What summarized in this paper is the progress in recent years' in the causdive mechanism on study of developmental toxicants as chemical teratogenesis in three aspects.(1) It is about the phenomena and the possibl...What summarized in this paper is the progress in recent years' in the causdive mechanism on study of developmental toxicants as chemical teratogenesis in three aspects.(1) It is about the phenomena and the possible reason of chemical teratogenesis in the preimplantation period. These research results are contrary to the past traditional concepts. (2) Due to using much more molecular biology methods, it can be observed more dead foetus phenomena before birth, which cannot be done previously and are of great value for reference. (3) When analyzing the genetic reason of chemical abnormal, a new research idea may be showed, i.e. the developmental abnormal due to chemical teratogenesis is induced with association of more relative genes and their expression abnormal. 13 references are involved in.展开更多
Background: Acute intermittent porphyria (AIP), due to halfnormal hydroxymethy lbilane synthase activity, is characterized by acute life threatening neurologi c attacks whose etiology remains unclear. To date, only 3 ...Background: Acute intermittent porphyria (AIP), due to halfnormal hydroxymethy lbilane synthase activity, is characterized by acute life threatening neurologi c attacks whose etiology remains unclear. To date, only 3 patients fconirmed to have homozygous dominant AIP (HD AIP) have been described (hydroxymethylbilane synthase genotypes R167Q/R167Q and R167W/R173Q). Objective: To investigate the genetic, biochemical, clinical, and neuroradiologic features of a severely affected infa nt with HD AIP. Design: Clinical, imaging, and genotype/phenotype studies were performed. Results: The proband, homoallelic for hydroxymethylbilane synthase mu tation R167W, had approximately 1%of normal hydroxymethylbilane synthase activi ty, elevated porphyrins and porphyrin precursors, severe psychomotor delay, and central and peripheral neurologic manifestations. When expressed in vitro, the R 167W mutant enzyme had less than 2%of normal activity but was markedly unstable , consistent with the probands severe phenotype. Mitochondrial respiratory cha in enzymes were normal. Neuroradiologic studies revealed a unique pattern of dee p cerebral white matter injury, with relative preservation of the corpus callosu m, anterior limb of the internal capsule, cerebral gray matter, and infratentori al structures. Conclusions: This severely affected patient with HD AIP expanded the phenotypic spectrum of HD AIP. His brain magnetic resonance imaging studie s suggested selective cerebral oligodendrocyte postnatal involvement in HD AIP, whereas most structures developed prenatally were intact. These findings indica te that the neurologic manifestations result from porphyrin precursor toxicity r ather than heme deficiency and suggest that porphyrin precursor toxicity is prim arily responsible for the acute neurologic attacks in heterozygous AIP and other porphyrias.展开更多
文摘What summarized in this paper is the progress in recent years' in the causdive mechanism on study of developmental toxicants as chemical teratogenesis in three aspects.(1) It is about the phenomena and the possible reason of chemical teratogenesis in the preimplantation period. These research results are contrary to the past traditional concepts. (2) Due to using much more molecular biology methods, it can be observed more dead foetus phenomena before birth, which cannot be done previously and are of great value for reference. (3) When analyzing the genetic reason of chemical abnormal, a new research idea may be showed, i.e. the developmental abnormal due to chemical teratogenesis is induced with association of more relative genes and their expression abnormal. 13 references are involved in.
文摘Background: Acute intermittent porphyria (AIP), due to halfnormal hydroxymethy lbilane synthase activity, is characterized by acute life threatening neurologi c attacks whose etiology remains unclear. To date, only 3 patients fconirmed to have homozygous dominant AIP (HD AIP) have been described (hydroxymethylbilane synthase genotypes R167Q/R167Q and R167W/R173Q). Objective: To investigate the genetic, biochemical, clinical, and neuroradiologic features of a severely affected infa nt with HD AIP. Design: Clinical, imaging, and genotype/phenotype studies were performed. Results: The proband, homoallelic for hydroxymethylbilane synthase mu tation R167W, had approximately 1%of normal hydroxymethylbilane synthase activi ty, elevated porphyrins and porphyrin precursors, severe psychomotor delay, and central and peripheral neurologic manifestations. When expressed in vitro, the R 167W mutant enzyme had less than 2%of normal activity but was markedly unstable , consistent with the probands severe phenotype. Mitochondrial respiratory cha in enzymes were normal. Neuroradiologic studies revealed a unique pattern of dee p cerebral white matter injury, with relative preservation of the corpus callosu m, anterior limb of the internal capsule, cerebral gray matter, and infratentori al structures. Conclusions: This severely affected patient with HD AIP expanded the phenotypic spectrum of HD AIP. His brain magnetic resonance imaging studie s suggested selective cerebral oligodendrocyte postnatal involvement in HD AIP, whereas most structures developed prenatally were intact. These findings indica te that the neurologic manifestations result from porphyrin precursor toxicity r ather than heme deficiency and suggest that porphyrin precursor toxicity is prim arily responsible for the acute neurologic attacks in heterozygous AIP and other porphyrias.
