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Biomedical subjects

M L Morris

Publications and source records attributed to M L Morris.

At least 19 recordsLinked to original sources
PubMed2004

Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine.

CPG 7909, a 24-mer B-Class CpG oligodeoxynucleotide (ODN), was tested for safety, tolerability and its ability to augment the immunogenicity of a commercial trivalent killed split influenza vaccine (Fluarix containing A/Beijing/262/95, A/Sydney/5/97 and B/Harbin/7/94; SmithKline Beecham) in a phase Ib blinded, randomized, controlled clinical trial. Sixty healthy volunteers were recruited in two consecutive cohorts of 30 subjects, who were randomly assigned to receive Fluarix plus 1mg CPG 7909 or Fluarix plus saline control (15 subjects each). Vaccines were administered by intramuscular injection on a single occasion with subjects in the first cohort receiving a 1/10th dose of Fluarix and those in the second cohort receiving the full-dose. All safety measures including physical evaluation, laboratory blood assays, and assays for DNA autoimmunity were within normal values except for transient and clinically inconsequential decreases in total white blood cell counts in groups receiving CPG 7909. All vaccines were found to be generally well tolerated with similar frequency and intensity for most adverse reactions for groups receiving CPG 7909 as controls. Exceptions were injection site pain and headache, which were reduced in frequency in subjects receiving the 1/10th Fluarix dose without CpG, compared to the frequency in all other groups. There was a lack of pre-existing immunity, defined as hemagglutinin inhibition (HI) activity < or =20, for all subjects to the influenza strains A/Beijing/262/95 and B/Harbin/7/94 and for some subjects to A/Sydney/5/97. Post-vaccination humoral immune responses, as determined 2 and 4 weeks later by assay of HI activity and ELISA to detect antibodies against hemagglutinin (anti-HA) were similar for both full and reduced Fluarix doses but the cellular immune responses (measured as PBMC antigen-specific IFN-gamma secretion) were reduced in the 1/10th Fluarix dose group. Humoral responses were not significantly enhanced by the addition of CPG 7909, except in individuals with pre-existing immunity to A/Sydney/5/97 strain (baseline HI activity titre >20), where there was a trend to higher HI activity with CPG 7909 (P = 0.06). The addition of CPG 7909 to the 1/10th dose of Fluarix did however result in significantly higher levels of IFN-gamma secretion from peripheral blood mononuclear cells recovered at 4 weeks and restimulated ex vivo with A/Beijing/262/95 (P = 0.048) and B/Harbin/7/94 (P = 0.0057), restoring these to the level seen with full-dose vaccine. These results suggest that addition of CPG 7909 to Fluarix may allow the use of reduced vaccine doses without reduced immunogenicity.

Adjuvants, Immunologic↗
PubMed2004

CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study.

Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN) act as potent Th1-like immune enhancers with many antigens in animal models. We have extended these observations to the first clinical evaluation of the safety, tolerability and immunogenicity of CPG 7909 when added to a commercial HBV vaccine. In a randomized, double-blind phase I dose escalation study, healthy volunteers aged 18-35 years were vaccinated at 0, 4 and 24 weeks by intramuscular injection with Engerix-B (GlaxoSmithKline). The regular adult dose of 20 microg recombinant hepatitis B surface antigen (HBsAg) adsorbed to alum was administered mixed with saline (control) or with CPG 7909 at one of three doses (0.125, 0.5 or 1.0 mg). HBsAg-specific antibody responses (anti-HBs) appeared significantly sooner and were significantly higher at all timepoints up to and including 24 weeks in CPG 7909 recipients compared to control subjects (p< or = 0.001). Strikingly, most CpG 7909-vaccinated subjects developed protective levels of anti-HBs IgG within just two weeks of the priming vaccine dose. A trend towards higher rates of positive cytotoxic T cell lymphocyte responses was noted in the two higher dose groups of CPG 7909 compared to controls. The most frequently reported adverse events were injection site reactions, flu-like symptoms and headache. While these were more frequent in CPG 7909 groups than in the control group (p<0.0001), most were reported to be of mild to moderate intensity regardless of group. In summary, CPG 7909 as an adjuvant to Engerix-B was well-tolerated and enhanced vaccine immunogenicity. CPG 7909 may allow the development of a two-dose prophylactic HBV vaccine.

Adjuvants, Immunologic↗
PubMed2003

Development and implementation of an electrochemiluminescence immunoassay for the determination of an angiogenic polypeptide in dog and rat plasma.

A quantitative method based on electrochemiluminescence immunoassay for the determination of the angiogenic agent aFGF-S117 has been developed and validated. Two polyclonal antibodies specific to aFGF-S117 and a wild-type aFGF antibody were selected for the analysis. The assay was based on the non-competitive sandwich immunoassay principle in which the drug is trapped with a biotinylated antibody that is immobilized on a streptavidin magnetic particle. The drug is then sandwiched with a ruthenium chelated second antibody. The assay demonstrates good accuracy and reproducibility at plasma concentration of 0.5 ng/ml.

Angiogenic Proteins↗
PubMed2000

Effect of membrane lipid composition on the conformational equilibria of the nicotinic acetylcholine receptor.

The effects of cholesterol (Chol) and an anionic lipid, dioleoylphosphatidic acid (DOPA) on the conformational equilibria of the nicotinic acetylcholine receptor (nAChR) have been investigated using Fourier transform infrared difference spectroscopy. The difference between spectra recorded in the presence and absence of agonist from the nAChR reconstituted into 3:1:1 egg phosphatidylcholine (EPC)/DOPA/Chol membranes exhibits positive and negative bands that serve as markers of the structural changes associated with the resting to desensitized conformational change. These markers are absent in similar difference spectra recorded from the nAChR reconstituted into EPC membranes lacking both Chol and DOPA, indicating that the nAChR cannot undergo conformational change in response to agonist binding. When low levels of either Chol or DOPA up to 25 mol % of the total lipid are included in the EPC membranes, the markers suggest the predominant stabilization of a conformation that is a structural intermediate between the resting and desensitized states. At higher levels of either Chol or DOPA, the nAChR is stabilized in a conformation that is capable of undergoing agonist-induced desensitization, although DOPA appears to be required for the nAChR to adopt a conformation fully equivalent to that found in native and 3:1:1 EPC/DOPA/Chol membranes. The ability of these two structurally diverse lipids, as well as others (Ryan, S. E., Demers, C. N., Chew, J. P., Baenziger, J. E. (1996) J. Biol. Chem. 271, 24590-24597), to modulate the functional state of the nAChR suggests that lipids act on the nAChR via an indirect effect on some physical property of the lipid bilayer. The data also suggest that anionic lipids are essential to stabilize a fully functional nAChR. We propose that membrane fluidity modulates the relative populations of nAChRs in the resting and desensitized states but that subtle structural changes in the presence of anionic lipids are essential for full activity.

Animals↗
PubMed2000

The relational-interdependent self-construal and relationships.

Three studies describe the development and validation of a measure of the relational-interdependent self-construal, which is defined as the tendency to think of oneself in terms of relationships with close others. Study 1 reports the development, psychometric properties, and tests of validity of this new measure. Individuals who scored high on the Relational-Interdependent Self-Construal (RISC) Scale characterized their important relationships as closer and more committed than did individuals who scored low on this measure (Study 1) and were more likely to take into account the needs and wishes of others when making decisions (Study 2). In Study 3, using a dyadic interaction paradigm with previously unacquainted participants, the partners of persons who scored high on the RISC scale viewed them as open and responsive to their needs and concerns; these perceptions were related to positive evaluations of the relationship.

Adult↗
PubMed1999

Internal dynamics of the nicotinic acetylcholine receptor in reconstituted membranes.

The structure and 1H/2H exchange kinetics of affinity-purified nAChR reconstituted into egg phosphatidylcholine membranes with increasing levels of either dioleoylphosphatidic acid (DOPA) or cholesterol (Chol) have been examined using infrared spectroscopy. All spectra of the reconstituted nAChR membranes recorded after 72 h in 2H2O exhibit comparable amide I band shapes, suggesting a similar secondary structure for the nAChR in each lipid environment. Increasing levels of either DOPA or Chol, however, lead to an increasing intensity of the amide II band, indicating a decreasing proportion of nAChR peptide hydrogens that have exchanged for deuterium. Spectra recorded as a function of time after exposure of the nAChR to 2H2O show that the presence of either lipid slows down the 1H/2H exchange of those peptide hydrogens that normally exchange on the minutes to hours time scale. The slowing of peptide 1H/2H exchange correlates with both an increasing ability of the nAChR to undergo agonist-induced conformational change [Baenziger, J. E., Morris, M.-L., Darsaut, T. E., and Ryan, S. E. (1999) in preparation] and possibly a decreasing membrane fluidity. Our data suggest that lipid composition dependent changes in nAChR peptide 1H/2H exchange kinetics reflect altered internal dynamics of the nAChR. Lipids may influence protein function by changing the internal dynamics of integral membrane proteins.

Animals↗
PubMed1997

Investigations of the taxonomy and systematics of Fusobacterium nucleatum using allozyme electrophoresis.

Fusobacterium nucleatum forms part of the resident microbiota in both oral and extraoral sites in humans and animals. It is also involved in infections in such sites. Despite the genetic heterogeneity within the species, it has been divided into five subspecies, the validities of which have been questioned. In the present study, 44 F. nucleatum isolates were examined at 21 enzyme loci by using the allozyme electrophoretic technique to establish an accurate genetic framework for taxonomic purposes. Three distinct genetic clusters were identified; one cluster consisted exclusively of extraoral isolates, another cluster consisted predominantly of human oral isolates, and the third cluster consisted of a single human oral isolate. Our results highlight the urgent need for extensive biochemical, immunological, and epidemiological studies to accurately define the systematics of the genus fusobacterium based on the framework derived in this study by using 21 independent genetic characteristics.

Alleles↗
PubMed1996

The use of allozyme electrophoresis to assess genetic heterogeneity among previously subspeciated isolates of Fusobacterium nucleatum.

Fusobacterium nucleatum has been implicated in the pathogenesis of periodontal diseases. Five subspecies have previously been proposed. The validity of these subdivisions was investigated using allozyme electrophoresis for 21 enzyme mobilities. The 18 F. nucleatum isolates tested had previously been subspeciated and included type strains as well as isolates from both oral and extraoral sites. The results showed 2 distinct genetic groups with fixed differences at 82.5% of the test loci, indicative of a species complex with a number of subspecies within each of the 2 groups. There was also evidence of a correlation between the 2 major groups of isolates and the site from which they were taken. It was concluded that there is a high degree of genetic heterogeneity within the species F. nucleatum and that its current subspeciation is of questionable validity.

Abscess↗
PubMed1993

The presence of an inhibitor of human skin collagenase in the roots of healthy and periodontally diseased teeth: changes that occur with age.

The amount of anti-collagenase in the root has been reported in a group 18 to 35 years of age. Healthy roots had more than the diseased; and apical more than the cervical. The purpose of the present study is to determine the effect of age on these values. In a group 50 to 92 years of age, all values were markedly higher than in the younger group. In addition, all relationships between values were preserved. These include location and presence of disease. The higher levels might be due to an aging process or a protective defense against collagenase in the gingival crevice.

Aged↗
PubMed1990

Praxis on verbal command and imitation.

Nondysfunctional 4-year-old and 6-year-old children were administered the Praxis on Verbal Command subtest of the Sensory Integration and Praxis Tests (SIPT) (Ayres, 1989) under two conditions. One condition was administered in the standardized manner on verbal command; the other involved administration of the same items on imitation. An analysis of variance indicated that the variables of age and condition were significant, whereas sex was not significant. The Age x Condition interaction was also significant. Scheffé multiple comparisons revealed a significant difference between 4-year-olds and 6-year-olds on verbal command but not on imitation. Verbal-command scores were significantly lower than imitation scores for the 4-year-olds but not for the 6-year-olds.

Age Factors↗
PubMed1986

Family studies of Alzheimer's dementia: results and prospects.

Studies of families located through a proband with dementia of the Alzheimer type have demonstrated transmission of the disorder within families, probably through shared genes. Increasing closeness of genetic relationship and increasing severity of illness are both associated with increasing risk to relatives. Families at high risk are especially valuable for studies of the biology of dementing illness including, in particular, their molecular genetics. Associations at several levels between Down's syndrome and Alzheimer's dementia provide important clues for molecular hypotheses.

Alzheimer Disease↗
PubMed1986

Seizures and myoclonus in patients with Alzheimer's disease.

We reviewed 81 patients with dementia and autopsy findings of Alzheimer's disease (AD) to identify patients with seizures or myoclonus after onset of dementia. Eight (10%) had seizures, and eight others (10%) had myoclonus. The incidence of seizures was 10 times more than expected in a reference population. Seizures occurred in any stage of AD, but myoclonus was often a late manifestation. Both seizures and myoclonus, individually or together, are manifestations of AD and may be seen at any time in the course of the illness.

Aged↗
PubMed1985

The inductive properties of human dentin and cementum.

Studies of the inductive properties of human dentin and cementum have yielded differing results. Comparisons are difficult to draw because of variations in time, donor tissue, host immunologic status, implant site, decalcifying agents and degree of decalcification. Analysis of the many experiments intimates that the answers may lie in the use of citric acid and/or the degree of decalcification. The direction of future investigations is suggested.

Animals↗