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Biomedical subjects

J B Jensen

Publications and source records attributed to J B Jensen.

At least 55 records · Page 3Linked to original sources
PubMed1993

Increased plasma levels of soluble ICAM-1 and ELAM-1 (E-selectin) during acute Plasmodium falciparum malaria.

Acute P. falciparum malaria is associated with a loss of antigen-responsiveness of peripheral T cells, depletion of T cells characterized by high surface expression of the adhesion molecule LFA-1, and increased plasma levels of the T-cell activation marker soluble IL-2 receptor (sIL-2R). In the present study we show that clinical episodes of P. falciparum malaria produced an increase in plasma levels of soluble ICAM-1 (sICAM-1) and ELAM-1 (sELAM-1). The increase was transient and subsided slowly (sICAM-1) or rapidly (sELAM-1) following drug cure. The increases in plasma sICAM-1 and sELAM-1 were significantly correlated, and were furthermore associated with a concomitant increase in plasma levels of sIL-2R. Finally, plasma levels of sICAM-1, but not sELAM-1, were inversely correlated to the fraction of peripheral T cells having high surface expression of LFA-1, the receptor for T-cell adhesion to ICAM-1. Taken together, these observations suggest that acute P. falciparum malaria is characterized by a state of endothelial inflammation associated with the adherence of activated T cells.

Acute Disease↗
PubMed1993

Obsessive compulsive disorder in children and adolescents.

During 1992, further progress has been made in determining the incidence of obsessive compulsive disorder and change in symptoms over time. Advances have been made in determining what category of mood disorder obsessive compulsive disorders belong to; contributions have been made in the theoretic understanding of the cause of obsessive compulsive disorder, and why it may be associated with trichotillomania and Tourette's syndrome. Finally, the treatment of children with both medication and behavior therapy has been explored.

Adolescent↗
PubMed1993

Reactivity profile of human anti-82-kilodalton rhoptry protein antibodies generated during natural infection with Plasmodium falciparum.

Immunization of monkeys with the 82-kDa rhoptry protein (p82) of Plasmodium falciparum can protect them against a lethal blood stage challenge, and monoclonal antibodies to p82 inhibit parasite growth in vitro. The role that a p82-specific immune response might play in human immunity to the parasite is not known. To determine to what extent humans produce antibodies to p82 following infection with P. falciparum, sera from individuals believed to be hyperimmune, semi-immune, or never infected with the parasite were examined. Portions of the p82 gene were expressed separately as fusion proteins and used on immunoblots to test for antibodies to the recombinant proteins. All but 1 of the 30 immune sera possessed antibodies to p82, while nonimmune sera produced, at best, only a marginal signal to the fusion proteins. The signal intensity produced with the human immune sera depended on the region of p82 being assayed, with the N-terminal 37% of p82 producing stronger signals than more C-terminal parts of p82. This N-terminal domain contains a tandem octapeptide repeat (consensus KSSSPSXT/V) of the structure (repeat)2-Q-T-S-G-S/L-(repeat)3. It is shown here that the sequence of this repetitive motif is conserved among four parasite isolates at both the nucleotide and amino acid levels; the five-residue repeat interruption peptide QTSGS/L separating the two sets of repeats contains the only amino acid substitution (Ser or Leu) detected in this region to date. Despite their conservation of structure, the repeats do not appear to be the only epitope recognized by the human antibodies, since sera which recognize the N-terminal fusion protein containing the repeats also bind a related protein after truncation and removal of the repeats. These results indicate that the structurally conserved p82 molecule contains multiple B-cell epitopes and is likely to be immunogenic in most individuals during natural infections with P. falciparum. These observations are consistent with the idea that antibodies to p82 generated during parasite infection have a role in the development of immunity to the organism.

Amino Acid Sequence↗
PubMed1993

Antimalarial activity of azithromycin and erythromycin against Plasmodium berghei.

Several antibiotics that inhibit protein synthesis on 70S ribosomes, including the macrolide erythromycin, and the azalides azithromycin (ZITHROMAX) and CP-63,956, demonstrated antimalarial activity against two strains of Plasmodium berghei. In a four-day in vivo test, the azalides were 25-fold more potent than erythromycin against the chloroquine-sensitive P. berghei N strain, and displayed additive effects with chloroquine. This effect was not observed with the erythromycin-chloroquine combination. Against the chloroquine-resistant P. berghei MSU/RC strain, the azalides were 60-fold more potent than erythromycin. Additive effects were observed with azalide-chloroquine combinations against this strain, but these results were not significantly different from the erythromycin-chloroquine combination.

Animals↗
PubMed1992

Modulation of the cellular immune response during Plasmodium falciparum infections in sickle cell trait individuals.

Plasma and peripheral blood mononuclear cells (PBMC) were obtained from P. falciparum-infected individuals with and without the sickle cell trait at diagnosis and 7 days after treatment. HbAA and HbAS patients were compared for levels of plasma soluble IL-2 receptors (IL-2R) and the in vitro cellular reactivity to affinity-purified soluble P. falciparum antigens (SPAg), PPD and phytohaemagglutinin (PHA). At diagnosis, HbAS patients with clinical disease had lower plasma-soluble IL-2R levels and parasite counts than the corresponding HbAA patients, whereas HbAS and HbAA patients with asymptomatic infections had comparable soluble IL-2R levels and parasite counts. PBMC from HbAS patients had higher proliferation and IFN-gamma production in response to SPAg than PBMC from HbAA patients. The difference in the lymphoproliferative responses to SPAg between the two groups was evident in patients with asymptomatic infections. In all patients, the clinical severity, the soluble IL-2R levels and the parasite counts were directly related. The former two were inversely related to the proliferative responses to SPAg. After treatment, all the studied parameters were comparable in the two groups. The study indicates that during P. falciparum infection, HbAS compared with HbAA patients had lower in vivo cellular activation and higher in vitro cellular reactivity in response to soluble malaria antigens.

Adolescent↗
PubMed1992

Activity of azithromycin (CP-62,993) and erythromycin against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum in vitro.

Several antibiotics, including the macrolide erythromycin and the azalides azithromycin (CP-62,993) and CP-63,956, that inhibit protein synthesis on 70S ribosomes demonstrated antimalarial effects in vitro against two strains of Plasmodium falciparum, one sensitive to chloroquine and the other resistant. In 48-hr incubations, erythromycin was 10-fold less potent than the azalides against the chloroquine-resistant strain. Erythromycin and the azalides were essentially equipotent against the chloroquine-sensitive strain. An additive effect occurred with the azalides in combination with chloroquine against both strains, but this was not seen with erythromycin.

Animals↗
PubMed1992

Agglutination of Plasmodium falciparum-infected erythrocytes from east and west African isolates by human sera from distant geographic regions.

Plasmodium falciparum-infected erythrocytes (PfE) were collected from acutely infected children in The Gambia and Tanzania and cultured for more than 30 hr until the parasites were mature trophozoites. Sera collected from these countries, other African countries, Asia, and South America were used in the PfE microagglutination test to determine whether PfE from East and West Africa share surface antigens. From the patterns of agglutination reactivity, we identified extensive antigenic diversity in surface antigens, but obtained no evidence for greater differences between isolates from East or West Africa and those within one region. The majority of sera from immune adults from The Gambia, Tanzania, Sudan, Nigeria, or Ghana were pan-agglutinating, and agglutinated all PfE isolates from The Gambia and Tanzania. Some sera from immune adults of Irian Jaya also agglutinated each of the seven African isolates, while others agglutinated many but not all of the isolates, similar to sera from immune adults of Flores, Indonesia. In contrast, sera from nonimmune adults from Colombia agglutinated few of the African isolates. It was remarkable, however, that sera from nonimmune Colombians agglutinated any African isolates. Our results are consistent with the following conclusions: some PfE surface antigen(s) are very diverse; this diversity is a feature of the parasite worldwide; the repertoire of isolate-specific surface antigens, although large, includes antigens that are either identical or antigenically cross-reactive in geographically very distant parasite populations; and African adults have pan-agglutinating antibodies that may contribute to protective immunity. Such pan-agglutinating antibodies could reflect the accumulation of a large repertoire of isolate-specific antibodies. The contribution of antibody against any shared PfE surface antigen to the pan-agglutinating reactivities is unknown and awaits development of the appropriate reagents.

Adolescent↗
PubMed1991

Transient depletion of T cells with high LFA-1 expression from peripheral circulation during acute Plasmodium falciparum malaria.

Acute P. falciparum malaria is associated with loss of in vitro T cell responsiveness to antigenic stimulation, and with high plasma levels of soluble interleukin 2 receptor (IL 2R). In the present study peripheral T cells from acute P. falciparum malaria patients from a malaria-endemic area of Sudan were analyzed for expression of cell surface antigens associated with T lymphocyte adhesion, activation and maturation. The results were compared to results from T cells obtained from the same donors either before the attack, or during convalescence. Most donors showed a remarkable loss of T cells with high expression of the surface marker LFA-1 (CD11a/CD18) during the clinical episode, in addition to the functional changes described above. Two donors that did not show phenotypic changes were furthermore characterized by having an unabated proliferative response and normal plasma IL 2R levels. All peripheral CD3+ T lymphocytes expressed LFA-1, which had a clearly bimodal distribution on these cells. The T cell subpopulation having high LFA-1 expression (LFA-1++) was composed of both memory and unprimed T cells, according to their expression of CD45RA and CD45R0. Analysis of expression of membrane-bound IL 2R (CD25) and ICAM-1 (CD54) did not reveal in vivo activated T cells in the peripheral blood of the patients. Taken together, these data suggest that circulating T cells recognizing parasite antigens are temporarily withdrawn from peripheral circulation during P. falciparum malaria.

Acute Disease↗
PubMed1991

Lymphoproliferative responses to Plasmodium falciparum antigens in children with and without the sickle cell trait.

Blood mononuclear cells (BMNC) were isolated from sickle cell trait (HbAS) healthy donors and normal haemoglobin (HbAA) healthy donors resident in a P. falciparum endemic area of eastern Sudan. Blood samples were collected during the malaria season. BMNC were tested for their proliferative responses to phytohaemagglutinin (PHA), purified protein derivative of tuberculin (PPD) and to soluble P. falciparum antigens (SPAg). Higher responses to SPAg and PPD were observed in the HbAS children compared with the HbAA children, whereas no differences were observed among adults of the two phenotypes. Proliferative responses to PHA were comparable in all individuals tested. The significance of these findings in relation to haemoglobin phenotype, age and the possible immunoregulatory mechanisms operating in HbAS and HbAA children during the malaria season is discussed.

Animals↗
PubMed1991

Loss of cellular immune reactivity during acute Plasmodium falciparum malaria.

Sixteen patients suffering from acute Plasmodium falciparum malaria were studied. All were residents of an area of unstable malaria-transmission in Eastern Sudan. Blood-samples were drawn at diagnosis, and 7 and 30 days later. Blood-samples from thirteen donors, drawn outside the malaria transmission season 5 months prior to the attack, were included in the study. Lymphoproliferative responsiveness to purified soluble malarial antigens and to the unrelated antigen PPD was lost during the acute phase of the disease in most donors, but was regained during convalescence, except in four donors recrudescing or reinfected by day 30. In contrast to the suppression of antigenic responses, cellular responses to phytohaemagglutinin (PHA) remained virtually unaffected. All donors showed elevated plasma-levels of soluble IL-2 receptor during the acute phase of the disease which normalized during convalescence. Five donors examined by fluorescence-activated cell sorting (FACS) showed no increase in surface expression of IL-2 receptor on peripheral lymphocytes. The data indicate that acute P. falciparum malaria causes a depletion of antigen-reactive T-cells from the peripheral circulation, probably due to homing of this cell-population to lymphoid tissues. It was also found that acute-phase plasma was suppressive to PPD-induced proliferative responses, indicating an additional suppressive mechanism operating in vivo.

Acute Disease↗
PubMed1991

Growth hormone response patterns in sexually or physically abused boys.

The ratio of growth hormone response to clonidine and L-dopa challenge was compared in 74 boys: 15 with purported physical abuse, 7 with purported sexual abuse, 13 normal controls, and 39 psychiatric controls. Sexually abused boys demonstrate a statistically significant elevated ratio of growth hormone response to clonidine versus response to L-dopa. Physically abused boys demonstrate lower clonidine/L-dopa growth hormone response ratios compared with controls. These effects widen with increasing physical development.

Adolescent↗
PubMed1990

Kinetic modelling of the response of Plasmodium falciparum to chloroquine and its experimental testing in vitro. Implications for mechanism of action of and resistance to the drug.

The antimalarial mode of action of chloroquine (CQ) has been investigated in great detail in recent years, but the overall mechanism is still controversial. Instead of further probing the molecular aspects of partial reactions, a model based on the weak base properties of CQ and its delta pH-driven accumulation in acid parasite compartments has been devised, and the integrated response of the parasite to the drug under different experimental conditions has been assayed to verify the validity of the model. Factors such as inoculum size (parasitemia.hematocrit) and medium pH were altered using CQ-sensitive (FCC1) and -resistant (FCR3, VNS) isolates of Plasmodium falciparum. Experimental results were in full agreement with the predictions of the model, implying that therapeutic concentrations of CQ do not raise the pH of the food vacuole, i.e. that alkalinization of the acid parasite compartments is an insufficient explanation for the antimalarial activity of CQ, and that there is no need to invoke an active QC efflux pump to explain drug resistance. Calculations based on the model and the experimental data demonstrate that resistance to CQ is correlated with higher pH and/or higher resistance of the intracellular target to the drug concentration in the parasite food vacuole. The data also have implications for the design and interpretation of in vitro CQ inhibitory tests.

Animals↗
PubMed1990

Growth hormone response to L-dopa and clonidine in autistic children.

Studies have shown abnormal pituitary hormone responses to neuroendocrine agonists in autistic subjects. Two probes (clonidine and L-Dopa) were used to investigate neuroendocrine responses through changes in growth hormone levels. Seven medication-free autistic subjects (ages 6.6 to 19.1) were evaluated and compared to 14 normal controls. Growth hormone was collected at 30-min intervals during the entire study. Clonidine was administered first (dose: 0.15 mgm2), and samples were collected for 180 min. L-Dopa was then administered (dose: 250 mg for subjects less than 70 lb and 500 mg for subjects greater than 70 lb), and samples were collected for 120 min. There was no difference in the amplitude of the clonidine or L-Dopa peak growth hormone responses in the control versus the autistic subjects. In the autistic subjects, the L-Dopa-stimulated growth hormone peak was delayed and the clonidine growth hormone peak was premature. A statistical difference with the control subjects was found when consideration was given to both the premature response of growth hormone to clonidine and the delayed response to L-Dopa (p = .01, Fisher's Exact Test). These findings suggest possible abnormalities of both dopaminergic and noradrenergic neurotransmission in subjects with autism.

Adolescent↗
PubMed1990

Reduced cellular immune reactivity in healthy individuals during the malaria transmission season.

Antigen-induced cellular immune responses are suppressed during acute malaria. The present study engages the possibility that malaria-induced alterations in cellular immune reactivity extend beyond the clinical disease. Thus, lymphoproliferative responses of healthy individuals were diminished during the malaria transmission period in individuals living in an area of highly seasonal, unstable malaria transmission. This finding may have important implications for the design of studies of stimulatory properties of antigens using lymphocytes of endemic origin.

Adolescent↗
PubMed1990

Cell-mediated immune responses to Plasmodium falciparum purified soluble antigens in sickle-cell trait subjects.

To determine the possible differences in the immune response to Plasmodium falciparum between sickle-cell trait (Hb AS) and normal haemoglobin (Hb AA) individuals, we examined 35 Hb AS and 24 Hb AA subjects matched for age and microenvironment. Their age was 2-55 years and all lived in a malaria endemic area 300 km south of Khartoum. Antibodies to ring-infected erythrocyte surface antigen (Pf155/RESA) and to circumsporozoite (CS) protein (anti-NANP40) indicated equal exposure to falciparum malaria. Peripheral blood mononuclear cells (BMNCs) from 20/35 (57%) Hb AS subjects compared with 10/24 (42%) Hb AA subjects, responded to affinity-purified P. falciparum soluble antigens (SPAg). Of those responding to SPAg, 9 (26%) Hb AS subjects and only two (8%) Hb AA subjects had high responses. The mean proliferative response to SPAg of BMNCs from Hb AS individuals was significantly higher than in Hb AA individuals (P less than 0.025). Responses of BMNCs to PPD and PHA were also higher among Hb AS individuals and correlated positively with responses to SPAg. These findings support the hypotheses that the sickle-cell trait protects individuals from P. falciparum infections, at least in part, by modulating the immune response.

Adolescent↗
PubMed1990

Growth hormone dysregulation in children with major depressive disorder.

The growth hormone response to stimulation with oral clonidine and L-dopa was measured in 14 boys with major depressive disorder (MDD) and 15 normal boys. The six MDD boys who were prepubertal or in early puberty were significantly lower than the 10 normal subjects of this age in peak growth hormone response following clonidine administration (p = 0.029) and area under the curve for clonidine (p = 0.030) and L-dopa (p = 0.028). The eight later puberty MDD boys did not differ from the five later puberty normal boys on any measures.

Brain↗