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M Webb

Publications and source records attributed to M Webb.

At least 73 records · Page 4Linked to original sources
PubMed1995

Molecular studies on kinin receptors.

We describe the results of functional studies on DNA clones encoding functional bradykinin receptors derived from human, rat, and mouse sources and including both genomic and complementary DNA clones. In both the Xenopus oocyte and the COS cell expression systems, the receptors from human and rat showed the pharmacological properties of B2 receptors, but receptors from mouse displayed both B1- and B2-like pharmacological properties. We further investigated the molecular relationship between the B1 and B2 receptor subtypes expressed by a human fibroblast cell line, and we demonstrate that these two receptor subtypes are encoded by distinct mRNA species.

Amino Acid Sequence↗
PubMed1995

First admission incidence study of mania, 1975-1981.

BACKGROUND: A previous cross-national epidemiological study of first admission rates in London and in Aarhus, Denmark, found that the incidence of mania was virtually identical for both centres. This study sought to examine the corresponding rate for a defined catchment area in Dublin, Ireland, and to establish whether the impression of a higher rate could be validated. METHOD: The study combined a six-year retrospective review and one-year prospective collection of first-admission cases of mania from a defined catchment area. Diagnosis was according to ICD criteria and the Syndrome Check List of the Present State Examination (PSE). Cross-national comparisons were made using standardised incidence rate ratios (SIRs). RESULTS: The crude incidence rate for Dublin in the age range 18-60 years was established at 4.5 per 100,000 per year. A comparison of SIRs for the three centres showed the Dublin rate to be higher than expected (P < 0.02). Age-specific analysis indicated that this increase came mainly from the age range 18-29 (chi 2 = 9.08, P = 0.01). CONCLUSIONS: The study confirmed the impression that the local incidence of mania in Dublin is higher than that reported from two other North European centres. A variation in rates from contrasting socioeconomic districts within the catchment area points to some caution in the interpretation of the results and suggests further study from wider catchment areas.

Adolescent↗
PubMed1994

Deletions within the DNA recognition subunit of M.EcoR124I that identify a region involved in protein-protein interactions between HsdS and HsdM.

The DNA recognition subunit (HsdS) of type I restriction endonucleases can be divided into domains by means of amino acid identity between subunits from the same family. It has been proposed that DNA-protein interactions occur within the variable domains of the subunit and that protein-protein interactions involve the conserved domains. We have constructed a number of deletion mutants of HsdS that have allowed us to investigate protein-protein interactions. Using a combination of a "competitive" complementation assay and the ability of HsdM to "solubilize" HsdS, we have defined a region within the central conserved domain of HsdS that is responsible for HsdS-HsdM interaction. Computer analysis of amino acid identity between the N-terminal half and the C-terminal half of HsdS identifies a region (repeated in both conserved domains), one copy of which overlaps the region we have identified as essential for HsdS-HsdM interactions, which may be responsible for such protein-protein interactions.

Amino Acid Sequence↗
PubMed1994

Cerebral lupus.

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Adolescent↗
PubMed1994

B1 and B2 bradykinin receptors encoded by distinct mRNAs.

Bradykinin receptors have been subdivided into at least two major pharmacological subtypes, B1 and B2. The cDNAs encoding functional B2 receptors have recently been cloned, but no molecular information exists at present on the B1 receptor. In this article, we describe experiments examining the possible relationship between the mRNAs encoding the B1 and B2 types of receptor. We showed previously that the human fibroblast cell line WI38 expresses both B1 and B2 receptors. In this report, we describe oocyte expression experiments showing that the B1 receptor in WI38 human fibroblast cells is encoded by a distinct mRNA approximately 2 kb shorter than that encoding the B2 receptor. We have used an antisense approach in conjunction with the oocyte expression system to demonstrate that the two messages differ in sequence at several locations throughout the length of the B2 sequence. Taken together with the mixed pharmacology exhibited in some expression systems by the cloned mouse receptor, the data indicate that B1-type pharmacology may arise from two independent molecular mechanisms.

Amino Acid Sequence↗
PubMed1993

Percutaneous transluminal coronary angioplasty of one major coronary artery when the contralateral vessel is occluded.

OBJECTIVES: In 193 patients we evaluated the safety and efficacy of angioplasty of a critical stenosis of the right coronary artery (52 patients) or the left anterior descending coronary artery (141 patients), with the contralateral coronary artery occluded and the circumflex artery being without significant stenosis. BACKGROUND: Attempted angioplasty of either the left anterior descending or the dominant right coronary artery when the contralateral vessel is occluded may trigger overwhelming left ventricular dysfunction or hemodynamic collapse, or both. METHODS: Immediate and late outcome (33 +/- 18 months) in the study group were compared with outcome in 214 patients who had angioplasty in both the left anterior descending and right coronary arteries and in 194 patients who had coronary artery surgery and were matched for number and location of significant lesions, ejection fraction, age, gender and study period. RESULTS: Left ventricular function was normal (38%) or mildly (34%), moderately (22%) or severely (6%) compromised. There were 11 (5.7%) emergency and 5 (2.6%) elective coronary artery operations, 3 (1.6%) myocardial infarctions and 1 in-hospital death in the study group. After discharge there were 25 (13.1%) elective coronary operations, 7 (3.7%) myocardial infarctions and 9 (4.7%) deaths in the study group. The incidence of death and myocardial infarction was similar in all groups, with 80% power to detect a 7% difference in adverse events. The study group had more elective surgery before and after discharge than did the surgical control group (p = 0.02). CONCLUSIONS: Dilating one major vessel when the contralateral vessel is occluded appears to be as safe as coronary surgery or two-vessel angioplasty. Incomplete revascularization in study group patients did not impair survival or increase myocardial infarction compared with the angioplasty and surgical control groups.

Actuarial Analysis↗
PubMed1993

A deletion mutant of the type IC restriction endonuclease EcoR1241 expressing a novel DNA specificity.

We have developed a complementation assay which allows us to distinguish between mutations affecting subunit assembly and mutations affecting DNA binding in the DNA recognition subunit (HsdS) of the multimeric restriction endonuclease EcoR1241. A number of random point mutations were constructed to test the validity of this assay. Two of the mutants produced were found to be truncated polypeptides that were still capable of complementation with the EcoR1241 Hsd subunits to give an active restriction enzyme of novel DNA specificity. The N-terminal variable domain (responsible for recognition of GAA from the EcoR1241 recognition sequence GAAnnnnnnRTCG) and the spacer region (central conserved region) is intact in both of these mutants. One of these mutant genes (hsdS(delta 50) has been cloned as an active Mtase. Purification of the Mtase proved to be difficult because the complex is weak. However, Mtase activity was obtained from a soluble cell extract, and this allowed us to determine the DNA recognition sequence of the Mtase to be GAAnnnnnnnTTC. This recognition sequence is an inverted repeat of 5'-end of the EcoR1241 recognition sequence. This suggests that the mutant Mtase is assembled from two inverted HsdS(D50) subunits, possibly held together by the HsdM subunits.

Amino Acid Sequence↗
PubMed1993

Can a surgical treatment centre reduce waiting lists? Results of a natural experiment.

STUDY OBJECTIVE: To determine the effectiveness of the Welsh general surgery (hernia and varicose veins) treatment centre established as part of the NHS reforms, in terms of its impact upon throughput and waiting lists. DESIGN: This was a natural experiment with two control groups--other surgical specialties without treatment centre provision, and general surgery in districts that made only minor use of the facility. SETTING: General Surgery Treatment Centre, Bridgend General Hospital. SUBJECTS: All patients referred between 1 April 1990 and 31 March 1991. MEASUREMENTS AND MAIN RESULTS: Main outcome measures were throughput for hernia and varicose vein operations, non-urgent inpatient waiting list lengths before and after the opening of the centre and patient satisfaction. Altogether 1097 patients were referred during the year. Of these, 160 (15%) did not attend outpatient assessment and 79 (8%) of those who did were unsuitable for surgery. A total of 750 operations were performed--448 (60%) for varicose veins and 261 (35%) hernia repairs. Among the residents of the four main districts using the centre (with valid data available), there was a significant increase in the total number of varicose vein operations performed but no significant increase in hernia repairs. In the six districts that made major use of the centre, general surgery waiting lists for non-urgent cases fell significantly (p < 0.0001) while those for ear, nose, and throat showed no significant change and gynaecology lists lengthened significantly (p < 0.0001). In the three districts that made minor use of the centre general surgery waiting lists showed no change. CONCLUSIONS: Relations between inputs and waiting lists are often unpredictable, but after controlling for confounding trends there is sound evidence that such a centre provides an acceptable and effective approach to the waiting list problem.

Age Factors↗
PubMed1993

Preparation of highly purified human myelin oligodendrocyte glycoprotein in quantities sufficient for encephalitogenicity and immunogenicity studies.

Myelin oligodendrocyte glycoprotein, (MOG), a quantitatively minor central nervous system (CNS) myelin component, is a candidate target antigen for autoimmune-mediated demyelination. It is a highly hydrophobic protein present in very small amounts in CNS tissue and thereby difficult to purify. Our aim was to devise a purification procedure that would yield sufficient quantities of highly purified MOG to subsequently test its potential encephalitogenic activity, as well as investigate the humoral and cell-mediated responses to this antigen in naturally occurring and experimentally induced autoimmune demyelinating diseases. MOG was purified from human CNS white matter using immunoaffinity chromatography, a procedure that gave a final yield of MOG corresponding to 0.02% total white matter protein. The final product, which migrated as two bands of molecular weight 28 kDa and 58 kDa, was highly pure as shown also by specific reactivity with monoclonal anti-MOG antibodies on immunoblots in the absence of any detectable reactivity with antibodies specific for myelin basic protein, proteolipid protein and myelin-associated glycoprotein. Partial amino acid sequence was obtained from both MOG bands separated by SDS-PAGE and electroblotted onto PVDF. The sequence of the first 17 N-terminal amino acids had approximately 55% homology with the reported rat MOG sequence deduced from the cloned cDNA sequence; small internal sequences obtained showed also very high homology. Our purified MOG preparations have been used to investigate T cell response to MOG by peripheral blood lymphocytes of multiple sclerosis patients and to induce a relapsing remitting demyelinating disease in Lewis rats.

Amino Acid Sequence↗
PubMed1993

Cloned murine bradykinin receptor exhibits a mixed B1 and B2 pharmacological selectivity.

We have isolated DNA clones encoding functional bradykinin receptors from human, rat, and mouse sources. Genomic bradykinin receptor clones have been isolated from mouse and human cosmid libraries and cDNA clones have been isolated from the human lung fibroblast cell line W138, from the neuroblastoma/glioma hybrid NG108-15, and from rat dorsal root ganglion cells. The receptor protein is encoded by an intronless region of the gene in both mouse and human. There is evidence of a splice acceptor site 8 bases upstream from the initiation codon in all three species. The function of the expressed receptor proteins from mouse, rat, and human was tested by electrophysiological assays after injection of cRNA into Xenopus laevis oocytes and also by binding assays with membranes from COS-7 cells transfected with cloned receptor-encoding DNA. The receptors from human and rat showed the pharmacological properties of B2 receptors in both expression systems when tested with a variety of bradykinin analogues, but receptors from mouse divided into two populations, one population with pharmacological properties of B1-like receptors and another, larger, population with properties of B2 receptors.

Amino Acid Sequence↗
PubMed1992

Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.

We report the occurrence of Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl who was one of identical twins. Molecular studies showed nonrandom X-inactivation in both her fibroblasts and lymphocytes, while her normal twin showed equal usage of both X chromosomes. In view of previous reports of 7 pairs of identical female twins in which one had Duchenne muscular dystrophy, it seems that twinning may be strongly associated with nonrandom X-inactivation, and is not specific to the properties of the disease causing gene.

DNA Probes↗
PubMed1992

Monoclonal antibodies reveal molecular differences between terminal fields in the rat dentate gyrus.

We have derived a number of monoclonal antibodies which detect molecular differences correlating with the afferent inputs to the molecular layer of the adult rat hippocampal dentate gyrus. One group, dubbed OM-1 to OM-4, strongly stain the outer zone of the molecular layer, which receives its major innervation from the ipsilateral entorhinal cortex. A second group, IM-1 and IM-2, show a complementary pattern and preferentially stain the inner molecular layer, which receives inputs from the ipsilateral and contralateral hippocampus. These antigens are not, however, restricted to these layers, being found outside the hippocampus in several other areas of neuropil in the adult brain. In the developing brain the IM-1 antigen appears ubiquitously from the earliest age studied, embryonic day 12. Within the dentate gyrus, its restriction to the inner terminal field of the molecular layer only occurs during the second postnatal week. In contrast, OM staining appears only sparsely and late in the prenatal brain, appearing in developing cortical white matter between embryonic days 18 and 20. The outer dentate molecular layer becomes OM-positive from birth onwards, corresponding to the time of arrival of entorhinal axons during the first postnatal week. These two groups of monoclonal antibodies recognize a number of different glycoproteins. Ultrastructural immunohistochemistry shows they are cell surface molecules, and as such may be involved in the recognition events required for the establishment of specific patterns of neuronal connectivity.

Animals↗