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Biomedical subjects

D Walker

Publications and source records attributed to D Walker.

At least 289 records · Page 16Linked to original sources
PubMed1989

Neuronal maturation in the foetal brain in Down's syndrome.

Biochemical indices of neuronal maturation have been examined in postmortem cerebral cortex tissue from Down's syndrome (DS) and control foetuses matched for age. No differences were found in the concentration of neural cell adhesion molecule (N-CAM), or in the proportion of the 'adult' form of N-CAM, in the total concentration or composition of gangliosides, or in the activity of choline acetyltransferase (ChAT). The concentration of major lipid classes was also examined, and the DS specimens differed only in having a small but significantly higher proportion of phosphatidylcholine. The findings suggest that, by the indices examined, there is no delay in neuronal maturation, nor a major abnormality in lipid composition although anomalies in the polyunsaturated fatty acid composition of phosphoglycerides do exist at this stage of brain development in DS (J. Neurochem., 44 (1985) 869-874). Furthermore, the normal activity of ChAT found in the DS foetal cerebral cortex suggests that the impaired cortical cholinergic innervation which is apparent later in life may not be due to initial defects in cholinergic differentiation.

Antigens, Surface↗
PubMed1989

An investigation of apparent leukaemia clusters in Fife by validation of cancer register data and a case-control study.

Validation of the Fife haematological cancer register data from 1968 to 1981 for patients aged 0 to 24 submitted to the Black Advisory Group demonstrated 'catastrophic' or 'major' errors in 23 (19%) of the 124 records. A case-control study of 43 children with acute lymphoblastic leukaemia aged 0 to 14 at diagnosis in Fife between 1970 and 1985 showed that the Mantel-Haenszel odds ratio (ORMH) was significantly higher for children resident at birth in the post code district KY8 (ORMH = 3.86, 95% confidence interval 1.31-11.36) or who had ever lived in post code districts KY8 (ORMH = 4.00, 95% CI 1.51-10.58) or KY11 (ORMH = 2.35, 95% CI 1.08-5.12). We conclude that routine cancer registration data require extensive validation before they can be used for epidemiological purposes; case-control studies can overcome some of the methodological problems involved in investigating apparent leukaemia clusters; and further environmental investigations are needed in two post code districts of Fife.

Adolescent↗
PubMed1989

Alpha 1 antitrypsin (PI) phenotypes in two rheumatic diseases: a reappraisal of the association of PI subtypes in rheumatoid arthritis.

alpha 1 Antitrypsin phenotypes were determined by isoelectric focusing in 225 adult white patients with rheumatoid arthritis (RA), 60 patients with severe rheumatoid arthritis (grade III and IV), 17 sibling pairs--HLA identical but discordant for rheumatoid arthritis, and 122 random patients with Sjögren's syndrome. No significant increase in non-M phenotypes was found in either of the groups of patients with RA, but the association between M subvariants was striking. There was a significant increase in M1M2 phenotype and M2 allotype in both the RA and severe RA groups. This increase in M1M2 was also supported by DR4 positive patients with RA compared with DR4 positive siblings without RA. No apparent association of variant phenotype was found in four subgroups of patients with Sjögren's syndrome.

Alleles↗
PubMed1989

Measles--mumps--rubella immunization: the role of the general practitioner in achieving a high uptake.

A survey of all general practitioners in Fife conducted prior to the introduction of measles-mumps-rubella immunization on a pilot basis in May 1987 showed that 85% considered mumps worth preventing and 94% believed the rubella programme worth augmenting with universal childhood immunization. Ninety seven per cent considered measles worth preventing and 98% were prepared to recommend measles-mumps-rubella immunization to parents instead of measles vaccine. One year after introducing the measles-mumps-rubella vaccine in Fife, 91% of children had been immunized with the combined vaccine or measles vaccine before their second birthday. This compares with the 83% that received measles vaccine before the combined vaccine was introduced. Eighty per cent of preschool children were also immunized with the combined vaccine at school entry in a catch-up exercise. This study demonstrates that there are few major professional barriers to achieving a high uptake of the measles-mumps-rubella vaccine in this area. The vaccine was introduced nationally on 1 October 1988 and its uptake is likely to exceed the current unsatisfactory level achieved with measles vaccine. However, this outcome will largely depend on the commitment of doctors to the programme.

Humans↗
PubMed1989

Early Language Milestone Scale and language screening of young children.

The purpose of this project was to evaluate the use of the Early Language Milestone Scale (ELM) in screening language skills in young children. In this study, 657 children from birth to 36 months of age were evaluated with the ELM. The overall failure rate was 8%. Children who failed the ELM screening were evaluated with the Sequenced Inventory of Communication Development (SICD) that was used as the "gold standard" for diagnosing language disorders. In the 12-month age and younger group, there was poor agreement between the ELM Scale and the SICD. For infants 13 to 24 months of age, there was moderately good agreement between the SICD and a second ELM that was administered 1 to 2 weeks after the initial screening. In the 25- to 36-month age group, there was excellent agreement between the SICD and a rescreen ELM. The agreement between the two instruments indicated that the rescreen ELM correctly classified 79% of the 13- to 24-month-old infants and 89% of the 25- to 36-month-old toddlers.

Child, Preschool↗
PubMed1988

Enhancement of release of granulocyte- and granulocyte-macrophage colony-stimulating factors from phytohemagglutinin-stimulated sorted subsets of human T lymphocytes by recombinant human tumor necrosis factor-alpha. Synergism with recombinant human IFN-gamma.

The influence of purified recombinant human TNF-alpha (rhuTNF-alpha) was assessed, alone and in combination with purified recombinant human IFN-gamma (rhuIFN-gamma), for its effects on enhancing release from human T lymphocytes of activities that stimulate colony formation by granulocyte-macrophage, erythroid, and multipotential progenitor cells. rhuTNF-alpha or rhuIFN-gamma enhanced the release of CSF, which were determined to be granulocyte-CSF and granulocyte-macrophage-CSF by human bone marrow colony assays, morphologic assessment of colony types, and neutralization studies with rabbit anti-human granulocyte-CSF and monoclonal mouse anti-human granulocyte-macrophage-CSF. The CSF were released only when PHA was used, whether or not rhuTNF-alpha and/or rhuIFN-gamma were present while the lymphocytes conditioned the medium. T lymphocytes were sorted into subsets by using three-color immunofluorescence and a dye laser flow cytometry system with cells incubated with biotin anti-Leu-4 labeled with Texas Red, FITC-conjugated anti-Leu-3a, and phycoerythrin-conjugated anti-Leu-2a. Both the Leu-4+3a+2a- and the Leu-4+2a+3a- cells released CSF in response to PHA, but the release of CSF from PHA-stimulated lymphocytes was enhanced by rhuTNF-alpha and rhuIFN-gamma only from the Leu-4+3a+2a- subset of cells. Use of the three-color cell sorting made it highly unlikely that NK cells were involved, because both sorted subsets were positive for Leu-4. rhuTNF-alpha and rhuIFN-gamma synergized to enhance release of CSF such that low concentrations of each molecule, which were inactive when used alone, were active when the two molecules were used together. These studies suggest a role, at least in vitro, for TNF-alpha and IFN-gamma in the release of CSF from subsets of T lymphocytes stimulated with PHA.

Adjuvants, Immunologic↗
PubMed1988

Two copies of the human apolipoprotein C-I gene are linked closely to the apolipoprotein E gene.

The gene for human apolipoprotein (apo) C-I was selected from human genomic cosmid and lambda libraries. Restriction endonuclease analysis showed that the gene for apoC-I is located 5.5 kilobases downstream of the gene for apoE. A copy of the apoC-I gene, apoC-I', is located 7.5 kilobases downstream of the apoC-I gene. Both genes contain four exons and three introns; the apoC-I gene is 4653 base pairs long, the apoC-I' gene 4387 base pairs. In each gene, the first intron is located 20 nucleotides upstream from the translation start signal; the second intron, within the codon of Gly-7 of the signal peptide region; and the third intron, within the codon for Arg39 of the mature plasma protein coding region. The upstream apoC-I gene encodes the known apoC-I plasma protein and differs from the downstream apoC-I' gene in about 9% of the exon nucleotide positions. The most important difference between the exons results in a change in the codon for Gln-2 of the signal peptide region, which introduces a translation stop signal in the downstream gene. Major sequence differences are found in the second and third introns of the apoC-I and apoC-I' genes, which contain 9 and 7.5 copies, respectively, of Alu family sequences. The apoC-I gene is expressed primarily in the liver, and it is activated when monocytes differentiate into macrophages. In contrast, no mRNA product of the apoC-I' gene can be detected in any tissue, suggesting that it may be a pseudogene. The similar structures and the proximity of the apoE and apoC-I genes suggest that they are derived from a common ancestor. Furthermore, they may be considered to be constituents of a family of seven apolipoprotein genes (apoE, -C-I, -C-II, -C-III, -A-I, -A-II, and -A-IV) that have a common evolutionary origin.

Amino Acid Sequence↗
PubMed1988

Immunosuppression and murine polyomavirus infection.

Murine polyomavirus (MPYV) infection in mice has many similarities to human infections by BK virus (BKV) and JC virus (JCV) and provides a model for the human infections. MPYV causes acute, inapparent infection with virus appearing in numerous organs, including brain and kidney, and then subsides and becomes latent. At a later time it can be reactivated by corticosteroid treatment or pregnancy (McCance and Mims, 1979, McCance, 1983). To determine the effect of prolonged immunosuppression on virus activity in brain and kidney during acute infection, mice were treated with methotrexate, cyclophosphamide, or prednisone and azathioprine and inoculated with murine polyomavirus. Prednisone/azathioprine and cyclophosphamide caused protracted kidney infection and methotrexate had no effect. In the brain, prednisone/azathioprine and cyclophosphamide had minor effects on virus titers and course of infection, but methotrexate prevented MPYV from appearing in the brain. When mice were immunosuppressed with prednisone/azathioprine one week prior to inoculation, titers were much higher in the kidneys, but virus did not appear in the brain until late in the course of infection.

Animals↗
PubMed1988

The effects of progressive muscular relaxation on subjectively reported disturbance due to hospital noise.

Hospital noise has repeatedly been demonstrated to exceed levels recommended by the Environmental Protection Agency. Hospital noise from staff and machinery has been implicated in the etiologies of many behavioral disorders such as sleep deprivation, sensory overload, and altered comfort levels. Relaxation techniques have been shown to be effective in decreasing the aversiveness of many situations. This study tested the effects of progressive muscular relaxation (PMR) on subjectively reported disturbance due to hospital noise. In addition, noise sensitivity as a personality attribute was correlated with disturbance due to hospital noise and efficacy of PMR. A sample of 100 acutely ill hospitalized patients were randomly assigned to an experimental group or control group. The experimental group was instructed in the Bernstein-Borkovec technique of PMR; the control group received a short visit. Results revealed that the experimental groups had a significantly lower amount of disturbance due to hospital noise after being instructed in the use of PMR than prior to the intervention. Control group subjects demonstrated no such change. Noise sensitivity was found to be unrelated to either disturbance due to hospital noise or efficacy of PMR in decreasing disturbance due to hospital noise.

Affective Symptoms↗
PubMed1988

Observations on the causes of rheumatoid arthritis.

Inflammatory, symmetrical peripheral polyarthritis is observed in a small proportion of patients following a variety of parasitic, viral and microbial infections. The development of such a post-infective arthritis disorder may depend on a sequence of events, which need not be confined to one extrinsic pathogenic organism.

Arthritis, Infectious↗
PubMed1988

Enhancement of release from MHC class II antigen-positive monocytes of hematopoietic colony stimulating factors CSF-1 and G-CSF by recombinant human tumor necrosis factor-alpha: synergism with recombinant human interferon-gamma.

The influence of purified recombinant human tumor necrosis factor-alpha (rhuTNF-alpha) was assessed alone and in combination with purified recombinant human interferon gamma (rhuIFN-gamma) for its effects on enhancing release from human monocytes of activities that stimulate colony formation by granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells. RhuTNF-alpha or rhuIFN-gamma enhanced release of colony stimulating factors (CSFs), which were determined by a combination of human and mouse colony assays, morphological assessment of colony types and neutralization studies with anti-human macrophage CSF (CSF-1) and anti-human granulocyte (G)-CSF to be CSF-1 and G-CSF. The activity in the uninduced and induced monocyte conditioned media (CM) for CFU-GM-type colonies and clusters was attributed to the presence of both CSF-1 and G-CSF, while the activity in the monocyte CM for BFU-E and CFU-GEMM colonies was attributed to the presence of G-CSF. Monocytes were separated by two-color fluorescence using a dye laser flow cytometry system with cells labeled with anti-leu M3 conjugated with fluorescein isothiocyanate and anti-HLA-DR conjugated with phycoerythrin. While "constitutive" release of CSFs from monocytes was apparent from both the leu M3+, HLA-DR+ and the leu M3+, HLA-DR- (low density or negative DR) fractions, enhanced release of CSFs in response to rhuTNF-alpha or rhuIFN-gamma was confined to the leu M3+, HLA-DR+ population of cells. RhuTNF-alpha and rhuIFN-gamma synergized to enhance release of CSFs such that low concentrations of each molecule, which were inactive when used alone, were active when the two molecules were used together. These studies suggest a role, at least in vitro, for TNF-alpha and IFN-gamma in the release of CSFs from cells of the mononuclear phagocytic lineage.

Animals↗
PubMed1988

The detection of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes.

Study of very closely linked DNA variants at various loci has frequently shown linkage disequilibrium. We studied three closely linked RFLPs at the apolipoprotein AI-CIII locus. Two variants detected by MspI and SstI were in strong linkage disequilibrium; but when conventional statistical tests were used, a third variant (PstI), located between the MspI and SstI markers, appeared to be in linkage equilibrium with these two "outside" markers. Similar discrepancies from the expected monotone relationship between physical distance and linkage disequilibrium have been reported by others. To investigate these discrepancies, the power to detect linkage disequilibrium was calculated. It could be shown that, for the gene frequencies encountered, very large sample sizes would be required to demonstrate negative (i.e., repulsion-phase) linkage disequilibrium. Such numbers are usually very difficult to attain in human studies. Failure to demonstrate linkage disequilibrium by conventional methods therefore does not imply its absence. Appropriate nomograms and tables are provided.

Apolipoprotein A-I↗