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Biomedical subjects

J Carlson

Publications and source records attributed to J Carlson.

At least 199 records · Page 11Linked to original sources

Disruption of Plasmodium falciparum erythrocyte rosettes by standard heparin and heparin devoid of anticoagulant activity.

We have studied the ability of heparin to disrupt spontaneous rosettes formed between Plasmodium falciparum-infected and uninfected red blood cells, which has been proposed to have importance in the pathogenesis of cerebral malaria. Substantial variation in this activity was found among six laboratory stains of P. falciparum. Rosettes formed by three of these strains were highly sensitive to heparin (50% disruption at 0.5-25 micrograms/ml; 1 microgram/ml corresponds to 0.15 IU/ml). The rosettes formed by two other strains showed a much lower sensitivity (50% disruption at 700-2,500 micrograms/ml), while the rosettes formed by another strain were almost completely resistant to heparin (20% disruption at 6,500 micrograms/ml). The ability of heparin (65 or 650 micrograms/ml) to disrupt rosettes formed by 54 fresh Gambian isolates of P. falciparum also varied. Rosettes of 27 (50%) of the 54 isolates were disrupted to a significant degree (greater than or equal to 15%), while rosettes of the other 27 isolates remained unaffected at the concentrations tested. Heparin was fractionated by molecular weight and/or affinity for antithrombin III. We found that its property of rosette disruption was associated, to some extent, with size (high molecular weight) but not with its anticoagulant potential (affinity for antithrombin III). A heparin fraction with low affinity for antithrombin III and one with combined high molecular weight and low affinity for antithrombin III were as effective at disrupting rosettes as standard heparin, while a chemically modified (N-acetylated) high molecular weight-heparin fraction, similarly devoid of anticoagulant activity, lacked strong anti-rosette potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

acj6: a gene affecting olfactory physiology and behavior in Drosophila.

Mutations affecting olfactory behavior provide material for use in molecular studies of olfaction in Drosophila melanogaster. Using the electroantennogram (EAG), a measure of antennal physiology, we have found an adult antennal defect in the olfactory behavioral mutant abnormal chemosensory jump 6 (acj6). The acj6 EAG defect was mapped to a single locus and the same mutation was found to be responsible for both reduction in EAG amplitude and diminished behavioral response, as if reduced antennal responsiveness to odorant is responsible for abnormal chemosensory behavior in the mutant. acj6 larval olfactory behavior is also abnormal; the mutation seems to alter cellular processes necessary for olfaction at both developmental stages. The acj6 mutation exhibits specificity in that visual system function appears normal in larvae and adults. These experiments provide evidence that the acj6 gene encodes a product required for olfactory signal transduction.

Animals↗

Stage IB glassy cell carcinoma of the cervix diagnosed during pregnancy and recurring in a transposed ovary.

A case report of glassy cell carcinoma of the cervix occurring during pregnancy is presented. Clinical staging was FIGO IB and treatment consisted of a radical hysterectomy, bilateral ovarian transposition, and postoperative pelvic radiation therapy. The patient had a relapse in one of the transposed ovaries. A review of ovarian conservation in Stage IB carcinoma of the cervix is discussed.

Adult↗

Olfaction in Drosophila: genetic and molecular analysis.

Drosophila melanogaster has a sophisticated yet relatively simple olfactory system, the function of which can be studied in vivo by either physiological or behavioral methods. Several genetic and molecular approaches have been applied to isolating and characterizing genes required for the function or development of the olfactory system. Recent analysis of some of these genes is beginning to provide insight into their functions.

Aldehydes↗

Forces and torques produced by a 640-gauss permanent magnet of ferromagnetic objects.

Magnetic forces and torques were measured in a 640-G permanent magnet. The forces on external objects were directed in such a way and of such a strength that the likelihood of injury from unsupported ferromagnetic objects was very small. The forces and torques on ferromagnetic objects within the subject were comparable to those produced by gravitational and inertial efforts in daily living.

Equipment Safety↗

Development of a self-theory and measurement scale.

In this study, we examined a theoretical model of self-development and a scale to measure 12 aspects of the self. The theory, called developmental self-theory, proposes a hierarchical arrangement of dimensions of the self. The 12 scales are collectively called the Omnibus Self-Test and measure Self-Esteem, Positive Self-Regard, Moral Self-Concept, Self-Confidence, Self-Reliance, Self-Control, Selfishness, Self-Disclosure, Self-as-Agent, Self-Critical, Self-Identity, and Self-Reflection. Preliminary data on the reliability and validity of the Omnibus Self-Test is reported along with intercorrelations among the scales.

Adult↗

Human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies.

Plasmodium falciparum isolates from 24 Gambian children with cerebral malaria and 57 children with mild forms of the disease were assessed for their ability to form erythrocyte rosettes. All isolates from the children with cerebral malaria were able to form rosettes, whereas those from children with mild forms of the disease did not form rosettes, or had a significantly lower rosetting rate. Plasma of children with cerebral malaria lacked anti-rosetting activity, whereas plasma of children with mild disease could often disrupt rosettes in vitro. A monoclonal antibody to P falciparum histidine rich protein (PfHRP1/KP/KAHRP) disrupted rosettes of many of the isolates in vitro indicating that the rosetting ligand is relatively conserved compared with ligands associated with endothelial cytoadherence. The findings strongly support the hypothesis that erythrocyte rosetting contributes to the pathogenesis of cerebral malaria and suggest that anti-rosetting antibodies protect against cerebral disease.

Acute Disease↗

Time course of salamander spinal cord regeneration and recovery of swimming: HRP retrograde pathway tracing and kinematic analysis.

The time course of regeneration of supraspinal and descending brachial intraspinal axons was studied using HRP retrograde tracing and kinematic analysis. Five groups of salamanders (10 salamanders/group) received complete thoracic transection 1.0 cm rostral to the hind limbs abolishing swimming. Groups 1-4 recovered for 2, 4, 6, and 8 weeks, respectively, before being filmed to record the animal's ability to swim. After filming, a second transection was made 1.0 cm caudal to the first (at the level of the lumbar enlargement) and HRP was used to label descending axons which had grown past the first lesion. The fifth group was filmed every 2 weeks for 12 weeks before the second transection was made for HRP application. The films were used to perform frame by frame computer analysis of the amplitude and timing of cyclic lateral flexion waves which make up swimming behavior. The earliest return of coordinated swimming behavior was seen 4 weeks after transection (1 of 20 animals). At 6 weeks post-transection, 5 of 10 animals exhibited coordinated swimming. However, the behavior in these animals was subnormal. In the group surviving 8 weeks post-transection, 5 of 10 animals recovered coordinated swimming behavior. In the group that was filmed every 2 weeks, 5 of the 10 salamanders which did recover, exhibited coordinated swimming behavior by the eighth week post-transection. Kinematic analysis of salamanders that exhibited a return of coordinated swimming revealed quantitative differences compared to normal salamanders. While continuous head to tail undulatory waves were present, the propagation time and period were faster than those in normal salamanders. Retransection of the spinal cord abolished coordinated swimming. The numbers and distribution of HRP-labeled supraspinal neurons varied greatly among the animals that displayed recovery of locomotor abilities. In the salamanders examined 6 weeks post-transection the majority of labeled cells were found in medullary nuclei. In recovered salamanders examined 8 and 12 weeks post-transection, HRP-labeled neurons were found in the red nucleus, in the interstitial nucleus of the fasciculus longitudinalis medialis, and in the mesencephalic as well as the medullary reticular neurons. Recovery of coordinated swimming was only observed in salamanders in which descending supraspinal and intraspinal axons were present at the level of the lumbar enlargement (as demonstrated by HRP retrograde labeling). These results indicate that recovery of locomotion is dependent on the reestablishment of descending input and is not a result of changes in spinal reflexes or propagation of electrical activity through the body wall.

Animals↗

Antibodies to a histidine-rich protein (PfHRP1) disrupt spontaneously formed Plasmodium falciparum erythrocyte rosettes.

Cerebral involvement in Plasmodium falciparum malaria is associated with sequestration of infected red blood cells and occlusion of cerebral vessels. Adhesion of infected erythrocytes along the vascular endothelium as well as binding of uninfected erythrocytes to cells infected with late-stage asexual parasites (rosetting) may be important in erythrocyte sequestration. We report that the recently discovered rosetting phenomenon shares characteristics with other human cell-cell interactions (heparin sensitivity, temperature independence, Ca2+/Mg2+ and pH dependence). Mono- and polyclonal antibodies specific for PfHRP1, a histidine-rich protein present in the membrane of P. falciparum-infected erythrocytes, disrupt rosettes but do not affect attachment of infected erythrocytes to endothelial cells. The inhibitory anti-PfHRP1 antibodies reacted with rosetting parasites in indirect immunofluorescence and with P. falciparum polypeptides of Mr 28,000 and Mr 90,000 in immunoprecipitation and immunoblotting, respectively. No inhibitory effects on erythrocyte rosetting were obtained with antibodies to related histidine-rich or other antigens of P. lophurae or P. falciparum. Whether the epitope that mediates rosetting, and is recognized by the anti-PfHRP1 antibodies, is located on PfHRP1 or on a crossreactive antigen remains to be established. The results suggest that endothelial cytoadherence and erythrocyte rosetting involve different molecular mechanisms.

Animals↗

smellblind: a gene required for Drosophila olfaction.

In this article we define and characterize the smellblind gene (sbl). We show that two mutants, sbl and olfDx9, both isolated by virtue of their olfactory phenotypes and analyzed extensively by others with respect to courtship behavior, contain mutations at a single locus. Meiotic recombination, duplication, and deficiency mapping are used to localize this gene, sbl, to cytogenetic position 14F6-15A2-3 on the X chromosome. Mutations of the locus are shown to produce severe defects not only in larval olfactory response to several volatile chemicals, but also in larval contact chemosensory response. Both sbl and olfDx9 give a robust response, however, in a new test of larval phototactic response, which we describe here. Both alleles are shown to be heat-sensitive lethals. Four additional recessive lethal alleles, two EMS-induced, one dysgenic, and one spontaneous, are also described.

Alleles↗

Delineation of canine parvovirus T cell epitopes with peripheral blood mononuclear cells and T cell clones from immunized dogs.

Three synthetic peptides derived from the amino acid sequence of VP2 of canine parvovirus (CPV) which were recently shown to represent three distinct T cell epitopes for BALB/c mice could prime BALB/c mice for a CPV-specific proliferative T cell response upon immunization. Proliferative responses of peripheral blood mononuclear cells (PBMC) from CPV-immunized dogs upon stimulation with these and other peptides, covering the major part of the sequence of VP2', identified the presence of T cell epitopes for this species. Most of these epitopes were recognized by PBMC from only a minority of the dogs tested. With three newly generated canine Thyl+ T cell clones, which recognized CPV antigen in association with major histocompatibility complex class II molecules, two distinct T cell epitopes were identified within the unique sequence of VP1.

Amino Acid Sequence↗

A synthetic peptide derived from the amino acid sequence of canine parvovirus structural proteins which defines a B cell epitope and elicits antiviral antibody in BALB c mice.

Synthetic peptides, recombinant fusion proteins and mouse monoclonal antibodies were used to delineate a B cell epitope of the VP'2 structural protein of canine parvovirus (CPV). Although this epitope is not preferentially recognized in the normal antibody response to CPV, virus-specific antibodies could be induced in BALB/c mice with a synthetic peptide representing the epitope. The potential of this non-dominant B cell epitope to induce antiviral immunity in the presence of maternal CPV-specific antibodies, is discussed.

Animals↗

Establishment and characterization of canine parvovirus-specific murine CD4+ T cell clones and their use for the delineation of T cell epitopes.

Canine parvovirus (CPV)-specific T cell clones were generated by culturing lymph node cells from CPV-immunized BALB/c mice at limiting dilutions in the presence of CPV antigen and interleukin-2 (IL-2). All isolated T cell clones exhibited the cell surface phenotype Thy1+, CD4+, CD8- and proliferated specifically in response to CPV antigen. After stimulation with CPV antigen in culture the T cell clones produced IL-2 and proliferated in the absence of exogenous IL-2. Naive mice to which CPV-specific T cell clones had been adoptively transferred developed a CPV-specific delayed type hypersensitivity reaction upon simultaneous intracutaneous injection of CPV in their ears. The ability of recombinant viral fusion proteins, representing the VP2 capsid protein of the antigenically closely related feline panleukopenia virus and of synthetic peptides derived from the amino acid sequence of the VP2 of CPV, to stimulate these T cell clones enabled the identification of T cell epitopes.

Amino Acid Sequence↗