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Biomedical subjects

C Davey

Publications and source records attributed to C Davey.

25 records · Page 2Linked to original sources

Structure of the green heme in myeloperoxidase.

A 3-A-resolution X-ray crystal structure of canine myeloperoxidase has previously revealed the overall structure of the molecule, including the polypeptide backbone conformation, but did not provide an unambiguous structure for the covalently bound heme. A higher resolution (2.28 A) X-ray crystal structure of human myeloperoxidase has now shown that the heme is a novel derivative of protoporphyrin IX in which three ring substituents form covalent bonds with amino acid side chains in the protein. Modified methyl groups on pyrrole rings A and C form ester linkages with glutamate 242 and aspartate 94, while a covalent bond between the vinyl group on ring A and the sulfur atom of methionine 243 results in a sulfonium ion linkage. The heme tetrapyrrole ring also shows considerable distortion from the planar conformation seen in most heme-containing proteins. The observed bending appears to result from these covalent bonds between diametrically opposed pyrrole rings A and C and the protein. Sequence comparisons suggest that the two ester linkages to the heme may also occur in other homologous mammalian peroxidases, but that the sulfonium ion linkage may be a unique feature of myeloperoxidase.

Crystallography, X-Ray↗

Nucleosome positioning on chicken and human globin gene promoters in vitro. Novel mapping techniques.

We have developed two new techniques to assess the positions adopted by core histone octamers when reconstituted onto DNA. These, together with a previously described technique, were applied to mapping binding sites on plasmid DNAs containing either the human zeta-globin or chicken beta-globin gene promoters. Each of the approaches enabled the sites occupied by histone octamers to be measured at high resolution and, in qualitative terms, revealed the same pattern of multiple, overlapping sites. Monomer extension, one of the novel techniques, can be used to reveal binding sites over extensive stretches of a single reconstitute (approximately 1000 bp). We found the distribution of histone octamer binding sites to be largely independent of the conditions employed for reconstitution, the topology of the DNA substrate and prolonged incubation under various post-reconstitution conditions. These properties, and features of the binding site maps that we derived, suggest that histone octamer positioning on these DNAs is predominantly a characteristic of the DNA sequence itself and, by implication, that nucleosome-nucleosome interactions and the formation of nucleosome arrays are of minor influence. Some of the techniques provide quantitative information concerning the relative binding strengths of the core histone octamer for different positioning sequences. In this context, it is notable that the majority of potential binding sites compete very poorly for the histone octamer, demonstrating that under the conditions pertinent to our analysis, the range of binding strengths exhibited by the octamer for particular DNA sequences is extensive, and greater than that observed when competitive binding has been studied by methods that do not reflect precise positioning.

Animals↗

Congenital hypertrophy of retinal pigment epithelium in patients with colonic polyps associated with cancer family syndrome.

Congenital hypertrophy of retinal pigment epithelium (CHRPE) has been shown to be a frequent extracolonic manifestation of adenomatous polyposis coli (APC). The presence of CHRPE in patients with adenomatous polyps from families with cancer family syndrome suggests possible involvement of the APC gene locus in syndromes associated with less florid polyp formation than seen in APC. It also emphasises that caution must be exercised in using the presence of CHRPE clinically as a marker for APC in isolated at-risk individuals.

Adenoma↗

Candidal endophthalmitis in Glaswegian heroin addicts: report of an epidemic.

Nine heroin addicts with presumed candidal endophthalmitis were seen in Glasgow between November 1982 and April 1984. Six patients during a two month period in 1983. The physical symptoms and signs observed, results of laboratory investigations and responses to anti-fungal chemotherapy are reported. Epidemiological factors relating to possible sources of infection are explored.

Adolescent↗

Very small air bubbles (10 - 70 microl) cause clinically significant variability in syringe pump fluid delivery.

AIM: The goal of this study was to analyse flow disturbances resulting from the presence of small air bubbles in syringe pump delivery lines incorporating pressure-sensing discs. METHODS: Laboratory based gravimetric measurement of syringe pump flow rate with concurrent fluid pressure monitoring. RESULTS: Small air bubbles can become lodged in the pressure-sensing disc part of syringe pump delivery lines. This can give rise to serious disturbances in fluid delivery from minute to minute, but does not trigger pump alarms. Small air bubbles being delivered through non-horizontal sections of delivery line can also cause significant transient disturbances to fluid delivery. CONCLUSIONS: The demonstrated disruptions to fluid delivery could be sufficient to cause adverse effects on patients, particularly in the case of a vulnerable patient receiving a potent fast-acting drug at a low flow rate. The prevalence of these effects in clinical settings would be difficult to establish, but careful efforts to remove air from syringe delivery lines before starting infusions would be recommended to minimize the risks.

Equipment Design↗