Structure of pre-pro-von Willebrand factor and its expression in heterologous cells

Von Willebrand factor (vWF), a multifunctional haemostatic glycoprotein derived from endothelial cells and megakaryocytes, mediates platelet adhesion to injured subendothelium and binds coagulation factor VIII in the circulation. Native vWF is a disulphide-bonded homopolymer; the monomeric subunits, of apparent relative molecular mass (Mr) 220,000 (220K) are derived from an intracellular precursor estimated at 260-275K. Multimer assembly is preceded by the formation of dimers, linked near their C-termini, which then assemble into filamentous polymers. The importance of the removal of the large vWF pro-polypeptide during multimer assembly, and whether this or other stages of the complex post-translational processing require components specific to endothelial cells or megakaryocytes, is unknown. Here we report an analysis of the complete sequence of pre-pro-vWF and expression of the molecule in heterologous cells. The vWF precursor is composed of several repeated subdomains. When expressed in COS and CHO cells, it is cleaved and assembled into biologically active high relative molecular mass disulphide bonded multimers. This suggests that the information for assembly of this complex molecule resides largely within its primary structure.     

Orientation-specific cortical responses develop in early infancy

Neurones in the visual cortex of higher mammals differ from those elsewhere in the visual pathway in that the majority respond selectively to particular edge or bar orientations in the stimulus. We have developed a visually evoked potential (VEP) technique which isolates the response of orientation-selective mechanisms from that of cortical or sub-cortical neurones which lack orientation selectivity. We are unable to find such orientation-selective responses in newborn human infants within the sensitivity of our method, but repeated longitudinal testing of individual infants shows that measurable responses emerge around 6 weeks of age. This result is consistent with the idea that human cortical visual function is very immature at birth, but develops rapidly in the first two postnatal months.     

Ratio between large and small carboxy-terminal molecular forms of cholecystokinin in brains of different species

The ratio between large and small carboxy-terminal forms of cholecystokinin in brain extracts from man, pig, dog, rat, chicken, frog and trout was determined by two sequence-specific radioimmunoassays. It was found that the relative amounts of large forms of cholecystokinin; are higher in mammalian brain than in brains of lower species.     

Immunoquantitation of some cytochrome P-450 isozymes in liver microsomes from streptozotocin-diabetic rats

Streptozotocin-diabetes in rats leads to a decrease of cytochrome P-450 UT-A (the major form in control rats) and an increase of cytochrome P-450 PB-B (the major one induced by phenobarbital treatment) in liver microsomes. The increased benzphetamine-N-demethylase activity can be related to the induction of cytochrome P-450 PB-B.     

HLA-D region beta-chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulin-dependent diabetic individuals

The human HLA-D histocompatibility region encodes class II antigens each of which consists of two polypeptide chains (alpha and beta) inserted in the plasma membrane. These molecules are implicated in the regulation of the immune response but several human diseases are also found to be associated with certain HLA-DR antigens. The occurrence of insulin-dependent (type I) diabetes (IDDM) is strongly associated with HLA-DR3 and/or 4 (ref. 5). The class II antigens, however, show a marked genetic polymorphism associated with the beta-chains which seem, from hybridization studies, to be encoded by several genes. We have therefore used the beta-chain cDNA probe, pDR-beta-1 (refs 8, 10) to test whether there are differences in hybridization pattern between DNA from healthy individuals and diabetic patients, after digestion with restriction endonucleases. Among the HLA-DR 4 and 3/4 individuals, the IDDM patients showed an increased frequency of a PstI 18 kilobase (kb) fragment. A BamHI 3.7 kb fragment, frequent among controls (30-40%), was rarely detected in the IDDM patients (0-2%). These differences may be related to susceptibility to develop the disease.     

ABO genes are differentially distributed in socio-economic groups in England

No direct evidence is available concerning what average genetic differences, if any, characterize the segments of socially stratified human populations, although theoretical considerations suggest that genetic differentiation within such populations is to be expected. We have now analysed two large samples of data from blood donors in England to test whether the distributions of the ABO and Rhesus blood group phenotypes are random with respect to socio-economic groups as determined by occupational classification. We have found that in both native and migrant sections of the populations of two widely separated regions (south-west England and part of Yorkshire) and in both sexes, the A phenotype is highly significantly more, and the O phenotype significantly less, frequent than expected in social classes I and II, while the converse is seen in social classes III-V. An individual of the A phenotype has thus about 15% greater probability than chance would dictate of being placed in classes I and II. The distribution of the Rh+ and Rh- phenotypes does not differ significantly between classes. It seems unlikely that this nonrandom distribution of the ABO phenotypes among socio-economic groups results from sampling, historical or migrational effects and we conclude that the observed association is likely to result from pleiotropic effects of the ABO alleles (or genes closely linked to them) on attributes influencing occupational type, social mobility and social class.