Waardenburg syndrome: clinical differentiation between types I and II

Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the I variant of WS.     

A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts

Recent studies of the genome architecture of vertebrates have uncovered two unforeseen aspects of its organization. First, large regions of the genome, called gene deserts, are devoid of protein-coding sequences and have no obvious biological role. Second, comparative genomics has highlighted the existence of an array of highly conserved non-coding regions (HCNRs) in all vertebrates. Most surprisingly, these structural features are strongly associated with genes that have essential functions during development. Among these, the vertebrate Iroquois (Irx) genes stand out on both fronts. Mammalian Irx genes are organized in two clusters (IrxA and IrxB) that span >1 Mb each with no other genes interspersed. Additionally, a large number of HCNRs exist within Irx clusters. We have systematically examined the enhancer activity of HCNRs from the IrxB cluster using transgenic Xenopus and zebrafish embryos. Most of these HCNRs are active in subdomains of endogenous Irx expression, and some are candidates to contain shared enhancers of neighboring genes, which could explain the evolutionary conservation of Irx clusters. Furthermore, HCNRs present in tetrapod IrxB but not in fish may be responsible for novel Irx expression domains that appeared after their divergence. Finally, we have performed a more detailed analysis on two IrxB ultraconserved non-coding regions (UCRs) duplicated in IrxA clusters in similar relative positions. These four regions share a core region highly conserved among all of them and drive expression in similar domains. However, inter-species conserved sequences surrounding the core, specific for each of these UCRs, are able to modulate their expression.     

Metabolic polymorphisms and the micronucleus frequency in buccal epithelium of adolescents living in an urban environment

Micronuclei and other biomarkers were evaluated in oral cells from 11- to 16-year-old girls living in a foster home in the central area of México City. Variables analyzed for possible association with these biomarkers include smoking habits, body mass index, metabolic polymorphisms for NAT1 and GSTM1 and whether the cells were obtained from the cheek or pharynx. The results indicated that individuals having the NAT1*10 homozygous genotype showed a significant increase in chromatin buds and binucleated cells. When the damage in the cheek was compared with damage in the pharynx, a significant increase in micronuclei and binucleated cells was found for the latter tissue in all the individuals analyzed.     

Antibodies to staphylococcal enterotoxins and toxic shock syndrome toxin 1 in sera of patients and healthy people in Rio de Janeiro, Brazil.

Sera from 33 persons with staphylococcal infections and from 37 healthy persons were surveyed for the presence of antibody to staphylococcal enterotoxins A, B, C, D, and E and toxic shock syndrome toxin 1. Thirty-one (93.9%) of the patients and 35 (94.6%) of the control group had antibodies to one or more of the enterotoxins. The numbers of patients with antibody to the enterotoxins were as follows: A, 8; B, 9; C, 7; D, 17; E, 21; and toxic shock syndrome toxin 1, 11. The numbers of healthy individuals with antibody to the enterotoxins were as follows: A, 6; B, 12; C, 8; D, 27; E, 21; and toxic shock syndrome toxin 1, 9.     

Eel calcitonin induces creatine kinase BB activity in the rat kidney medulla.

We have studied the effect of intravenous injection of eel calcitonin (ECT) on creatine kinase E.C.2.7.3.2. BB isozyme (CKBB) in the kidney of male Wistar rats. CKBB immunoreactivity was detected by the peroxidase-antiperoxidase method. Eel calcitonin increased CKBB immunoreactivity in the renal medulla in a dose-dependent fashion. Its effect peaked at 2 h and lasted up to 24 h. The distribution of activated CKBB in the kidney occurs in the same areas where highly specific CT-binding sites have been previously demonstrated, and is in agreement with the current concepts on renal actions of this hormone.