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Biomedical subjects

J E Bell

Publications and source records attributed to J E Bell.

151 records · Page 9Linked to original sources
PubMedDate not supplied

Examination of the potential structure of human salivary cystatins based on computer modelling.

The cystatin family of proteins exists in both excreted and intracellular forms, and appears to be involved in protective and regulatory roles, inhibiting a variety of bacterial, viral and intracellular proteases. The amino acid sequences of several human forms of cystatin are known, but currently only the structure of chicken cystatin (approx. 40% homologous to the human forms) has been experimentally determined. The objective of this study was to use the X-ray coordinates of chicken cystatin to construct computer models of the structures of three human salivary forms (SN, S and SA). These structures were energy-minimized and subjected to dynamic simulations. The resultant structures were compared to determine conformational differences. Global root mean square deviations between equivalent atoms ranged from 1.4 A to 3.9 A. The closest structural similarity to chicken cystatin involved cystatin SN, which also showed the highest (68%) functional sequence homology. Local secondary structure was examined in more detail. In comparisons of alpha-carbon position the third beta-strand (77% functional sequence conservation) and its preceding loop (60% conserved) showed the highest structural conservation in S, while beta-strand 4 showed the highest structural conservation in SN and SA. Throughout their structures, SN and SA were more structurally similar to chicken cystatin than to salivary cystatin S. There are two regions of conserved, negatively charged residues in the salivary cystatins, which appear to be spaced so that they are capable of interaction with hydroxypatite. It is concluded that not only does structural modelling by analogy provide detailed models of salivary cystatins that can be tested by future experimentation, but also that examination of the models has revealed potential sites of interaction with hydroxyapatite.

Amino Acid Sequence↗
PubMedDate not supplied

The association of hydrocephalus and Arnold--Chiari malformation with spina bifida in the fetus.

Twenty-one fetuses with spina bifida and twenty apparently normal fetuses of between 14--23 weeks gestation were examined for the presence of hydrocephalus and Arnold--Chiari malformation. Sacral, lumbo-sacral, lumbar, thoraco-lumbo-sacral and thoraco-lumbar lesions were found. Some were closed, some were open. The amount of neural tissue at the site of the lesion was very variable. In three cases, diastematomyelia was found. The heads of spina bifida fetuses were not enlarged. Hydrocephalus was found in eleven of them and the Arnold--Chiari malformation in twelve. In nine fetuses the abnormalities co-existed. Hydrocephalic brain showed depression of the tentorium, abnormalities in the corpus callosum and absence of the lateral fissure. The more cephalad and extensive the spinal lesion, the more likely it was to be accompanied by brain abnormalities. Isolated sacral defects were not associated either with hydrocephalus or with the Arnold--Chiari malformation. Pathological changes in the brain occurred in the presence of both open and closed spinal lesions and were apparently unrelated to fetal age. No evidence was found as to the sequence in which these brain abnormalities appeared.

Arnold-Chiari Malformation↗