was isolated from the plant Veratrum Californicum and identified as the teratogen responsible for craniofacial birth defects including cyclops in the offspring of sheep grazing on mountain ranges in the western United States. Cyclopamine was found to inhibit the hedgehog (Hh) signaling pathway, which plays a critical role in embryonic development. More recently, aberrant Hh signaling has been implicated in several types of cancer. Thus, inhibitors of the Hh signaling pathway, including cyclopamine derivatives, have been targeted as potential treatments for certain cancers and other diseases associated with the Hh signaling pathway. A brief history of cyclopamine and cyclopamine derivatives investigated for the treatment of cancer is presented.
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Development of an Enzyme-Linked Immunosorbent Assay for the Veratrum Plant Teratogens: Cyclopamine and Jervine
Journal of agricultural and food chemistry, 2003Co-Authors: Stephen T. Lee, William Gaffield, Kip E. Panter, Bryan L. StegelmeierAbstract:Veratrum Californicum was responsible for large losses of sheep grazing high mountain ranges in central Idaho in the 1950s. Veratrum induces various birth defects including the cyclopic-type craniofacial defect (monkey-faced lambs) that is specifically induced in lambs after pregnant ewes grazed the plant on the 14th day of gestation. The steroidal alkaloids cyclopamine (1) and jervine (2) were isolated from Veratrum and shown to be primarily responsible for the malformations. Cyclopamine (1) and jervine (2) are potent teratogens that inhibit Sonic hedgehog (Shh) signaling during gastrulation-stage embryonic development, producing cyclopia and holoprosencephaly. Although losses to the sheep industry from Veratrum are now relatively infrequent, occasional incidents of toxicoses and craniofacial malformations are still reported in sheep and other species. However, the benefits to biomedical research using cyclopamine (1) as a tool to study human diseases have greatly expanded. A competitive inhibition enzyme-linked immunosorbent assay (ELISA) to detect and measure cyclopamine (1) and jervine (2) was developed using polyclonal antibodies produced in ewes. The limits of detection of the assay were 90.0 and 22.7 pg for cyclopamine (1) and jervine (2), respectively. This assay was used for the detection and measurement of cyclopamine (1) spiked into sheep blood. The simple extraction-ELISA methods developed in this study demonstrate the potential of using these techniques for the rapid screening of biological samples to detect the presence and concentration of cyclopamine (1) and jervine (2) and will be beneficial to pharmacological studies and livestock diagnostics.
