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D May

Publications and source records attributed to D May.

At least 37 records · Page 2Linked to original sources
PubMed2000

Molecular characterization of the first non-mammalian p73 cDNA.

The p53 gene is believed to be mutated or deficient in over 50% of human tumours, and is therefore considered to be instrumental in the process of carcinogenesis. Recently in humans, homologues of p53 (such as p73 and p63) have been isolated. In our studies in fish, we have been isolating tumour suppressor genes with a view to their potential use to study genotoxins in the aquatic environment. In this paper, we report the characterisation of the first non-mammalian p73 cDNA, isolated from barbel (Barbus barbus), a freshwater cyprinid fish indigenous to UK rivers. The deduced barbel p73 amino acid sequence has a high homology with human p73 alpha: the proteins are 641 and 636 aa in length, respectively, and there is a 72% identity over the entire sequence length of the protein (over 90% in the putative DNA binding domain). The level of conservancy for p73 is considerably higher across class (from man to fish), than for p53 and it may therefore have particular value in studies on environmental mutagenesis. Northern analysis showed expression of three p73 mRNA transcripts/homologues. The patterns of p73 tissue expression in the barbel differed from the expression of p53 mRNA, suggesting specific functional roles for the two genes.

3' Untranslated Regions↗
PubMed2000

Continuity and change in the use of residential services by adults with intellectual disability: the Aberdeen cohort at mid-life.

The present paper reports a follow-up study of a representative cohort of people with intellectual disability, now in middle age, who entered adult services on leaving school in the late 1960s, and whose adult years have coincided with a period of radical policy change and considerable service expansion. The present authors focus on the changes which have taken place in their use of residential services over this period. Firstly, the situation in early adulthood when they were last studied is examined. At this time, 60% of the cohort were still living at home, almost all with both parents. The remaining 40% were in institutions, mainly long-stay mental handicap hospitals. Out-of-home placement is associated with gender (maleness), challenging behaviour, and the absence of one or both parents. The present authors compare this with the situation 20 years later. The most significant change in this time is the expansion of the community sector, accounting for about half of the surviving cohort, with numbers still at home or in hospital correspondingly reduced. Almost half of the cohort had experienced little or no change in residential situation. On average, they were less intellectually and socially able than those who had moved into community provision.

Activities of Daily Living↗
PubMed1999

Studies on the GH/SL gene family: cloning of African lungfish (Protopterus annectens) growth hormone and somatolactin and toad (Bufo marinus) growth hormone.

The lungfishes (lobe-finned fish) occupy a unique position in vertebrate phylogeny, being regarded as the closest extant relatives to the tetrapods. The putative pituitary hormone somatolactin (SL) has hitherto been found only in teleost fishes, and the presence of this protein in tetrapods or lobe-finned fishes has not been ascertained. It was therefore of interest to determine the structure of SL in the African lungfish (Protopterus annectens), as this information would be useful for designing probes to facilitate the detection of SL genes in amphibians and other tetrapods. The structural relationships between SL, growth hormone (GH), and prolactin (PRL) strongly suggest that these proteins evolved from a common ancestor. To obtain a more complete picture of the evolution of these hormones in lungfish, African lungfish GH has been cloned and sequenced. The cDNA sequence of a toad (Bufo marinus) GH was determined to facilitate maximum parsimony analysis of GH sequences. Cladistic analysis confirmed that lungfish and amphibian GH sequences form a clade distinct from the GH sequences of ray-finned fishes. A distance matrix analysis of SL sequences indicated that lungfish SL had the lowest primary sequence identity with goldfish SL (47%) and the highest with flounder SL (66%). The detection of SL in a lungfish indicates that the gene duplication within the SL/GH/PRL family, which gave rise to SL, must have occurred in a common ancestor of the ray-finned fishes (Actinopterygii) and the lungfishes (Sarcopterygii) and tetrapods.

Amino Acid Sequence↗
PubMed1999

Determinants of the DNA-binding specificity of the Avian homeodomain protein, AKR.

AKR (Avian Knotted-Related) was the first example of a vertebrate homeodomain protein with a highly divergent Ile residue at position 50 of the DNA-recognition helix. The protein was cloned from a liver cDNA expression library of a day-9 chick embryo by virtue of its ability to bind to the F' site in the proximal promoter of the avian apoVLDLII gene. Expression of the apoVLDLII gene is completely estrogen dependent, and mutation or deletion of the F' site decreases estrogen inducibility 5- to 10-fold. Subsequent data indicated that AKR is capable of repressing the hormone responsiveness of the apoVLDLII promoter, specifically through binding to F'. Involvement of the F' site in the hormone-dependent activation of apoVLDLII gene expression, as well as AKR-mediated repression, strongly suggests that both positive and negative regulatory factors interact with this site. Although several mammalian proteins have now been isolated whose homeodomains share many of the structural features of AKR, including the Ile at position 50, little is known of their functions in vivo or the identities of the genes they regulate. Consequently, the elements through which they exert their effects and the structural determinants of their binding specificities remain largely uncharacterized. In this study, we defined the sequence specificity of binding by AKR using polymerase chain reaction-assisted optimal site selection and determined the affinity with which the protein binds to both the optimized site and the F' site. Additionally, we generated a three-dimensional model of the AKR homeodomain binding to its optimized site and probed the validity of the model by examining the consequences of mutating amino acid residues in recognition helix 3 and the N-terminal arm on the binding specificity of the homeodomain. Finally, we present evidence that the F' site itself may act as an estrogen response element (ERE) when in the vicinity of imperfect or canonical EREs and that AKR can repress hormone inducibility mediated via this site.

Animals↗
PubMed1999

PGP9.5: a marker for cellular neurothekeoma.

Neurothekeomas are benign, predominantly cutaneous neoplasms that are divided histologically into myxoid, intermediate, and cellular types. Although it is generally agreed that the myxoid type of neurothekeoma has a neural origin, the lack of consistent immunoreactivity to neural markers and insufficient ultrastructural evidence of neural differentiation in cellular neurothekeoma have brought the origin of cellular neurothekeoma into question. In this report the authors show that immunoreactivity to protein gene product 9.5 (PGP9.5)--a broad neural marker--is positive in 100% of cases of cellular neurothekeoma using microwave antigen retrieval, as well as in all cases of myxoid and intermediate neurothekeoma. In contrast, immunoreactivity to S-100 protein is only positive in 3 of 12 cases of cellular neurothekeoma. These results show that PGP9.5 is a useful marker for identifying cellular neurothekeoma, as well as other types of neurothekeomas using the antigen retrieval method. The results are consistent with the notion that cellular neurothekeoma has a neural differentiation.

Adolescent↗
PubMed1999

Posterior lumbar interbody fusion with cages: an independent review of 71 cases.

OBJECT: The authors conducted a retrospective study to provide an independent evaluation of posterior lumbar interbody fusion (PLIF) in which impacted carbon cages were used. Interbody cages have been developed to replace tricortical interbody grafts in anterior and PLIF procedures. Superior fusion rates and clinical outcomes have been claimed by the developers. METHODS: In a retrospective study, the authors evaluated 71 consecutive patients in whom surgery was performed between 1995 and 1997. The median follow-up period was 28 months. Clinical outcome was assessed using the Prolo scale. Fusion results were interpreted by an independent radiologist. The fusion rate was 90%. Overall, 67% of the patients were satisfied with their outcome and would undergo the same operation again. Based on the results of the Prolo scale, however, in only 39% of the patients were excellent or good results achieved. Forty-six percent of the work-eligible patients resumed their working activity. Clinical outcome and return-to-work status were significantly associated with socioeconomic factors such as preoperative employment (p = 0.03), compensation issues (p = 0.001), and length of preoperative sick leave (p = 0.01). Radiographically demonstrated fusion was not statistically related to clinical outcome (p = 0.2). CONCLUSIONS: This is one of the largest independent series in which PLIF with cages has been evaluated. The results show that the procedure is safe and effective with a 90% fusion rate and a 66% overall satisfaction rate, which compare favorably with those of traditional fixation techniques but fail to match the higher results claimed by the innovators of the cage techniques. The authors' experience confirms the reports of others that many patients continue to experience incapacitating back pain despite successful fusion and neurological recovery.

Analysis of Variance↗
PubMed1999

Rise and fall.

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Accident Prevention↗
PubMed1999

Fish p53 as a possible biomarker for genotoxins in the aquatic environment.

The p53 gene is a tumour suppressor gene which has a fundamental role in cell cycle control and division, and in mammals certain genotoxic agents induce specific mutations in p53, leading to tumourigenesis. Fish have been investigated as models for studying carcinogens, but as yet very little data exists that links exposure to specific chemicals with the aetiology of tumours found in wild populations. In this study, p53 was sequenced from five species of fish with a view to the possible use of mutations in the highly conserved domains of p53 to identify genotoxins in the aquatic environment. A 0.8 kb fragment of the cDNA encompassing the conserved DNA-binding domain of p53 was sequenced in three Oncorhynchus salmonid fish: coho (O. kisutch), chum (O. keta), and chinook (O. tshawytscha) and full-length p53 cDNAs were sequenced in the puffer fish (Tetraodon miurus) and the barbel (Barbus barbus). The full-length puffer fish and barbel p53 cDNAs were 1834 bp and 1790 bp in length, encoding a 367 aa protein and a 369 aa protein, respectively. The deduced aa sequences of the p53 cDNA in the Oncorhynchus salmon shared a 100% identity in the five conserved regions (I-V). Comparisons of the deduced aa sequences for puffer fish and barbel p53 with other fish p53s revealed a high homology within the conserved DNA binding domain (68-86% for puffer fish and between 66-88% for barbel). "Conserved" domain I was not highly conserved in fish, as it is in mammals, and, therefore, conserved domains II-V are most likely to provide the valuable sequences in fish p53 for use in mutational studies to fingerprint genotoxins in the aquatic environment.

Amino Acid Sequence↗