Ehlers-Danlos syndrome – vascular type (ecchymotic variant): cutaneous and dermatopathologic features

Ehlers-Danlos syndrome – vascular type, the only lethal form, is rarely reported in dermatology literature. It is characterized by translucent, atrophic skin, easy bruising, arterial, intestinal and/or uterine fragility manifesting as varicose veins, aneurysms and vascular/visceral/uterine rupture. As its dermatopathologic features are not well elucidated, diagnosis is often made after a catastrophic complication or at autopsy. This 36 year-old non-consanguineous male had brown-black plaques with atrophy and frequent ulceration over legs and dorsal feet and tortuous varicose veins around ankles for the past 15 years. Perivenous skin was translucent and hypopigmented. He had multiple and ecchymotic keloids and small atrophic, pityriasis versicolor-like lesions over trunk. He did not have hypermobile/hyperextensible skin and joints and showed no systemic or investigative abnormality. Histopathologic features of atrophic lesion included blood extravasation in atrophic epidermis/dermis, focal clustering and dilatation of blood vessels, malformed vessel walls, abundant hemosiderin in the dermis and homogenously stained/whorled patterned collagen especially around blood vessels. Pathology of keloidal lesion showed new collagen and vascular fragility. These histopathologic features appear of diagnostic value especially in patients who have compatible clinical findings but cannot afford confirmation by biochemical testing for abnormal synthesis of type III procollagen or identification of mutations in the COL3A1 gene.     

ORL-HNS training in South Africa

An out line of the scheme of training specialists in Otorhinolaryngology-Head and Neck Surgery (ORL-HNS) in South Africa is given and the difference with Indian training discussed     

Regulation of immunoglobulin heavy-chain gene rearrangements

Summary: Regulated assembly of antigen receptor gene segments to produce functional genes is a hallmark of B‐ and T‐lymphocyte development. The immunoglobulin heavy‐chain (IgH) and T‐cell receptor β‐chain genes rearrange first in B and T lineages, respectively. Both loci require two recombination events to assemble functional genes; D‐to‐J recombination occurs first followed by V‐to‐DJ recombination. Despite similarities in overall rearrangement patterns, each locus has unique regulatory features. Here, we review the characteristics of IgH gene rearrangements such as developmental timing, deletion versus inversion, D_H gene segment utilization, ordered recombination of V_H gene segments, and feedback inhibition of rearrangement in pre‐B cells. We summarize chromatin structural features of the locus before and during recombination and, wherever possible, incorporate these into working hypotheses for understanding regulation of IgH gene recombination. The picture emerges that the IgH locus is activated in discrete, independently regulated domains. A domain encompassing D_H and J_H gene segments is activated first, within which recombination is initiated. V_H genes are activated subsequently and, in part, by interleukin‐7. These observations lead to a model for feedback inhibition of IgH rearrangements.     

Geographic contiguity and genetic affinity among five ethnic populations of Manipur,India: further molecular studies based on VNTR and STR loci

BACKGROUND: Apart from traditional markers studied among a few numerically small, geographically defined surveys among Mongoloid populations in northeastern parts of India, very little is known about their genomic diversity at the molecular level. PRIMARY OBJECTIVE: This study seeks to investigate how best the variable number tandem repeat (VNTR) and short tandem repeat (STR) loci together can detect the patterns of the genetic affinity among five geographically contiguous, linguistically and socio-culturally diverse Mongoloid-affiliated populations of Manipur in northeastern regions of India. SUBJECT AND METHODS: Blood samples were collected from unrelated and randomly selected volunteers of five ethnic populations (Meitei, Kuki, Naga, Hmar and Manipuri Muslim) from different parts of the state. Allelic variation in four minisatellite loci (D1S7, D4S139, D5S110 and D17S79) and three STR loci (vWA, FESFPS and F13AO1) was studied. RESULTS: Average heterozygosity values among the five groups for the minisatellite range from 68% to 94%, while the hypervariable three STR loci were between 60% and 88%. In the populations, all the studied loci were highly polymorphic, with almost no departure from Hardy-Weinberg equilibrium. The gene differentiation for the VNTR loci was lower and moderate (G(st) = 0.030) in comparison with microsatellites (G(st) = 0.043). The neighbour-joining method of clustering based on both type of molecular markers reveals a close cluster for the tribal groups of Kuki, Naga and Hmar, while Manipur Muslim stand distinct in both the trees. The clustering pattern obtained from the combined DNA marker loci matches more closely the pattern from STR loci than that obtained from VNTR loci. CONCLUSIONS: The results reinforce that using both VNTR and STR loci in detecting regional genetic affinity among the populations is more effective than using VNTR or STR independently, and also confirm the results obtained from the serological and electrophoretic data. However, the clustering pattern obtained from combined DNA markers is more in conformity with the pattern obtained by STR loci rather than with VNTR loci. Despite linguistic, geographical and cultural barriers, the populations show genetic affinity among the four populations except in the case of the migrant Manipur Muslim group.     

Probiotic lactobacilli: an innovative tool to correct the malabsorption syndrome of vegetarians?

Vegetarians may have subtle nutritional deficiencies which have been related to the occurrence of an unrecognized malabsorption syndrome. The excess phytate content in cereals, nuts, legumes and oilseeds which represent the mainstay of their food intake, seems to play a central role in the pathogenesis of this malabsorption syndrome as an inverse relationship has been shown to link the phytate content of the diet with the intestinal absorption of trace minerals and proteins. We postulate that manipulating the endogenous digestive microflora of subjects on a vegetarian diet through administering probiotic lactic bacteria would represent an innovative tool to counteract the occurrence of the malabsorption syndrome dependent on the high phytate content of their diet. Even though there are no data about the composition of endogenous digestive microflora in subjects on a vegetarian diet, we expect that probiotic lactobacilli can interact with or affect distinct yet interrelated components within the intestinal milieu, such as epithelial cells, enteric flora, and/or mucosal immune cells. This would ultimately translate into the correction of the unregulated mechanisms implicated in the altered intestinal absorption of trace metals and proteins commonly seen in vegetarians. Clinical experience with probiotic therapy of patients with inflammatory bowel disease fully agrees with this view. One additional point of interest is that probiotic lactobacilli, and other species of the endogenous digestive microflora as well, are an important source of the enzyme phytase which catalyses the release of phosphate from phytate and hydrolyses the complexes formed by phytate and metal ions or other cations, rendering them more soluble ultimately improving and facilitating their intestinal absorption. The regular intake of probiotic preparation, may represent a cheap and safe tool in order to convert a diet with a low potential for bioavailability of trace minerals and proteins, such as the vegetarian diet, into a diet with a high bioavailability potential. The benefit of such an approach would not be restricted to vegetarians.     

Allele sharing at six VNTR loci and genetic distances among three ethnically defined human populations

Because of their high degree of polymorphisms, the variable number of tandem repeat (VNTR) loci have become extremely useful in studies involving gene mapping, determination of identity and relatedness of individuals, and evolutionary relationships among populations. However, there are some concerns regarding whether or not the patterns of such genetic variation can be studied by the classical population models that are developed for studying genetic variation at blood groups and protein loci, since VNTR alleles detected by molecular size may not always be identical by descent. Although theoretical and empirical studies demonstrate that this concern is overstated, this study provides further support of the application of the traditional mutation-drift models to predict the pattern of intra- and inter-populational variation at VNTR loci. By comparing genetic variation at six VNTR loci with that at 16 blood groups and protein loci in three ethnically defined populations, we show that the patterns of variability at these two sets of loci are in general parallel to each other. Shared VNTR alleles among populations are generally more frequent than the ones which are not present in every population; the proportion of shared alleles among populations increases with increasing genetic similarity of populations; and the number of VNTR alleles is positively correlated with gene diversity at these loci. All of these observations are in agreement with the prediction of the mutation-drift models, particularly when the possibility of forward-backward mutations are taken into account. This parallelism of genetic variation at VNTR loci and blood groups/protein loci further asserts the potential of using such hypervariable loci for microevoltionary studies, where closely related populations may exhibit considerably less allele frequency differences at the classical blood group and protein loci. © 1992 Wiley-Liss, Inc.     

Processing of interaural temporal disparities in the medial division of the ventral nucleus of the lateral lemniscus

The medial division of the ventral nucleus of the lateral lemniscus (VNLLm) contains a specialized population of neurons that is sensitive to interaural temporal disparities (ITDs), a potent cue for sound localization along the azimuth. Unlike many ITD-sensitive neurons elsewhere in the auditory system, neurons in the VNLLm respond only at the onset of tones. An onset response may be significant for behavior because, under echoic conditions, tones require sharp onsets for accurate localization. In contrast, noise can generally be localized even with gradual onsets, presumably because transients occur at random intervals in noise. We recorded responses of neurons in the VNLLm to tones and noise in unanesthetized rabbits. We found that although tones elicited a transient response, noise elicited a sustained response as if it was a sequence of transients. The responses to tones indicate that these neurons represent a secondary stage in the processing of ITDs. The onset response to tones was only weakly synchronized to the phase of the tone, indicating that neurons in the VNLLm inherit their sensitivity to ITDs from their inputs. The latencies were short (~8 ms), implying that the ITD sensitivity is derived from ascending inputs. Most neurons in the VNLLm discharged maximally at the same ITD at all frequencies, a characteristic shared with neurons of the medial superior olive. However, the latency of neurons in the VNLLm to interaurally delayed stimuli is linked strongly to the timing of the contralateral stimulus. This suggests that these neurons receive a suprathreshold, contralateral input that is modulated by a subthreshold input conveying information about ITDs. Other stations in the auditory pathway contain a subset of neurons that respond transiently to tones and are sensitive to ITDs. These neurons may represent a novel pathway that assists in localizing sounds in the presence of reflections.