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Biomedical subjects

A J Russell

Publications and source records attributed to A J Russell.

At least 55 records · Page 3Linked to original sources
PubMed1998

Molecular barriers to biomaterial thrombosis by modification of surface proteins with polyethylene glycol.

For cardiovascular biomaterials, thrombosis, thromboembolism and vascular graft occlusion are believed to be precipitated by the adsorption of proteins containing adhesive ligands for platelets. Polyethylene-glycol-diisocyanate (PEG-diisocyanate, 3400 MW) may potentially react with protein amines to form molecular barriers on adsorbed proteins on biomaterials, thereby masking adhesive ligands and preventing acute surface thrombosis. To test this notion, PE, PTFE, and glass microconduits were pre-adsorbed with fibrinogen and treated with PEG-diisocyanate, non-reactive PEG-dihydroxyl, or remained untreated. Following perfusion of 111In-labeled platelets in whole human blood for 1 min (wall shear rate = 312 s(-1)), PEG-diisocyanate treated surfaces experienced 96% (PE), 97% (PTFE) and 94% (glass) less platelet deposition than untreated surfaces. Similar reductions were seen for PEG-diisocyanate versus PEG-dihydroxyl treatment. Low shear perfusions of plasma for 1 h prior to blood contact did not reduce the inhibitory effect of PEG-diisocyanate. Platelet adhesion onto collagen-coated glass coverslips and platelet deposition onto preclotted Dacron were also reduced by treatment with PEG-diisocyanate (93 and 91%, respectively). Protein-reactive PEG may thus have utility in forming molecular barriers on surface-associated proteins to inhibit acute thrombosis on cardiovascular biomaterials.

Adsorption↗
PubMed1997

Differential expression of CD32 isoforms following alloactivation of human T cells.

Receptors for the Fc region of immunoglobulin G (IgG) (Fc gamma Rs) exist in three main forms: membrane bound, soluble and cytoplasmic. The function of cytoplasmic Fc gamma Rs is poorly understood. We have previously demonstrated cytoplasmic Fc gamma RII (cCD32) within most normal human peripheral blood lymphocytes (PBL), including T cells. In this study we have investigated the hypothesis that following lymphocyte activation, up-regulation of cCD32 occurs, resulting in increased expression at the cell surface. Normal PBL were activated in vitro using a two-way mixed lymphocyte reaction (MLR) and expression of CD32 monitored by flow cytometry and by immunoperoxidase staining using specific monoclonal antibodies and aggregated mouse IgG subclasses. Furthermore, we designed oligonucleotide probes specific for the three main isoforms of CD32 and looked for changes in mRNA expression throughout the MLR using an in situ hybridization technique. Increased surface expression of CD32 was found on both activated human T and B lymphocytes, but this was found only in the early stages of the MLR, on days 3 and 4, and was virtually absent by day 7. An inverse relationship between cell surface expression of CD32 and mRNA for the IIb isoforms was noted with strong mRNA expression for IIb isoforms occurring in the later stages of the MLR (days 6-7) when interleukin-2R (IL-2R)-positive T cells were predominant. A soluble IgG binding factor (soluble CD32?) was also detected in the MLR culture supernatant. These observations provide support for the hypothesis that synthesis of IIb isoforms of CD32 occurs following alloantigen activation of human T lymphocytes.

Flow Cytometry↗
PubMed1997

Schizophrenia and the myth of intellectual decline.

OBJECTIVE: The authors' goal was to investigate the issue of intellectual deterioration in schizophrenia. METHOD: They examined the childhood IQs of adult patients with schizophrenia who had attended a child psychiatry service where measurement of intelligence was routine. Follow-up IQs of 34 of these patients were obtained an average of 19.4 years later. RESULTS: The mean child and adult IQs were greater than one standard deviation lower than those of the general population. There were no significant differences between the child and adult IQs, however, suggesting that the impairment in intelligence during childhood was stable over the follow-up period. CONCLUSIONS: The deficit in intellectual function observed in these patients, and reported in the literature, is lifelong and predates the onset of schizophrenia.

Adolescent↗
PubMed1997

Guidelines for dyspepsia management in general practice using focus groups.

BACKGROUND: There is a paucity of published guidelines on managing dyspepsia in general practice. Existing guidelines emphasize the role of investigations and drugs rather than management approaches. Focus groups are a means of uncovering the way in which the participants think and work in the pragmatic-setting, and have not previously been formally used in creating guidelines. AIM: To develop guidelines for the management of dyspepsia and to assess the use of focus groups of general practitioners (GPs) in order to do so. METHOD: Initial evidence-based guidelines were proposed by a group of four GPs with an audit facilitator, and used for discussion in three focus groups using a standard format. An anthropological analysis of the proceedings led to modifications of the original guidelines, based on knowledge, perceptions and attitudes. The study was set in three distinct locations involving 30 GPs. The outcome measures consisted of feedback, categorized by types of responses, from the analysis of the focus groups and the creation of guidelines. RESULTS: The resulting guidelines were patient centred and based on the principles of good consultation. They encompassed patients' fears and doctors' clinical uncertainties, and allowed flexibility in the individual patient's management. The focus group methodology exposed a substantial number of GPs to guideline development, and had the added benefits of dissemination, peer review and educational challenge. CONCLUSION: It was possible to develop guidelines for dyspepsia using focus groups. The methodology had the added benefits of ownership, peer review, exposure of educational gaps and locality factors, and dissemination of good practice. It included steps from evidence review to implementation strategies. The development of this technique could lead to a strategy towards the creation and application of evidence-based and professionally acceptable clinical guidelines and practice on a locality basis nationally.

Dyspepsia↗
PubMed1996

The moss, Physcomitrella patens, transformed with apoaequorin cDNA responds to cold shock, mechanical perturbation and pH with transient increases in cytoplasmic calcium.

The gene for apoaequorin has been used previously to indicate cytosolic calcium changes in higher plants. Here we report the transformation of the moss Physcomitrella patens with the cDNA for apoaequorin. Stable transformants were obtained in the wild type which reconstitute the calcium-sensitive luminescent protein aequorin in vivo after incubation in coelenterazine, and continue to grow normally. The wild type responds to cold-shock (0-10 degrees C) with increases in cytosolic calcium. Mechanical perturbation, in the form of touch, also induces transient increases in cytosolic calcium. A smaller response to pH, distinct from the touch response and exhibiting different kinetics, can also be detected.

Aequorin↗
PubMed1996

The care of pregnant women with epilepsy--a survey of obstetricians in Scotland.

There is concern regarding the teratogenic risks of antiepileptic drugs (AEDs) and the effect of seizures during pregnancy. Pre-pregnancy assessment and collaboration with the patient's neurologist may improve outcome. This study examined by postal questionnaire how senior obstetricians in Scotland cared for their patients with epilepsy in March 1994. One hundred and nine of 127 (86%) practising obstetricians representative of those working in both teaching and district general hospitals in Scotland responded. Only 16% of district general hospital obstetricians had an accessible epilepsy clinic/service and 19% a neurologist. Only 21% of all respondents considered that pregnancy counselling was being provided by a neurologist/epilepsy specialist, and only 43% were usually able to organize combined specialist care with an interested physician/neurologist. Most (79%) were happy with the concept of collaborative care. Many were uncertain as to the importance of recording epilepsy severity, genetic aspects, making changes to AEDs, monitoring drug levels, the use of vitamin K and breast feeding. Sixty-four per cent did not change their management of labour. Twenty per cent were dissatisfied with the present care of their patients with epilepsy. Over 90% considered guidelines to be important. This survey demonstrates the need for existing epilepsy services to be more accessible to all obstetricians in Scotland, particularly for those working in district general hospitals.

Abnormalities, Drug-Induced↗
PubMed1995

Effects of mechanical signaling on plant cell cytosolic calcium.

Mechanical signals are important influences on the development and morphology of higher plants. Using tobacco transformed with the Ca(2+)-sensitive luminescent protein aequorin, we recently reported the effects of mechanical signals of touch and wind on the luminescence and thus intracellular calcium of young seedlings. When mesophyll protoplasts are isolated from these transgenic tobacco plants and mechanically stimulated by swirling them in solution, cytoplasmic Ca2+ increases immediately and transiently up to 10 microM, and these transients are unaffected by an excess of EGTA in the medium. The size of the transient effect is related to the strength of swirling. Epidermal strips isolated from transgenic tobacco leaves and containing only viable guard cells and trichomes also respond to the strength of swirling in solution and can increase their cytoplasmic Ca2+ transiently up to 10 microM. Finally, the moss Physcomitrella patens containing recombinant aequorin exhibits transient increases in cytoplasmic Ca2+ up to 5 microM when swirled in solution. This effect is strongly inhibited by ruthenium red. Our data indicate that the effect of mechanical stimulation can be found in a number of different cell types and in a lower plant as well as tobacco and suggest that mechanoperception and the resulting increase in cytoplasmic Ca2+ may be widespread.

Aequorin↗
PubMed1995

New members of the 3 beta-hydroxysteroid dehydrogenase gene family.

Several bands of hydridization are detected when southern blots of human genomic DNA are proved with cDNA of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) type I. Two experimental approaches were adopted to estimate the size of the 3 beta-HSD gene family. Firstly, primer designed to amplify 3 beta-HSD type I and II genes were found on occasion to amplify DNA products of appropriate length but which were resolved as distinct sequences by denaturing gradient gel electrophoresis (DGGE). Five of these novel bands were cloned and their sequences were found to be closely related to 3 beta-HSD types I and II. Secondly, 57 genomic clones were selected from two lambda genomic libraries by hybridization with exonic probes of 3 beta -HSD type I. These were screened for novel members of the gene family by pcr amplification using various combinations of PCR primers to the type I and II genes, particularly those primers that previously amplified novel PCR products from genomic DNA. Amplification products from (lambda) clones were screened for novel sequences by DGGE. As a result of these approaches, at least five new members of the 3 beta-HSD gene family were found, one of which locates to the 3 beta -HSD type I and II gene cluster on 1p13. The existence of additional closely related but distinct members of the gene family should be recognized as a potential complication when screening PCR fragments for mutations in the type I and II genes. DGGE was found to be an exceedingly rapid means of screening amplification products from (lambda) clones to search for novel members of the gene family.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

The human 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene cluster on chromosome 1p13 contains a presumptive pseudogene; 3 beta-HSD and CYP17 do not segregate with dominantly inherited hirsutism.

Four hirsute females from a family exhibiting idiopathic dominant hirsutism were examined. Basal blood levels of delta 5 and delta 4 steroids were within the normal range, but ACTH stimulation led to increases in 17-hydroxypregnenolone and dehydroepiandrosterone that were significantly above control levels. Using polymorphic genetic markers, the genes for cytochrome P450c1717 encoded by CYP17, and the type I and II forms of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) were found not to segregate with hirsutism in this family, though a base substitution was detected in the 3' end of exon 1 of the gene for 3 beta-HSD type I in three of the four patients investigated. Analysis of PCR patients amplification products by denaturing gradient gel electrophoresis (DGGE) and sequencing revealed a novel homologue of exon 3 of 3 beta-HSD. DNA of one of the affected patients was used to create a genomic library in lambda gem 11 and clones containing the novel homologue were obtained and partially sequenced. The equivalent clone was obtained from a genomic library of an unrelated normal individual. The sequences of the clones from patient and control were identical and homologous to exons 2-4 of human 3 beta-HSD types I and II. No difference was found in the PCR primer sites that flanked the exons 3 homologue which led to its detection on DGGE gels. In both clones, stop codons and deletions were identified in the exon 4 homologue, leading to the deduction that the sequence comes from a pseudogene, which we call 3 beta-HSD psi 1. The pseudogene mapped to chromosome 1p13. It was concluded that dominantly inherited idiopathic hirsutism in this rare kindred was not due to deficiencies in 3 beta-HSD types I, II, or psi or of CYP17).

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

Mutation in 3 beta-hydroxysteroid dehydrogenase type II associated with pseudohermaphroditism in males and premature pubarche or cryptic expression in females.

A mutation (A82T) is described in the coding sequence of the gene for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) type II that is associated with variable clinical consequences. Four homozygotes are described, all of which showed elevated levels of delta 5 steroids consistent with 3 beta-HSD deficiency. Two males from a consanguineous family were found to be homozygous for A82T and were affected with pseudohermaphroditism. They differed in their degree of mild salt loss. In the same family a female was found to be homozygous for A82T, but was clinically normal and had no history of premature pubarche or of abnormal menstrual cycles. However, in an apparently unrelated family, the A82T mutation was found in a female affected with premature pubarche. This is the first report of a proven mutation in 3 beta-HSD type II associated with premature pubarche.

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

Mutation in the human gene for 3 beta-hydroxysteroid dehydrogenase type II leading to male pseudohermaphroditism without salt loss.

A 5-year-old XY pseudohermaphrodite was found to have a defect of steroid biosynthesis consistent with a partial deficiency of the enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). Circulating concentrations of delta 5 steroids and delta 5 urinary steroid metabolites were elevated and remained elevated after orchidectomy. There was no evidence of salt loss, plasma renin being within normal limits, and no detectable glucocorticoid abnormality. The coding sequences of the genes for 3 beta-HSD types I and II were amplified by PCR and screened for mutations by denaturing gradient gel electrophoresis (DGGE) and manual and automatic DNA sequencing. A mutation in the gene for 3 beta-HSD type II was observed at codon 173 (CTA-->CGA), leading in the affected patient to a homozygous substitution in which the leucine at residue 173 was altered to an arginine (L173R). The propositus's 2-year-old XX sister was also homozygous for L173R and showed the biochemical characteristics of partial 3 beta-HSD deficiency without clinical symptoms or signs. The mutation segregated as an autosomal recessive. Three related heterozygous adult females showed evidence of a small over-production of delta 5 steroids and steroid metabolites and a variable reduction in ovarian function. Concentrations of delta 5 steroids and steroid metabolites in the heterozygous father of the propositus were within the normal range. These data are discussed in relation to the endocrine causes of pseudohermaphroditism and hirsutism. Evidence for tight linkage between the genes for 3 beta-HSD types I and II was obtained using a microsatellite polymorphism in the third intron of the gene for 3 beta-HSD type II and synonymous and non-synonymous mutations and polymorphisms in the gene for 3 beta-HSD type I. The latter polymorphisms were located 88 bp apart at the 3' end of the type I coding sequence and could be physically resolved as haplotypes using DGGE. The application of DGGE to the analysis of mutations in members of a multigene family is discussed.

3-Hydroxysteroid Dehydrogenases↗
PubMed1993

Biocatalytic synthesis of acrylates in supercritical fluids: tuning enzyme activity by changing pressure.

Supercritical fluids are a unique class of nonaqueous media in which biocatalytic reactions can occur. The physical properties of supercritical fluids, which include gas-like diffusivities and liquid-like densities, can be predictably controlled with changing pressure. This paper describes how adjustment of pressure, with the subsequent predictable changes of the dielectric constant and Hildebrand solubility parameter for fluoroform, ethane, sulfur hexafluoride, and propane, can be used to manipulate the activity of lipase in the transesterification of methylmethacrylate with 2-ethyl-1-hexanol. Of particular interest is that the dielectric constant of supercritical fluoroform can be tuned from approximately 1 to 8, merely by increasing pressure from 850 to 4000 psi (from 5.9 to 28 MPa). The possibility now exists to predictably alter both the selectivity and the activity of a biocatalyst merely by changing pressure.

Acrylates↗
PubMed1993

Use of Blount's epiphyseal staples to control massive iliac venous haemorrhage.

Significant injuries to major veins are life-threatening events and may lead to patient exsanguination. Treatment usually consists of direct suture repair. A case in which a serious iliac venous haemorrhage was not able to be controlled with the usual surgical procedures is reported. A desperate attempt to achieve haemostasis using orthopaedic staples was successful. The simplicity of this technique makes it a useful addition to the surgeon's armamentarium when dealing with life-threatening venous haemorrhage.

Aged↗
PubMed1992

Role of diffusion in nonaqueous enzymology. 1. Theory.

Using a set of standard equations, we have calculated the role of internal and external mass transfer in limiting the rate of enzyme-catalysed reactions in anhydrous organic solvents and supercritical fluids. We have shown that enzyme particles suspended in anhydrous organic solvents will be subject to increasing diffusional limitation as the enzyme activity and particle size increase. Using particle dimensions, as measured by scanning electron microscopy, we have prepared a series of graphs that will enable investigators to determine whether their combination of particle size and activity will result in internal or external diffusional limitations. We have shown that supercritical fluids can be expected to enhance the activity of enzymes in nonaqueous environments as a result of the high diffusivity of the bulk solvent. The plots also clearly indicate that enzyme particles in supercritical fluids require nearly two orders of magnitude less agitation than those suspended in conventional solvents in order to overcome any external mass transfer limitations.

Catalysis↗