K. Winkel, G. Hawdon, P. Fenner, L. Gershwin, A. Collins, J. Tibballs
If snake antivenoms are considered orphan drugs, then jellyfish antivenoms are the poorest of the orphans. Despite the diversity, ubiquity and toxicity of the venomous cnidarians, only a single antivenom is available for jellyfish stings worldwide. That antivenom, an ovine whole IgG product, is directed against the ‘box’ jellyfish, Chironex fleckeri, and is manufactured by CSL Limited (Melbourne, Australia). It also neutralises the venom of closely related cubozoans such as Chiropsalmus quadrigatus. The recognition of the life‐threatening effects of various other jellyfish demonstrates the need for broadening the specificity of the existing product and/or developing additional specific jellyfish antivenoms. These emerging threats include the irukandji syndrome, due to Carukia barnesi and other carybdeids, as well as those from scyphozoans such as Stomolophus spp. The role of ancillary drug therapy, in addition to, or instead of, antivenoms remains controversial. This review will consider the development of jellyfish antivenoms, their clinical utility and future developments in the field.
{"title":"Jellyfish Antivenoms: Past, Present, and Future","authors":"K. Winkel, G. Hawdon, P. Fenner, L. Gershwin, A. Collins, J. Tibballs","doi":"10.1081/TXR-120019024","DOIUrl":"https://doi.org/10.1081/TXR-120019024","url":null,"abstract":"If snake antivenoms are considered orphan drugs, then jellyfish antivenoms are the poorest of the orphans. Despite the diversity, ubiquity and toxicity of the venomous cnidarians, only a single antivenom is available for jellyfish stings worldwide. That antivenom, an ovine whole IgG product, is directed against the ‘box’ jellyfish, Chironex fleckeri, and is manufactured by CSL Limited (Melbourne, Australia). It also neutralises the venom of closely related cubozoans such as Chiropsalmus quadrigatus. The recognition of the life‐threatening effects of various other jellyfish demonstrates the need for broadening the specificity of the existing product and/or developing additional specific jellyfish antivenoms. These emerging threats include the irukandji syndrome, due to Carukia barnesi and other carybdeids, as well as those from scyphozoans such as Stomolophus spp. The role of ancillary drug therapy, in addition to, or instead of, antivenoms remains controversial. This review will consider the development of jellyfish antivenoms, their clinical utility and future developments in the field.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84271759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Craik, Daniel G. Barry, R. Clark, N. Daly, L. Sando
The traditional idea of proteins as linear chains of amino acids is being challenged with the discovery of miniproteins that contain a circular backbone. The cyclotide family is the largest group of circular proteins and is characterized by an amide‐circularized protein backbone and six conserved cysteine residues. These conserved cysteines are paired to form a knotted network of disulfide bonds. The combination of the circular backbone and a cystine knot, known as the cyclic cystine knot (CCK) motif, confers exceptional stability upon the cyclotides. This review discusses the role of the circular backbone based on studies of both the oxidative folding of kalata B1, the prototypical cyclotide, and a comparison of the structure and activity of kalata B1 and its acyclic permutants.
{"title":"Structure‐Function Studies of the Plant Cyclotides: The Role of a Circular Protein Backbone","authors":"D. Craik, Daniel G. Barry, R. Clark, N. Daly, L. Sando","doi":"10.1081/TXR-120026914","DOIUrl":"https://doi.org/10.1081/TXR-120026914","url":null,"abstract":"The traditional idea of proteins as linear chains of amino acids is being challenged with the discovery of miniproteins that contain a circular backbone. The cyclotide family is the largest group of circular proteins and is characterized by an amide‐circularized protein backbone and six conserved cysteine residues. These conserved cysteines are paired to form a knotted network of disulfide bonds. The combination of the circular backbone and a cystine knot, known as the cyclic cystine knot (CCK) motif, confers exceptional stability upon the cyclotides. This review discusses the role of the circular backbone based on studies of both the oxidative folding of kalata B1, the prototypical cyclotide, and a comparison of the structure and activity of kalata B1 and its acyclic permutants.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84346131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Hokama, C. Whang, K. Chun, C. Suma, N. Higa, B. Or, A. Cocchetto, G. Kansky
The membrane immunobead assay results on the acetone lipid fraction of serum from chronic fatigue syndrome (CFS) patients (60 samples) and normal individuals (with no clinical CFS or other disease symptoms) showed significant differences with 4 exceptions (4 normals showed 1:40 and 1:80 titres). This represented approximately 10.8% of the normal samples, with 3 samples at 1:20, the majority of the CFS titred 1:40 through 1:160. This represented 95.0% of the samples. The small numbers of hepatitis patients and chronic ciguatera fish poisoning patients also had titres of 1:40 to 1:80 in all of the serum samples examined. The weights of the lipids in mg/ml serum essentially are very similar, except 1 or 2 of CFS and hepatitis B showed values at the upper level. Comparison of sexes showed 65% females and 35% men with CFS, representing a ratio of approximately 2:1 (female/male). It is concluded that certain disease conditions and environmental exposures to deleterious factors (toxin, chemicals, microorganisms) trigger the release of lipids (probably by the liver) with similar epitopes to ciguatoxin, and that they react with MAb–CTX. We designate these lipids as “chronic phase lipids” comparable to “acute phase protein” in inflammatory and traumatic diseases.
{"title":"Chronic Phase Lipids in Sera of Several Chronic Diseases Reacting with MAB–CTX (Antibody to Ciguatoxin)","authors":"Y. Hokama, C. Whang, K. Chun, C. Suma, N. Higa, B. Or, A. Cocchetto, G. Kansky","doi":"10.1081/TXR-120026913","DOIUrl":"https://doi.org/10.1081/TXR-120026913","url":null,"abstract":"The membrane immunobead assay results on the acetone lipid fraction of serum from chronic fatigue syndrome (CFS) patients (60 samples) and normal individuals (with no clinical CFS or other disease symptoms) showed significant differences with 4 exceptions (4 normals showed 1:40 and 1:80 titres). This represented approximately 10.8% of the normal samples, with 3 samples at 1:20, the majority of the CFS titred 1:40 through 1:160. This represented 95.0% of the samples. The small numbers of hepatitis patients and chronic ciguatera fish poisoning patients also had titres of 1:40 to 1:80 in all of the serum samples examined. The weights of the lipids in mg/ml serum essentially are very similar, except 1 or 2 of CFS and hepatitis B showed values at the upper level. Comparison of sexes showed 65% females and 35% men with CFS, representing a ratio of approximately 2:1 (female/male). It is concluded that certain disease conditions and environmental exposures to deleterious factors (toxin, chemicals, microorganisms) trigger the release of lipids (probably by the liver) with similar epitopes to ciguatoxin, and that they react with MAb–CTX. We designate these lipids as “chronic phase lipids” comparable to “acute phase protein” in inflammatory and traumatic diseases.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85514353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haruo Kobayashi, Michiru Uchida, I. Sato, Tadahiko Suzuki, Muhammad M Hossain, Koichi Suzuki
Manganese (Mn) is known to cause neurotoxicity in the central nervous system similar to Parkinsonism in man, but the mechanism underlying remains to be well clarified. Catalepsy is used to observe Parkinsonism in laboratory animals. In the present study, effects of repeated injection of Mn chloride (MnCl2) on catalepsy, dopamine receptors and distribution of 54Mn in the brain were investigated. [Methods] Female ICR mice were injected with 0, 10, 30 or 50 mg/kg/day of MnCl2 for 3 days, and examined for catalepsy and the binding ability of striatum, hippocampus and cerebral cortex to [3H]haloperidol to detect and change of dopamine D2‐receptors. Whole‐body burden and disposition of 54Mn in the brain regions and liver were determined after the repeated injection of 54MnCl2. Mice were given l‐dopa at 25 mg/kg 2 hr prior to MnCl2 injection to examined if the catalepsy was abolished. [Results] Mice showed catalepsy following injection of MnCl2 at 50 mg/kg, but not with less than 30 mg/kg. The catalepsy initiated about 60, 60 and 30 min after injection of MnCl2 on the 1st, 2nd and 3rd day, respectively, and lasted for about 60 min. l‐dopa slightly reversed the catalepsy. The binding of [3H]haloperidol in the three brain regions from mice treated with MnCl2 was lower than that from control. The concentration of 54Mn in the striatum and remaining areas, including substantia nigra, was the highest in the brain regions examined. [Conclusion] Since l‐dopa slightly alleviated catalepsy by MnCl2, and binding of [3H]haloperidol was decreased in brain regions, MnCl2 might induce catalepsy by suppressing D2 receptors in the striatum‐substantia nigra.
{"title":"Neurotoxicity and Brain Regional Distribution of Manganese in Mice","authors":"Haruo Kobayashi, Michiru Uchida, I. Sato, Tadahiko Suzuki, Muhammad M Hossain, Koichi Suzuki","doi":"10.1081/TXR-120026921","DOIUrl":"https://doi.org/10.1081/TXR-120026921","url":null,"abstract":"Manganese (Mn) is known to cause neurotoxicity in the central nervous system similar to Parkinsonism in man, but the mechanism underlying remains to be well clarified. Catalepsy is used to observe Parkinsonism in laboratory animals. In the present study, effects of repeated injection of Mn chloride (MnCl2) on catalepsy, dopamine receptors and distribution of 54Mn in the brain were investigated. [Methods] Female ICR mice were injected with 0, 10, 30 or 50 mg/kg/day of MnCl2 for 3 days, and examined for catalepsy and the binding ability of striatum, hippocampus and cerebral cortex to [3H]haloperidol to detect and change of dopamine D2‐receptors. Whole‐body burden and disposition of 54Mn in the brain regions and liver were determined after the repeated injection of 54MnCl2. Mice were given l‐dopa at 25 mg/kg 2 hr prior to MnCl2 injection to examined if the catalepsy was abolished. [Results] Mice showed catalepsy following injection of MnCl2 at 50 mg/kg, but not with less than 30 mg/kg. The catalepsy initiated about 60, 60 and 30 min after injection of MnCl2 on the 1st, 2nd and 3rd day, respectively, and lasted for about 60 min. l‐dopa slightly reversed the catalepsy. The binding of [3H]haloperidol in the three brain regions from mice treated with MnCl2 was lower than that from control. The concentration of 54Mn in the striatum and remaining areas, including substantia nigra, was the highest in the brain regions examined. [Conclusion] Since l‐dopa slightly alleviated catalepsy by MnCl2, and binding of [3H]haloperidol was decreased in brain regions, MnCl2 might induce catalepsy by suppressing D2 receptors in the striatum‐substantia nigra.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90741386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aspergillus flavus has received a considerable amount of attention due to its ability to produce aflatoxin, a secondary metabolite that is both immunosuppressive and carcinogenic to animals and humans. Research on aflatoxin over the last 40 years has made it one of the best studied fungal secondary metabolites. In spite of the large volume of research in this area, many unanswered questions remain concerning the genetic regulation of aflatoxin production and the molecular signals that intimately associate the synthesis of aflatoxin with specific environmental and nutritional conditions. It is anticipated that the tools now available in the field of genomics will build upon our existing knowledge and provide answers to some of these questions. Complete genome sequences are now available for a number of fungal species that are closely related to A. flavus. This information can be used along with current genomic analyses in A. flavus to more closely examine the biosynthesis and regulation of secondary metabolism. The intent of this review is to summarize the large body of knowledge that exists from many years of research on A. flavus, with the hope that this information in the light of new genomic studies may bring scientists closer to unraveling the web of regulatory circuits that govern aflatoxin biosynthesis. Specifically, scientific findings in the following areas will be presented: classification and phylogenetic analyses of A. flavus, population biology, ecology and pathogenicity in agricultural environments, classical genetics including linkage group and mutant analyses, gene clusters, regulation of aflatoxin biosynthesis, and genomics.
{"title":"Unlocking the Secrets Behind Secondary Metabolism: A Review of Aspergillus flavus from Pathogenicity to Functional Genomics","authors":"K. Scheidegger, G. Payne","doi":"10.1081/TXR-120024100","DOIUrl":"https://doi.org/10.1081/TXR-120024100","url":null,"abstract":"Aspergillus flavus has received a considerable amount of attention due to its ability to produce aflatoxin, a secondary metabolite that is both immunosuppressive and carcinogenic to animals and humans. Research on aflatoxin over the last 40 years has made it one of the best studied fungal secondary metabolites. In spite of the large volume of research in this area, many unanswered questions remain concerning the genetic regulation of aflatoxin production and the molecular signals that intimately associate the synthesis of aflatoxin with specific environmental and nutritional conditions. It is anticipated that the tools now available in the field of genomics will build upon our existing knowledge and provide answers to some of these questions. Complete genome sequences are now available for a number of fungal species that are closely related to A. flavus. This information can be used along with current genomic analyses in A. flavus to more closely examine the biosynthesis and regulation of secondary metabolism. The intent of this review is to summarize the large body of knowledge that exists from many years of research on A. flavus, with the hope that this information in the light of new genomic studies may bring scientists closer to unraveling the web of regulatory circuits that govern aflatoxin biosynthesis. Specifically, scientific findings in the following areas will be presented: classification and phylogenetic analyses of A. flavus, population biology, ecology and pathogenicity in agricultural environments, classical genetics including linkage group and mutant analyses, gene clusters, regulation of aflatoxin biosynthesis, and genomics.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81392557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mycotoxin losses and costs of mycotoxin management are overlapping areas of concern. Costs of mycotoxin management include research production practices, testing and research necessary to try to prevent the toxins from appearing in food and feed products of affected commodities. Mycotoxin losses result from (American Association of Veterinary Laboratory Diagnosticians (AAVLD), ) lowered animal production and any human toxicity attributable to the presence of the toxin, (CAST (Council for Agricultural Science and Technology), ) the presence of the toxin in the affected commodity which lowers its market value, as well as (Hawk, ) secondary effects on agriculture production and agricultural communities.
{"title":"The Costs of Mycotoxin Management to the USA: Management of Aflatoxins in the United States","authors":"J. Robens, K. Cardwell","doi":"10.1081/TXR-120024089","DOIUrl":"https://doi.org/10.1081/TXR-120024089","url":null,"abstract":"Mycotoxin losses and costs of mycotoxin management are overlapping areas of concern. Costs of mycotoxin management include research production practices, testing and research necessary to try to prevent the toxins from appearing in food and feed products of affected commodities. Mycotoxin losses result from (American Association of Veterinary Laboratory Diagnosticians (AAVLD), ) lowered animal production and any human toxicity attributable to the presence of the toxin, (CAST (Council for Agricultural Science and Technology), ) the presence of the toxin in the affected commodity which lowers its market value, as well as (Hawk, ) secondary effects on agriculture production and agricultural communities.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89393770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent discovery of new and bioactive taxane diterpenoids from the roots, barks, seeds, leaves and the stems of Taxus mairei and T. sumatrana, Taiwanese yew trees are described. More than thirty new compounds including taxumatrols A and B (36, 37) have been isolated and their structures determined by spectroscopic analysis and chemical derivatization and correlation. Some of the isolated taxoids exhibited potent cytotoxicity against human tumor cells.
{"title":"Novel Taxane Diterpenoids from Taiwanese Yew Trees","authors":"Ya‐Ching Shen, Yao-To Chang, Shih-Sheng Wang, Yu-Ling Pan, Kuang-Liang Lo, Yu-Chi Lin","doi":"10.1081/TXR-120026912","DOIUrl":"https://doi.org/10.1081/TXR-120026912","url":null,"abstract":"Recent discovery of new and bioactive taxane diterpenoids from the roots, barks, seeds, leaves and the stems of Taxus mairei and T. sumatrana, Taiwanese yew trees are described. More than thirty new compounds including taxumatrols A and B (36, 37) have been isolated and their structures determined by spectroscopic analysis and chemical derivatization and correlation. Some of the isolated taxoids exhibited potent cytotoxicity against human tumor cells.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90503063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Preharvest kernel infection by Aspergillus flavus and the subsequent accumulation of aflatoxin in maize grain are chronic problems in the southeastern United States. Aflatoxin is a natural carcinogen, and its presence markedly reduces the value of grain. Losses to aflatoxin contamination reach devastating levels some years. Development and deployment of maize hybrids with resistance to aflatoxin contamination is generally considered the most feasible method of reducing or eliminating the problem. Research to address the aflatoxin problem was initiated by USDA–ARS at Mississippi State, MS, in the late 1970s. The goals of the research were to identify and develop aflatoxin‐resistant maize germplasm. First, reliable techniques for screening germplasm were developed. Then, germplasm from numerous sources was screened. The release of Mp313E in 1988 was the first release of maize germplasm with resistance to aflatoxin contamination. Two other germplasm lines, Mp420 and Mp715, were released in 1991 and 1999, respectively. Additional germplasm lines have been developed, but not yet released. Efforts are currently underway to identify other sources of resistance.When used in crosses with other lines, the aflatoxin‐resistant lines markedly reduce the level of aflatoxin contamination in the resulting hybrids. Analysis of a diallel cross indicated that general combining ability was a significant source of variation in the inheritance of resistance to aflatoxin contamination. Efforts to combine resistance to aflatoxin combination and agronomic qualities using both conventional breeding methods and molecular marker assisted selection have been initiated.
{"title":"Enhancing Maize Germplasm with Resistance to Aflatoxin Contamination","authors":"W. Williams, G. Windham, P. Buckley","doi":"10.1081/TXR-120024091","DOIUrl":"https://doi.org/10.1081/TXR-120024091","url":null,"abstract":"Preharvest kernel infection by Aspergillus flavus and the subsequent accumulation of aflatoxin in maize grain are chronic problems in the southeastern United States. Aflatoxin is a natural carcinogen, and its presence markedly reduces the value of grain. Losses to aflatoxin contamination reach devastating levels some years. Development and deployment of maize hybrids with resistance to aflatoxin contamination is generally considered the most feasible method of reducing or eliminating the problem. Research to address the aflatoxin problem was initiated by USDA–ARS at Mississippi State, MS, in the late 1970s. The goals of the research were to identify and develop aflatoxin‐resistant maize germplasm. First, reliable techniques for screening germplasm were developed. Then, germplasm from numerous sources was screened. The release of Mp313E in 1988 was the first release of maize germplasm with resistance to aflatoxin contamination. Two other germplasm lines, Mp420 and Mp715, were released in 1991 and 1999, respectively. Additional germplasm lines have been developed, but not yet released. Efforts are currently underway to identify other sources of resistance.When used in crosses with other lines, the aflatoxin‐resistant lines markedly reduce the level of aflatoxin contamination in the resulting hybrids. Analysis of a diallel cross indicated that general combining ability was a significant source of variation in the inheritance of resistance to aflatoxin contamination. Efforts to combine resistance to aflatoxin combination and agronomic qualities using both conventional breeding methods and molecular marker assisted selection have been initiated.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87054392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The focus of my research was snake venom research and application of Raman spectroscopy for the biological compounds. In snake venom research, the emphasis was on hemorrhagic toxins, myonecrotic toxins from rattlesnake venoms, and postsynaptic neurotoxins from sea snake venoms. Structure–function relationship of these toxins was pursued using different methods such as biochemical, immunological, electronmicroscopy, biophysical, physiological, and pathological techniques. Many pure components were isolated and their amino acid sequences and biochemical properties were studied. Since a Raman spectrometer was purchased in 1976, it was possible to examine many biological compounds by Raman spectroscopy. Peptide backbone conformation and some side chain microenvironment of many proteins, kidney stones, and gallstones, etc. were examined by Raman scattering method. Raman spectroscopy can identify many biological compounds directly by focusing laser light without using wet chemical analysis. I was extremely fortunate to receive large sums of research grants from many agencies: National Institutes of Health, Office of Naval Research, U. S. Army, Food and Drug Administration, Colorado Heart Association, and others. In total ∖5.5 million were awarded in 40 years. With this financial assistance and many students' and postdoctoral fellows' work, I was able to publish over 260 original papers. I am thankful for all of this assistance.
{"title":"Reflections on 40 Years of Research","authors":"A. Tu","doi":"10.1081/TXR-120026908","DOIUrl":"https://doi.org/10.1081/TXR-120026908","url":null,"abstract":"The focus of my research was snake venom research and application of Raman spectroscopy for the biological compounds. In snake venom research, the emphasis was on hemorrhagic toxins, myonecrotic toxins from rattlesnake venoms, and postsynaptic neurotoxins from sea snake venoms. Structure–function relationship of these toxins was pursued using different methods such as biochemical, immunological, electronmicroscopy, biophysical, physiological, and pathological techniques. Many pure components were isolated and their amino acid sequences and biochemical properties were studied. Since a Raman spectrometer was purchased in 1976, it was possible to examine many biological compounds by Raman spectroscopy. Peptide backbone conformation and some side chain microenvironment of many proteins, kidney stones, and gallstones, etc. were examined by Raman scattering method. Raman spectroscopy can identify many biological compounds directly by focusing laser light without using wet chemical analysis. I was extremely fortunate to receive large sums of research grants from many agencies: National Institutes of Health, Office of Naval Research, U. S. Army, Food and Drug Administration, Colorado Heart Association, and others. In total ∖5.5 million were awarded in 40 years. With this financial assistance and many students' and postdoctoral fellows' work, I was able to publish over 260 original papers. I am thankful for all of this assistance.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82638409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
There are several groups of medically important araneomorph and mygalomorph spiders responsible for serious systemic envenomation. These include spiders from the genus Latrodectus (family Theridiidae), Phoneutria (family Ctenidae) and the subfamily Atracinae (genera Atrax and Hadronyche). The venom of these spiders contains potent neurotoxins that cause excessive neurotransmitter release via vesicle exocytosis or modulation of voltage‐gated sodium channels. In addition, spiders of the genus Loxosceles (family Loxoscelidae) are responsible for significant local reactions resulting in necrotic cutaneous lesions. This results from sphingomyelinase D activity and possibly other compounds. A number of antivenoms are currently available to treat envenomation resulting from the bite of these spiders. Particularly efficacious antivenoms are available for Latrodectus and Atrax/Hadronyche species, with extensive cross‐reactivity within each genera. In the case of Latrodectus antivenoms this is of considerable importance in countries where antivenom is unavailable or where certain antivenoms are associated with an unacceptably high risk of adverse reactions. Moreover, Latrodectus and Atrax antivenoms appear to be effective in the treatment of envenomation by closely related Steatoda spiders (family Theridiidae) or the unrelated spider Missulena bradleyi (family Actinopodidae), respectively. The effectiveness of Loxosceles antivenom in the treatment of the necrotic arachnidism resulting from the bite of recluse spiders is less clear mainly due to late presentation of victims. Antivenom is also available for Phoneutria envenomation but is reserved only for severe cases.
{"title":"Antivenoms for the Treatment of Spider Envenomation","authors":"G. Nicholson, A. Graudins","doi":"10.1081/TXR-120019019","DOIUrl":"https://doi.org/10.1081/TXR-120019019","url":null,"abstract":"There are several groups of medically important araneomorph and mygalomorph spiders responsible for serious systemic envenomation. These include spiders from the genus Latrodectus (family Theridiidae), Phoneutria (family Ctenidae) and the subfamily Atracinae (genera Atrax and Hadronyche). The venom of these spiders contains potent neurotoxins that cause excessive neurotransmitter release via vesicle exocytosis or modulation of voltage‐gated sodium channels. In addition, spiders of the genus Loxosceles (family Loxoscelidae) are responsible for significant local reactions resulting in necrotic cutaneous lesions. This results from sphingomyelinase D activity and possibly other compounds. A number of antivenoms are currently available to treat envenomation resulting from the bite of these spiders. Particularly efficacious antivenoms are available for Latrodectus and Atrax/Hadronyche species, with extensive cross‐reactivity within each genera. In the case of Latrodectus antivenoms this is of considerable importance in countries where antivenom is unavailable or where certain antivenoms are associated with an unacceptably high risk of adverse reactions. Moreover, Latrodectus and Atrax antivenoms appear to be effective in the treatment of envenomation by closely related Steatoda spiders (family Theridiidae) or the unrelated spider Missulena bradleyi (family Actinopodidae), respectively. The effectiveness of Loxosceles antivenom in the treatment of the necrotic arachnidism resulting from the bite of recluse spiders is less clear mainly due to late presentation of victims. Antivenom is also available for Phoneutria envenomation but is reserved only for severe cases.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89383786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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