Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca.

BACKGROUND: Variant transthyretin amyloidosis (A-ATTRv) is an autosomal dominant disease caused by a range of TTR gene variants which entail great phenotypical heterogeneity and penetrance. In Majorca, the A-ATTRv caused by the V30M gene variant (A-ATTRV30M) is the most common. Since asymptomatic carriers are at risk of developing the disease, estimating age of onset is vital for proper management and follow-up. Thus, the aim of this study was to estimate age-related penetrance in ATTRV30M variant carriers from Majorca. METHODS: The disease risk among carriers from ATTRV30M families from Majorca was estimated by Non-parametric survival estimation. Factors potentially involved in the disease expression, namely gender and parent of origin were also analysed. RESULTS: A total of 48 heterozygous ATTRV30M families (147 affected patients and 123 were asymptomatic carriers) were included in the analysis. Penetrance progressively increased from 6% at 30 years to 75% at 90 years of age. In contrast to other European populations, we observe a similar risk for both males and females, and no difference of risk according to the parent of origin. CONCLUSIONS: In this first study assessing the age-related penetrance of ATTRV30M variant in Majorcan families, no effect of gender or parent of origin was observed. These findings will be helpful for improving management and follow-up of TTR variant carrier individuals.

Sucralfate modulates uPAR and EGFR expression in an experimental rat model of cervicitis.

Sucralfate is a drug used in the treatment of gastric and duodenal ulcer; it is cytoprotective and able to increase the bioavailability of several growth factors, modulating the wound healing process. In this study we tested the possible therapeutic effect of Sucralfate in the treatment of ulcerative lesions occurring in uterine cervix; to investigate such effect we used an experimental rat model of cervicitis in which the uPAR and EGFR expression were evaluated. Cervicitis was induced in wild and ovariectomized Wistar female rats by an acetic acid-soaked tampon. The animals were divided into two main groups (4 and 7 days) and Sucralfate was administered topically until the day they were sacrificed. In order to distinguish physiological and drug-induced healing, quantitative and qualitative uPAR and EGFR expression were evaluated by using Western blot and Immunohistochemistry techniques. Western blot analysis demonstrated an increased expression of both receptors after 4 days from wounding in wild and ovariectomized animals. In particular in ovariectomized animals the expression of uPAR and EGFR increased after 4 days while it reduced following the administration of Sucralfate. In wild rats the same was observed for uPAR expression, while EGFR was different; in fact, its expression increased significantly at day 4 in the animals treated with the drug and only at day 7 in those untreated. Immunohistochemistry highlighted a noteworthy epithelial colocalization of EGFR and uPAR after 4 days in the animals treated with Sucralfate. We conclude that Sucralfate can promote the healing of ulcerative cervicitis and moreover, it reduces the normal healing time because of its modulatory property on uPAR and EGFR expression.

Purification of immunomodulatory factors in human peripheral blood leukocytes.

Procedure is described for purifying low-molecular-weight factors with antigen-aspecific properties from a dialysate of human leukocyte extract. It includes gel chromatography on Sephadex G-25 and G-15, ion-exchange chromatography, reversed-phase high-performance liquid chromatography (HPLC) on a C18 hydrophobic column and gel permeation HPLC. The immunosuppressive factor (mol.wt. 800-1000) was purified to near homogeneity. It is probably of peptidic nature, although it is pronase resistant. The enhancer factor (mol.wt. 300-600) is eluted from chromatographic columns together with a hypoxanthine-like substance. Nevertheless, the biological activity cannot be attributed to the purine derivative. Identification of this amplifier activity is still lacking.

Bovine seminal plasma contains a low-molecular-weight factor that inhibits RNA synthesis.

A low-MW factor (800-1000 daltons) extracted from bovine seminal plasma (bSP) and partially purified by a five-step fractionation is very active in inhibiting RNA synthesis by E. coli RNA polymerase with calf thymus DNA as template (70% inhibition at factor:DNA ratio of about 1:100). The same factor also inhibits RNA synthesis in isolated liver nuclei but to a lesser extent. The bSP factor probably exerts its inhibitory activity on initiation rather than on the elongation processes. DNA heat denaturation experiments indicate that the factor stabilizes double-stranded DNA. The activity of bSP factor is almost destroyed by protease (pronase) digestion. Trypsin digestion is ineffective. Consequently, peptide integrity seems to be important for the biological activity. The factor is heat stable and does not contain nucleic acid components. Preliminary analysis indicates the presence of acidic amino acids with no basic or aromatic ones and that the active factor is not a product of histone or protamine degradation. When injected i.p. into 25-day-old female rats, the bSP factor has an inhibinlike activity.