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Biomedical subjects

J B Jensen

Publications and source records attributed to J B Jensen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Continuous culture of Plasmodium falciparum: its impact on malaria research.

The methods developed by us in 1976 for the continuous culture of the erythrocytic stages of Plasmodium falciparum make this organism available to a large variety of scientists. As a result, much has been learned about P. falciparum during the past 20 years. Here we attempt to emphasize recent developments in the diverse aspects for which the culture method has been particularly useful: chemotherapy; drug resistance; vaccine development; pathogenesis; export of proteins into the host cell; cell biology, the mitochondrion and the plastid; innate resistance involving mutant human erythrocytes; gametocytogenesis; genetics, transfection; molecular biology; biochemistry; extracellular cultivation.

Animals↗
PubMed1997

Human T-cell recognition of synthetic peptides representing conserved and variant sequences from the merozoite surface protein 2 of Plasmodium falciparum.

Merozoite surface protein 2 (MSP2) is a malaria vaccine candidate currently undergoing clinical trials. We analyzed the peripheral blood mononuclear cell (PBMC) response to synthetic peptides corresponding to conserved and variant regions of the FCQ-27 allelic form of MSP2 in Ghanaian individuals from an area of hyperendemic malaria transmission and in Danes without exposure to malaria. PBMC from 20-39% of Ghanaians responded to each of the peptides by proliferation and 29-36% had PBMC which produced interferon-gamma (IFN-gamma) in response to peptide stimulation. In Danes, there was no proliferation to two of the peptides and only PBMC from 5% of the individuals proliferated to the other three peptides. IFN-gamma production was not detected to any peptide. In both Danes and Ghanaians in only a few instances was IL-4 detected in the PBMC cultures. Overall PBMC from 79% of the Ghanaians responded by proliferation and/or cytokine secretion to at least one of three peptides tested, whereas responses were only observed in 14% of Danes (P = 0.002). These data suggest that the Ghanaians had expanded peripheral blood T-cell populations recognizing the peptides as a result of natural infection. The findings are encouraging for the development of a vaccine based on these T-epitope containing regions of MSP2, as the peptides were broadly recognized suggesting that they can bind to diverse HLA alleles and also because they include conserved MSP2 sequences. Immunisation with a vaccine construct incorporating the sequences present in these peptides could thus be expected to be immunogenic in a high percentage of individuals and lead to the establishment of memory T-cells, which can be boosted through natural infection.

Adult↗
PubMed1997

Altered protein phosphorylation in the rat brain following chronic lithium and carbamazepine treatments.

Lithium and carbamazepine (CBZ) alter levels of specific kinase-activating second messengers generated by adenylate cyclases and the phosphoinositide system. Thus, lithium and CBZ may change endogenous protein phosphorylation mediated by cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC). The present study aimed at comparing the chronic effects of lithium and CBZ on protein phosphorylation in the rat brain by using quantitative autoradiography. Long-term treatments yielded plasma levels within the therapeutic range. In the particulate hippocampal fraction PKA-mediated phosphorylation of a 42 kDa protein and PKC-mediated phosphorylation of a 88 kDa protein were decreased after lithium treatment. In the cortical particulate fraction approximately 30% reduction in the PKA-mediated protein phosphorylation of several proteins was observed after lithium and CBZ treatments. In the same fraction, CBZ treatment significantly reduced PKC-mediated phosphorylation of several substrates by 30-40%. PKA activity was significantly reduced in cortex, but not in the hippocampus. Thus, both drugs exhibited fraction and region specificities.

Animals↗
PubMed1997

Antibody responses to Rhoptry-Associated Protein-1 (RAP-1) of Plasmodium falciparum parasites in humans from areas of different malaria endemicity.

Plasma IgM and IgG antibody reactivities against the recombinant Plasmodium falciparum protein, Rhoptry Associated Protein-1 (rRAP-1) were measured by ELISA in individuals from Sudan, Indonesia, Kenya and The Gambia living in areas of different malaria endemicity. IgG and IgM reactivities to rRAP-1 increased with malaria endemicity. IgG reactivities were associated with spleen rates in Indonesia with high malaria endemicity while IgM reactivities were associated with spleen rates in Kenya with low malaria endemicity. IgG and IgM reactivities to rRAP-1 increased during acute episodes of P. falciparum malaria in Sudanese adults and IgG reactivities remained high one month after treatment in all adults tested. Antibody reactivities to rRAP-1 in Gambian children in the dry season were higher in children with parasitaemia than in children without detectable parasitaemia. Antibody reactivities were not associated with protection against clinical episodes in the following rainy season but higher antibody reactivities were detectable at the end of the rainy season. There was no difference in antibody reactivity to rRAP-1 between Gambian children with mild or severe malaria.

Adolescent↗
PubMed1996

Antibody reactivities to glutamate-rich peptides of Plasmodium falciparum parasites in humans from areas of different malaria endemicity.

Synthetic P. falciparum peptides were evaluated as tools in epidemiological investigations of malaria. Plasma IgM and IgG antibody reactivities against synthetic peptides covering sequences of glutamate-rich protein (GLURP) and acidic-basic repeat antigen (ABRA) were measured by ELISA in individuals from malaria-endemic areas of Sudan, Indonesia and The Gambia to study antibody responses to these peptides in donors living in areas of different malaria endemicity. IgG and IgM reactivities to the peptides increased with malaria endemicity, although there were no differences in reactivities to the GLURP peptide between non-exposed donors and donors living in areas of low malaria endemicity. IgG reactivities to the GLURP peptide in Sudanese adults were high one month after treatment in all adults tested, while IgG reactivities to the ABRA peptide were infrequent. IgM responses to the peptides tested were shortlived in most patients. In Gambian children with malaria, IgM reactivities but not IgG antibody reactivities against the ABRA peptide were higher in those with mild malaria than in those with severe malaria. The peptides may be useful in future epidemiological studies, especially in areas of low malaria endemicity.

Adolescent↗
PubMed1996

Augmented hypoxic cerebral vasodilation in men during 5 days at 3,810 m altitude.

The fractional increase in cerebral blood flow (CBF) velocity (VCBF) from the control value with 5-min steps of isocapnic hypoxia and hyperoxic hypercapnia was measured by transcranial Doppler in six sea-level native men before and during a 5-day sojourn at 3,810 m altitude to determine whether cerebral vasoreactivity to low arterial O2 saturation (SaO2) gradually increased [as does the hypoxic ventilatory response (HVR)] or diminished (adapted, in concert with known slow fall of CBF) at altitude. A control resting PCO2 value was chosen each day during preliminary hyperoxia to set ventilation at 140 ml.kg-1.min-1 for this and the parallel HVR study, attempting to establish control cerebrospinal fluid (CSF) and brain extracellular fluid pH values unaltered by acclimatization. The relationship of CBF to SaO2 was nonlinear, steepening at a lower SaO2. A hyperbolic equation was used to describe hypoxic cerebrovascular reactivity: fractional VCBF = x[60/ (SaO2-40)-1], where X is the fractional increase of VCBF at 70%.X rose from 0.346 +/- 0.104 (SD) at sea level to 0.463 +/- 0.084 on altitude day 5 (P < 0.05 by paired t-test, justified by the a priori experimental plan). For comparison with CO2 sensitivity, from these X values, we estimate the rise in CBF in response to a 1% fall in SaO2 at 80% to be 1.30% at sea level and 1.74% after 5 days at altitude. CBF sensitivity to increased end-tidal PCO2 rose from 4.01 +/- 0.62%/Torr at sea level to 5.12 +/- 0.79%/Torr on day 5 (P < 0.05), as expected, at the lower PCO2 due to the logarithmic relationship of PCO2 to CSF pH. This change was not significant after correction to log PCO2. We conclude that the cerebral vascular response to acute isocapnic hypoxia may increase during acclimatization at high altitude. The mechanism is unknown but is presumably unrelated to the parallel carotid chemosensitization that, in these subjects, increased the HVR by 60% in the same 5-day period from 0.91 +/- 0.38 to 1.46 +/- 0.59 l.min-1.% fall in SaO2-1).

Adult↗
PubMed1996

Use of random amplified polymorphic DNA (RAPD) technique in inheritance studies of Plasmodium falciparum.

Effectiveness of random amplified polymorphic DNA (RAPD), a technique using 1 10-base primer to amplify random segments of genomic DNA, and some of its possible uses were tested in the A + T-rich genome of Plasmodium falciparum. The best concentrations of MgCl2, 60% G + C primer, and DNA were determined to be 4.0 mM, 0.4 microM, and 90-180 ng/15 microliters reaction, respectively. Use of 30% G + C primers did not allow amplification to occur. Application of RAPD to DNA of parent and progeny clones from a P. falciparum cross showed that polymorphisms identified in the parentals and tracked in the progeny were inherited in a Mendelian fashion and that RAPD-identified polymorphisms could be used as genetic markers. Some of these polymorphic markers were located on more than 1 chromosome, whereas others were specific for a single chromosome. Two of these markers, each located on chromosome 3 of 1 of the parental parasites, were missing from 2 of the 18 progeny, suggesting that deletions, or crossover events had occurred. RAPD markers also identified a higher number of nonparental-type progeny than expected, thus confirming previous observations for high genetic variability in malaria parasites.

Animals↗
PubMed1995

[Episodic hypoxemia and coinciding ECG changes after acute myocardial infarction].

This study was conducted to document the trend in arterial hypoxaemia and electrocardiographic (ECG) abnormalities on second to sixth night after acute myocardial infarction (AMI). Nineteen consecutive patients with AMI were monitored continuously during the night with a Holter tape recorder and a pulse oxymeter. Five patients had > 30 episodic oxygen desaturations of > or = 5%, and many patients had episodes with oxygen desaturations < 80% ranging from 46-61% (from 7/15-11/18) during the nights of monitoring. Constant hypoxaemia was found in 11-13% of the patients. Many patients had simultaneous occurrence of episodic hypoxaemia and episodic sinustachycardia, ST-deviation and arrhythmias, giving a summarized simultaneous occurrence of episodic hypoxaemia and ECG-abnormalities ranging from 13/18 (72%) patients on the third night to 7/15 (46%) patients on the sixth night. Episodic and constant hypoxaemia are thus common during the first week after AMI. Episodic hypoxaemia was associated with ECG-abnormalities in the majority of patients.

Adult↗
PubMed1995

Catabolism of indole-3-acetic acid and 4- and 5-chloroindole-3-acetic acid in Bradyrhizobium japonicum.

Some strains of Bradyrhizobium japonicum have the ability to catabolize indole-3-acetic acid. Indoleacetic acid (IAA), 4-chloro-IAA (4-Cl-IAA), and 5-Cl-IAA were metabolized to different extents by strains 61A24 and 110. Metabolites were isolated and analyzed by high-performance liquid chromatography and conventional mass spectrometry (MS) methods, including MS-mass spectroscopy, UV spectroscopy, and high-performance liquid chromatography-MS. The identified products indicate a novel metabolic pathway in which IAA is metabolized via dioxindole-3-acetic acid, dioxindole, isatin, and 2-aminophenyl glyoxylic acid (isatinic acid) to anthranilic acid, which is further metabolized. Degradation of 4-Cl-IAA apparently stops at the 4-Cl-dioxindole step in contrast to 5-Cl-IAA which is metabolized to 5-Cl-anthranilic acid.

Chromatography, High Pressure Liquid↗
PubMed1995

High proportion of subclinical Plasmodium falciparum infections in an area of seasonal and unstable malaria in Sudan.

In the present longitudinal study, a cohort (n = 98) of children and adults 5-30 years of age living in an area of highly seasonal and unstable malaria transmission were followed for malaria morbidity during several successive transmission seasons. Based on morbidity surveillance during 1993 and measurements of antibody titers to the Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA), the cohort was divided into three groups: those who had at least one episode of clinical malaria (Group 1, n = 31), those who did not suffer from clinical malaria but had (Group 2, n = 63) or had not (Group 3, n = 4) a significant increase in antibody titers against the Pf155/RESA antigen. This increase was defined as equal to or greater than a four-fold increase in antibody titer in samples from same individuals taken at the beginning and the end of the malaria transmission season. Such increases in specific antibody levels suggested that the donors had been exposed to a P. falciparum blood-stage infection. Measurements of antibody titers to a peptide derived from the glutamate-rich protein exoantigen gave data parallel to those for Pf155/RESA. A surprisingly high fraction of individuals in the study cohort (approximately 66%) showed evidence of infection without ensuing clinical disease (Group 2).

Adolescent↗
PubMed1994

Differential T-cell expression of LFA-1 in residents from Africa and Denmark. Description of the phenomenon and its possible basis.

All circulating T cells constitutively express the adhesion molecule leukocyte function-associated antigen 1 (LFA-1; CD11a/CD18) at either low or high surface density. In the present paper we have compared the expression of the LFA-1 alpha-chain CD11a on peripheral T cells obtained from indigenous Africans with permanent residence in Africa to T cells from indigenous Danes with permanent residence in Denmark. The Africans had a higher percentage of T cells with high CD11a expression than did Danish donors. The difference was evident in both the CD3-, CD4+, and CD8+ subsets. The difference did not appear to reflect a higher degree of peripheral T-cell activation in the African donors, as T-cell expression of the activation marker IL-2 receptor (CD25) was similar in the two groups. Furthermore, we observed no apparent correlation between CD3+ CD11a(hi) and CD3+ CD25+ values in individual donors. LFA-1 expression on T cells obtained from expatriate Africans with long-term residence in Denmark resembled that of Danish permanent residents more than that of Africans with permanent residence in Africa. In addition, T cells obtained from two expatriate Danes with long-term residence in rural Africa were phenotypically similar to those from African permanent residents. The data suggest that the observed difference is environmental rather than ethnic and may reflect the degree of exposure to infectious agents.

Africa↗
PubMed1994

Emergency cardiopulmonary support with circulatory support devices.

Emergency cardiopulmonary support has been used in the United States since 1986, mainly by physicians at participating centers for the National Registry of Elective Supported Angioplasty. Data from the National Registry as well as the experience in three institutions from a number of operators were analyzed to assess the benefits of the emergency cardiopulmonary support application in patients with hemodynamic collapse. Patients who had experienced either cardiac arrest or hemodynamic collapse with cardiogenic shock unresponsive to pressors were placed emergently on cardiopulmonary support. They were either then treated with angioplasty or with revascularization surgery. Patients placed on cardiopulmonary support in less than 15 min experienced a 48% survival rate across the whole registry of the participating centers of the National Cardiopulmonary Bypass Registry. A two-center experience has demonstrated a 69% survival rate. Patients treated with emergency cardiopulmonary support who have experienced hemodynamic collapse have improved survivorship over any other hemodynamic support system. With increasing experience by the operators, the results have improved for survivorship, particularly in the early application group.

Angioplasty, Balloon, Coronary↗
PubMed1994

Evidence of endothelial inflammation, T cell activation, and T cell reallocation in uncomplicated Plasmodium falciparum malaria.

To explain the observation that acute Plasmodium falciparum malaria is associated with a transient inability of peripheral blood cells to respond to antigenic stimulation in vitro, we have postulated the disease-induced reallocation of peripheral lymphocytes, possibly by adhesion to inflamed endothelium. We measured plasma levels of soluble markers of endothelial inflammation and T cell activation in 32 patients suffering from acute, uncomplication P. falciparum malaria, as well as in 10 healthy, aparasitemic control donors. All donors were residents of a malaria-endemic area of Eastern State Sudan. In addition, we measured the T cell surface expression of the interleukin-2 receptor (CD25) and the lymphocyte function-associated antigen (LFA-1; CD11a/CD18). We found that the plasma levels of all inflammation and activation markers were significantly increased in the malaria patients compared with the control donors. In addition, we found a disease-induced depletion of T cells with high expression of the LFA-1 antigen, particularly in the CD4+ subset. The results obtained provide further support for the hypothesis of T cell reallocation to inflamed endothelium in acute P. falciparum malaria.

Adolescent↗