The Cancer Prevention Reminder System

The Cancer Prevention Reminder System is a computer-based system designed to increase the delivery of periodic health maintenance procedures. The program provides printed reminders that identify patients' overdue procedures, prints summary reports of the percentage of patients who are eligible and overdue for a procedure, and prints mailing labels for patients. We performed a randomized, controlled trial in which the effects of computer-based reminders were compared with those of two other interventions among residents in a university-based group practice.     

Obstructive sleep apnoea following rapid weight gain secondary to treatment with vigabatrin (Sabril)

To examine a possible involvement of p21 protein, an inhibitor of cyclin-dependent kinases (CDKs), in the transition from hyperplastic to hypertrophic growth of rat ventricular myocytes during the first postnatal week, we analysed day-by-day changes in the number of p21 positive cells using specific antibodies against this protein. Paraffin-embedded sections of the left ventricular myocardium were examined by means of immunoperoxidase technique and hematoxylin-eosin counterstaining. While during the first three postnatal days, the positive reaction for p21 was detected only in a small fraction of myocytes (12-20%), a sudden increase in positivity occurred on day 4 (54%) and continued till day 6 when the fraction of cells expressing p21 reached 87%. Our results show that the induction of CDK inhibitor p21 in rat ventricular myocytes is developmentally regulated. Moreover, the fact that the sudden increase in p21 positivity occurred at the same stage when the myocyte proliferation rapidly ceases, suggests that this protein is likely to be involved in mediating this key event of cardiac development.     

Evidence for association of HLA-A2 allele with onset age of Alzheimer's disease

Our earlier studies had suggested a possible association between the HLA-A2 allele and Alzheimer's disease (AD). In the present study we tested the hypothesis that A2 is associated with earlier AD onset. We performed two independent studies: a collaborative study with 111 patients and a confirmatory study with 96 patients. We found similar patterns of reduced age at onset as a function of A2 in both data sets. Overall, A2 was associated with a significant 3-year shift to earlier onset. The effects of A2 and epsilon 4 on age at onset appeared additive. Our results suggest A2, or a closely linked gene, modulates onset age of AD. Association with A2 would suggest an immune/inflammatory response mechanism for AD.     

Isolation of an ovine genomic sequence containing the full-length angiotensin II type-1 receptor

We have isolated from a genomic library using PCR amplification an 1171 base sequence containing a putative ovine AT1-R protein coding sequence of 1080 bases. As expected the protein coding sequence is of greater than 99% homology to the partial protein coding sequence reported by Robillard et al, with only one base difference. Relative to other species, highest homology at the level of the cDNA protein coding sequence is to bovine (97.6%) and lowest homology to rat Type 1a (83.3%). The predicted protein amino acid sequence in turn encodes a protein with the properties of a seven alpha-helix transmembrane receptor (by TMPred) sharing closest homology (98.6%) to the bovine receptor and lowest to the rat Type 1a (90.2%). As expected from such a high degree of interspecies homology, amino acids identified by site-directed mutagenesis of the human or rat AT1A-R as involved in binding and action of AII are very highly conserved in the ovine sequence. In addition, both bovine and ovine AT1-R are known to exhibit lower affinity for DuP753 than human AT1-R, and in bovine AT1-R this has been suggested to coincide with the amino acid substitutions Ala->Thr (163) and Leu->Met (262) relative to the human sequence. Our ovine AT1-R cDNA sequence shares these same bovine substitutions.     

Structural aspects of heparin responsible for interactions with von Willebrand factor

Unfractionated heparin (UFH) binds von Willebrand factor (vWF) and inhibits the vWF-platelet GP Ib interaction. For vWF, a heparin-binding domain has been identified, but for heparin, the structures that confer such activity are unknown. To investigate this, UFH was depolymerized by methods that yield structurally distinct fragments. The glycosaminoglycans (GAGs) produced were separated into five groups of homogeneous molecular weight (MW). Anti-Xa activity, vWF binding affinity, and vWF-dependent platelet agglutination were measured. Periodate oxidation but not heparinase digestion destroyed anti-Xa activity. At all MWs, periodate conferred greater vWF binding affinity and greater ability to inhibit platelet agglutination than heparinase. As an example, at MW 6100, the binding IC50 was 100+/-19 micromol/L for a periodate-derived GAG and 527+/-70 micromol/L for a heparinase-derived GAG. At the same MW, the agglutination IC50 was 17+/-5 micromol/L for periodate and 135+/-18 micromol/L for heparinase. This suggests that the disaccharide GlcNS[6S]-IdoA2S, destroyed by heparinase but not periodate, is crucial to heparin-vWF interactions. An MW dependency was also noted, with a minimum dodecasaccharide required for activity inhibition. To further investigate the heparin/vWF interaction, affinity fractionation of heparins was performed with an immobilized peptide derived from a heparin-binding domain of vWF. Disaccharide analysis of high-affinity heparins revealed an increased ratio of IdoA2S-GlcN[S/Ac]6S to IdoA2S-GlcN[S/Ac]. Affinity fractionation of oligosaccharides (MW 3500) diminished the relative content of all disaccharides except IdoA2S-GlcNS6S, which was increased. These data suggest that the disaccharide structures IdoA2S-GlcNS6S and GlcNS6S-IdoA2S are crucial to heparin/vWF interactions. Understanding the structural aspects that confer such activity may be useful in designing heparin-based antithrombotic drugs.     

Authorship patterns in marine mammal science, 1985–1993

Authorship studies in such disciplines as physics and economics show that with the passage of time there has been an increase in the number of authors per paper, indicating a trend toward more collaboration. In this study, a search was run on the Aquatic Sciences and Fisheries Abstracts database to identify marine mammal science papers published from 1985 to 1993. A total of 1308 papers published in scientific journals was examined. There were weak but statistically significant trends in the increase in the number of authors per paper as well as in the number of multi-authored papers written by authors from different institutions, with the passage of time. Possible reasons for these results include the increasing specialization of researchers necessitating collaboration, more access to electronic means of communication, and more competition for research funds. Confounding factors in this analysis include the possibility that different journals have different publication patterns and regional vs. national/international journal differences.