Folding and aggregation of export-defective mutants of the maltose-binding protein

We previously characterized a defective-folding variant of the periplasmic maltose-binding protein, MalE31. To examine the alternative folding pathways open to the MalE31 precursor, we have analyzed the cellular fates of this aggregation-prone protein carrying altered signal sequences. Our results are most easily interpreted by a kinetic competition between exportation, folding, and degradation.     

Ethnicity in pressure ulcer risk assessment,with specific relation to the Pakistani ethnic minority in Burton,England

BACKGROUND: There has been little work on ethnicity related to pressure ulcers in general and little or nothing specific to South Asians, and the Pakistani ethnic group in particular. AIM: To explore the relevance of ethnicity in pressure ulcers. METHODS: All admissions over a 5-year period to a District General Hospital in Burton, United Kingdom (UK) were considered where data were present on Waterlow Score, ethnicity and pressure sore status. Logistic regression analysis was conducted using ethnicity and other variables to predict ulcer formation. RESULTS; Age is predictive, but ethnicity was not found to be a significant predictor. CONCLUSION: There is no evidence that members of the Pakistani ethnic minority are at higher risk than the majority White population in Burton, with respect to pressure ulcers.     

Fabry's disease and hypoparathyroidism

INTRODUCTION: Fabry's disease is due to alpha-galactosidase deficiency. This rare lysosomal storage disease is transmitted by recessive X-linked heredity. Sphingolipids (galactosyl-glucosyl-ceramide) accumulate in many organs. CASE REPORT: A 19-year-old man with known hypoparathyroidism presented with telangiectasia and angiokeratomas on the buttocks, the hips, the hands and around the navel. For many years, he suffered from paroxysmal pain in the hands and feet. From childhood, he had complained of diffuse abdominal pain, associated with diarrhea. Ophthalmological slit lamp fundus examination showed corneal telangiectasia and cornea verticella. There was no kidney or heart involvement. The diagnosis of Fabry's disease was confirmed by very low levels of alpha-galactosidase. DISCUSSION: We did not find any other association of hypoparathyroidism and Fabry's disease in the literature. Hypoparathyroidism is not a manifestation of Fabry's disease. Idiopathic hypoparathyroidism is very rare and a genetic origin is known. This disease can be recessive X-linked. A co-transmission of idiopathic hypoparathyroidism and Fabry's disease is probable in our patient.     

Combined detection of mannanaemia and antimannan antibodies as a strategy for the diagnosis of systemic infection caused by pathogenic Candida species

A novel strategy for the diagnosis of systemic candidosis was evaluated, based on the combination of two enzyme immunoassays that detect a candida oligomannoside repetitive epitope expressed in large amounts by Candida albicans (Platelia Candida Ag), and antibodies against C. albicans mannan, the major cell-wall immunogen in which this epitope is present (Platelia Candida Ab). Sera were selected retrospectively from intensive care and haematology patients with clinically suspected systemic candidosis, and from whom Candida spp. had been isolated from normally sterile sites. Of the 21 patients infected with C. albicans, 13 had positive antigenaemia and 14 had a positive antibody response, including eight patients who were antigenaemia negative. The sensitivity of the combined tests was 100%. In patients infected with C. glabrata (n = 12) or C. tropicalis (n = 10), the sensitivity was 83% and 80%, respectively. For the remaining patients, infected with C. parapsilosis (n = 10), C. krusei (n = 8) or C. kefyr (n = 2), the sensitivity of the combined tests was 40%, 50% and 50%, respectively. At least one of the serological tests was positive before yeast growth occurred in 60% of patients for whom a serum sample was available before blood culture sampling. An increase in serological test positivity to >80% was observed for sera obtained around the date of positive culture, irrespective of the Candida species isolated. These results suggest that regular serological monitoring for both mannanaemia and anti-mannan antibodies in at-risk patients may contribute to the early diagnosis of candidosis.     

Uniform range of conduction times from the lateral amygdala to distributed perirhinal sites

Much data indicate that the perirhinal (PRH) cortex plays a critical role in declarative memory and that the amygdala facilitates this process under emotionally arousing conditions. However, assuming that the amygdala does so by promoting Hebbian interactions in the PRH cortex is hard to reconcile with the fact that variable distances separate amygdala neurons from their PRH projection sites. Indeed, to achieve a synchronized activation of distributed PRH sites, amygdala axons should display a uniform range of conduction times, irrespective of distance to target. To determine if amygdala axons meet this condition, we measured the antidromic response latencies of lateral amygdala (LA) neurons to electrical stimuli delivered at various rostrocaudal levels of the PRH cortex in cats anesthetized with isoflurane. Although large variations in antidromic response latencies were observed, they were unrelated to the distance between the PRH stimulation sites and LA neurons. To determine whether this result was an artifact due to current spread, two control experiments were performed. First, we examined the antidromic response latency of intrinsic PRH neurons. Although we used the same methods as in the first experiment, the antidromic response latency of PRH neurons to electrical stimuli applied in the PRH cortex increased linearly with the distance between the stimulating and recording sites. Second, we measured the antidromic response latency of PRH neurons projecting to the LA. In this pathway, we also found a statistically significant correlation between conduction times and distance to target. Thus these results support the intriguing possibility that the conduction velocity and/or trajectory of LA axons are adjusted to compensate for variations in distance between the LA and distinct rostrocaudal PRH sites. We hypothesize that because of their uniform range of conduction times to the PRH cortex, LA neurons can generate short time windows of depolarization facilitating Hebbian associations between coincident, but spatially distributed, activity patterns in the PRH cortex. In this context, the temporal scatter of conduction times in the LA to PRH pathway is conceived as a mechanism used to lengthen the period of depolarization to compensate for conduction delays within intrinsic PRH pathways. In part, this mechanism might explain how the amygdala promotes memory storage in emotionally arousing conditions.