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Biomedical subjects

C Lyons

Publications and source records attributed to C Lyons.

At least 19 recordsLinked to original sources
PubMed1995

Implications for viral uncoating from the structure of bovine enterovirus.

We have determined the crystal structure of a bovine enterovirus, revealing that the topologies of the major capsid proteins and the overall architecture of the virion are similar to those of related picornaviruses. The external loops joining beta-strands are truncated and the canyon region is partially filled by an extension of the VP3 G-H loop giving the viral capsid a relatively smooth appearance. These changes may have implications for cell attachment. In spite of these differences the virus maintains a hydrophobic pocket within VP1, occupied by a specific 'pocket factor' which appears to be myristic acid. These observations support the proposal that a kinetic equilibrium exists between occupied and unoccupied pocket states, with occupation inhibiting uncoating.

Animals↗
PubMed1994

The role of the general practitioner hospital in inpatient care.

The rationale of the general practitioner hospital continues to be questioned. A study of the services and case-mix of two of the four remaining general practitioner hospitals in Northern Ireland was undertaken to determine whether the nature and cost of inpatient care in these hospitals was comparable to the available alternatives. The case-notes of all non-maternity admissions (n = 509) were reviewed. The two hospitals provide acute medical care for a wide range of patients. The majority of patients appeared to require hospitalisation. It is likely that the beds at the two hospitals were mainly a substitute for district general hospital care. The general practitioner hospitals were estimated to be less costly than alternative forms of care, although it was doubtful whether they fulfilled all the structural criteria of quality generally regarded as important for hospitals of this type.

Family Practice↗
PubMed1993

Preliminary crystallographic analysis of bovine enterovirus.

Bovine enterovirus (BEV) strain VG-5-27 derived from an infectious cDNA clone has been crystallized as extended hexagonal plates. Virus recovered from crystals produced cytopathic effect in BHK cells. These crystals diffract X-rays from high energy synchrotron sources to beyond 2.7 A. The crystal system is monoclinic, space group P2(1) with unit cell dimensions a = 388 A, b = 390 A, c = 360 A, beta = 113 degrees. The virion is 300 A in diameter and one whole particle constitutes the crystallographic asymmetric unit, giving rise to 60-fold non-crystallographic redundancy.

Animals↗
PubMed1992

Demonstration of antibodies in archival sera from Canadian seals reactive with a European isolate of phocine distemper virus.

Sera from seals infected during the 1988 European epizootic of phocine distemper virus and sera from Canadian seals collected since 1972 have been tested for the presence of antibodies to morbillivirus. Approximately one third of the Canadian sera have been shown to contain anti-morbillivirus antibodies; the possibility that these populations of seals provided a source of infection for European seals is discussed.

Animals↗
PubMed1992

Characteristics of a cetacean morbillivirus isolated from a porpoise (Phocoena phocoena).

A virus isolated from a porpoise during the 1988 seal epizootic was shown to be a morbillivirus. In order to determine the relationship of the virus to phocine distemper virus (PDV) a battery of monoclonal antibodies raised against canine distemper virus (CDV), PDV or the porpoise isolate were assessed for their ability to bind to CDV, PDV or porpoise virus epitopes in indirect immunofluorescence assays and ELISAs. The porpoise isolate contained several unique epitopes and several epitopes present on CDV and PDV were absent on the porpoise isolate. The data presented in this study indicate that the porpoise virus is an antigenically distinct morbillivirus and as such has been tentatively named as delphinoid distemper virus (DDV).

Animals↗
PubMed1992

Osteoclast recruitment in response to human bone matrix is age related.

The effect of bone matrix age on the recruitment and differentiation of osteoclast precursors was studied using the chick chorioallantoic membrane (CAM) implant system. Devitalized mineralized bone particles (75-250 microns) were prepared from human femoral cortical bone obtained postmortem from 8 men (age range: 18-72 years). The particles were implanted onto the CAM and 8 days later implants were harvested and processed for light microscopic, morphometric or immunohistochemical analysis. Histomorphometric analysis was performed on samples representing each donor age. The analysis was grouped into three categories consisting of bone from young adults (18-20 years), adults (34-53 years) and aged individuals (67 years and older). Total osteoclast number, osteoclast number per bone particle, cell area, cell size, number of nuclei per cell profile, nucleocytoplasmic ratio, and the presence of a distinctive osteoclast antigen defined by monoclonal anti-body 121F were determined. Bone matrix from older individuals, and therefore the oldest age group (67 years and older), elicited significantly fewer multinucleated cells when compared to bone matrix from younger donors. The number of nuclei per cell profile was highest in the adult population (34-53 years), and there was a continuous increase in cell area with aging. As a consequence, the nucleocytoplasmic ratio decreased from the youngest to the oldest age group. These findings indicate that, relative to factors that affect the recruitment and differentiation of osteoclast precursor cells, bone matrix of older individuals is changed in quality and/or quantity compared to bone matrix from younger individuals. It is hypothesized that this decline in osteoclast formation in response to older bone matrix may contribute to the impaired bone remodeling associated with aging.

Adolescent↗
PubMed1991

Cloning of the gene and amino acid sequence for glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides.

Amino acid sequencing of glucose 6-phosphate dehydrogenase (Glc6PD) from Leuconostoc mesenteroides yielded sequence for over 75% of the protein. Two oligonucleotides based on the amino acid sequence were used to isolate a partial Glc6PD gene clone (pLmz delta N65), from a pUC9 library, containing 85% of the coding sequence and the 3'-untranslated DNA, but lacking the 5'-noncoding DNA sequence and the portion of the gene encoding the 65 N-terminal amino acids. Attempts to obtain a full-length clone from lambda libraries were unsuccessful, possibly due to restriction of L. mesenteroides DNA by Escherichia coli host cells. The 5'-untranslated DNA was amplified by the polymerase chain reaction and partially sequenced. To obtain unmodified DNA for the gene, oligonucleotides corresponding to the 5'- and 3'-noncoding sequences were used to amplify the gene by the polymerase chain reaction, and a 1.8-kilobase pair fragment was isolated and cloned into pUC19. The recombinant plasmid, pLmz, contains the entire Glc6PD gene and expresses the gene in E. coli. pLmz was sequenced showing that the enzyme consists of 485 amino acids. L. mesenteroides Glc6PD is 31% identical to the human enzyme.

Amino Acid Sequence↗
PubMed1991

An interdistrict audit of vascular surgery.

The Interdistrict Audit of Vascular Surgery project entails the compilation of data on all new vascular patients who are referred, investigated and/or treated in three UK health authorities. The main aim is to create an accurate database containing process/outcome criteria, which can be interpreted as quality measures and which facilitates review of current practices. Data collection, which began in June 1990 and is scheduled to continue until March 1992, is by a series of proformas. Currently 503 patients are registered on the database, and preliminary results have shown that 28% of initial assessment patients go on to have an arteriogram, 9% are admitted to the hospital immediately and 7% are discharged back to the care of their general practitioner. At follow-up consultation, the patient's main presenting symptom had been cured in 38% of cases, but remained unchanged in 27% and had worsened in 5%. The paper concludes by examining the project against some success criteria and recounting some of the practical difficulties of data collection encountered so far.

Adolescent↗
PubMed1990

Medical audit data: counting is not enough.

OBJECTIVE: To assess the meaningfulness of a year's worth of audit data relating to all the inpatients of one consultant general surgeon and to question the usefulness of certain outcome measures. DESIGN: Analysis of records entered on to audit computer (Dunnfile) and relating to inpatient episodes for one consultant general surgeon over one year. Data obtained were compared with ward records and the patient administration system to check their accuracy. SETTING: The three hospitals and 12 wards in Brighton health district where the surgeon admitted patients. SUBJECTS: 859 Records relating to inpatient episodes from 1 January to 31 December 1988. These covered 655 main procedures and 79 secondary procedures performed at the same time. MAIN OUTCOME MEASURES: Procedures were analysed by complexity of operation (BUPA code) and grade of surgeon; complications were counted and rates constructed by surgeon and by BUPA code: returns to theatre were analysed. RESULTS: Simple counts revealed some data, such as the fact that one registrar performed more major operations (32) than the senior registrars (22 and 14), and an analysis of complications showed that he had a lower complication rate (11.4% v 20.0% and 19.4%). But the simple complication rate disclosed nothing about whether the complication was avoidable. Likewise, the number of returns to theatre needed further qualification. Analysis of data collection for February to April 1988 showed a 30% deficit of information on the audit system compared with ward records and prompted a re-examination of everyone's role in collecting data. After the year's audit there was still a 17% shortfall compared with the district's patient administration system, though some of this was accounted for by a backlog of work. CONCLUSIONS: It is difficult to ensure adequate data collection and entails everyone in an unfamiliar discipline. Connecting the audit system to the patient administration system would help. Despite the limitations of crude analyses of workload and complications rates, the audit data helped to measure activity and in the management of the firm. Nevertheless, time and care have to be taken in presenting and interpreting audit data carefully. IMPLICATIONS: Counting is not enough.

Aged↗
PubMed1990

Cloning and expression of human aldose reductase.

The complete amino acid sequence of human retina and muscle aldose reductase was determined by nucleotide analysis of cDNA clones isolated using synthetic oligonucleotide probes based on partial amino acid sequences of purified human psoas muscle aldose reductase. The cDNA sequence differs substantially in the noncoding and coding regions of recently published sequences of this enzyme. The mRNA for aldose reductase was abundantly expressed in HeLa cells, but only scarcely in a neuroblastoma cell line. Recombinant baculovirus containing one of the muscle cDNA clones was constructed and used to infect Spodoptera frugiperda (SF9) cells. A prominent protein with an apparent molecular size of 36 kDa was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the culture medium as well as in the homogenate of SF9 cells after 2 days of infection. Culture medium or the supernatant fraction of cell homogenates containing this protein had high aldose reductase activity which showed characteristics of the reported human enzyme. These findings indicate that the amino acid sequence reported in this paper represents human retina and muscle aldose reductase and that functional human aldose reductase can be expressed in large amounts in a baculovirus expression system. The result should facilitate refined structural analysis and the development of new specific aldose reductase inhibitors for the treatment of diabetic complications.

Aldehyde Reductase↗
PubMed1990

Enhancement of aldose reductase activity by modification of an active site lysine: a possible mechanism for in vivo activation.

Reaction of aldose reductase (ALR2) from pig muscle with pyridoxal 5'-phosphate (pyridoxal-P) and other lysine modifying reagents resulted in activation of the enzyme. The activation by pyridoxal-P showed pH and concentration dependence that was prevented by incubation with NADPH and various cofactor analogues but not by the aldehyde substrate. Spectral analysis of the reaction showed characteristic peaks associated with Schiff's base formation between a lysine amino group and the aldehyde of pyridoxal-P. Subsequent reduction produced spectra characteristic of a phosphopyridoxyllysine bond. Phosphopyridoxyllysine was isolated by amino acid analysis of modified ALR2. Determination of the stoichiometry of bound phosphopyridoxyllysine indicated one mole of pyridoxal-P per mole of enzyme under conditions that produced maximal activation. A single [3H]phosphopyridoxyllysine containing peptide was isolated by high performance liquid chromatography after enzymatic cleavage of the modified enzyme. This 34 residue peptide exhibited considerable sequence homology to the region comprising residues 242 to 275 of human liver ALR1 and a similar region in rat lens ALR2, human muscle ALR2 and human placental ALR2. The activation of ALR2 via formation of a Schiff's base suggests a possible mechanism of activation of the enzyme in vivo by glucose.

Aldehyde Reductase↗