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Biomedical subjects

D Walker

Publications and source records attributed to D Walker.

At least 307 records · Page 17Linked to original sources
PubMed1988

Abnormalities of visual evoked responses in hyperprolactinaemia.

The relationship between the visual evoked response (VER) and chiasmal lesions remains unclear, although a few published studies have reported waveform distortions as the major abnormality. In this study of 10 female and 2 male patients we carried out a retrospective analysis of the latencies and waveforms of their full field and half field VERs to pattern reversal stimulus. CT scanning showed minimal suprasellar involvement in 3 patients. The VER in 2 of these 3 patients showed slight prolongation in latency and waveform distortions. In 4 of the remaining 9 patients with no suprasellar involvement, the VER showed waveform distortions but normal latencies. We conclude that waveform distortion of the VER is an early finding in patients with pituitary tumours, even in the absence of suprasellar extension.

Adolescent↗
PubMed1987

The immune response to Schistosoma mansoni infections in inbred rats. VI. Regulation by T cell subpopulations.

These studies assess the roles of subpopulations of T lymphocytes in inducing and modulating resistance to Schistosoma mansoni. CDF rats were depleted of RT 7.1+ (anti-Pan-T), W3/25+ (anti-T helper/inducer), or OX8+ (anti-T suppressor) cells by the in vivo administration of monoclonal antibodies (mAb). The development of parasites and immunity to challenge by S. mansoni were compared with results in undepleted normal and congenitally athymic rats. Discrete subpopulations of T lymphocytes were adoptively transferred to ascertain effects upon parasite development and the protective immune response. In vitro studies, involving utilizing cocultivation of cell subpopulations +/- cyclosporin A, were utilized to dissect mechanisms. Depletion of T lymphocytes by anti-RT7.1 mAb and anti-W3/25 mAb resulted in augmented initial worm development, suboptimal resistance, and decreased antibody and delayed-type hypersensitive reactivity directed against schistosome antigens. Depletion with OX8 mAb produced opposite effects. The adoptive transfer of T cell subpopulations produced concordant results with T cell regulation expressed B cell-dependent effector mechanisms. The coadoptive transfer of cells resulted in the suppression of resistance afforded by the W3/25+ cells by OX8+ cells, which could be augmented in vitro by cyclosporin A. Thus, protective immunity to S. mansoni in rats is regulated by discrete subpopulations of T lymphocytes. The findings suggest the possibility of selective immune regulation of resistance based on the manipulation of specific T cell subpopulation.

Animals↗
PubMed1987

Characterization of adult human marrow hematopoietic progenitors highly enriched by two-color cell sorting with My10 and major histocompatibility class II monoclonal antibodies.

Monoclonal antibodies, My10 (HPCA-1) and major histocompatibility class II (HLA-DR), were used to enrich and phenotype normal human marrow colony-forming unit: granulocyte-macrophage (CFU-GM), burst-forming unit: erythroid (BFU-E), and multipotential colony-forming unit: granulocyte-erythroid-macrophage-megakaryocyte (CFU-GEMM) progenitor cells. Nonadherent low density T lymphocyte-depleted marrow cells were sorted on a Coulter Epics 753 dye laser flow cytometry system with the use of Texas Red-labeled anti-My10 and phycoerythrin conjugated anti-HLA-DR. Cells were separated into populations with nondetectable expression of antigens (DR-My10-) or with constant expression of one antigen and increasing densities of the other antigen. More than 98% of the CFU-GM, BFU-E, and CFU-GEMM were found in fractions containing cells expressing both HLA-DR and My10 antigens. The cloning efficiency (CE) of cells in the DR-My10- cell fraction was 0.01%. In the antigen-positive sorted fractions, the CE was highest (up to 47%) in the fractions of cells expressing high My10 and low DR (My10 DR+) antigens and was lowest (2.5%) in the fraction of cells expressing low My10 and low DR (My10+DR+) antigens. Populations of cells varying in the density of HLA-DR, but not My10, antigens varied in the proportion and types of progenitor cells present. When My10-positive cells were sorted for HLA-DR density expression, the CE for CFU-GM was similar in the DR+ and DR++ fractions, but most of the BFU-E and CFU-GEMM were found in the DR+ fraction. Within the CFU-GM compartment, most of the eosinophil progenitors were found in the DR+ fraction, whereas a greater proportion of macrophage progenitors were detected in the DR++ fraction. CFU-GM and BFU-E in the fractions of cells positive for DR and My10 were assessed for responsiveness to the effects of recombinant human tumor necrosis factor-alpha, recombinant human interferon-gamma, and prostaglandin E1. Colony formation from CFU-GM was suppressed by the three molecules, and colony formation by BFU-E was suppressed by recombinant human tumor necrosis factor-alpha and interferon-gamma and enhanced, in the presence of T lymphocyte-conditioned medium, by prostaglandin E1 in all antigen-positive fractions.(ABSTRACT TRUNCATED AT 400 WORDS)

Alprostadil↗
PubMed1987

Structure and evolution of human apolipoprotein genes: identification of regulatory elements of the human apolipoprotein E gene.

The structures of the major human apolipoprotein genes have been determined. The genes for apoE, apoC-I, apoC-II, apoC-III, apoA-I, apoA-II and apoA-IV have similar structures, consisting of four exons and three introns, which suggests that they evolved from a common ancestral gene. The third and fourth exons of the ancestral gene appear to have evolved from the duplication of a 66-nucleotide repeat unit that encodes a 22-residue alpha-helical peptide element of amphipathic character. The apoA-I, apoC-III and apoA-IV genes are linked closely within a 20-kilobase (kb) span of chromosome 11. The apoE and apoC-I genes, together with an apoC-I' pseudogene, are linked closely within a 25-kb span of chromosome 19. To characterize potential functional relationships among the apolipoprotein genes, initial studies have been done to identify the molecular elements involved in the regulation of the human apoE gene. Fragments of the 5'-flanking portion of this gene were inserted into appropriate plasmid vectors, which contained the bacterial chloramphenicol acetyl transferase gene, and were examined for promoter activity and potential enhancer activity after transfection into cultured mammalian cells. Deletion mapping of the promoter region has identified multiple functional elements, including an enhancer, two G-C boxes (Sp 1 transcription factor binding sites) and an upstream control element. In addition, there is an enhancer located in the first intron. Interactions among these various control elements are likely to determine the ways in which the expression of the apoE gene is regulated.

Apolipoproteins E↗
PubMed1987

Analysis of immediate-early and early proteins of murine cytomegalovirus in permissive and nonpermissive cells.

The immediate-early (IE) and early proteins induced by murine cytomegalovirus (Smith strain) in permissively infected 3T3-L1 murine fibroblasts were identified by SDS polyacrylamide gel electrophoresis. Ten proteins were classified as IE by their time of synthesis and by their synthesis in the presence of actinomycin D following reversal of a cycloheximide mediated protein synthesis block. By exclusion, seven proteins were classified as early class. Eleven of these proteins were precipitated by MCMV antiserum. The role of IE and early proteins in the replication of the virus was studied by infection of a murine macrophage cell line (J 774A.1) and human foreskin fibroblast (HFF) cells. The infections were characterized as nonpermissive by several criteria, including lack of production of infectious virus or viral DNA. However, the major IE and early MCMV proteins were detected in the nonpermissively infected cells. The block to virus replication in the macrophage and human fibroblast cells appeared to occur after the switch from IE to early protein synthesis, but before viral DNA replication.

Animals↗
PubMed1987

Evaluation of isradipine (PN 200-110) in mild to moderate hypertension.

The efficacy and safety of isradipine (PN 200-110), a new dihydropyridine calcium antagonist, was evaluated in 87 hypertensive patients in a placebo-controlled, double-blind, randomized multicenter trial. After a 3-week single-blind washout phase, isradipine (or matching placebo) was administered for 4 weeks, beginning at 2.5 mg b.i.d. with increments of 2.5 mg b.i.d. at weekly intervals if supine diastolic blood pressure remained greater than or equal to 90 mm Hg. At the end of 1 week average supine blood pressure in the isradipine group (n = 45) fell from a baseline of 156 +/- 13/104 +/- 4 mm Hg to 146 +/- 14/97 +/- 7 mm Hg. By week 4 blood pressure was reduced by 19/14 mm Hg compared with 4/5 mm Hg in the placebo group (P less than 0.001 between groups). Supine and standing pulse rates were slightly increased initially with isradipine therapy but returned to baseline with increasing isradipine doses. Blood pressure responses at week 4 were good or excellent (supine diastolic less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg decrease from baseline) in 87% of isradipine-treated patients and in 26% of placebo-treated patients. Headache, edema, abdominal discomfort, and constipation occurred slightly more frequently in isradipine-treated patients than in placebo-treated control subjects. The results indicate that isradipine, administered as monotherapy in doses of 2.5 to 10 mg b.i.d., is safe and effective in patients with mild to moderate essential hypertension.

Adult↗
PubMed1987

Erythrocyte sedimentation rate, plasma and serum viscosity as measures of disease activity in rheumatoid arthritis.

The activity of rheumatoid arthritis was assessed in 96 unselected out-patients by performing a number of clinical measurements and comparing them to ESR, plasma and serum viscosity. It was found that ESR correlated with clinical parameters better than did both plasma and serum viscosity. These tests were repeated 3 months later in 87 of the same patients and again change in ESR correlated with change in disease activity better than did change in plasma viscosity. Plasma viscosity was a consistently more reliable measure of disease activity than was serum viscosity.

Arthritis, Rheumatoid↗
PubMed1987

Studies with an enthesis index as a method of clinical assessment in ankylosing spondylitis.

The histopathological characteristic of ankylosing spondylitis (AS) is the presence of chronic enthesitis. Our aim was to develop a clinical measurement of the severity of tenderness over entheses. The scoring system was based on the patients' response to palpation over entheses easily accessible to examination. The enthesis index (EI) correlated with pain (r = 0.67, p less than 0.01) and stiffness (r = 0.46, p less than 0.05) scores. A single, blind, crossover study was conducted to determine the sensitivity of the index to change in clinical state associated with non-steroidal antirheumatic drug therapy and to record the interobserver variability. The index showed significantly lower scores after one week's drug treatment (p less than 0.05). The EI is a convenient, non-invasive measure of disease severity in patients with AS. Potential applications include the assessment of enthesitis in other polyarthritides and a means of distinguishing clinically between severity of enthesitis and synovitis in different types of polyarthritis.

Adolescent↗
PubMed1987

Selective increase in cytoplasmic calcium by anesthetic in lymphocytes from malignant hyperthermia-susceptible pigs.

Anesthetic-induced malignant hyperthermia in pigs and humans is characterized by muscle rigidity and rapid, often fatal, increases in body temperature. A defect in Ca2+ homeostasis has been suspected as underlying the disease, based on the preventive effect of dantrolene sodium, an agent thought to reduce Ca2+ levels in the cytoplasm. We describe here direct measurements of cytoplasmic ionized Ca2+ levels in lymphocytes from seven normal and 12 malignant hyperthermia-susceptible pigs, using the fluorescent indicator quin2. No differences in the concentration of cytoplasmic ionized Ca2+ were found in cells from malignant hyperthermia-susceptible pigs (160 +/- 10 nM) relative to the controls (150 +/- 10 nM). However, addition of halothane in vitro caused a significant increase (to 270 +/- 30 nM) in lymphocytes from malignant hyperthermia-susceptible pigs, but not from normal pigs (180 +/- 10 nM). The halothane-mediated increase in cytoplasmic ionized Ca2+ required extracellular Ca2+. It is suggested that general anesthetics such as halothane increase the permeability of the cell surface to Ca2+, and that this increase may, on its own or indirectly, increase the cytoplasmic level of ionized Ca2+ during a malignant hyperthermia crisis. The detection of a halothane-dependent increase in cytoplasmic ionized Ca2+ selectively in malignant hyperthermia-susceptible pigs could be the basis for a noninvasive test for malignant hyperthermia.

Aminoquinolines↗
PubMed1986

Epitopic and paratopically directed anti-idiotypic factors in the regulation of resistance to murine schistosomiasis mansoni.

In this study we investigated aspects of targets and regulatory mechanisms of immunologically mediated resistance to schistosomiasis. The interactions of antigen, monoclonal antibodies (MAb), and anti-idiotypic antibodies were studied by using competitive inhibition ELISA, radioimmunoprecipitation, and direct-binding ELISA techniques. MAb, either protective or nonprotective against challenge with Schistosoma mansoni, recognize either discrete or shared epitopes. MAb that recognize the same specific epitope may or may not express the ability to adoptively transfer resistance to syngeneic recipients. These results suggest that the functional as well as the epitopic specificity must be considered in an evaluation of protective mechanisms. The antibodies also can be characterized by both unique and cross-reacting idiotypic determinants. In addition, a relationship between antigen and anti-idiotypic antibody activity has been demonstrated. The immunologic analogy between antigenic epitopes and anti-idiotypic antibodies has been demonstrated by the ability of these two moieties to reciprocally inhibit the recognition of paratope-associated idiotypes, expressed by the protective MAb. This anti-idiotypic activity can be demonstrated in serum of infected animals. In this study we have identified two specific epitopes related to protection, and we illustrate here the steric relationship between antigen and anti-idiotypic antibody. The presence of idiotypically directed regulatory pathways within actively infected animals suggests that the immune response can be differentially regulated at the clonal level.

Animals↗
PubMed1986

Insulin stimulation of glucose uptake and the transmembrane potential of muscle cells in culture.

The membrane potential of L6 muscle cells was measured with the fluorescent dye bis-oxonol. Hyperpolarizations of up to 15 mV were caused by gramicidin (in N-methyl-D-glucamine+ medium), or by monensin or ionomycin. Depolarization was achieved with gramicidin (in Na+ medium), or with K+. Insulin did not change the resting membrane potential of -70 mV, yet it effectively stimulated 2-deoxy-D-glucose uptake. Conditions that hyperpolarize the cells did not alter the basal rate of hexose uptake. Moreover, insulin was still capable of stimulating hexose uptake in depolarized cells. It is concluded that modulation of the membrane potential is probably not a signalling event in insulin stimulation of hexose uptake.

Biological Transport↗
PubMed1986

Measles, mumps, and rubella: the need for a change in immunisation policy.

There is growing evidence that the present policy of childhood immunisation in the United Kingdom is inadequate. It is unlikely ever to achieve complete eradication of the congenital rubella syndrome and measles, and the problem of mumps has not even begun to be addressed. After a coordinated campaign to increase uptake of immunisation in Fife the uptake of rubella immunisation in teenage girls increased from 75% in 1981 to 94% in 1985 and the uptake of measles vaccination in preschool children from 55% in 1981 to 81% in 1985. There are a few girls each year who do not accept rubella immunisation, whose immune state is unknown, and who are consequently at risk of rubella during future pregnancies. Despite the increased uptake of measles vaccine over the past four years there is currently an epidemic of measles in Fife, with 544 notified cases in the first quarter of 1986. In 1984, 19 Fife residents were admitted to hospital because of complications of mumps. The time is ripe for a complete reassessment of the national immunisation policy.

Adolescent↗