Relatedness and social organization of coypus in the Argentinean pampas.

Behavioural and trapping studies of the social organization of coypus have suggested the occurrence of kin groups and a polygynous mating system. We used 16 microsatellite markers to analyse parentage and relatedness relationships in two populations (Jáuregui and Villa Ruiz) in the Argentinean Pampas. At Jáuregui, a dominant male monopolized most paternities, leading to a high variance in reproductive success between males and a high level of polygyny. At Villa Ruiz, variance in reproductive success was low among resident males and males were the fathers of zero to four offspring each. For females, no significant differences were found. Two different social groups in each study site were used to assess genetic relatedness within and between groups. These groups were neighbouring at Jáuregui but not at Villa Ruiz. At Villa Ruiz, coypus were significantly more related within than between groups, suggesting that behavioural groups were also genetic ones, and adult females were more related within than between groups, as should be expected for kin groups. This relationship was not found at Jáuregui. Our results provide support to previous studies based on behavioural and trapping data, which indicate that coypus form social groups and have a polygynous mating system. However, we found differences in social organization between the two populations. This is the first study to determine parentage and/or relatedness in coypus.

The macrophage in MS: just a scavenger after all? Pathology and pathogenesis of the acute MS lesion.

Advances in the neuropathology of multiple sclerosis (MS) have contributed greatly to our understanding of the mechanisms of tissue injury in the condition. Particular interest has focussed on the active MS lesion, defined by macrophage activity in the presence of partially demyelinated axons. This has led to the prevailing consensus that a T-cell dependent, macrophage-mediated, autoimmune attack on constituents in the normal myelin sheath underlies the disease. This hypothesis, which has been largely supported by comparisons with the animal model, experimental allergic encephalomyelitis, has recently been questioned by an analysis of the pathological events preceding myelin phagocytosis in nascent MS lesions. The prephagocytic changes in evolving lesions examined shortly after the onset of an MS relapse raise the possibility that oligodendrocyte cell death and associated changes within the myelin sheath initiate local macrophage scavenger activity, with subsequent amplification of the inflammatory response. The presence of such lesions in patients with a spectrum of pathological changes in nearby or distant active phagocytic plaques suggests that pathological heterogeneity in MS is largely due to evolution of lesional pathology, rather than pathogenic heterogeneity.

Adducts of N-terminal valines in hemoglobin with isoprene diepoxide, a metabolite of isoprene.

Isoprene (2-methylbuta-1,3-diene) is a multi-site carcinogen in rodents. To evaluate the role of the diepoxide metabolite (1,2:3,4-diepoxy-2-methylbutane) in carcinogenesis, measurements of in vivo doses of the diepoxide are needed. The in vivo dose may be inferred from levels of reaction products with hemoglobin (Hb adducts). This report presents in vitro studies of the adduct formation by the diepoxide of isoprene with valinamide and oligopeptides as model compounds of N-terminal valines in hemoglobin (Hb). In the reaction with valinamide it was shown that isoprene diepoxide forms as the main product a ring-closed adduct, which is a pyrrolidine derivative [N,N-(2,3-dihydroxy-2-methyl-1,4-butadiyl)valinamide, MPyr-Val]. The analysis was performed by gas chromatography/mass spectrometry (GC/MS) (EI and PICI) after acetylation. The ring-closed adduct was also identified by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) as the main product in the reaction between isoprene diepoxide and standard hepta- or (2H8)octapeptides, corresponding to the N-terminal peptides of the alpha-chains in mouse and rat Hb. These peptides, alkylated with isoprene diepoxide, to be used as internal standards and calibration standards for quantification of MPyr-adduct levels in vitro and in vivo, were analyzed with respect to the degree of MPyr-alkylation by two independent methods, amino acid analysis and HPLC-UV; similar results were obtained using these methods. A method for measurement of Hb adducts as modified peptides, used earlier to measure a similar adduct to N-terminal valines in Hb from the diepoxide of 1,3-butadiene, has in the present work been tested for application to isoprene diepoxide. The method is based on tryptic degradation of globin and LC/ESI-MS analysis of N-terminal Pyr-heptapeptides of the Hb alpha-chain enriched by HPLC. MPyr-adduct levels in isoprene diepoxide alkylated hemolysate from mouse erythrocytes incubated with different concentrations of isoprene diepoxide (2 and 10 mM) for 1 h were quantified. The adduct level was about 50 nmol/g alpha-chain Hb per mM x h. From the adduct levels the rate constant of isoprene diepoxide for reaction with N-terminal valine was calculated to be about 1.6 times faster than for diepoxybutane.

Risk of dysplasia in the columnar cuff after stapled restorative proctocolectomy.

BACKGROUND: Stapled restorative proctocolectomy (SRP) for ulcerative colitis retains a 'cuff' of columnar epithelium, which carries a risk of undergoing malignant change. The risk of neoplastic transformation was studied in a series of patients who underwent SRP for ulcerative colitis. METHODS: One hundred and thirty-five patients who underwent SRP for ulcerative colitis between 1988 and 1998 were followed up by cuff surveillance biopsy. The median follow-up was 56 (range 12-145) months and the median time since diagnosis of ulcerative colitis was 8.8 (range 2-32) years. RESULTS: The cuff biopsies showed no dysplasia or carcinoma. The accuracy of obtaining cuff mucosa in the biopsy was 65 per cent. Chronic inflammation was present in 94 per cent of cuff biopsies. CONCLUSION: This study shows no evidence of either dysplasia or carcinoma in the columnar cuff mucosa, up to 12 years after pouch formation. This suggests that cuff surveillance in the first decade after SRP, in the absence of dysplasia or carcinoma in the original colectomy specimen, may be unnecessary. Regular cuff surveillance biopsies after SRP should continue for patients with high-grade dysplasia or carcinoma in the original resection specimen.