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Biomedical subjects

R Williamson

Publications and source records attributed to R Williamson.

At least 145 records · Page 8Linked to original sources
PubMed1995

Retention of teeth with reduced root length through use of a resin-bonded splint: a case report.

Orthodontic relapse and tooth migration are commonly observed in patients with severe postorthodontic root resorption. If conventional removable retention is not adequate, fixed splint retention is necessary. Proponents of flexible splints suggest that the difference in mobility between natural teeth and the rigid systems is responsible for the loss of cement seal in the rigid systems. Proponents of rigid splints suggest that the flexibility that allows physiologic movement of the teeth also contributes to fatigue and subsequent failure of the material in the flexible splint systems. A clinical technique for increasing retention, consequently improving the prognosis of a resin-bonded fixed splint, is described.

Adolescent↗
PubMed1995

In vitro liposome-mediated DNA transfection of epithelial cell lines using the cationic liposome DC-Chol/DOPE.

Clinical trials using cationic liposome-mediated DNA transfer have now been initiated for several disorders including cystic fibrosis. Previous studies have shown that the level of gene expression achieved may be dependent on the formulation of the DNA-liposome complex and the cell type transfected. We have investigated, in vitro, the effect of parameters such as DNA:liposome ratio, dose and concentration on the level of transgene expression in epithelial cell lines using the cationic liposome DC-Chol/1,2-dioleoyl phosphatidylethanolamine (DOPE). A narrow range of conditions was found to produce maximal level of transgene expression within a particular cell line, as detected using the reporter molecule beta-galactosidase (beta-gal). beta-Gal expression was significantly enhanced by formulation of the DNA-DC-Chol/DOPE complexes in physiological solution at pH 9.0. Under standard in vitro transfection conditions, increased incubation time of the DNA-liposome complexes with cells resulted in increased transgene expression. In contrast, at relatively high DNA and liposome dose and concentrations, beta-gal activity was maximal after only 1 h of incubation, with a subsequent decrease in expression with time. The maximum level of expression that could be produced using fully optimised transfection conditions, however, was still highly dependent on each cell type analysed. Correlation of these findings with similar studies in vivo are now critical to determine the optimal formulation of DNA-liposome complexes for clinical application.

Animals↗
PubMed1995

Gene delivery and expression mediated by an integrin-binding peptide.

The ability to transfer sufficient DNA to specific target cells remains one of the main limitations to the development of gene therapy. For this reason much attention is being paid to the development of new gene delivery systems, both viral and non-viral. We describe gene transfer with a polycation-DNA complex which contains an integrin-binding domain. Integrin-mediated gene delivery has several potential advantages. Such complexes are less likely than other receptor-mediated gene delivery complexes to be constrained by the size of the complex. The ligands are small peptides, resembling naturally occurring integrin ligands, which minimises the possibility of complexes inducing an immune response in vivo.

Amino Acid Sequence↗
PubMed1994

Second locus for Hirschsprung disease/Waardenburg syndrome in a large Mennonite kindred.

We have studied a large Mennonite kindred in which 20 members were affected with Hirschsprung disease (HSCR), 5 of whom had one or more manifestations of Waardenburg syndrome (WS) type II (WS2). Eleven additional relatives had signs of WS2 without HSCR. Since HSCR and WS2 each represent perturbations of neural crest migration/differentiation, this large pedigree with apparent cosegregation of HSCR and WS2 offered an opportunity to search for linkage between these loci, candidate genes, and random DNA markers, particularly in view of recent discoveries of genes for Waardenburg syndrome type I (WS1) and Hirschsprung disease (c-ret). We have examined the following possible linked markers in 69 relatives in this family: the c-ret gene (HSCR); the human PAX3 gene (HuP2) on chromosome 2q (WS1) and placental alkaline phosphatase (ALPP) on chromosome 2q (linked to WS1); argininosuccinate synthetase (ASS) on chromosome 9q, close to ABO blood groups which have shown weak linkage to WS; and the beta 1 GABA receptor gene (GABARB1) on chromosome 4q13-11, close to c-kit, deletions of which cause piebaldism. Linkage between any of these loci and HSCR/WS in this kindred was excluded, demonstrating that there is at least one further locus for HSCR other than c-ret.

Christianity↗
PubMed1994

Peptides related to the Diploptera punctata allatostatins in nonarthropod invertebrates: an immunocytochemical survey.

The allatostatins are a family of peptides isolated originally from the cockroach, Diploptera punctata. Related peptides have been identified in Periplaneta americana and the blowfly, Calliphora vomitoria. These peptides have been shown to be potent inhibitors of juvenile hormone synthesis in these species. A peptide inhibitor of juvenile hormone biosynthesis has also been isolated from the moth, Manduca sexta; however, this peptide has no structural homology with the D. punctata-type allatostatins. Investigations of the phylogeny of the D. punctata allatostatin peptide family have been started by examining a number of nonarthropod invertebrates for the presence of allatostatin-like molecules using immunocytochemistry with antisera directed against the conserved C-terminal region of this family. Allatostatin-like immunoreactivity (ALIR) was demonstrated in the nervous systems of Hydra oligactis (Hydrozoa), Moniezia expansa (Cestoda), Schistosoma mansoni (Trematoda), Artioposthia triangulata (Turbellaria), Ascaris suum (Nematoda), Lumbricus terrestris (Oligochaeta), Limax pseudoflavus (Gastropoda), and Eledone cirrhosa (Cephalopoda). ALIR could not be demonstrated in Ciona intestinalis (Ascidiacea). These results suggest that molecules related to the allatostatins may play an important role in nervous system function in many invertebrates as well as in insects and that they also have an ancient evolutionary lineage.

Amino Acid Sequence↗
PubMed1994

Cell binding and internalization by filamentous phage displaying a cyclic Arg-Gly-Asp-containing peptide.

Ligands that bind mammalian cell surface integrins with high affinity can mediate cellular internalization. We show that particles of the bacteriophage fd that display the cyclic integrin-binding peptide sequence GGCRGDMFGC in a proportion of their major coat protein subunits bind to cells and are efficiently internalized. In the displayed peptide the conformation of the RGD motif is restricted within a hairpin loop formed by a disulfide bridge between the 2 cysteine residues. Cellular internalization of phage was demonstrated by confocal and non-confocal immunofluorescence microscopy of tissue-cultured cells incubated with phage particles. The phage were contained in juxtanuclear vesicles in the same serial sections as transferrin receptor but were not colocalized with the cell surface marker alkaline phosphatase. Cell binding and internalization was inhibited by preincubation of cells with the integrin-binding peptide GRGDSP, whereas the control peptide GRGESP had no inhibitory effect. These results indicate that cyclic integrin-binding peptides can be used to target and enter cells and that it should be possible to exploit such peptides for the introduction of DNA, drugs, or other macromolecules.

Amino Acid Sequence↗
PubMed1994

Prenatal diagnosis of Klippel-Trénaunay-Weber syndrome by ultrasound.

Ultrasound examination due to an elevated maternal serum alpha-fetoprotein level showed lower extremity asymmetry. The findings were felt to be consistent with Klippel-Trénaunay-Weber syndrome. The pregnancy was terminated based on these findings. The ultrasound findings, confirming post-mortem examination, and counselling issues are discussed.

Abortion, Induced↗
PubMed1994

Unusual genotypes in the COL6A1 gene in parents of children with trisomy 21 and major congenital heart defects.

Collagen type VI is a candidate for a role in the pathogenesis of congenital heart defects (CHD) in Down's syndrome. Three restriction fragment length polymorphisms of the COL6A1 gene were used to determine COL6A1 genotypes in 50 families of affected children with trisomy 21 (29 with congenital heart defects and 21 without) and 37 unrelated volunteers. We found seven unusual genotypes in the parents of affected children with Down's syndrome, five being unique to the parents of children with trisomy 21 and CHD. There were no unusual genotypes associated with other chromosome 21 loci. No single COL6A1 genotype was associated with CHD. Thus, the unusual genotypes unique to parents of affected children suggest that genetic variation in the COL6A1 gene region contributes to the pathogenesis of CHD in Down's syndrome.

Child↗
PubMed1994

Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17.

Fourteen Caucasian families with 81 affected individuals have been assessed in which polycystic ovaries/male pattern baldness (PCO/MPB) segregates as an autosomal dominant phenotype (1). The gene CYP17, coding for P450c17 alpha (17 alpha-hydroxylase; 17/20 lyase) on chromosome 10q24.3 is the rate-limiting step in androgen biosynthesis. We have identified a new single base change in the 5' promoter region of CYP17 by heteroduplex analysis. This creates an additional SP1-type (CCACC box) promoter site, which may cause increased expression. This base change also creates a recognition site for the restriction enzyme MspA1 allowing a simple screening procedure. There is a significant association between the presence of this base change (A2) and the affected state for consecutively identified Caucasian women with PCO as compared either to consecutively matched controls (P = 0.03) with an odds ratio for those with at least one A2 allele of 3.57, or to a random population (P = 0.02) with an odds ratio of 2.50. Within the fourteen families, members with PCO or MPB have a significant association with the occurrence of at least one A2 allele compared to their normal relatives, with an odds ratio of 2.20 (P = 0.05). The base change does not cosegregate with the affected phenotype within the families showing association, demonstrating that this mutation of CYP17 does not cause PCO/MPB. Variation in the A2 allele of the CYP17 gene is a significant factor modifying the expression of PCO/MPB in families where it has been demonstrated to segregate as a single gene disorder, but it is excluded as the primary genetic defect.

Alleles↗
PubMed1994

Genetic analysis of glucokinase and the chromosome 20 diabetes susceptibility locus in families with type 2 diabetes.

Mutations of the glucokinase gene (chromosome 7p) have been shown to cause some cases of familial maturity onset diabetes of youth (MODY) but few, if any, cases of late onset familial Type 2 diabetes. A further single large pedigree with MODY has shown linkage to a marker for the adenosine deaminase gene (ADA, chromosome 20q), although the diabetes susceptibility gene at this locus has not been identified. We have studied members of 19 families with familial Type 2 diabetes (including 10 European families, 6 families from the Indian subcontinent, and 3 families of Afro-Caribbean origin), 2 of which were of MODY type (and both European), with a glucokinase marker and a marker linked to ADA, to examine whether glucokinase, or the unknown defect on chromosome 20, are implicated in diabetes in our pedigrees. Several models were constructed for standard two-point linkage analysis. Glucokinase is not the cause of diabetes in all of these families but was excluded in only one MODY family. It was possible to exclude both loci in the second MODY pedigree. No evidence was found of linkage to either marker in this multi-ethnic population under the models used. At least one further locus is involved in determining susceptibility to MODY.

Adult↗
PubMed1994

Physical and genetic map of 5q31: use of fluorescence in situ hybridization data to identify errors in the CEPH database. Centre d'Etude de Polymorphisme Humain.

Chromosome 5, band q31, contains the genes responsible for a number of interesting genetic and malignant diseases, as well as many cloned genes. To prepare a high-resolution map of this region, eight anonymous DNA markers were mapped by combining genetic data derived from linkage analysis, with physical data obtained using two-color fluorescent in situ hybridization (FISH). Probe order was determined by FISH on metaphase cells, supplemented with interphase analysis, while genetic distance and likely order were determined by multipoint linkage analysis using genotype data from Centre d'Etude de Polymorphisme Humain (CEPH) pedigrees. Discrepancies between the genetic and physical maps suggested that there was a high rate of genotyping errors in the CEPH data for these markers, and prompted a statistical analysis to identify these errors. By assuming a known physical order (as determined by FISH) it was possible to identify markers which had the greatest degree of error. The average typing error was estimated at 1.8%, but several markers had much higher error rates; a 14% error rate was predicted for one locus, which was subsequently confirmed by retyping. The analysis led to the preparation of a revised map spanning 24.5 cM of 5q31. This study illustrates the power of FISH to determine physical order over a wide genomic distance, and demonstrates how order can be used as an adjunct to linkage analysis, particularly in the identification of genotyping errors.

Chromosome Mapping↗