A bacterial artificial chromosome-based framework contig map of human chromosome 22q

We have constructed a physical map of human chromosome 22q using bacterial artificial chromosome (BAC) clones. The map consists of 613 chromosome 22-specific BAC clones that have been localized and assembled into contigs using 452 landmarks, 346 of which were previously ordered and mapped to specific regions of the q arm of the chromosome by means of chromosome 22-specific yeast artificial chromosome clones. The BAC-based map provides immediate access to clones that are stable and convenient for direct genome analysis. The approach to rapidly developing marker-specific BAC contigs is relatively straightforward and can be extended to generate scaffold BAC contig maps of the rest of the chromosomes. These contigs will provide substrates for sequencing the entire human genome. We discuss how to efficiently close contig gaps using the end sequences of BAC clone inserts.     

Satellite-delivered continuing medical education in Europe

There is increasing recognition of the need for continuing medical education in the medical profession. There are now many ways of delivering medical education including conferences, books, journals amongst others. This paper describes a novel method of delivering medical education using satellite transmission. This medium allows live medical education programmes to be broadcast to over 150 receiver sites in Europe. It also enables two-way live satellite links to be made between countries during the broadcast. EuroTransMed has an editorial board, in much the same way as a journal, which is representative of the differing medical societies in Europe. As the barriers between the various countries fall, EuroTransMed is an ideal medium to promote high quality, easily accessible, continuing medical education at a pan-European level.     

Hyaluronan and chondroitin sulfate proteoglycans are colocalized to the ciliary zonule of the rat eye: a histochemical and immunocytochemical study

In previous studies, chondroitin sulfate proteoglycans have been localized to the periphery of the zonular fibers and the individual zonular fibrils (or microfibrils) after Cuprolinic blue staining in conjunction with chondroitinase digestions and immunogold labelling with 2-B-6 antibody. In the present study, we wished to determine if these proteoglycans are linked to hyaluronan to form a large multimolecular aggregate. To accomplish this, we localized the hyaluronan using a biotinylated hyaluronan-binding protein fragment of chondroitin sulfate proteoglycan, containing also the link protein, purified from bovine nasal cartilage. The results showed that the ciliary zonule of the rat eye was reactive with the biotinylated hyaluronan-binding probe as demonstrated by streptavidin-peroxidase-diaminobenzidine staining and streptavidin-gold labelling. Hyaluronan-gold labelling showed that the gold particles were mostly localized on the periphery of the zonular fibers, which was similar to the localization pattern of the zonule associated-proteoglycans. This hyaluronan-binding probe also strongly labelled the sites of zonule insertion over the basement membrane of the inner ciliary epithelium at the pars plana and the lens capsule at the equatorial region, which suggests its probable role in the attachment of ciliary zonule to the basement membranes. To demonstrate whether these two molecules are linked to one another, ultrastructural colocalization of both hyaluronan and chondroitin sulfate proteoglycans was performed on the same sections by double-gold labelling, and combined Cuprolinic blue staining and hyaluronan-gold labelling. Gold particles of 15 and 10 nm in sizes labelling both hyaluronan and chondroitin 4-sulfate, were colocalized to the surface of the zonular fibers. The combined Cuprolinic blue staining and hyaluronan-gold labelling showed that the gold particles were localized towards the ends of the Cuprolinic blue-stained rodlets, which strongly suggests that these chondroitin sulfate proteoglycans are linked to the hyaluronan chain to form a large aggregate surrounding the periphery of the zonular fibers. These ciliary zonule-associated proteoglycan-hyaluronan aggregates may play a role in organizing the individual zonular fibrils (microfibrils) into bundles of zonular fibers.     

Factors affecting the ultrasonic properties of equine digital flexor tendons

Dietary treatment with three diets differing in vitamin E, Low E (15 mg of vitamin E/kg diet), Medium E (150 mg/kg), or High E (1,500 mg/kg), resulted in guinea pigs with low (but nondeficient), intermediate, or high heart alpha-tocopherol concentration. Neither the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and reductase, nor the nonenzymatic antioxidants, GSH, ascorbate, and uric acid were homeostatically depressed by increases in heart alpha-tocopherol. Protection from both enzymatic (NADPH dependent) and nonenzymatic (ascorbate-Fe2+) lipid peroxidation was strongly increased by vitamin E supplementation from Low to Medium E whereas no additional gain was obtained from the Medium E to the High E group. The GSH/GSSG and GSH/total glutathione ratios increased as a function of the vitamin E dietary concentration closely resembling the shape of the dependence of heart alpha-tocopherol on dietary vitamin E. The results show the capacity of dietary vitamin E to increase the global antioxidant capacity of the heart and to improve the heart redox status in both the lipid and water-soluble compartments. This capacity occurred at levels six times higher than the minimum daily requirement of vitamin E, even in the presence of optimum dietary vitamin C concentrations and basal unstressed conditions. The need for vitamin E dietary supplementation seems specially important in this tissue due to the low constitutive levels of endogenous enzymatic and nonenzymatic antioxidants present of the mammalian heart in comparison with those of other internal organs.     

Gastrointestinal complications following cardiac surgery

This study sought to determine which factors influence the mortality rate in patients developing gastrointestinal complications following cardiac surgery. Between July 1988 and January 1992, 2054 patients underwent cardiac surgical procedures at the Boston University Medical Center. Of these, 29 (1.4%) developed postoperative gastrointestinal complications. The overall mortality rate among these patients was 27% (8/29). Those who died following such complications had a higher incidence of New York Heart Association (NYHA) class IV and unstable symptoms (8/8, 100% versus 3/21, 14%; P < 0.0001), and an increased need for preoperative intra-aortic balloon pump support (4/8, 50% versus 1/21, 5%; P < 0.004). The need for gastrointestinal surgical intervention increased the mortality rate significantly compared with patients managed medically (8/18, 44% versus 0/11, 0%; P < 0.01). Patients with ischemic bowel also had a significantly higher mortality (5/5, 100% versus 3/24, 12%; P < 0.001). It is concluded that most patients with gastrointestinal complications following cardiac surgery can be treated, and with acceptable mortality rates. The presence of unstable symptoms, preoperative intra-aortic balloon pump support, ischemic bowel and the need for gastrointestinal surgical intervention adversely affect mortality.     

In vitro study of enzymatic degradation of biological tissues fixed by glutaraldehyde or epoxy compound

RATIONALE AND OBJECTIVES: The authors performed this study to clarify and systematize the large number of variances and correlations observable with variance-component models of receiver operating characteristic (ROC) index estimates. MATERIALS AND METHODS: The authors present a variance-component model for ROC index estimates (and for differences between estimates) and show correspondences between the method of experimental replication and the random components in the model. The authors introduce a notation that identifies both the method of replication and, when examining estimate differences, the estimate pairing scheme. RESULTS: For models with three factors (modality, reader, case sample), the authors delineated four methods of replication and eight pairing schemes for generating estimate differences. For each of the resulting 32 replication-pairing combinations, the authors gave expressions for the variance of the difference and for the correlation between the two ROC index estimates. CONCLUSION: The variance-component approach is a useful statistical tool for modeling different sources of variation that contribute to the overall variance of ROC data and index estimates derived from those data.     

Cyclin D1 expression in invasive breast cancer. Correlations and prognostic value

Cyclin D1 overexpression, detected by standard immunohistochemistry, was correlated with other prognostic variables and its prognostic value was evaluated in a group of 148 invasive breast cancers with long-term follow-up. Overexpression of cyclin D1 (59% of cases) was negatively correlated (chi 2 test) with histological grade (P = 0.0001), mean nuclear area (P = 0.004), mean nuclear volume (P = 0.02), and mitotic activity (P = 0.03) and positively correlated with estrogen receptor (P = 0.0001). There was a strong correlation between cyclin D1 overexpression and histological type (P = 0.0001). Positive cyclin D1 staining was seen in 11 of 13 tubular carcinomas, 3 of 3 mucinous carcinomas, 4 of 4 invasive cribriform carcinomas, and 17 of 20 lobular carcinomas. Of 102 ductal cancers, 52 were positive, and all 6 medullary carcinomas were negative. There were no significant correlations with lymph node status, tumor size, or DNA ploidy. In survival analysis, cyclin D1 overexpression did not provide significant univariate or multivariate prognostic value. In conclusion, cyclin D1 is mainly overexpressed in the well differentiated and lobular types of invasive breast cancer and is strongly associated with estrogen receptor positivity. It is negatively correlated with the proliferation marker mitoses count and with the differentiation markers nuclear area and nuclear volume. However, cyclin D1 overexpression does not seem to have prognostic value in invasive breast cancer when no adjuvant treatment is given.