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Biomedical subjects

S Williamson

Publications and source records attributed to S Williamson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Loss of Apc and the entire chromosome 18 but absence of mutations at the Ras and Tp53 genes in intestinal tumors from Apc1638N, a mouse model for Apc-driven carcinogenesis.

The Apc1638N mouse carries a targeted mutant allele at the endogenous adenomatous polyposis coli (Apc) gene and represents a unique in vivo model to study intestinal tumor formation and progression. Heterozygous Apc+/Apc1638N mice progressively develop 5-6 adenomas and adenocarcinomas of the small intestine within the first 6 months of life following a histologic sequence similar to that observed in human intestinal tumors. Here, we present the somatic mutation analysis of a total of 57 tumors. The results indicate that in > or = 75% of the lesions tested the wild type copy of the Apc gene is lost and that this LOH event extends to the entire mouse chromosome 18. Unexpectedly, mutations at the K-, N- and H-ras genes have not been found in these tumors. Immunohistochemical analysis of the Apc1638N tumors failed to detect accumulation of the Tp53 protein. Also, no mutations have been found in exons 7 and 8 of the Tp53 gene. These results indicate that, although the genetic inactivation of Apc is involved in the initiating event of the human as well as murine intestinal tumorigenesis, tumor growth and progression follow different mutational pathways in these two species.

Adenocarcinoma↗
PubMed1996

Conservation of neutralizing determinants between the sporozoite surface antigens of Theileria annulata and Theileria parva.

The sporozoite surface antigens SPAG-1 of Theileria annulata and p67 of Theileria parva are postulated to contain determinants necessary for host cell invasion and/or recognition and are both being considered as candidates for inclusion in subunit vaccines. Preliminary data suggest that these are related molecules. In this paper we describe the investigation of the relationship between these sporozoite antigens further by analysis of the immunological cross-reactivity using Mabs and sera raised against each antigen. The cross-reactions were examined by carrying out Western blots, IFA tests, and in vitro sporozoite neutralization assays. In addition, sequence comparison data which clearly establish that these surface antigens are encoded by related genes are presented. The regions of SPAG-1 identified as containing cross-reactive epitopes recognized by p67 antiserum correlated to regions of high predicted homology between p67 and SPAG-1, which are located at their respective N- and C-termini. Furthermore, p67 and SPAG-1 were found to contain cross-reactive determinants responsible for neutralization of sporozoite infectivity in vitro, and at least some of these were located in the C-termini of both molecules. The relevance of these findings to the possible roles for these molecules in host cell invasion is discussed.

Amino Acid Sequence↗
PubMed1996

GABA and nitric oxide synthase immunoreactivities are colocalized in a subset of inhibitory motor neurons of the guinea-pig small intestine.

Simultaneous immunofluorescence labelling was used to determine the patterns of colocalization of immunoreactivity for gamma-aminobutyric acid (GABA-IR) with immunoreactivity for nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP) and tachykinins (TK) in nerve cells and fibres of the guinea-pig small intestine. GABA-IR nerve cell bodies were located in the myenteric plexus and varicose fibres innervated the circular and longitudinal muscle, but did not form pericellular endings in the myenteric ganglia. GABA-IR nerve cells comprised 4-5% of all nerve cells in the myenteric ganglia. Of GABA-IR myenteric nerve cells, about 85% had NOS-IR and of GABA-IR nerve fibres in both muscle layers, about 75% were NOS-IR. Conversely, 20% of NOS-IR nerve cells were GABA-IR. About 6% of GABA-IR nerve fibres innervating the circular muscle, but none innervating the longitudinal muscle, were TK-IR. Most GABA-IR fibres supplying the circular muscle, but none of those supplying the longitudinal muscle, were VIP-IR. From this study, and previous studies of projections of enteric neurons, it is concluded that most GABA-IR neurons in the guinea-pig small intestine are inhibitory motor neurons that also contain NOS-IR. A small proportion represents anally directed excitatory motor neurons that innervate the circular muscle and are also immunoreactive for TK.

Animals↗
PubMed1996

Women's satisfaction with antenatal care in a changing maternity service.

OBJECTIVES: 1) to provide a descriptive analysis of women's views of the antenatal care provided in the study centre; 2) to identify which aspects of antenatal care were important to women; 3) to assess whether or not women 'booked' for delivery at the study centre would welcome the formal introduction of a midwifery-led service and 4) to audit sources of satisfaction and dissatisfaction identified in the survey. DESIGN: descriptive survey using a self-administered questionnaire, and a self-administered audit questionnaire using a modified Measure of Satisfaction. SETTING: the antenatal clinic of one teaching hospital in the north of England between July 1993 and August 1993. The audit was conducted between December 1994 and February 1995. PARTICIPANTS: 110 women attending four 'follow up' antenatal clinics participated in the survey and 151 women participated in the audit. FINDINGS: many women felt they were already having midwifery-led care and that it was important to them to see a doctor during pregnancy. Generally the women were satisfied with antenatal care. Factors which caused dissatisfaction were, lack of continuity of care, quality of advice, waiting time and these were the focus of the audit. IMPLICATIONS FOR PRACTICE: local needs should be assessed before implementing changes in service. Elements of good practice should be identified to ensure that they are not compromised in a changing service. Further evaluation of the changing maternity service is needed to monitor satisfaction and dissatisfaction.

Adolescent↗
PubMed1996

Pharmacokinetics of caffeine in the oestrogen-implanted ovariectomized ewe.

The disposition kinetics of caffeine and its metabolites theophylline, theobromine and paraxanthine in the oestrogen-implanted ovariectomized ewe following single intravenous doses of 5, 10, 15 or 20 mg/kg caffeine are described in this paper. Blood was collected at 5, 30 and 60 min, and at 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192 and 240 h after dosing. Caffeine concentrations peaked within 30 min of administration but remained in a plateau phase for 3-6 h before declining over a prolonged period of time. For caffeine the mean elimination half-life was calculated to be 47 h. Detectable caffeine concentrations remained for 10 days after administration in all groups. The area under the plasma concentration-time curve (AUC) values were used to compare tissue caffeine exposure and were, approximately, linearly related to dose. Metabolite concentrations were maintained at peak and near peak concentrations for 6-24 h after caffeine administration followed by prolonged elimination. Because of significant species differences in drug elimination rates, it is concluded that the ewe is not a suitable animal model in the clinical context. However, the sheep may well provide insights into caffeine's mechanism of action of relevance to veterinary drug research.

Animals↗
PubMed1995

Transcription and translation of two glutamate decarboxylase genes in the ileum of rat, mouse and guinea pig.

gamma-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter, synthesised from glutamate by glutamate decarboxylase (GAD), in the central nervous system. Two forms of GAD, designated GAD 65 and GAD 67, are encoded by distinct genes and have been demonstrated in the mammalian brain. GABA has been postulated to be synthesised in neurons of the enteric nervous system (ENS), but evidence for its role as an enteric neurotransmitter is equivocal. We therefore aimed to determine whether GAD 65 and GAD 67 messenger RNAs (mRNAs) and proteins were expressed in the ileum of mice, rats and guinea pigs. Using an RNase protection assay, both GAD 65 and GAD 67 mRNAs were detected in the rodent small intestine. Antisera specific for GAD 65 or GAD 67, used in immunoblot analyses, revealed GAD 65-like and GAD 67-like immunoreactivity in rat and guinea pig ileum. Anti-GAD 65 antisera detected a major band of 65 kDa. Anti-GAD 67 antisera detected a major band of 55 kDa, which probably represented a breakdown product, and a minor band of 67 kDa. Analysis of immunoblot extracts of rat and guinea pig ileum revealed more GAD 67-like than GAD 65-like immunoreactivity. GAD enzymatic activity was high in the rat and guinea-pig brain, and low in the whole and dissected ileum. These results demonstrate that both GAD 65 and GAD 67 genes are transcribed and translated in the ileum of three rodent species and lend indirect support to the postulate that GABA is synthesised by neurons of the ENS and intestinal endocrine cells.

Amino Acid Sequence↗
PubMed1995

Feasibility study for identifying adverse events attributable to vaccination by record linkage.

To investigate the feasibility of using a record linkage method for identifying vaccine attributable adverse events, computerized hospital admissions and vaccination records from South East Kent district were linked and checked for accuracy. Records for 90% of children under 2 years of age admitted to hospital over a 2-year period were matched with vaccination records using a computer algorithm based on name, date of birth, sex, and post-code supplemented by visual inspection. Relative to this gold standard, matching on date of birth, sex and postcode alone had a sensitivity of 60% and an incorrect match rate of 0.2% after matches to more than one vaccine recipient were excluded. Manual checking of a sample of admissions showed that only 4% had been assigned incorrect International Classification of Disease (ICD) codes. Routine record linkage of ICD admission codes to vaccination records therefore yields data of good quality which may be used for surveillance purposes.

Adverse Drug Reaction Reporting Systems↗
PubMed1995

Research on hospital administrators' ethics: an agenda.

This discussion argues that whereas ethically questionable practices have been identified in many industries, the moral consequences of many hospital management decisions make this industry particularly worthy of ethics studies. Because health care, the hospital's product, typically represents more immediate, intimate, and possibly irreversible benefit or harm to its customer, the patient, than does the typical product of general industry, hospital executives should be held to higher ethical standards in their decision making. Yet little is known about the ethical thinking of hospital managers. Kohlberg's moral reasoning development theory and Rest's Defining Issues Test offer the theoretical base and the means to compare the ethical reasoning of hospital executives to that of their nonhospital counterparts in general industry. This research agenda can offer important clues regarding the need to emphasize ethics in health care industry educational programs.

Decision Making, Organizational↗
PubMed1995

An assessment tool for older patients.

A full and detailed assessment of older patients should include social circumstances. An assessment should identify problems of functional activity and use screening tools to aid referral to specialist multidisciplinary staff.

Activities of Daily Living↗