PubMed Health⌕ Search

Biomedical subjects

R Anders

Publications and source records attributed to R Anders.

At least 19 recordsLinked to original sources
PubMed2002

[Time-correlated measurement of autofluorescence. A method to detect metabolic changes in the fundus].

The detection of metabolic changes opens the possibility for intervention of reversible pathological alterations. Measurements of oxygen saturation are limited to the blood vessel system. Detection of alterations in oxygen concentrations are up to 3 orders of magnitude more sensitive by autofluorescence of coenzymes than by measurement of oxygen saturation. Because of limited transmission of the ocular media no specific excitation of endogenous fluorophores can be realised. For this reason it was investigated if the fluorescence lifetime after pulse excitation can be detected at the human fundus. Applying a laser scanner ophthalmoscope and mode-locked Ar(+) laser as well as time-correlated single photon counting, lifetime images of the living fundus were obtained. In mono-exponential approximation, a mean lifetime of 5 ns was detected from the optic disc and large vessels whereas about 1.5 ns were detected in the parapapillary area. By evaluating the frequency of lifetimes, lipofuscin, free FAD, and collagen are probably detectable. Comparative measurements were performed in fundus specimens and on free FAD.

Collagen↗
PubMed2001

Nature and chlorine reactivity of organic constituents from reclaimed water in groundwater, Los Angeles County, California.

The nature and chlorine reactivity of organic constituents in reclaimed water (tertiary-treated municipal wastewater) before, during, and after recharge into groundwater at the Montebello Forebay in Los Angeles County, CA, was the focus of this study. Dissolved organic matter (DOM) in reclaimed water from this site is primarily a mixture of aromatic sulfonates from anionic surfactant degradation, N-acetyl amino sugars and proteins from bacterial activity, and natural fulvic acid, whereas DOM from native groundwaters in the aquifer to which reclaimed water was recharged consists of natural fulvic acids. The hydrophilic neutral N-acetyl amino sugars that constitute 40% of the DOM in reclaimed water are removed during the first 3 m of vertical infiltration in the recharge basin. Groundwater age dating with 3H and 3He isotopes, and determinations of organic and inorganic C isotopes, enabled clear differentiation of recent recharged water from older native groundwater. Phenol structures in natural fulvic acids in DOM isolated from groundwater produced significant trihalomethanes (THM) and total organic halogen (TOX) yields upon chlorination, and these structures also were responsible for the enhanced SUVA and specific fluorescence characteristics relative to DOM in reclaimed water. Aromatic sulfonates and fulvic acids in reclaimed water DOM produced minimal THM and TOX yields.

Amino Acids↗
PubMed2001

Xemilofiban/orbofiban: insight into drug development.

A number of studies have reported on the successful use of intravenous glycoprotein IIb/IIIa receptor antagonists in patients with unstable angina or undergoing percutaneous interventions. The promise of interrupting the aggregation of platelets in the setting of unstable plaques on a chronic basis had led to the evaluation of several oral agents for longer-term administration. The development program of two of these agents, xemilofiban and orbofiban, will be reviewed and evaluated to understand the selection process of therapeutic targets for use based upon complex pharmacokinetic and pharmacodynamic responses. A review of the pivotal phase III trial results will also be provided along with insights into the potential reasons for the lack of significant benefit shown with these agents to date.

Alanine↗
PubMed2000

Safety and immunogenicity of a three-component blood-stage malaria vaccine in adults living in an endemic area of Papua New Guinea.

A Phase I safety and immunogenicity study with a three-component blood-stage malaria vaccine was conducted in adult male subjects living in an endemic area of Papua New Guinea. The preparations were recombinant proteins which corresponded to parts of the two merozoite surface proteins of Plasmodium falciparum (MSP1 and 2), and of the ring-infected erythrocyte surface antigen (RESA). The three proteins were emulsified with the adjuvant Montanide ISA720. Ten subjects were injected twice (four weeks apart) with the vaccine formulation and two with the adjuvant alone. Mild pain at the site of injection was reported by about half of the subjects but no systemic reaction related to the formulation occurred. There was a sharp rise in geometric mean stimulation index after the second dose compared to baseline for MSP1 and RESA, while the rise was small for MSP2. Geometric mean antibody titres increased for MSP1 during the study, whereas they hardly changed for MSP2 and RESA. The vaccine formulation was safe when used in an already immune population. The vaccine induced good cellular responses, especially for MSP1 and RESA. Boosting of humoral responses was weak, probably because of high baseline antibody levels.

Adjuvants, Immunologic↗
PubMed2000

Long-term treatment with a platelet glycoprotein-receptor antagonist after percutaneous coronary revascularization. EXCITE Trial Investigators. Evaluation of Oral Xemilofiban in Controlling Thrombotic Events.

BACKGROUND: When administered intravenously at the time of percutaneous coronary revascularization, glycoprotein IIb/IIIa receptor antagonists decrease the incidence of death and nonfatal myocardial infarction and the need for urgent revascularization. We hypothesized that long-term administration of oral glycoprotein IIb/IIIa antagonists, which block the aggregation of platelets, might stabilize intravascular plaque and prevent additional ischemic cardiac events. METHODS: We conducted a prospective, double-blind trial in which 7232 patients were randomly assigned to receive 20 mg of oral xemilofiban or placebo 30 to 90 minutes before undergoing percutaneous coronary revascularization, with maintenance doses of 10 or 20 mg of xemilofiban or placebo administered three times daily for up to 182 days. There were two primary composite end points: one was death, nonfatal myocardial infarction, or urgent revascularization at 182 days, and the other was death or nonfatal myocardial infarction at 182 days. RESULTS: Death, myocardial infarction, or urgent revascularization occurred within 182 days in 324 patients who received placebo (Kaplan-Meier cumulative event rate, 13.5 percent), 332 who received 10 mg of xemilofiban (13.9 percent, P=0.82 for the comparison with placebo), and 306 who received 20 mg of xemilofiban (12.7 percent, P=0.36 for the comparison with placebo). The incidence of death or myocardial infarction was also similar in all three groups. Clinically significant hemorrhagic complications and thrombocytopenia were infrequent. CONCLUSIONS: The administration of the glycoprotein IIb/IIIa antagonist xemilofiban before percutaneous coronary revascularization and for up to six months thereafter does not significantly reduce the incidence of important clinical end points.

Administration, Oral↗
PubMed2000

Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in non-immune volunteers.

A placebo controlled, randomised, double blind trial was conducted in human volunteers to test a mixture of three recombinant Plasmodium falciparum blood stage antigens for its ability to reduce the initial growth rates of parasites. The vaccine contained recombinant MSP2 (3D7 allele), a portion of MSP1 (190LCS.T3) and part of the RESA antigen (C terminal 771 amino acids) in the Montanide ISA 720 adjuvant (SEPPIC). Twelve volunteers received two doses of the vaccine, 6 weeks apart. The five participants in the placebo group received an equivalent volume of the adjuvant emulsion using the same schedule. Antibody responses were low, as has been reported in earlier studies with this combination, while T cell responses were stronger. All the volunteers were challenged with approximately 140 ring infected red cells of the 3D7 cloned line, 4 weeks after the second dose. Parasitaemia was determined once daily from day 4 using a sensitive and quantitative PCR assay. All the volunteers were infected and were treated on day 8, before any developed symptoms. There was no significant difference in initial parasite growth rates between the verum and placebo groups, nor was there any significant correlation between parasite growth rates and any of the measured immunological responses. These results suggest that the formulation tested in this trial did not generate immune responses that were strong enough to reduce parasite growth in naive volunteers.

Adult↗
PubMed2000

The NMR solution structure of the ion channel peptaibol chrysospermin C bound to dodecylphosphocholine micelles.

Chrysospermin C is a 19-residue peptaibol capable of forming transmembrane ion channels in phospholipid bilayers. The conformation of chrysospermin C bound to dodecylphosphocholine micelles has been solved using heteronuclear NMR spectroscopy. Selective 15N-labeling and 13C-labeling of specific alpha-aminoisobutyric acid residues was used to obtain complete stereospecific assignments for all eight alpha-aminoisobutyric acid residues. Structures were calculated using 339 distance constraints and 40 angle constraints obtained from NMR data. The NMR structures superimpose with mean global rmsd values to the mean structure of 0. 27 A (backbone heavy atoms) and 0.42 A (all heavy atoms). Chrysospermin C bound to decylphosphocholine micelles displays two well-defined helices at the N-terminus (residues Phe1-Aib9) and C-terminus (Aib13-Trp-ol19). A slight bend preceding Pro14, i.e. encompassing residues 10-12, results in an angle of approximately 38 degrees between the mean axes of the two helical regions. The bend structure observed for chrysospermin C is compatible with the sequences of all 18 long peptaibols and may represent a common 'active' conformation. The structure of chrysospermin C shows clear hydrophobic and hydrophilic surfaces which would be appropriate for the formation of oligomeric ion channels.

Amino Acid Sequence↗
PubMed1998

Phase I/IIa safety, immunogenicity, and efficacy trial of NYVAC-Pf7, a pox-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria.

Candidate malaria vaccines have failed to elicit consistently protective immune responses against challenge with Plasmodium falciparum. NYVAC-Pf7, a highly attenuated vaccinia virus with 7 P. falciparum genes inserted into its genome, was tested in a phase I/IIa safety, immunogenicity, and efficacy vaccine trial in human volunteers. Malaria genes inserted into the NYVAC genome encoded proteins from all stages of the parasite's life cycle. Volunteers received three immunizations of two different dosages of NYVAC-Pf7. The vaccine was safe and well tolerated but variably immunogenic. While antibody responses were generally poor, cellular immune responses were detected in >90% of the volunteers. Of the 35 volunteers challenged with the bite of 5 P. falciparum-infected Anopheles mosquitoes, 1 was completely protected, and there was a significant delay in time to parasite patency in the groups of volunteers who received either the low or high dose of vaccine compared with control volunteers.

Adolescent↗
PubMed1998

A solution NMR study of the selectively 13C, 15N-labeled peptaibol chrysospermin C in methanol.

The conformation of the 19-residue peptaibol chrysospermin C in methanol has been investigated by NMR spectroscopy using selective 15N and 13C labeling of the alpha-aminoisobutyric acid (Aib) residues. Complete 1H and 13C sequential assignments, including stereospecific assignments for the heavily overlapped resonances from the two Cbeta methyl groups of the eight Aib residues, are reported for a peptaibol for the first time. An Aib residue followed by a Pro is an exception to previous suggestions regarding stereospecific assignment of the two Cbeta methyl groups of Aib residues. Local nuclear Overhauser effects and 3J(HNC') and 3J(HNCbeta) scalar couplings indicate that the phi angles of the Aib residues are restricted sterically to local conformations consistent with right-handed helices. Despite these constraints on the eight Aib residues, the NMR data for chrysospermin C in methanol are generally most consistent with an ensemble of transient conformations, including backbone conformations inconsistent with helical structures. Initial NMR measurements for chrysospermin C bound to micelles suggest structural and dynamic differences relative to alamethicin bound to micelles which may be related to differences in gating voltages for formation of ion channels.

Amino Acid Sequence↗
PubMed1997

Cellular immunity to merozoite surface protein 2 (FC27 and 3D7) in Papua New Guinean children. Temporal variation and relation to clinical and parasitological status.

A prospective study in 207 children aged 0.5-15 years was carried out in a highly endemic area of Papua New Guinea to examine the relationship between cellular responses to Plasmodium falciparum merozoite surface protein 2 (MSP2) and malaria infection and morbidity. In vitro proliferation, IFN-gamma and IL-4 induction were measured against two recombinant proteins of MSP2, FC27 and 3D7 as well as against a form of the 3D7 MSP2 lacking the central repetitive sequences (d3D7). The prevalence of proliferative response was generally low, 6% for FC27, 9% for 3D7 and 11% for d3D7. A higher prevalence of IL-4 response was obtained being 27% for FC27, 34% for 3D7 and 30% for d3D7 while the prevalence of IFN-gamma response was 13%, 15% and 18%, respectively. There was no correlation between age and proliferative responses; in contrast cytokine production increased with age for all three antigens. When proliferation or stimulation of either cytokine was used to assess T-cell activation the frequency of responders increased to 39%, 47% and 46% for FC27, 3D7 and d3D7 respectively. Analysis of the relation of T cell responses to concurrent infection and morbidity showed that lymphoproliferative response only to d3D7 was significantly associated with parasitaemia; while lymphoproliferative responses to all 3 MSP2 antigens were highest in the group of clinical malaria cases. There was no significant correlation between proliferation or cytokine production to MSP2 and concurrent or subsequent malaria morbidity.

Adolescent↗
PubMed1997

Association between cellular response (IL-4) to RESA/Pf155 and protection from clinical malaria among Papua New Guinean children living in a malaria endemic area.

A prospective study in 207 children aged 0.5-15 years was carried out to examine the relationship between cellular responses to Plasmodium falciparum ring-infected erythrocyte surface antigen (RESA) and malaria infection and morbidity. The prevalence of lymphoproliferative response to RESA was 13%, IFN-gamma prevalence was 40% and IL-4 prevalence was 22%. Only the IFN-gamma, response to RESA increased significantly with age. When proliferation or stimulation of either cytokine was used to assess T-cell activation the overall frequency of responders increased to 55%. The proliferative and IFN-gamma response to RESA were positively associated. Although there was no association between any of the CMI responses to RESA and concurrent morbidity the prevalence of IL-4 response to RESA was significantly lower in children who experienced clinical malaria in the following year. These results coupled with our earlier data showing a negative relationship between humoral responses to RESA and malaria morbidity support the inclusion of RESA in a subunit vaccine against malaria.

Adolescent↗
PubMed1995

Assessment of the role of the humoral response to Plasmodium falciparum MSP2 compared to RESA and SPf66 in protecting Papua New Guinean children from clinical malaria.

The prevalence and concentration of naturally acquired humoral response (IgG) to merozoite surface protein 2 (MSP2), RESA, SPf66 and crude schizont extract were measured in a population living in a malaria highly endemic area of Papua New Guinea. A prospective longitudinal study in 0.5-15 year old children was conducted for one year in order to examine the relationship between the humoral response to these antigens and subsequent susceptibility to clinical malaria using a series of clinical definitions. The prevalence and concentration of antibodies to all antigens increased with age. Such correlation with age was most marked for MSP2 recombinant proteins. When age and previous exposure were controlled for, only antibody levels to MSP2 recombinant proteins (3D7 and d3D7) and to RESA predicted a reduction in incidence rate of episodes of clinical malaria. Our results support the inclusion of the recombinant proteins of the 3D7 allelic family of merozoite surface antigen 2 and RESA into a subunit vaccine against malaria.

Adolescent↗
PubMed1995

Safety, immunogenicity, and pilot efficacy of Plasmodium falciparum sporozoite and asexual blood-stage combination vaccine in Swiss adults.

This study was part of a larger program to develop a vaccine effective against Plasmodium falciparum infection caused by sporozoites and clinical malaria caused by asexual blood stages. In a phase 1 study of safety and immunogenicity, two recombinant proteins (Ro 46-2717, a circumsporozoite [CS] protein) construct with a molecular mass of 35 kD, and Ro 46-2924, a merozoite surface antigen [MSA-2] construct with a molecular mass of 25 kD) adsorbed onto alum were injected in two low (20 micrograms) or two high (100 micrograms) doses in the right and left deltoid muscles of 33 healthy Swiss volunteers; six other volunteers received a placebo (alum alone). Twenty-six participants reported 51 immunization-related adverse events, mainly pain at the injection site. Mean antibody titers to CS protein and MSA-2 in an indirect immunofluorescence assay peaked four weeks after the second immunization without evidence of boosting (i.e., sharp increase in titer). By that time, 56% and 31% of the vaccinees seroconverted to CS protein and MSA-2, respectively, with the increase in MSA-2 titer being weaker than that for the CS protein. After a third immunization, five vaccinees volunteered to be challenged by three or four infective bites of Anopheles stephensi. Prepatent and incubation periods in all five were comparable with unvaccinated historic controls challenged under similar conditions, and all had symptoms of clinical falciparum malaria. We conclude that the vaccine components were safe and immunogenic but there was no evidence that this immunization regimen with the CS protein plus MSA-2 component was able to prevent infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Plasmodium falciparum: mapping the membrane-binding domain in the ring-infected erythrocyte surface antigen.

The ring-infected erythrocyte surface antigen (RESA) associates with spectrin in the erythrocyte membrane (Foley, M., Tilley, L., Sawyer, W. H., and Anders, R. F., 1991, Mol. Biochem. Parasitol. 46, 137-148). In this study, we have used deletion mutagenesis combined with an in vitro binding assay to identify a region of the RESA polypeptide that is involved in the attachment of this parasite protein to the host membrane skeleton. It was found that the tandem repeat sequences of RESA do not appear to be involved in the association of this protein with the erythrocyte membrane and that large deletions of the N-terminal region of RESA did not affect binding. The membrane-binding domain has been mapped to a 48-amino-acid region of RESA located between the two blocks of repetitive amino acid sequence. This binding domain does not overlap the region of RESA that shares homology with the Escherichia coli molecular chaperone, DnaJ. Identification of the amino acid sequence which is critical for the binding of RESA to erythrocyte spectrin may provide important clues to the functional consequences of RESA attachment to the host membrane.

Amino Acid Sequence↗
PubMed1993

Specificity variants in monoclonal antibodies reactive with peptide epitopes of the ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum.

It has been suggested that repeat sequence antigens of Plasmodium falciparum may serve the parasite in immune evasion by modifying the host antibody response and impairing the development of protective immunity. According to this proposal networks of cross-reactive, repeat sequence malarial antigens have the ability to stimulate a high proportion of all somatically mutated B cells with altered antibody specificity, and thus to hinder the normal process of antibody affinity maturation. To determine the rate at which immunoglobulin mutations produce new reactivities with repeat sequence antigens, hybridoma cell lines specific for the ring-infected erythrocyte surface antigen (RESA) were examined for the incidence of specificity variants that arose naturally or as a result of treatment with the chemical mutagen ethylmethane sulphonate (EMS). From one of the cell lines variants were readily isolated having reactivity towards a very closely related repeat sequence epitope within the same RESA antigen. However, the other hybridoma/antigen combinations revealed no variants. In general, mutations giving rise to antibodies with altered specificity for related repetitive antigens were not readily induced and only limited support of the hypothesis was obtained.

Amino Acid Sequence↗
PubMed1992

Carboxypeptidase N concentration during cardiopulmonary bypass in humans.

Carboxypeptidase N (CPN) is an inactivator of anaphylatoxins and kinins, peptides implicated in the pathogenesis of complications in extracorporeal circulation. To investigate whether the level of CPN is altered during cardiopulmonary bypass (CPB) we studied 15 patients undergoing cardiac surgery utilizing CPB. The concentration of CPN decreased to about 48% of the initial value upon initiation of CPB and remained low throughout the procedure. A similar decrease was observed in the level of alkaline phosphatase, an enzyme that was measured to assess the degree of haemodilution. When the data were normalized for dilution, no difference in the concentration of CPN was observed during CPB. Moreover, no changes in the concentration of CPN were observed when protamine was given to neutralize heparin and none of the 15 patients experienced any side-effects of protamine administration. We conclude that the decrease in CPN during CPB was due primarily to dilution and not to changes in CPN synthesis or catabolism. Protamine administration is not associated with significant changes in the level of CPN in patients who have an asymptomatic reversal of heparin anticoagulation.

Aged↗
PubMed1991

The development of a malaria vaccine.

This paper is a progress report and summarises R & D by the consortium to develop a malaria vaccine. The research strategies and research progress are discussed. The business arrangements and the roles of each partner are given.

Antigens, Protozoan↗