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.     

The radiation dose to the lens in radiology of the orbit

This paper describes research into measurement and reduction of the radiation dose to the lens during various examinations, namely skull and orbit, optic canal and optic strut, superior and inferior orbital fissure, localisation of foreign bodies in the eye, calcifications, orbital fractures, macrodacryography and orbital venography. Using rare-earth screens and high-sensitivity films, without an antiscattering grid, and with an added filtration of 0.5 mm Cu, it is possible to reduce the radiological risk during all investigations involving skull, orbit and eyeballs, while maintaining a good image quality. Particularly in those examinations with direct magnification (macrodacryography and venography, foreign bodies in the eye, orbital fractures), the dose to the lens is very low: less than 0.2 mGy/radiograph.     

Transplantation of normal hepatocytes modulates the development of chronic liver lesions induced by a pyrrolizidine alkaloid, lasiocarpinet

Laipcarpine (LC), a pyorrolizidine alkaloid, is able to inducea series of chronic and progressive lesions in rat liver, includingalong-lasting block in the cell cycle, the appearance of enlargedhepatocytes (megalocytosis), fibrosis, cirrhosis and malignantneoplasms. In this study the effect of transplantation of normalhepatocytes on the development of LC (80 µmol/kg i.p.).Four weeks later all animals were subjected to 2/3 paroticlhepatectomy (PH). In addition, at the time of PH one group ofrats were transplanted with normal hepatocytes isolated froma syngeneic donor (10⁶ cells/rat via the portal vein), whilethe other group received only the culture medium. All rats werekilled 14 weeks after the operation. Grossly, the liver of ratsexposed to LC followed by PH with no transplantation of normalhepatocytes was small in size (% liver wt/body wt 1.66 ±0.08) and exhibited a few whitish nodules. Histologically,     

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.     

Bancroftian filariasis in Pondicherry, south India--epidemiological impact of recovery of the vector population.

An Integrated Vector Management (IVM) strategy was implemented from 1981 to 1985 in one part of Pondicherry, South India, for the control of the bancroftian filariasis vector Culex quinquefasciatus (the IVM area). The rest of the town (the comparison area) received the conventional larvicidal input. After 1985 both the areas were managed conventionally. The switch to conventional strategy resulted in an increase of vector density in both areas. The microfilaraemia prevalence in humans showed a general decline (P less than 0.05) from 1986 to 1989 only in the IVM area whereas its intensity did not change significantly in either area. While the age-specific rate of gain of infection was generally unchanged in the IVM area, an increase in all age classes was observed after 1985 in the comparison area, where the Annual Transmission Index was high during the previous years. In both areas the rate of loss of infection increased during 1986-9 compared to 1981-6. The results suggest that 3 years is too short a period to relate the changes in entomological parameters to those in the microfilaraemia status of the population.     

Recent advances in understanding the pathogenesis of polyglutamine diseases: involvement of molecular chaperones and ubiquitin-proteasome pathway

Polyglutamine diseases consist of a group of familial neurodegenerative disorders caused by expression of proteins containing expanded polyglutamine stretch. Over the past several years, tremendous progress has been made in identifying the molecular mechanisms by which the expanded polyglutamine tract leads to neuronal dysfunction and neurodegeneration. A common feature of most polyglutamine disorders is the occurrence of ubiquitin-positive neuronal intranuclear inclusions. The appearance of ubiquitinated aggregates implies an underline incapability of the cellular chaperones and proteasome machinery that normally functions to prevent the accumulation of misfolded proteins. Here we review the recent studies that have revealed a critical role for molecular chaperones and ubiquitin-proteasome pathway in the pathogenesis of polyglutamine diseases.     

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.