Teratology最新文献

{"title":"2001 Teratogen Update Workshop summaries: Introduction","authors":"L. Holmes","doi":"10.1002/TERA.10055","DOIUrl":"https://doi.org/10.1002/TERA.10055","url":null,"abstract":"","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"94 1","pages":"199-199"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83994753","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}

{"title":"2001 Warkany lecture: to die or not to die, the role of apoptosis in normal and abnormal mammalian development.","authors":"P. Mirkes","doi":"10.1002/TERA.10049","DOIUrl":"https://doi.org/10.1002/TERA.10049","url":null,"abstract":"Cell death is a common and reproducible feature of the development of many mammalian tissues/organs. Two well-known examples of programmed cell death (PCD) are the cell deaths associated with fusion of the neural folds and removal of interdigital mesenchymal cells during digit formation. Like normal development, abnormal development is also associated with increased cell death in tissues/organs that develop abnormally after exposure to a wide variety of teratogens. At least in some instances, teratogens induce cell death in areas of normal PCD, suggesting that there is a link between programmed and teratogen-induced cell death. Although researchers recognized early on that cell death is an integral part of both normal and abnormal development, little was known about the mechanisms of cell death. In 1972, Kerr et al. ('72) showed conclusively that cell deaths, induced in a variety of contexts, followed a reproducible pattern, which they termed apoptosis. The next breakthrough came in the 1980s when Horvitz and his colleagues identified specific cell death genes (ced) that controlled PCD in the roundworm, Caenorhabditis elegans (C. elegans). Identification of ced genes in the roundworm quickly led to the isolation of their mammalian homologues. Subsequent research in the 1990s led to the identification of a cadre of proteins controlling cell death in mammals, i.e., receptors/ligands, caspases, cytochrome c, Apaf-1, Bcl-2 family proteins, and IAPs. Two major pathways of apoptosis have now been elucidated, the receptor-mediated and the mitochondrial apoptotic pathways. The latter pathway, induced by a wide variety of toxic agents, is activated by the release of cytochrome c from mitochondria. Cytochrome c then facilitates the activation of a caspase cascade involving caspase-9 and -3. Activation of these caspases results in the cleavage of a variety of cellular proteins leading to the orderly demise of the cell. Work from my laboratory in the last 5 years has shown that teratogens, such as hyperthermia, 4-hydroperoxycyclophosphamide, and staurosporine, induce cell death in day 9 mouse embryos by activating the mitochondrial apoptotic pathway, i.e., mitochondrial release of cytochrome c, activation of caspase-9 and -3, inactivation of poly (ADP-ribose) polymerase (PARP), and systematic degradation of DNA. Our work, as well as the work of others, has also shown that different tissues within the early post implantation mammalian embryo are differentially sensitive to the cell death inducing potential of teratogens, from exquisite sensitivity of cells in the developing central nervous system to complete resistance of cells in the developing heart. More importantly, we have shown that the resistance of heart cells is directly related to the failure to activate the mitochondrial apoptotic pathway in these cells. Thus, whether a cell dies in response to a teratogen and therefore contributes to the pathogenesis culminating in birth defects, depends, at least","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"29 1","pages":"228-39"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82296647","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}

{"title":"Problems with informing women adequately about teratogen risk: some barriers to preventing exposures to known teratogens.","authors":"M. Honein, Cynthia A. Moore, K. L. Daniel, J. Erickson","doi":"10.1002/TERA.10057","DOIUrl":"https://doi.org/10.1002/TERA.10057","url":null,"abstract":"","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"60 1","pages":"202-4"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77367597","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}

{"title":"Putative new teratogens.","authors":"L. Holmes","doi":"10.1002/TERA.10056","DOIUrl":"https://doi.org/10.1002/TERA.10056","url":null,"abstract":"","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"10 1","pages":"204-5"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75394945","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}

{"title":"Exencephaly in a subset of animals heterozygous for AP-2α mutation","authors":"A. Kohlbecker, A. E. Lee, H. Schorle","doi":"10.1002/TERA.10037","DOIUrl":"https://doi.org/10.1002/TERA.10037","url":null,"abstract":"Background \u0000 \u0000Transcription factor AP-2α has been implicated as a cell-type-specific regulator of gene expression during vertebrate embryogenesis based on its expression pattern in neural crest cells, ectoderm, and the nervous system in mouse, chick, and frog embryos. AP-2α is prominently expressed in cranial neural crest cells, a population of cells migrating from the lateral margins of the neural folds during closure of the neural tube in E (embryonic day of development) 8–9 mouse embryos. Homozygous AP-2α mutant mice die perinatally with cranio-abdominoschisis, full facial clefting, and defects in cranial ganglia and sensory organs. \u0000 \u0000 \u0000 \u0000Methods \u0000 \u0000Mice heterozygous for the AP-2α mutation on a 129/Sv strain were crossed with wildtype mice from the strain 129/Ola. The resulting embryos were genotyped, examined and used for histological analysis. \u0000 \u0000 \u0000 \u0000Results \u0000 \u0000A subset of animals heterozygous for the AP-2α mutation develop a midbrain exencephaly after the mutation was crossed for one generation in the 129/Ola mouse strain. Up to 14% of the animals show a failure of the cranial neural folds to close resulting in a partial exencephaly, all of them being heterozygous for the mutation. The affected animals show reduced rostrocaudal dimensions of the skull and malformations of the bones of the cranial vault. The neural tube defects vary from pure midbrain exencephaly to a forebrain/midbrain exencephaly where the proliferating neural tissue covers the eyes completely. \u0000 \u0000 \u0000 \u0000Conclusions \u0000 \u0000The results support a role of AP-2α in the etiology of exencephalic disorders. The phenotype observed might be due to a downregulation of the remaining allele suggesting the presence of an upstream modifier gene. Teratology 65:213–218, 2002. © 2002 Wiley-Liss, Inc.","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"15 1","pages":"213-218"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73893482","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}

{"title":"Epidemiology of Down syndrome (Trisomy 21), Hawaii, 1986-97.","authors":"M. Forrester, R. D. Merz","doi":"10.1002/TERA.10042","DOIUrl":"https://doi.org/10.1002/TERA.10042","url":null,"abstract":"BACKGROUND\u0000The live birth prevalence of Down syndrome is approximately 10 per 10,000 live births in the United States. Down syndrome prevalence has been reported to change over time and to vary by selected demographic factors.\u0000\u0000\u0000METHODS\u0000Data from a population-based birth defects registry in Hawaii involving 363 Down syndrome cases delivered during 1986-97 were used to calculate overall prevalence and to investigate secular trends and differences by selected demographic factors.\u0000\u0000\u0000RESULTS\u0000The total (live birth, fetal death, and elective termination) prevalence was 14.74 per 10,000 live births and fetal deaths. The unadjusted live birth prevalence was 8.67 per 10,000 live births. The adjusted live birth (live births and proportion of elective terminations expected to have resulted in live births) prevalence was 12.59 per 10,000 live births. No significant secular trends were observed for either total prevalence (P = 0.688) or adjusted live birth prevalence (P = 0.604). The total Down syndrome prevalence per 10,000 live births was highest for Far East Asians (22.01), followed by whites (17.06), Filipinos (15.94), and Pacific Islanders (9.21). Prevalence per 10,000 births was higher in metropolitan Honolulu (18.57) than in the rest of Hawaii (14.15). After adjusting for maternal age, however, the differences within the demographic groups were not statistically significant.\u0000\u0000\u0000CONCLUSIONS\u0000The live birth prevalence of Down syndrome in Hawaii during 1986-97 was lower than reported in the literature. Prevalence did not change significantly over time. Any differences in prevalence by maternal race/ethnicity and place of residence appeared to result from differences in maternal age distribution.","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"1 1","pages":"207-12"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88401067","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}

{"title":"Monitoring leflunomide (Arava) as a new potential teratogen.","authors":"K. Lyons Jones, Diana L. Johnson, C. Chambers","doi":"10.1002/TERA.10058","DOIUrl":"https://doi.org/10.1002/TERA.10058","url":null,"abstract":"","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"181 1","pages":"200-2"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77531834","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}

{"title":"Coarctation of the aorta and VSD: is there a reason for the association?","authors":"R. Tyl","doi":"10.1002/TERA.10036","DOIUrl":"https://doi.org/10.1002/TERA.10036","url":null,"abstract":"","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"370 1","pages":"206"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80451835","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}

{"title":"Investigation of the effects of folate deficiency on embryonic development through the establishment of a folate deficient mouse model.","authors":"Jennifer M Burgoon, J. Selhub, M. Nadeau, T. Sadler","doi":"10.1002/TERA.10040","DOIUrl":"https://doi.org/10.1002/TERA.10040","url":null,"abstract":"BACKGROUND\u0000Folic acid (FA) has been shown to reduce the incidence of neural tube, craniofacial, and cardiovascular defects and low birth weight. The mechanism(s) by which the vitamin is effective, however, has not been determined. Therefore, a folic acid deficient mouse model was developed.\u0000\u0000\u0000METHODS\u0000To create a folic acid deficiency, ICR female mice were placed on a diet containing no FA and including 1% succinyl sulfathiazole (SS) for 4 weeks before mating. Control mice were fed diets with either: 1) FA and 1% SS [+SS only diet]; 2) FA [normal diet]; or 3) a breeding diet. Dams and fetuses were examined during various days of gestation.\u0000\u0000\u0000RESULTS\u0000Blood analysis showed that by gestational day 18, plasma folate concentrations in the -FA+SS fed dams decreased to 1.13 ng/ml, a concentration approximately 3% of that in breeding diet fed dams (33.24 ng/ml) and 8% of that in +SS only/normal fed dams (13.59 ng/ml). RBC folate levels showed a similar decrease, whereas homocysteine concentrations increased. Reproductive outcome in the -FA+SS fed dams was poor with increased fetal deaths, decreased fetal weight, and delays in palate and heart development.\u0000\u0000\u0000CONCLUSIONS\u0000Female mice fed a folic acid deficient diet and 1% succinyl sulfathiazole exhibited many of the characteristics common to human folic acid deficiency, including decreased plasma and RBC folate, increased plasma homocysteine, and poor reproductive outcomes. Thus, an excellent model has been created to investigate the mechanism(s) underlying the origin of birth defects related to folic acid deficiency.","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"16 1","pages":"219-27"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81556012","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}

{"title":"Update on new developments in the study of human teratogens.","authors":"Thomas H. Shepard, Robert L. Brent, Jan M. Friedman, Kenneth L. Jones, Richard K. Miller, Cynthia A. Moore, J. Polifka","doi":"10.1002/TERA.10032","DOIUrl":"https://doi.org/10.1002/TERA.10032","url":null,"abstract":"BACKGROUND AND METHODS\u0000The purpose of this annual article is to highlight and briefly review new and significant information on agents that may be teratogenic in pregnant women. Various sources of on-line and printed information are given.\u0000\u0000\u0000RESULTS\u0000The following topics have been discussed: 1) lithium medication: decreased estimate of risk; 2) cigarette smoking and genotype as contributors to oral-facial clefts and clubfoot; 3) trimethoprim; 4) methimazole syndrome?; 5) glucocorticoids and oral-facial clefts; 6) binge drinking; 7) fetal valproate syndrome; and 8) carbamazepine.\u0000\u0000\u0000CONCLUSIONS\u0000We have highlighted several maternal exposures during pregnancy that are associated with small but increased rates of birth defects, generally only a few cases per 1,000 infants. These exposures include cigarette smoking, and treatment with lithium, trimethoprim, methimazole, or corticosteroids. This weak teratogenic effect was usually identified by the linkage of an uncommon treatment with an unusual birth defect outcome. The use of modern epidemiologic techniques, especially prospective multicenter studies that provide increased numbers, has helped to strengthen the evidence for these associations. We discuss how teratogenic risks that are small in comparison to the background risk can be presented to at-risk women and their doctors. We have briefly listed some elements that might be used in prioritizing further studies of suspected teratogenic exposures. Various existing methods for expressing the strength of evidence for human teratogenicity are also given.","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"16 1","pages":"153-61"},"PeriodicalIF":0.0,"publicationDate":"2002-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90766976","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}