Aromatic amines such as 4-aminobiphenyl (ABP) require biotransformation to exert their carcinogenic effects. Genetic polymorphisms in biotransformation enzymes such as N-acetyltransferase 2 (NAT2) ...may modify cancer risk following exposure. Nucleotide excision repair-deficient Chinese hamster ovary (CHO) cells stably transfected with human cytochrome P4501A1 (CYP1A1) and a single copy of either NAT2*4 (rapid acetylator), NAT2*5B (common Caucasian slow acetylator), or NAT2*7B (common Asian slow acetylator) alleles (haplotypes) were treated with ABP to test the effect of NAT2 polymorphisms on DNA adduct formation and mutagenesis. ABP N-acetyltransferase catalytic activities were detectable only in cell lines transfected with NAT2 and were highest in cells transfected with NAT2*4, lower in cells transfected with NAT2*7B, and lowest in cells transfected with NAT2*5B. Following ABP treatment, N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP) was the primary adduct formed. Cells transfected with both CYP1A1 and NAT2*4 showed the highest concentration-dependent cytotoxicity, hypoxanthine phosphoribosyl transferase (hprt) mutants, and dG-C8-ABP adducts. Cells transfected with CYP1A1 and NAT2*7B showed lower levels of cytotoxicity, hprt mutagenesis, and dG-C8-ABP adducts. Cells transfected with CYP1A1 only or cells transfected with both CYP1A1 and NAT2*5B did not induce cytotoxicity, hprt mutagenesis or dG-C8-ABP adducts. ABP-DNA adduct levels correlated very highly (r>0.96) with ABP-induced hprt mutant levels following each treatment. The results of the present study suggest that investigations of NAT2 genotype or phenotype associations with disease or toxicity could be more precise and reproducible if heterogeneity within the "slow" NAT2 acetylator phenotype is considered and incorporated into the study design.
2-Amino-1-methyl-6-phenylimidazo4,5-bpyridine (PhIP) is carcinogenic in multiple organs and numerous species. Bioactivation of PhIP is initiated by PhIP N2-hydroxylation catalysed by cytochrome ...P450s. Following N-hydroxylation, O-acetylation catalysed by N-acetyltransferase 2 (NAT2) is considered a further possible activation pathway. Genetic polymorphisms in NAT2 may modify cancer risk following exposure.
Nucleotide excision repair-deficient Chinese hamster ovary (CHO) cells stably transfected with human cytochrome P4501A1 (CYP1A1) and a single copy of either NAT2*4 (rapid acetylator) or NAT2*5B (slow acetylator) alleles were used to test the effect of CYP1A1 and NAT2 polymorphism on PhIP genotoxicity.
Cells transfected with NAT2*4 had significantly higher levels of N-hydroxy-PhIP O-acetyltransferase (p = 0.0150) activity than cells transfected with NAT2*5B. Following PhIP treatment, CHO cell lines transfected with CYP1A1, CYP1A1/NAT2*4 and CYP1A1/NAT2*5B each showed concentration-dependent cytotoxicity and hypoxanthine phosphoribosyl transferase (hprt) mutagenesis not observed in untransfected CHO cells.
dG-C8-PhIP was the primary DNA adduct formed and levels were dose dependent in transfected CHO cells in the order: CYP1A1 < CYP1A1 and NAT2*5B < CYP1A1 and NAT2*4, although levels did not differ significantly (p > 0.05) following one-way analysis of variance.
These results strongly support activation of PhIP by CYP1A1 with little effect of human NAT2 genetic polymorphism on mutagenesis and DNA damage.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Uncombable hair syndrome was first described some 3 decades ago as "cheveux incoiffables" and is also known as spun-glass hair and pili trianguli et canaliculi. Both inherited (autosomal dominant and ...recessive with variable levels of penetrance) and sporadic forms of uncombable hair syndrome have been described, both being characterized by scalp hair that is impossible to comb due to the haphazard arrangement of the hair bundles. A characteristic morphologic feature of hair in this syndrome is a triangular to reniform to heart shape on cross-sections, and a groove, canal or flattening along the entire length of the hair in at least 50%of hairs examined by scanning electron microscopy. Most individuals are affected early in childhood and the hair takeson a spun-glassappearance with the hair becoming dry, curly, glossy, lighter in color, and progressively uncombable. Only the scalp hair is affected. Several conditions are associated with uncombable hair, such as ectodermal dysplasia, retinal dysplasia/ pigmentary dystrophy, juvenile cataract, digit abnormalities, tooth enamel anomalies, oligodontia, and phalangoepiphyseal dysplasia. Other syndromes with hair abnormalities may also mimic uncombable hair syndrome clinically and these include, Rapp-Hodgkin ectodermal dysplasia; loose anagen hair syndrome; ectodermal dysplasia, ectrodatyly, cleft lip/ palate (EEC) syndrome; and familial tricho-odonto-onchyial ectodermal dysplasia with syndactyly. Unlike other conditions with an uncombable hair component, uncombable hair syndrome alone (cheveux incoiffables, pili trianguli etcanaliculi) is not associated with physical, neurologic, or mental abnormalities. In most cases of uncombable hair syndrome, the hair is grossly abnormal in infancy and early childhood, but may have improved manageability later in life. Scanning electron microscopy of hair samples provides definitive evidence for diagnosis of clinically suspected uncombable hair syndrome and eliminates other hair abnormalities from the differential diagnosis.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
: Psoriasis commonly affects children and adolescents, and the need for safe, effective therapy is a special consideration in the pediatric population. In recent years, the use of targeted ...immunomodulatory biologic agents has been increasingly studied for the treatment of psoriasis. Of these, etanercept, a tumor necrosis factor‐α antagonist, has been approved for the treatment of psoriasis and psoriatic arthritis in adults, and while it is approved for use in juvenile rheumatoid arthritis, formal studies are needed to demonstrate its safety and efficacy for childhood psoriasis. We present our preliminary experience of treating nine pediatric patients with generalized, recalcitrant psoriasis with etanercept therapy.
Although the majority of hemangiomas of infancy can be expected to follow a benign course, a significant subset may result in serious complications. Recently, hemangiomas of segmental morphology, or ...those which are large, plaque-like, and patterned in distribution, have been recognized as important markers for potential complications. PHACE syndrome represents the best known example of the variety of problems that can occur in this setting. The PHACE acronym, which stands for posterior fossa brain malformations, segmental cervicofacial hemangiomas, arterial anomalies, cardiac defects and coarctation of the aorta, and eye anomalies, is sometimes referred to as PHACE(S) when ventral developmental defects such as sternal clefting and supraumbilical raphe are present. This article reviews the specific manifestations of PHACE, reflects on pathogenesis, and discusses appropriate work-up and future directions for this complex and fascinating syndrome. We also discuss other complications associated with hemangiomas of segmental morphology, including ulceration, potential visceral involvement, and underlying anomalies related to the lumbosacral location.
PHACE is an acronym to describe the association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta, cardiac defects, and eye abnormalities. More than ...200 cases have been reported. The present report presents the cases of two female infants with PHACE syndrome, both of whom had additional congenital defects of subependymal gray matter heterotopia, craniofacial arterial anomalies, and pituitary dysfunction. One had an extensive segmental facial hemangioma with ipsilateral intracranial hemangiomas. The other had multiple cutaneous hemangiomas, but no segmental facial hemangioma. These two cases suggest a further expansion of the spectrum of PHACE to include other forms of disordered cerebral development and endocrine dysfunction.
Topical medications and therapies are necessary for the proper management of skin diseases in children; however, physicians must be aware of the differences in percutaneous absorption and the risks ...for toxicity from topical medications, which are often unique to infants and children. Topical therapy must be individualized, and success often depends on proper vehicle selection, ease of application, and cost to patients and their families. Although many commercially available topical therapies are not FDA approved for use in children, recently enacted legislation has served to stimulate much-needed drug research in pediatric patients. New therapies on the horizon, such as tacrolimus, may prove to be equally efficacious and less toxic.
Background PHACE syndrome (Online Mendelian Inheritance in Man database No. 606519) refers to the association of large, plaquelike, or segmental hemangiomas of the face, with one or more of the ...following anomalies: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects, supraumbilical raphe, or both. Objective The underlying pathogenesis of PHACE is unknown. A strong female predominance exists, leading some to suggest the possibility of X-linked dominant inheritance, with lethality in male patients. However, no familial cases have been reported, and disease severity among affected male patients has not been systematically studied. Methods We compared the incidence of syndrome-associated anomalies between 17 new and 42 published reports of male patients with PHACE versus 213 published reports of female patients with PHACE. Results A statistically significant difference was found only for structural brain anomalies, which were somewhat more common in male patients. Limitations This was a retrospective study. Information was limited on some new and many previously reported cases. Conclusions Overall, our results show no convincing trend toward greater or lesser disease severity among affected male patients with PHACE.
We describe a family in whom infantile myofibromatosis affected 3 generations. The disease expression in this family suggests an autosomal dominant inheritance pattern with variable penetrance.
Nonendemic pemphigus foliaceus in children Metry, Denise W.; Hebert, Adelaide A.; Jordon, Robert E.
Journal of the American Academy of Dermatology,
03/2002, Letnik:
46, Številka:
3
Journal Article
Recenzirano
Background: Pemphigus foliaceus is a cutaneous, autoimmune, blistering disease comprising two major categories: endemic and sporadic. The endemic form, also known as fogo selvagem, primarily affects ...children and young adults in rural Brazil. In contrast, the sporadic form of pemphigus foliaceus is generally a disease of the middle-aged and elderly. Objective and methods: Because the sporadic form of pemphigus foliaceus rarely affects children, information specific to this unique group is lacking. We describe a 3-year-old boy with the disease and retrospectively review data from 28 past cases. Results: In comparison to pediatric cases of pemphigus vulgaris, sporadic pemphigus foliaceus in children tends to follow a generally benign course of relatively short duration. However, long-term outcome studies are lacking. A pattern of skin lesions described as “arcuate,” “circinate,” or “polycyclic” appears to be a unique and specific presentation of this disease in children. Occasionally, as in our case, the diagnosis may prove difficult to establish by using routine histology or immunopathology. Conclusion: The commercial availability of antigen-specific techniques such as enzyme-linked immunosorbent assay for serum desmoglein 1 autoantibody should eliminate delay in diagnosis. Hydroxychloroquine may be another treatment option for those children with photodistributed lesions. Further experience and long-term outcome studies in children are needed to determine whether some medication side effects may outweigh the risks from the disease itself. (J Am Acad Dermatol 2002;46:419-22.)
PDF
