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Biomedical subjects

D Atherton

Publications and source records attributed to D Atherton.

9 recordsLinked to original sources
PubMed1992

Exclusion mapping of the X-linked dominant chondrodysplasia punctata/ichthyosis/cataract/short stature (Happle) syndrome: possible involvement of an unstable pre-mutation.

Homology with the mouse bare patches mutant suggests that the gene for the X-linked dominant chondrodysplasia punctata/ichthyosis/cataract/short stature syndrome (Happle syndrome) is located in the human Xq28 region. To test this hypothesis, we performed a linkage study in three families comprising a total of 12 informative meioses. Multiple recombinations appear to exclude the Xq28 region as the site of the gene. Surprisingly, multiple crossovers were also found with 26 other markers spread along the rest of the X chromosome. Two-point linkage analysis and analysis of recombination chromosomes seem to exclude the gene from the entire X chromosome. Three different mechanisms are discussed that could explain the apparent exclusion of an X-linked gene from the X chromosome by linkage analysis: (a) different mutations on the X chromosome disturbing X inactivation, (b) metabolic interference, i.e. allele incompatibility of an X-linked gene, and (c) an unstable pre-mutation that can become silent in males. We favour the last explanation, as it would account for the unexpected sex ratio (M:F) of 1.2:1 among surviving siblings, and for the striking clinical variability of the phenotype, including stepwise increases in disease expression in successive generations.

Body Height↗
PubMed1992

Internal protein sequence analysis: enzymatic digestion for less than 10 micrograms of protein bound to polyvinylidene difluoride or nitrocellulose membranes.

A procedure for the generation and isolation of internal peptide fragments for less than 10 micrograms of protein bound to either polyvinylidene difluoride (PVDF) or nitrocellulose membranes after electrophoretic transfer from sodium dodecyl sulfate-polyacrylamide gels (SDS-PAGE) is presented. This technique has produced internal sequence data for 120 peptides, with an average initial yield of 20 pmol. Membrane-bound proteins were enzymatically digested with either trypsin or endoproteinase Lys-C in the presence of 1% hydrogenated Triton X-100/10% acetonitrile/100 mM Tris-HCl, pH 8.0, for 24 h at 37 degrees C. The eluted peptides were then directly isolated by microbore HPLC for subsequent sequence analysis. One percent hydrogenated Triton X-100 did not inhibit enzymatic activity, distort HPLC resolution of peptides, or contain uv-absorbing contaminants that could interfere with peptide identification. Reproducible peptide maps and consistent recoveries are presented for standard proteins (3.5-8.0 micrograms) bound to either membrane, with higher recoveries for PVDF-bound proteins. Ninety percent of the proteins analyzed by this technique have produced results; representative peptide maps and sequence data are presented. This technique has a wide range of applications, particularly for proteins with blocked amino termini or those that can only be purified by SDS-PAGE or 2D isoelectric focusing SDS-PAGE.

Collodion↗
PubMed1988

The size, operation, and technical capabilities of protein and nucleic acid core facilities.

A survey of 40 protein and nucleic acid chemistry facilities has provided data about the capabilities of core facilities and the cost of the services they provide. Approximately 43% of the +158,000 average annual operating budget for a typical university facility is derived from service charges. After correcting for the various degrees of subsidization of the different facilities, it was found that it costs a typical university facility +65 to carry out an acid hydrolysis and amino acid analysis on a protein. A 25-residue peptide can be synthesized and cleaved for +2078, whereas sequencing the same peptide costs +874. A 25-residue oligonucleotide can be synthesized for +258. The total work output per month of an average facility corresponds to 65 amino acid analyses, 15 amino acid sequencing runs, three peptide syntheses, and 16 oligonucleotide syntheses. Depending on the approach used, from 85 to nearly 200 pmol of protein are required to obtain an accurate amino acid composition. To sequence the first 15 amino acids in a protein typically requires 150 pmol compared with 1.2 nmol of protein required to first carry out a tryptic digest and then isolate and sequence the first 15 residues in one of the resulting tryptic peptides.

Amino Acid Sequence↗
PubMed1982

Quantitative and functional deficit of suppressor T cells in children with atopic eczema.

Helper (OKT4+) and suppressor (OKT8+) T cells were enumerated in 16 children with severe atopic eczema. Compared to controls (median 1 . 8) the ratio of OKT4+/OKT8+ cells in the patients was significantly higher (median 2 . 65, P less than 0 . 002). Functional suppressor activity in these patients was assessed by concanavalin A (Con A) activation and suppression of pokeweed mitogen (PWM) induced immunoglobulin production by plasma cells and Con A proliferation of T cells. In both assays a lack of suppression was shown (Con A/PWM, P less than 0 . 02; Con A/Con A, P less than 0 . 05). There was a significant inverse correlation between the helper/suppressor ratio and functional suppressor activity (P less than 0 . 01). These results indicate that a defect of T cell regulation does exist in atopic eczema and if it is of primary pathogenic importance, immunotherapy to restore the balance may prove useful.

Adolescent↗
PubMedDate not supplied

Practical and psychological problems for parents of children with epidermolysis bullosa.

Parents of children with epidermolysis bullosa were sent a questionnaire seeking information on problems associated with the condition; 45% replied and their responses are discussed in terms of reported needs. Epidermolysis bullosa (EB) is the name given to a group of distinct, inherited disorders which are manifest as an exceptional liability of the skin to blister and ulcerate following mechanical trauma. There are three principal groups: EB simplex, dystrophic EB and junctional EB. All forms of EB simplex are inherited as autosomal dominant traits. These diseases are generally relatively mild but some patients are sufficiently disabled to prevent their walking more than 200 yards at a time. Dystrophic EB is of variable severity; not unknown are problems such as fusion of the fingers, fixation of the tongue, shrinkage of the mouth and oesophageal stenosis. When severe this is an exceptionally disabling disorder associated with a significant reduction in life expectancy. Junctional EB is always serious and death within the first few years of life, often within the first few weeks, is usual. DEBRA, the Dystrophic Epidermolysis Bullosa Research Association, is a self-help group of sufferers and their families. A questionnaire aimed at eliciting problems associated with this condition was sent to 138 members and their replies form the basis of this paper.

Adolescent↗