Biomedical subjects

G Hetland

Publications and source records attributed to G Hetland.

61 records · Page 4Linked to original sources

PubMed1986

Human alveolar macrophages synthesize the functional alternative pathway of complement and active C5 and C9 in vitro.

Attachment of protein to agarose beads cultured with macrophages in protein-free medium containing 3H-leucine, shows that de novo synthesis of protein with affinity to the beads takes place. We also found that monoclonal antibodies against human C3c, C3g, and a C9-neoantigen as well as polyclonal antibodies against human C5 and C9, bound to agarose beads that had been kept with the macrophage cultures. Demonstration of C3 derivatives on the agarose beads shows that the essential complement factors of the alternative pathway are synthesized and have been activated by the beads. Deposition of C5 and the detection of a neoantigen of C9 on the beads, indicates that the whole terminal complement pathway has been formed and activated. We conclude that human alveolar macrophages form in vitro the functional alternative pathway of complement, C5 and C9, and we have indirect evidence for synthesis of C6, C7, and C8.

Antibodies, Monoclonal↗

PubMed1986

Phagocytosis of agarose beads by receptors for C3b (CR1) and iC3b (CR3) on human alveolar macrophages cultured on fibronectin in vitro. A scanning electron microscopic study.

We studied the phagocytosis of agarose beads by human alveolar macrophages in terms of the morphology, the receptors involved, and the cellular substrates (plastic or fibronectin) used. Beads coated with C3b (58%) and iC3b (42%) by treatment with serum, were ingested during 45 min by CR1 and CR3 on the macrophages. This ingestion was inhibited 80-90% by the presence of polyclonal F(ab')2 anti-C3 fragments. Since the phagocytosis of both C3b- and iC3b-coated beads was about threefold stronger than for C3b-coated beads (trypsinized serum-treated beads), the results indicate that the CR3 is more phagocytic than the CR1. The phagocytosis of initially complement uncoated beads, which are slowly opsonized with macrophage-produced C3b and iC3b in vitro, was also strongly inhibited (70-80%) by the presence of anti-human C3 F(ab')2 fragments. There was an increased phagocytosis (10-17%) of complement precoated beads by macrophages cultured on the fibronectin substrate versus the plastic substrate. The morphology and rapid phagocytosis of the complement precoated beads was demonstrated by SEM. The general impression was that membranous protrusions stretched towards the beads, which became increasingly enclosed by plasma membrane.

Adult↗

PubMed1985

Susceptibility of Plasmodium falciparum to chloroquine in northern Liberia after 20 years of chemosuppression and therapy.

The in vivo and in vitro susceptibility of Plasmodium falciparum to chloroquine was investigated in northern Liberia after 20 years of continuous chemosuppression and therapy with 4-aminoquinolines. In all patients studied (n = 53) parasitaemias were cleared within four days. There were no recrudescences in 16 patients followed-up for 28 days. All isolates of P. falciparum tested in vitro (n = 26) showed sensitive patterns. Schizont maturation was inhibited by a chloroquine concentration of between 0.25 and 0.75 mumol-1. In this area of Liberia no resistance to chloroquine was found in spite of extensive use of 4-aminoquinolines. This may support the view that importation of at least partially resistant strains, rather than local mutation of P. falciparum, precedes selection of resistant strains. Hence, we conclude that regular intake of chloroquine by groups at risk is justified if it is combined with regular monitoring of drug susceptibility.

Child↗

PubMed1985

Malaria control by chlorproguanil. I. Clinical effects and susceptibility of Plasmodium falciparum in vivo after seven years of monthly chlorproguanil administration to children in a Liberian village.

For seven years, chlorproguanil (1.0 to 2.0 mg kg-1) was administered monthly to the children below 15 years of age in a village with holoendemic malaria. Malariometric indices were recorded every six months. Susceptibility in vivo was monitored by the clearance of Plasmodium falciparum parasitaemia after drug intake. Three parasite species were found initially: P. falciparum (52%), P. malariae (8%) and P. ovale (4%). The parasites found during the study were mainly P. falciparum, and parasite rates ranged from 37 to 87% at the different surveys one month after respective drug intake. A fifty-fold decrease of mean parasite density was generally observed seven days after drug intake. Splenomegaly was initially recorded in all two to nine year old children, with a mean size of 2.64 according to Hackett's index. From 18 months onwards as the mean spleen index was 1.15 in the same age group. Chlorproguanil may represent an important alternative drug to groups at risk in malaria control schemes.

Adolescent↗

PubMedDate not supplied

Uptake of C5a by polymorphonuclear leukocytes (PMNs) after focal cerebral ischemia. I. Effect of tirilazad mesylate intervention on C5a uptake by PMNs.

PMNs are believed to play an important role in ischemia and C5a uptake is an important functional indicator for G protein-coupled receptor trafficking. The ability of PMNs to internalize 125I-labeled C5a in vitro is an index of the functional state of these cells. We evaluated the effects of model preparation and focal cerebral ischemia by middle cerebral artery occlusion and reperfusion (MCA:O/R) on internalization of C5a by PMNs isolated from baboons (Papio anubis/cynocephalus). Similar assays were performed on PMNs isolated before and after exposing the animals undergoing MCA:O/R to an anti-inflammatory 21-aminosteroid, tirilazad mesylate (U74006F). Surgical implantation of the MCA occlusion device had no measureable effect on uptake of C5a to the cytosol by the PMN. In contrast, MCA:O/R appeared to decrease uptake of C5a. Both in vivo and in vitro administration of tirilazad, to otherwise untreated animals and to isolated cells, respectively, reduced baseline values of C5a uptake in the PMNs. Cytosolic uptake of C5a was also reduced in PMNs isolated from subjects that had undergone MCA:O/R and tirilazad treatment. These results suggest that focal cerebral ischemia, with or without exposure to tirilazad mesylate, may inhibit internalization of C5a by the PMN receptors. The effects of stroke on the ability of C5a to gain entry into the PMN may result from receptor down-regulation or "desensitization" of the cell, possibly due to activation of complement and generation of C5a which occupied the receptors. Alternatively, the effect of tirilazad presumably results from the ability of this drug to enter the membrane lipid layer and reduce fluidity.

Animals↗

PubMedDate not supplied

Prevalence of anti-HCV in Norwegian blood donors with anti-HBc or increased ALT levels.

Testing for hepatitis B core antibodies (anti-HBc) was performed in 12,104 consecutive blood donors, 139 (1.15%) of whom were found to be positive. The first 6036 donors were also screened for ALT; 91 (1.51%) had repeatedly elevated values. ALT screening was of no help in detecting anti-HBc-positive donors. Those with anti-HBc or repeatedly raised ALT levels were further tested for hepatitis C virus antibodies (anti-HCV), and 3 (2.16%) and 1 (1.10%) anti-HCV-positive donors were detected, respectively. This prevalence of anti-HCV (0.5%) is not significantly different from that found in 1000 unselected donors at our blood bank. Testing for ALT and anti-HBc as surrogate markers for hepatitis C is therefore not recommended in Norwegian blood donors and should be replaced by anti-HCV screening.

Alanine Transaminase↗

PubMedDate not supplied

Biocompatibility of white cell filters as evaluated by complement activation.

The biocompatibility of nine different white cell filters was examined by analysis of complement activation in plasma specimens obtained from blood components before and after filtration. Filters for both red cell (RBC) concentrates and platelet concentrates (PCs) were tested. It was found in all of the filters tested that the postfiltration levels of complement activation products were not higher than the prefiltration levels in RBC concentrates and PCs. One exception was the filtration of multiple PCs with Imugard IG-500, in which case a rise in C3 activation products was seen. Moreover, there was a significant rise in C3 activation products, but not the terminal complement complex, when plasma was filtered through Imugard E, which contrasted with results with the other filters. High initial and storage time-dependent levels, especially of C3 activation products, were observed in the PCs, probably due to their processing at room temperature. It can be concluded that the majority of the filters tested do not activate complement.

Blood Platelets↗