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Biomedical subjects

S Williamson

Publications and source records attributed to S Williamson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Calretinin-immunoreactive neurons and their projections in the guinea-pig colon.

The distribution of nerve cells and fibres with immunoreactivity for the calcium-binding protein, calretinin, was studied in the distal colon of the guinea-pig. The projections of the neurons were determined by examining the consequences of lesioning the myenteric plexus. Calretinin-immunoreactive neurons comprised 17% of myenteric nerve cells and 6% of submucous nerve cells. Numerous calretinin-immunoreactive nerve fibres were located in the longitudinal and circular muscle, and within the ganglia of the myenteric and submucous plexuses. Occasional fibres were found in the muscularis mucosae, but they were very rare in the lamina propria of the mucosa. Lesion studies revealed that myenteric neurons innervated the underlying circular muscle and provided both ascending and descending processes that gave rise to varicose branches in myenteric ganglia. Calretinin-immunoreactive fibres also projected to the tertiary component of the myenteric plexus, and are therefore likely to be motor neurons to the longitudinal muscle. Varicose fibres that supplied the submucous ganglia appear to arise from submucous nerve cells. Arterioles of the submucous plexus were sparsely innervated by calretinin-immunoreactive fibres. The submucous plexus was the principal source of immunoreactive nerve fibres in the muscularis mucosae. This work shows that calretinin-IR reveals different neuronal populations in the large intestine to those previously reported in the small intestine.

Animals↗
PubMed1994

Polymorphism of SPAG-1, a candidate antigen for inclusion in a sub-unit vaccine against Theileria annulata.

SPAG-1, a Theileria annulata sporozoite surface antigen, is a vaccine candidate. Data is presented, based on the clonal segregation of SPAG-1 associated RFLPs, showing that this antigen is encoded by a single copy gene. We have cloned and sequenced a full-length genomic copy of the SPAG-1 gene and a comparison of this with a previously published SPAG-1 cDNA sequence demonstrates a high degree of polymorphism. We infer that these sequences represent two distinct allelic SPAG-1 variants. The deduced polypeptides show an overall identity of 92% with the most variable stretch (60% identity) occurring towards the middle of the molecule. The N and C termini are more conserved with identities of 92% and 97% respectively. The elastin receptor ligand, VGVAPG, present 3 times in the protein sequence derived from the cDNA is not found in that deduced from the genomic copy. Evidence for 2 further SPAG-1 alleles was obtained from PCR based sequences using macroschizont clones containing different SPAG-1 associated RFLPs. In summary we have shown the existence of at least 4 highly polymorphic SPAG-1 alleles. The implications of such polymorphism between and within distinct geographical isolates for the development of a SPAG-1 based subunit vaccine is discussed.

Alleles↗
PubMed1994

Theileria annulata sporozoite surface antigen (SPAG-1) contains neutralizing determinants in the C terminus.

SPAG-1 is a surface antigen on Theileria annulata sporozoites that is a candidate both for inclusion in a subunit vaccine and as a ligand for host cell recognition. We have pinpointed major neutralizing epitopes to the C terminus. To facilitate this we expressed SPAG-1 as a series of defined fragments in the pGEX system. These constructs were validated by sequencing and by their spectrum of reactivity with monoclonal antibody (MoAb) BA4. This MoAb recognizes the elastin motif VGVAPG, that is predicted to occur three times in the N terminal half of SPAG-1. The recombinant proteins were then tested by Western blotting with a neutralizing MoAb (1A7) and two neutralizing bovine sera (10T and 34A). The results demonstrate that 1A7 and the bovine sera react with determinants unique to the C terminus. We mapped the neutralizing determinant recognized by MoAb 1A7 to a 16 residue sequence (residues 807-822) using synthetic peptides. Interestingly the bovine sera do not recognize the 1A7 epitope. The potential role of the C terminus as a ligand for host cell recognition and the implications for sub-unit vaccine production are discussed.

Amino Acid Sequence↗
PubMed1994

Synthesis and antiproliferative activity of tyrphostins containing heteroaromatic moieties.

A series of benzylidenemalononitrile derivatives previously synthesized by condensing aromatic aldehydes with malononitrile derivatives are known as tyrphostins. In this study, 32 tyrphostins were synthesized, 19 of which are novel compounds. Both hydroxylated derivatives and compounds containing heteroaromatic moieties were prepared. We have confirmed and extended the observation that the tyrphostins displayed an enhancement in their ability to inhibit the epidermal growth factor (EGF) receptor tyrosine kinase domain as the number of hydroxyl groups on the aromatic portion was increased. IC50 values of 1-5 microM were readily achieved. Some inhibitory activity was seen with the heteroaromatic structures, with two compounds exhibiting IC50 values of 56 and 77 microM. However, these derivatives were poor inhibitors of the EGF receptor tyrosine kinase activity as compared to the hydroxylated derivatives. The ability of the 32 tyrphostins synthesized in the present study to inhibit proliferation of a human breast adenocarcinoma cell line (MCF-7) was determined using [3H]thymidine incorporation as a measure of DNA synthesis. Some of the compounds containing pyridine, imidazole or thiophene portions displayed antiproliferative activity comparable to that of tyrphostins prepared from 3,4,5-trihydroxybenzaldehyde. The lack of inhibitory effect of these heteroaromatic compounds on the EGF receptor tyrosine kinase activity suggests that their antiproliferative activity is not related to inhibition of EGF receptor function. As the growth of the MCF-7 cell line is governed by other factors, such as the insulin-like growth factors (IGFs) and oestradiol, it is also still to be established whether the antiproliferative activity of the hydroxylated tyrphostins is directly related to inhibition of the EGF receptor tyrosine kinase activity.

Antineoplastic Agents↗
PubMed1993

Job satisfaction and dissatisfaction amongst neonatal nurses.

This study was conducted against the background of the concerns expressed in the press about the difficulties in recruiting and retaining nurses and midwives who were trained and experienced in the field of neonatal nursing. A small study (N = 50) was undertaken in one regional unit using semi-structured interviews. The interview schedule covered a broad range of topics which were identified in the literature as exerting an influence on job satisfaction and dissatisfaction. A relationship between job satisfaction/dissatisfaction, staff turnover, and recruitment was demonstrated. Unfortunately the clinical regrading exercise had a complex effect, which could not be fully assessed within the narrow terms of reference of this study. Interestingly the majority of the respondents found their work stimulating and rewarding. However, the overriding factor which was said to exert a negative influence at work was the way their individual contribution to neonatal care was valued by senior medical and nursing/midwifery colleagues.

Humans↗
PubMed1992

Mimicry of elastin repetitive motifs by Theileria annulata sporozoite surface antigen.

Theileria annulata is an important pathogen of cattle in the tropics. The gene sequence of a sporozoite surface antigen (SPAG-1) is reported. Data is also presented demonstrating that SPAG-1 is synthesised as a large precursor. This antigen, which is a candidate for inclusion in a subunit vaccine, shows a remarkable degree of molecular mimicry to the extracellular matrix protein elastin. It contains both repetitive motifs PGVGV and VGVAPG. Immunofluorescence using a monoclonal antibody against VGVAPG confirmed that this peptide is expressed on sporozoites as predicted. The presence of VGVAPG is particularly interesting since this is the ligand for elastin receptors on a range of cell types, including macrophages/monocytes which are a major class of host target cells. It is proposed that this antigen represents the ligand whereby T. annulata recognises its host cells.

Amino Acid Sequence↗
PubMed1992

A comparison of the matching of emotional information by depressive and organic patients.

The ability to match complex emotional stimuli was assessed in depressed and organic neuropsychiatric patients. Subjects were 13 nonorganic-depressed, 13 organic-depressed, 10 organic-nondepressed, and 10 nonorganic-nondepressed right-handed adults. They were required to match pictures, sentences, and faces on the basis of emotional content in order to determine whether depression resulted in difficulties in analyzing emotional information consistent with those seen in organic patients. Depression produced an error pattern for the matching of complex emotional information that was suggestive of right hemisphere dysfunction. It was unclear if this was due to emotional processing defects or a more generalized deficit in conceptual processes.

Journal Article↗
PubMed1991

Abnormal processing of affective words by psychopaths.

We tested the hypothesis that psychopathy is associated with abnormal processing of affective verbal material. Criminal psychopaths and nonpsychopaths, defined by the Psychopathy Checklist, performed a lexical decision task ("Is it a word or not?") while we recorded reaction time and event-related potentials in response to letter-strings consisting of affective and neutral words and pronounceable nonwords. On the assumption that they do not make efficient use of affective information, our primary prediction was that psychopaths would show less behavioral and event-related potential differentiation between affective and neutral words than would nonpsychopaths. The results were in accordance with this prediction. The lexical decisions of nonpsychopaths were significantly faster, and relevant event-related potential components were significantly larger, to affective words than to neutral words. In sharp contrast, psychopaths failed to show reaction time facilitation or larger amplitude event-related potentials to affective words. We suggest that psychopaths extract less information from affective words than do other individuals. Possible implications of these and related findings for understanding the behavior of psychopaths are discussed.

Adolescent↗
PubMed1990

The adenohypophysis of the Australian lungfish, Neoceratodus forsteri--an immunocytological study.

The cell types in the adenohypophysis of Neoceratodus resemble closely those already described for Lepidosiren and Protopterus. Four of these were immunocytochemically identified as prolactin cells, gonadotropes, corticotropes, and melanotropes. Antiserum to bullfrog growth hormone could not distinguish between prolactin cells and somatotropes. Anti-bullfrog prolactin, however, did selectively stain the prolactin cells, which allowed the identification of the somatotropes. The presumptive thyrotropes, as the only remaining cell type in the pars distalis, can then be tentatively identified by default. Likewise a PAS-positive cell type in the pars intermedia had no immunoreactivity to any of the antisera used. The functional significance of this cell remains to be demonstrated. One of the more unexpected findings was the presence of large numbers of cells immunoreactive to alpha-MSH in the proximal pars distalis. The implications of the presence of these cells in adult lungfish are discussed. The distribution of cell types within the pituitary of Neoceratodus showed more regionalization than is present in the other lungfish and corresponded more closely to that described for primitive actinopterygian fish. The general structure of the pituitary of Neoceratodus also resembled primitive actinopterygian fish more closely than it did amphibians, unlike the pituitaries of Lepidosiren and Protopterus. The evolutionary significance of this is also discussed.

Adrenocorticotropic Hormone↗
PubMed1990

Urinary growth hormone excretion as a screening test for growth hormone deficiency.

Overnight urinary growth hormone secretion was measured by an immunoradiometric assay incorporating commercially available reagents, in 41 normal prepubertal school-children from three age groups: 3-5 years, 6-7 years, and 9-10 years. There was no significant difference between the groups expressing the results as total microU/specimen and so they have been combined to provide a prepubertal reference range of 2.25-10.50 microU/night. Prepubertal children with growth hormone deficiency who had not been receiving growth hormone treatment for two days had overnight urinary growth hormone concentrations well below this range. Urinary growth hormone was assayed in 49 children undergoing investigation for short stature with conventional provocative testing, and those shown to have growth hormone deficiency had correspondingly low overnight urinary growth hormone concentrations. There was, in addition, a strong correlation between overnight urinary growth hormone concentrations and peak serum response to provocation. This simple urine assay may provide a useful screening test for growth hormone deficiency.

Adolescent↗