Ectodermal Lesions Research Articles

Chromosome 1p36.22p36.21 duplications/triplication causes Setleis syndrome (focal facial dermal dysplasia type III).

Focal facial dermal dysplasias (FFDD) are characterized by congenital bitemporal or preauricular atrophic skin lesions, and either autosomal dominant or autosomal recessive inheritance. Setleis syndrome (SS), FFDD type III, is a severe form of FFDD with the ectodermal lesions plus other striking facial features. Autosomal recessive nonsense and frameshift mutations in TWIST2 have been found to cause SS in some but not all individuals. Here, we report on four unrelated individuals, one with an unclassified FFDD and the other three with classic SS. Chromosomal microarray analyses revealed unique copy number variants of 1p36 in two individuals with duplications at 1p36.22p36.21 and one with a triplication at 1p36.22p36.21. The fourth patient had normal chromosomes by microarray analysis. All four patients had normal TWIST2 exonic sequences. We propose that a dosage effect of one or more of the 30 genes in the 1.3 Mb 1p36.22p36.21 region of overlap is responsible for FFDD/SS manifestations in some individuals, and this mechanism would be inherited as an autosomal dominant trait. In patients with no duplication/triplication of the 1p36.22p36.21 region and no mutations in TWIST2, there are mutation(s) in one of the 30 genes in this region or mutations in other as yet unidentified genes at different locations that may affect the expressions of genes in this region or act independently to cause this developmental disease phenotype.

Giant Suprasellar Rathke's Cleft Cyst Mimicking Craniopharyngioma: Implications for a Spectrum of Cystic Epithelial Lesions of Ectodermal Origin

Cystic epithelial lesions such as Rathke's cleft cysts (RCCs) and craniopharyngiomas may be difficult to distinguish on a clinical, radiographic, and sometimes histopathological basis. We describe a case of a giant 6.5 cm suprasellar cystic lesion that was presumed to be a craniopharyngioma based on the neuroimaging findings. The lesion extended from the anterior skull base and sella turcica to the lateral ventricle and sylvian fissure resulting in obstructive hydrocephalus. Complete surgical removal of the suprasellar lesion was achieved using an extended frontotemporal transbasal skull base approach. Intraoperatively, the cyst wall was thickened and partially calcified, resembling a craniopharyngioma. However, the histopathological examination revealed findings most consistent with a RCC with additional features of extensive squamous metaplasia, metaplastic bone formation, and chronic inflammation. The case raises the issue of whether there is a pathologic continuum of parasellar ectodermal lesions which may account for the overlap of features and transitional states. In this report, we discuss the possible spectrum between RCCs and craniopharyngiomas, and also emphasize the importance of complete resection of the cyst wall in RCCs that exhibit squamous metaplasia, inflammation, or ossification to minimize the probability of recurrence.

Incidence patterns of ectodermic lesions in wild populations of Common Wall Lizard (Podarcis muralis)

Skin lesions frequently present in adult lizards may be due to a variety of causes, both physical and infectious, including excessively high humidity and environmental temperature, malnutrition, concurrent disease etc. On the other hand, skin lesions in lizards could be simple evidence of various behavioural patterns and biotic interactions. However, studies on frequencies of dermal lesions and their anatomical and environmental correlates in lacertid lizards are rare. Here, we use Podarcis muralis to analyse the relations between occurrence of ectodermal lesions and three possible indicators of environmental stress (body condition index – BCI, infestation by ticks and tail condition) by evaluating differences among local populations at uni- and multivariate level. Our results showed that BCI, together with body size and sexual size dimorphism, varied between populations but had no direct influence on the presence of lesions. Males had higher frequencies of lesions and ticks but lower frequencies of broken tails than females. All three parameters varied between sites likely due to differences in predation/parasite exposures and agonistic interactions with conspecifics between sexes and populations. Results of multivariate analyses suggested that the occurrence of lesions is decoupled from the other morphological stress indicators. Detected associations indicated that relations between presence of lesions and other analysed variables are rather complex. Directions for further research on ectodermal lesions in lacertid lizards are provided.

IQGAP2 is required for the cadherin-mediated cell-to-cell adhesion in Xenopus laevis embryos

We have previously identified two Xenopus homologues of mammalian IQGAP, XIQGAP1 and XIQGAP2, which show high homology with human IQGAP1 and IQGAP2, respectively. In order to clarify function of the IQGAPs during development, we performed knock-down experiments on the XIQGAPs in Xenopus laevis embryos by microinjecting morpholino antisense oligonucleotides into blastomeres at the two-cell stage. Suppression of XIQGAP2 expression caused ectodermal lesions in the neurula stage embryos. While suppression of XIQGAP1 expression alone did not show any obvious defect in subsequent developmental processes, simultaneous knock-down of both XIQGAPs caused the ectodermal lesions during the gastrula stage. Histological studies suggested that a loss of cell adhesion in the ectodermal and mesodermal layers of the embryos caused the defect. The suppression of XIQGAP2 expression resulted in loss of actin filaments, β-catenin, and XIQGAP1 from cell borders in the ectoderm, although it did not affect the expression levels of these proteins. Furthermore, it inhibited Ca 2+-induced reaggregation of embryonic cells which had been dissociated in a Ca 2+/Mg 2+-free medium. These results strongly suggest that XIQGAP2 is crucial for cell adhesion during early development in Xenopus.

Selective disruption of E-cadherin function in early Xenopus embryos by a dominant negative mutant.

E-cadherin function was disrupted in vivo in developing Xenopus laevis embryos through the expression of a mutant E-cadherin protein lacking its cytoplasmic tail. This truncated form of E-cadherin was designed to act as a dominant negative mutant by competing with the extracellular interactions of wild-type endogenous E-cadherin. Expression of truncated E-cadherin in the early embryo causes lesions to develop in the ectoderm during gastrulation. In contrast, expression of a similarly truncated N-cadherin protein failed to cause the lesions. The ectodermal defect caused by the truncated E-cadherin is rescued by overexpression of wild-type E-cadherin, by co-injection of full-length E-cadherin RNA along with the RNA for the truncated form. Overexpression of full-length C-cadherin, however, is unable to compensate for the disruption of E-cadherin function and can actually cause similar ectodermal lesions when injected alone, suggesting that there is a specific requirement for E-cadherin. Therefore, E-cadherin seems to be specifically required for maintaining the integrity of the ectoderm during epiboly in the gastrulating Xenopus embryo. Differential cadherin expression reflects, therefore, the requirement for distinct adhesive properties during different morphogenetic cell behaviors.

Identification of carcinogens by measurement of cell-mediated immunity: I. Immunity induced by rat pancreas and colon carcinogens

Anti-tumor cell-mediated immunity was used as a measure of exposure to chemical carcinogens. The measurements involved determining the amount of cytotoxicity to cultured X-ray-induced rat small bowel adenocarcinoma cells exhibited by peripheral blood lymphoid-cells isolated from animals exposed to the carcinogens. Cytotoxicity was determined by the release of radioiodinated integral and peripheral proteins of the small bowel cancer cells. The studies indicate that exposures to 1,2-dimethylhydrazine (DMH) which induces colon adenocarcinomas and 7,12-dimethylbenz[ a]anthracene (DMBA) implants which produce pancreatic adenocarcinomas, can be detected within a 6- to 72-day postexposure interval. Dose response studies of the DMH indicate exposures to as little as 100 μg (1.7 μmol) can be detected within this time interval although this amount is insufficient to produce detectable cancer. The present results further outline the specificity of the assay since it was found that tumors of mesodermally derived tissues (asbestos-induced peritoneal mesotheliomas) and nonspecific injury (70% surgical resection of ileum and jejunum) will not induce cytotoxicity. Our previous studies had shown ectodermal lesions also will not evoke responses; therefore, these findings suggest the measured anti-tumor immunity is specific to carcinogens which interact with entodermally derived tissue. Thus, the findings support our suggestion that measurement of anti-tumor immunity offers a rapid, sensitive, and specific technique for detecting carcinogenic substances.

LINEAR NEVUS SEBACEOUS SYNDROME: REPORT OF TWO CASES AND A REVIEW OF THE LITERATURE

Two cases of linear nevus sebaceous syndrome are described and a review of the eleven cases now reported in the literature is undertaken. The first patient has retardation, seizures, and classic ectodermal lesions while the second patient manifests typical cutaneous lesions and only an elevated cerebrospinal fluid protein as evidence of neurologic disease. The rationale for defining the syndrome as an entity distinct from other neurocutaneous syndromes is discussed and a pleomorphic presentation of the syndrome is suggested.

The Cultivation of Tumours in the Fertile Egg, with Special Reference to Associated Ectodermal Lesions of the Chorioallantoic Membrane

The Cultivation of Tumours in the Fertile Egg, with Special Reference to Associated Ectodermal Lesions of the Chorioallantoic Membrane