Search PubMed⌕ Search

Biomedical subjects

D G Wilkinson

Publications and source records attributed to D G Wilkinson.

86 records · Page 5Linked to original sources

Sea urchin metallothionein sequence: key to an evolutionary diversity.

The metallothioneins (MTs) constitute a diverse family of proteins, which are enriched in cysteines and bind heavy metals. The amino acid sequence of sea urchin MT has been obtained from its mRNA sequence and compared with MT sequences of various sources. A largely conserved sequence of 10 amino acids, the "central segment," is located near the center of the MT molecules of Neurospora, yeast, and Drosophila and the center of putative domains in mammalian and sea urchin MTs. The sea urchin carboxyl-terminal-half MT resembles the mammalian 9-cysteine amino-terminal MT domain I, both in the presence of this central segment and in the relative placement of cysteine residues. Conversely, the sea urchin amino-terminal-half MT, containing 11 cysteines, resembles the mammalian carboxyl-terminal MT domain II in its exclusive enrichment in vicinal cysteines. The reversed order of these sea urchin and mammalian MT halves appears to be just one aspect of a diversity based on the elaboration of structures containing the central segment. Still another variation in this diversity is the duplication of the central segment, apparent in Drosophila and crab MTs.

Amino Acid Sequence↗

Synthesis of spore proteins during development of Dictyostelium discoideum.

The pattern of synthesis of the spore coat proteins during development of Dictyostelium discoideum has been determined by using immunoprecipitation with spore protein antibody. SP170, SP103, 'SP94', SP82, SP76 and SP55 are all first synthesized just prior to the 'Mexican hat' stage of development (16-18h), but the synthesis of SP72 is delayed. This protein is apparently synthesized as a precursor, P66, which is modified during spore maturation to yield SP72. The nature of the modification is unknown. At their peak period of synthesis during early culmination (18-20h), the spore coat proteins account for 5-9% of total protein synthesis. Shortly after synthesis, these proteins are inserted into the spore coat, where all except SP103 become disulphide-cross-linked during the period 24-30h. SP3 does not accumulate until disulphide-cross-linking of the major spore coat proteins occurs and is itself disulphide-cross-linked into the spore coat. Several additional proteins that are accumulated during development have also been identified, namely P31, P25, P21 and P18. P25 first appears at 18-20h and then continues to be made throughout development. P31 synthesis begins at 12-14h and then largely ceases after approx. 20 h of development. The genes for both P21 and P18 are first expressed early in development, starting at 9-12h. P21 synthesis ceases at approx. 14h, but P18 continues to be synthesized throughout the rest of development. The marked differences in the time period of accumulation of these proteins compared with the co-ordinated syntheses of SP170, SP103, 'SP94', SP82, SP76 and SP55 provide a useful system for analysis of the mechanism of temporal gene expression during development.

Cell Membrane↗

Phosphorylation of spore coat proteins during development of Dictyostelium discoideum.

Immunological evidence is presented which confirms that pp95, one of the major phosphoproteins accumulated in development of the cellular slime mould Dictyostelium discoideum, is identical with spore coat protein SP13. The site of phosphorylation is identified as phosphoserine. The second major phosphorylated component, pp74, corresponds to two co-migrating spore coat proteins known collectively as SP74.

Dictyostelium↗

Characterisation of the spore coat proteins of Dictyostelium discoideum.

Using a rapid purification protocol designed to minimise proteolysis in vivo and in vitro, combined with high-resolution one-dimensional and two-dimensional polyacrylamide gel electrophoresis, 11 spore coat proteins have been identified in Dictyostelium discoideum AX2 spores with apparent molecular weights of 170 000 (SP170), 103 000 (SP103), 97 000 (SP97), 90 000 (SP90), 82 000 (SP82), 76 000 (SP76), 72 000 (SP72), 55 000 (SP55), 39 000 (SP39), 33 000 (SP33) and 3400 (SP3). Control experiments rule out the possibility that any of these components are generated by crosslinking or proteolytic degradation artifacts. All of these spore coat proteins are disulphide-crosslinked in the spore coat except for SP103, the majority of which is extracted in the absence of thiol reagent. All of the spore coat proteins are single polypeptides as judged by two-dimensional polyacrylamide gel electrophoresis except for SP33 which is consistently composed of four isoelectric variants. SP170, SP103, SP97, SP90, SP82 and SP72 are extremely acidic with pI values in the range pH 4.5-4.7, SP76 and SP55 are slightly less acidic with pI values of 5.7 and 5.9 respectively, whilst the four SP33 polypeptides have pI values of pH 6.6-7.5. SP170, SP103, SP90, SP82 and SP76 are all glycoproteins as judged both by periodic acid/Schiff staining and radiolabelling in vivo with mannose, glucosamine and fucose.

Chemical Phenomena↗

Medical students' attitudes to psychiatry at the end of the clinical curriculum.

The significantly favourable changes in medical students' general attitude to psychiatry and intention to specialize in the subject, which we found after an 8-week psychiatric clerkship, were maintained one year later, at the time of the students' M.B., B.S. examinations. However, of 18 specific attitudes to psychiatry, only one changed significantly overall - fewer students agreed that 'psychiatrists are held in poor regard by most other doctors'. Contrary to other reports, these preliminary findings suggest that a psychiatric clerkship may be followed by stable attitudes and intent towards the specialty.

Attitude of Health Personnel↗

Medical students' attitudes to psychiatry.

A questionnaire was developed to elicit medical students' attitudes to psychiatry. All 94 second year clinical students at a London teaching hospital completed the instrument before and after an 8-week psychiatric clerkship. Although two-thirds of the sample had mixed feelings about psychiatry initially, by the end of the clerkship the students' general attitude to psychiatry had changed significantly in a favourable direction. Analysis of 18 specific attitudes to psychiatry revealed that the students' first responses showed anticipatory bias and lack of uniformity. Later, however, only two specific attitudes had changed significantly: more students agreed that 'problems presented by psychiatric patients are often particularly interesting and challenging', and more of them disagreed with the statement that 'psychiatric patients, generally speaking, are not easy to like'. The sexes differed on one attitude; more males than females agreed that 'psychiatry is too inexact; it seems to lack a proper scientific basis'. Finally, the proportion of students who considered the possibility of specializing in psychiatry rose from 6 to 17% during the clerkship. The students' reasons for or against such a career are discussed.

Adult↗

Homeobox genes and development of the vertebrate CNS.

The discovery of homeobox genes in vertebrates may allow analysis of a basic problem in developmental neurobiology: how regional differences in CNS organization are specified during development. This view is based on the roles defined for homologous genes in Drosophila development, and is supported by studies of the patterns of homeobox gene expression in vertebrate embryos. Homeobox genes comprise a multigene family, members of which are expressed in different spatially restricted domains along the anterior-posterior axis of the CNS. These observations are consistent with homeobox genes having roles in the positional specification of CNS organization, and experimental tests of this should be forthcoming shortly.

Animals↗

A multinational, randomised, 12-week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer's disease.

This 12-week, multinational study compared the tolerability and cognitive effects of donepezil (up to 10 mg once daily) and rivastigmine (up to 6 mg twice daily) in 111 patients with mild to moderate Alzheimer's disease. Both medications were administered open label according to recommended dosing regimens from the respective product labelling available during the conduct of the study. More patients in the donepezil group (89.3%) completed the study compared with the rivastigmine group (69.1%; p=0.009), and 10.7% of the donepezil group and 21.8% of the rivastigmine group discontinued due to adverse events (AEs); 87.5% of donepezil-treated patients and 47.3% of rivastigmine-treated patients remained on the maximum approved dose of each drug at the last study visit. Both groups showed comparable improvements on the ADAS-cog administered by raters blind to study medication at weeks 4 and 12. Thus, using the recommended dosing schedules, donepezil was better tolerated with fewer discontinuations due to AEs, and both agents improved cognition to a similar extent.

Aged↗