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Biomedical subjects

E Wade

Publications and source records attributed to E Wade.

14 recordsLinked to original sources
PubMed2004

Phylogeography of the false smooth snakes, Macroprotodon (Serpentes, Colubridae): mitochondrial DNA sequences show European populations arrived recently from Northwest Africa.

Mitochondrial DNA (1075 bp: cytochrome b, 300 bp; 12S rRNA, 393 bp; and 16S rRNA, 382 bp) corroborates the monophyly of the genus Macroprotodon and of the species M. mauritanicus, M. abubakeri, and M. brevis. The subspecies M. brevis ibericus is also monophyletic. The mtDNA tree presented here indicates that M. cucullatus consists of at least two separate units and may possibly represent a primitive morphology rather than a species in its own right. However, this hypothesis is tentative since it is only reflects the history of a single evolutionary unit (mtDNA). A definitive understanding of the evolution of M. cucullatus will not be possible until informative nuclear markers are added to the mitochondrial data. Macroprotodon appears to have originated in the Maghreb region of NW Africa and speciated there around 4-5.5 million years ago around the end of the Miocene period, after which its three main lineages may each have expanded north into more mesic conditions. The group also spread eastwards into coastal areas of Libya quite recently and on to Egypt and Israel. Later still, M. b. ibericus from extreme north Morocco reached the Iberian Peninsula, and M. mauritanicus from Tunisia or Algeria colonised the Balearic Islands of Menorca and Mallorca. Both these range extensions may result from very recent natural colonisations or even from accidental human introduction. Recency of origin of Iberian and Balearic populations is indicated by uniformity of their mtDNA even across large distances, and its great similarity to that of populations in source regions. Isolated populations assigned to M. cucullatus in the Hoggar mountains (southern Algeria) and Western Sahara are probably relicts from quite recent periods of climatic amelioration in the North African desert.

Africa↗
PubMed2000

The quantitative measurement of autoantibodies to thyroglobulin and thyroid peroxidase by automated microparticle based immunoassays in Hashimoto's disease, Graves' disease and a follow-up study on postpartum thyroid disease.

The aim of this study was to investigate the association between various autoimmune thyroid diseases and the presence of anti-TPO and anti-Tg antibodies using two novel automated microparticle based immunoassays developed for the AxSYM analyzer. Serum samples from 65 individuals with Hashimoto's Disease, 38 with Graves' Disease and 80 UK blood donors were assayed. In addition, samples were taken from 50 women known to be positive for TPO antibodies, for up to 24 weeks following delivery. Precision for both assays ranges from 5.7-9.1% CV, while analytical sensitivity was determined to be 1.0 IU/ml for Anti-Tg and 0.3 IU/ml for Anti-TPO. The Anti-TPO test showed positive results in 86% of Hashimoto's Disease and 87% of Graves' Disease. The figures obtained for Anti-Tg were 58% and 73% respectively. Specificity was 94% with Anti-TPO and 99% with Anti-Tg. The postpartum women were divided into 2 groups, group A remained symptomless while group B developed thyroid dysfunction. Within the 2 groups, medians calculated at each time point were compared between and within groups using the Mann-Whitney Rank Sum Test or the Kruskal-Wallis One Way ANOVA on Ranks. Anti-TPO baseline levels (week 6) were statistically different between both groups (median 36 vs. 167 IU/ml, p = 0.002). In group A, the median values increased from 36 to 87 IU/ml within the observation period, although the difference was not statistically significant. In group B, antibody titres showed a statistically significant increase from 168 IU/ml (week 6) up to 676 IU/ml after 20 weeks (p < 0.001). Anti-Tg baseline levels were not statistically different between the two groups. In group A, the median values did not change significantly over time (range: 47-86 IU/ml) whereas antibody titres in group B showed a statistically significant increase from 79 IU/ml (week 6) to 276 IU/ml after 24 weeks (p = 0.002). Results obtained indicate that these assays provide useful tools for the quantitative determination of autoantibodies in both primary diagnosis as shown with the Hashimoto's disease and Graves' disease samples and patient follow-up as demonstrated with the postpartum samples. The automation and high precision of the assays make them perfectly suited to routine diagnostic use.

Autoanalysis↗
PubMed1997

Xp54, the Xenopus homologue of human RNA helicase p54, is an integral component of stored mRNP particles in oocytes.

In investigating the composition of stored (maternal) mRNP particles in Xenopus oocytes, attention has focussed primarily on the phosphoproteins pp60/56, which are Y-box proteins involved in a general packaging of mRNA. We now identify a third, abundant, integral component of stored mRNP particles, Xp54, which belongs to the family of DEAD-box RNA helicases. Xp54 was first detected by its ability to photocrosslink ATP. Subsequent sequence analysis identifies Xp54 as a member of a helicase subfamily which includes: human p54, encoded at a chromosomal breakpoint in the B-cell lymphoma cell line, RC-K8; Drosophila ME31B, encoded by a maternally-expressed gene, and Saccharomyces pombe Ste13, cloned by complementation of the sterility mutant ste13. Expression studies reveal that the gene encoding Xp54 is transcribed maximally at early oogenesis: no transcripts are detected in adult tissues, other than ovary. Using a monospecific antibody raised against native Xp54, its presence in mRNP particles is confirmed by immunoblotting fractions bound to oligo(dT)-cellulose and separated by rate sedimentation and buoyant density. On isolating Xp54 from mRNP particles, it is shown to possess an ATP-dependent RNA helicase activity. Possible functions of Xp54 are discussed in relation to the assembly and utilization of mRNP particles.

Amino Acid Sequence↗
PubMed1996

Molecular mechanisms of anti-inflammatory action of glucocorticoids.

Glucocorticoid hormones are effective in controlling inflammation, but the mechanisms that confer this action are largely unknown. Recent advances in this field have shown that both positive and negative regulation of gene expression are necessary for this process. The genes whose activity are modulated in the anti-inflammatory process code for several cytokines, adhesion molecules and enzymes. Most of them do not carry a classical binding site for regulation by a glucocorticoid receptor, but have instead regulatory sequences for transcription factors such as AP-1 or NF-kappa B. This makes them unusual targets for glucocorticoid action and emphasizes the need for novel regulatory mechanisms. Recent studies describe an important contribution by protein-protein interactions, in which several domains of the receptor participate; these studies provide a better understanding of the action of the receptor and offer opportunities for the design of steroidal compounds that could function more effectively as anti-inflammatory drugs.

Animals↗
PubMed1996

Interaction of the Ubc9 human homologue with c-Jun and with the glucocorticoid receptor.

Glucocorticoid hormones convert the glucocorticoid receptor (GR) from an inactive cytosolic complex to a nuclear form that regulates transcription. Binding of GR to palindromic DNA-recognition sites (hormone response elements) leads to activated target gene transcription. GR also exerts negative actions on transcription, e.g., by interfering with the function of several other transcription factors such as AP-1, NK-kappa B, CREB, and Oct-1. Physical interactions of GR with AP-1 subunits are readily detectable but do not seem sufficient since nonrepressing GR mutants still interact in vitro, so that specific conformational changes and/or interactions with additional partner proteins may be required for negative action. In an attempt to find such partner proteins, we defined regions of c-Jun and GR essential for mutual interference and used in those a yeast two-hybrid screen for interacting proteins. Repeatedly we isolated overlapping cDNA sequences of one protein interaction with both c-Jun and GR. This protein does not interact with c-Fos or a non-repressing GR mutant and expressed in mammalian cells does not substantially affect AP-1 or GR activity. Interestingly, however, the protein rescues yeast cells from the toxic effects of the GR fragment used for screening. The protein represents the human homologue of the yeast E2 ubiquitin-conjugating enzyme, Ubc9; its specific interactions with both GR and c-Jun, but not mutant GR, suggest that it may exert physiologic regulatory functions.

Animals↗
PubMed1995

Generic enteral formulas: a new idea for the 1990s.

Generic equivalent enteral formulas are now commercially available. The purpose of this article is threefold: (1) to define generic equivalents and compare both their nutritional and monetary differences with brand name products, (2) to provide the clinician with factors to consider when evaluating generic formulas--the source and distribution of macronutrients and micronutrients, and patient tolerance, nutritional status and outcome--and (3) to provide information on how to incorporate generic enteral formulas onto an institution's enteral formulary. In today's environment of diminishing health care budgets, generic enteral formulas can play a role in cost containment without sacrificing quality nutritional care.

Aged↗
PubMed1990

Human immunodeficiency virus pseudotypes with expanded cellular and species tropism.

One mechanism for expanding the cellular tropism of a virus is through the formation of phenotypically mixed particles or pseudotypes, a process commonly occurring during viral assembly in cells infected with two or more viruses. We report here that dual infection of cells with human immunodeficiency virus (HIV) and a murine amphotropic retrovirus leads to the production of HIV pseudotypes that have acquired the host range of the amphotropic retrovirus and are capable of infecting not only CD4- human cells but also mouse cells. The replication of the HIV pseudotypes in the various CD4- cells was determined by measuring the appearance of HIV antigens in the supernatants, by cocultivation of CD4+ CEM cells with the infected CD4- cells, and in some cases by assaying the culture supernatants directly for infectious virus. Of the cells tested, human foreskin fibroblasts were the best host cells, and by in situ cytohybridization, we were able to document that all cells in the culture were infected. In addition, the temporal appearance of HIV-specific proteins in the HIV pseudotype-infected fibroblasts was similar to that seen in CD4+ CEM cells. If the human fibroblasts were first infected with the amphotropic retrovirus, they demonstrated the property of superinfection exclusion and were resistant to subsequent infection by the HIV pseudotype. In other cell lines, including the human glioblastoma-derived cell line U373MG, HeLa cells, BALB/c mouse embryo cells, and SC-1 wild mouse cells, although the HIV pseudotype infection appeared to be less efficient, substantial amounts of HIV were nevertheless produced. These results indicate that the HIV (amphotropic retrovirus) pseudotypes may be useful for studying the molecular biology of HIV infections in a wide range of cells.

Animals↗
PubMed1983

Prune perineum syndrome: report of a second case.

A child is reported with a constellation of anomalies which include acetabular dysplasia with bilateral dislocated hips, persistent cloaca, hypoplastic kidney, two umbilical vessels, anal atresia and no obvious external genitalia. These anomalies are strikingly similar to a case reported by Peeden et al ('79) which was referred to as prune perineum. A discussion on possible underlying cause(s) of caudal dysplasia is included.

Abnormalities, Multiple↗
PubMedDate not supplied

Spike glycoprotein cleavage recognition site analysis of infectious bronchitis virus.

The spike glycoprotein of infectious bronchitis virus (IBV), a coronavirus, is translated as a precursor protein (So), then cleaved into two subunits (S1 and S2) by host cell serine proteases. In this study, we compared the cleavage recognition site of 55 IBV isolates to determine if the cleavage recognition site sequence, which consists of five basic amino acid residues, correlates with host cell range, serotype, geographic origin, and pathogenicity as it does in orthomyxoviruses and paramyxoviruses. The most common cleavage recognition site observed (33 of 55 viruses) was Arg-Arg-Ser-Arg-Arg, representing at least 11 different serotypes. Thus, cleavage recognition site does not appear to correlate with serotype. We also determined that cleavage recognition site sequence does not correlate with pathogenicity because attenuated and pathogenic isolates (different passages of the same virus) contain identical cleavage recognition site sequences. In addition, nephropathogenic strains had the same cleavage recognition site sequence as many nonnephropathogenic isolates. Cleavage recognition site sequence does correlate with viruses in different geographic regions, which may be an important characteristic to examine in epidemiologic studies. An IBV monoclonal antibody neutralization-resistant mutant (NR 18) had an unusual substitution of Ile for Arg at the fourth position, giving the sequence Arg-Arg-Ser-Ile-Arg, which likely prevents cleavage and, thus, destroys the conformationally dependent monoclonal antibody binding epitope. Six residues on the amino-terminal side of the cleavage recognition site are conserved in 31% of the isolates and consist of only one or two basic amino acids. Thus, the number of basic residues around the cleavage recognition site does not appear to correlate with increased cleavability, host cell range, and increased virulence as it does with envelope glycoproteins in orthomyxoviruses and paramyxoviruses.

Amino Acid Sequence↗