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Biomedical subjects

S Jepsen

Publications and source records attributed to S Jepsen.

At least 109 records · Page 6Linked to original sources
PubMed1986

Lymphocyte response to purified Plasmodium falciparum antigens during and after malaria.

The peripheral blood lymphocyte response to affinity purified soluble Plasmodium falciparum antigens from in vitro cultures was studied in seven patients with acute falciparum malaria, on eight occasions, and in 15 persons having had malaria, at various times post infection, on 24 occasions. During infection, the response was low or absent in most patients (median stimulating index = [SI] = 1.4). One week post infection, a specific antigen response rose (SI = 2.9), but not to the levels found two weeks to one year post infection (SI = 5.8). At two to four years post infection, it was still present. During a recrudescence of malaria in a single patient, it was lost temporarily. The response to optimal concentrations of lectin mitogens and to tuberculin antigen was not suppressed in acute malaria.

Adult↗
PubMed1986

In vitro effect of chloroquine, mefloquine and quinine on human lymphocyte proliferative responses to malaria antigens and other antigens/mitogens.

The effect of 3 antimalarial quinoline derivatives, chloroquine, mefloquine and quinine on human blood mononuclear cells in vitro was studied. High concentrations profoundly suppressed the proliferation of mitogen- and antigen-stimulated lymphocytes, as indicated by decreased 14C-thymidine incorporation. On a weight base, the most potent drug was mefloquine. At clinically relevant doses, chloroquine and mefloquine did not affect the response to malaria antigens, but mefloquine decreased the response to phytohaemagglutinin; quinine suppressed the response to all mitogens (with the exception of pokeweed mitogen) and antigens studied, including P. falciparum merozoites. The drugs' potential adverse effect on the immune system is discussed.

Adult↗
PubMed1985

The susceptibility of Plasmodium falciparum in vitro to chlorpromazine and the stereo-isomeric compounds cis(Z)- and trans(E)-clopenthixol.

New antimalaria drugs are needed on the background of increasing resistance to chloroquine. This study was undertaken to elucidate whether other membrane stabilizers than chloroquine have anti-malarial activity in vitro. We here report the anti-plasmodial activity of chlorpromazine (CPZ) and the stereo-isomeric compounds cis(Z)- and trans(E)-clopenthixol. As a screening method we used a modified Desjardins' 3H-hypoxanthine assay. The IC50 = 50% inhibition of 3H-hypoxanthine uptake was found at 1.028 ng/ml = 3.2 microM CPZ, 758 ng/ml = 1.6 microM trans(E)-clopenthixol and 436 ng/ml = 0.9 microM cis(Z)-clopenthixol. The inhibitory effect of trans(E)-clopenthixol in these low concentrations on Plasmodium falciparum in vitro seems particularly promising, since it is known that trans(E)-clopenthixol has no neuroleptic effect.

Animals↗
PubMed1985

Specific proliferative response of human lymphocytes to purified soluble antigens from Plasmodium falciparum in vitro cultures and to antigens from malaria patients' sera.

Antigens of Plasmodium falciparum, in supernatants of in vitro cultures of the parasite were affinity purified on columns prepared with the IgG fraction of the serum of an immune individual. The purified antigens induced proliferation of lymphocytes from persons who had recently had malaria. The responses were strongest with lymphocytes from individuals infected with falciparum and ovale malaria; vivax malaria infections induced a lower level of response and lymphocytes of unsensitized individuals were little affected. Lymphocytes from unsensitized individuals did not respond to the affinity purified antigen preparations from malaria patients' sera indicating that significant amounts of non-specific mitogens were not present.

Adult↗
PubMed1984

Polymorphonuclear leucocytes defective in oxidative metabolism inhibit in vitro growth of Plasmodium falciparum. Evidence against an oxygen-dependent mechanism.

This report presents evidence that polymorphonuclear leucocytes (PMN) from chronic granulomatous disease (CGD) patients, who are defective in oxidative metabolism, are capable of inhibiting in vitro multiplication of Plasmodium falciparum. Using a microtitre in vitro inhibition assay, we incubated various numbers of peripheral blood neutrophils from CGD patients and from normal individuals with P. falciparum isolate F32 in the in vitro culture system. Inhibition of parasite growth by neutrophils was determined after 48 h of culture. At PMN to erythrocyte ratio of 1:50 there was an inhibition of parasite growth of 57% by normal neutrophils and 39% to 68% by CGD cells. When the neutrophils were stimulated by phorbol myristate acetate, both cell types enhanced inhibition of parasite growth. These findings indicate that the oxygen-independent systems of human neutrophils are involved in parasite destruction. Constituents of neutrophil granules such as acid hydrolases, lactoferrin, and cationic proteins could be regarded as potential mediators of parasite destruction.

Female↗
PubMed1984

Detection of antibodies to malaria: comparison of results with ELISA, IFAT, and crossed immunoelectrophoresis.

194 sera from Vietnamese refugees and 100 pairs of corresponding maternal and cord sera from Liberia were examined for malaria-IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence microscopy (IFAT). For both tests the antigen was prepared from P. falciparum cultures. 44% of the Vietnamese sera were positive in the ELISA and 36% in the IFAT, but results were discordant in 36% of cases. The Liberian sera were all reactive in the IFAT and 95% were reactive in the ELISA. Overall, there was a significant correlation (p less than 0.001) between reciprocal IFAT titer and ELISA extinction value. With both tests, cord serum was generally slightly less reactive than corresponding maternal serum. Results of the two tests on 19 pairs of maternal and cord sera were compared with the number of anti-malaria precipitins detected by crossed immunoelectrophoresis. A positive correlation (p less than 0.01) between ELISA extinction values and numbers of precipitating antibodies was found. It is concluded that ELISA is at least as useful as IFAT for epidemiology and blood donor screening.

Antibodies↗
PubMed1984

Enhanced inhibition of in vitro multiplication of Plasmodium falciparum by stimulated human polymorphonuclear leucocytes.

The effect of normal human peripheral blood polymorphonuclear leucocytes on in vitro multiplication of Plasmodium falciparum malaria parasites was investigated. It was shown that normal neutrophils were able to phagocytose parasitized erythrocytes and free parasites and thus inhibit in vitro multiplication of the parasite. Stimulation of the neutrophils by phorbol myristate acetate, a potent stimulus of leucocyte oxidative metabolism, resulted in enhanced inhibition of parasite growth. Superoxide dismutase, scavenger of superoxide anion, catalase, inhibitor of hydrogen peroxide, and sodium azide, inhibitor of myeloperoxidase, did not abrogate the inhibitory ability of the neutrophils. The results indicate that polymorphonuclear leucocytes play an important role in the defence against P. falciparum malaria.

Azides↗
PubMed1983

RII-RIII chloroquine resistant Plasmodium falciparum malaria from East Africa: studies of the in vivo and in vitro response to chloroquine.

A case is reported of Plasmodium falciparum malaria from East Africa resistant to chloroquine in the in vivo test at the RII level. Serum chloroquine concentrations and the in vitro test indicated RIII resistance. The need for further comparative studies of parasitaemia, serum chloroquine concentration and in vitro chloroquine sensitivity assessment is emphasized.

Adult↗
PubMed1983

Inhibition of in vitro growth of Plasmodium falciparum by purified antimalarial human IgG antibodies. Isolation of target antigens from culture supernatants.

In the search for candidate molecules for a malaria vaccine the in vitro inhibition of Plasmodium falciparum cultures by polyclonal or monoclonal antibodies has become a major tool. In the present study antigens identical to antigens circulating in plasma during attacks of malaria have been isolated from supernatants of P. falciparum cultures and used for immunoadsorbent purification of IgG antibodies from a pool of human immune serum collected in Liberia. Approximately 50% growth inhibition of three different P. falciparum isolates from Africa was obtained with the affinity-purified antibodies at a concentration of 25 micrograms ml-1 culture medium after 48 h of incubation. The target antigen/antigens for the protective antibodies have been partly characterized by radiolabelling, polyacrylamide gel electrophoresis and autoradiography but have not yet been identified unequivocally. However, the results indicate that one or more of the easily isolated antigens from the supernatant of P. falciparum cultures could be used in a malaria vaccine. The results also indicate that antigenic differences between strains from geographically disparate areas may not constrain the development of such a vaccine.

Adult↗
PubMed1981

Fansidar resistant falciparum malaria acquired in South East Asia.

A case of Plasmodium falciparum malaria resistant to Fansidar (sulphadoxine plus pyrimethamine) at a level corresponding to R III and resistant to chloroquine is reported. The infection was most certainly acquired in Malaysia, but diagnosed and treated in a non-malarious area. Normal resorption and elimination rates of the Fansidar components excludes cure failure due to abnormal drug fate in the host. P. falciparum parasites from the patient have been maintained in vitro cultures. The patient was permanently cured with mefloquine.

Adult↗