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Biomedical subjects

L Elson

Publications and source records attributed to L Elson.

14 recordsLinked to original sources

Onchocerciasis modulates the immune response to mycobacterial antigens.

Chronic helminth infection induces a type-2 cellular immune response. In contrast to this, mycobacterial infections commonly induce a type-1 immune response which is considered protective. Type-2 responses and diminished type-1 responses to mycobacteria have been previously correlated with active infection states such as pulmonary tuberculosis and lepromatous leprosy. The present study examines the immune responses of children exposed to both the helminth parasite Onchocerca volvulus and the mycobacterial infections, Mycobacterium tuberculosis and M. leprae. Proliferation of peripheral blood mononuclear cells (PBMC) and production of IL-4 in response to both helminth and mycobacterial antigen (PPD) decreased dramatically with increasing microfilarial (MF) density. Although interferon-gamma (IFN-gamma) production strongly correlated with cellular proliferation, it was surprisingly not related to MF density for either antigen. IL-4 production in response to helminth antigen and PPD increased with ascending children's age. IFN-gamma and cellular proliferation to PPD were not related to age, but in response to helminth antigen were significantly higher in children of age 9-12 years than children of either the younger age group (5-8 years) or the older group (13-16 years). Thus, there was a MF density-related down-regulation of cellular responsiveness and age-related skewing toward type 2 which was paralleled in response to both the helminth antigen and PPD. This parasite-induced immunomodulation of the response to mycobacteria correlates with a previous report of doubled incidence of lepromatous leprosy in onchocerciasis hyperendemic regions. Moreover, this demonstration that helminth infection in humans can modulate the immune response to a concurrent infection or immunological challenge is of critical importance to future vaccination strategies.

Adolescent↗

Role of adult worm antigen-specific immunoglobulin E in acquired immunity to Schistosoma mansoni infection in baboons.

Allergic-type immune responses, particularly immunoglobulin E (IgE), correlate with protective immunity in human schistosomiasis. To better understand the mechanisms of parasite elimination we examined the immune correlates of protection in baboons (Papio cynocephalus anubis), which are natural hosts for Schistosoma mansoni and also develop allergic-type immunity with infection. In one experiment, animals were exposed to a single infection (1,000 cercariae) or were exposed multiple times (100 cercariae per week for 10 weeks) and subsequently were cured with praziquantel prior to challenge with 1, 000 cercariae. Singly and multiply infected animals mounted 59 and 80% reductions in worm burden, respectively (P < 0.01). In a second experiment, animals were inoculated with S. mansoni ova and recombinant human interleukin 12 (IL-12). This produced a 37 to 39% reduction in adult worm burden after challenge (P < 0.05). Parasite-specific IgG, IgE, IgM, and peripheral blood cytokine production were evaluated. The only immune correlate of protection in both experiments was levels of soluble adult worm antigen (SWAP)-specific IgE in serum at the time of challenge infection and/or 6 weeks later. Baboons repeatedly infected with cercariae or immunized with ova and IL-12 developed two- to sixfold-greater levels of SWAP-specific IgE in serum than did controls, and this correlated with reductions in worm burden (r2, -0.40 to -0.64; P, <0. 01). Thus, in baboons and unlike mice, adult worm-specific IgE is uniquely associated with acquired immunity to S. mansoni infection. This similar association of parasite-specific IgE and protection among primates infected with schistosomiasis, along with similar pathology, anatomy, and genetic make-up, indicates that baboons provide an excellent permissive experimental model for better understanding the mechanisms of innate and acquired immunity to schistosomiasis in humans.

Animals↗

A cocktail of recombinant Onchocerca volvulus antigens for serologic diagnosis with the potential to predict the endemicity of onchocerciasis infection.

We report here the evaluation of the potential of a serologic test to determine the endemicity of onchocercal infection in hyper, meso, and hypoendemic communities by the detection of antibodies to a cocktail of recombinant antigens. Parasitologic parameters of infection prevalence and intensity were compared with serologic results. Infection prevalence by serology was consistently but not significantly higher than that defined by parasitology. Differences between the communities defined by microfilarial load (CMFL) and a measurement of Onchocerca volvulus-specific antibody levels (serologic index [SI]) were similar. When stratified by age, differences were more significant in the younger age groups. If a sentinel population of 5-15-year-old individuals was used to compare communities, all could be equally ranked by serologic and parasitologic parameters. The SI of the sentinel population gave a better distinction between each community than the SI of the whole and would be sufficiently sensitive to measure the changes in endemicity that would be required for onchocerciasis control programs.

Adolescent↗

In utero exposure to helminth and mycobacterial antigens generates cytokine responses similar to that observed in adults.

Neonates exposed to parasite antigens (Ags) in utero may develop altered fetal immunity that could affect subsequent responses to infection. We hypothesized that cord blood lymphocytes (CBL) from offspring of mothers residing in an area highly endemic for schistosomiasis, filariasis, and tuberculosis in Kenya would either fail to respond or generate a predominantly Th2-associated cytokine response to helminth and mycobacterial antigens (PPD) in vitro compared to maternal PBMC. Kenyan CBL generated helminth Ag-specific IL-5 (range 29-194 pg/ml), IL-10 (121-2,115 pg/ml), and/or IFN-gamma (78 pg/ml-10.6 ng/ml) in 26, 46, and 57% of neonates, respectively (n = 40). PPD induced IFN-gamma in 30% of Kenyan CBL (range 79-1,896 pg/ml), but little or no IL-4 or IL-5. No Ag-specific IL-4, IL-5, or IFN-gamma release was detected by CBL obtained in the United States (n = 11). Ag-driven cytokine production was primarily CD4-dependent. Cytokine responses to helminth and mycobacterial Ags by maternal PBMC mirrored that observed in neonates. CBL from helminth infected and/or PPD-sensitized mothers produced more Ag-specific cytokines compared to CBL from uninfected mothers (P < 0.05). These data demonstrate that the human fetus develops similar patterns of cytokine production observed in adults and indicates that prenatal exposure may not lead to tolerance or altered fetal immunity. .

Antigens, Bacterial↗

Hospital watch.

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Crime↗

Resistance to Onchocerca volvulus: differential cellular and humoral responses to a recombinant antigen, OvMBP20/11.

Persons putatively immune (PI) to Onchocerca volvulus (Ov) infection were identified in Ecuador on the basis of epidemiologic, clinical, and parasitologic findings. Immune responses of PI subjects to a recombinant onchocercal protein, OvMBP20/11, were determined and compared with those of a comparable infected (INF) group from the same Ov-endemic area. PI subjects had significantly less antibody reactivity to this molecule; however, not all INF subjects had an antibody response. IgG1 and IgG4 were the predominant IgG subclasses induced to this molecule, and the amount of IgG1 produced was the only significant difference between the PI and INF groups. In contrast to the antibody responses, proliferative responses to OvMBP20/11 were significantly higher in PI than in INF subjects. Cytokine analysis of peripheral blood mononuclear cell culture supernatants revealed that INF subjects produced significantly more interleukin-10 in response to OvMBP20/11 than did PI subjects. This antigen induced few other cytokines, and there were no differences between study groups.

Animals↗

Isotype-specific characterization of antibody responses to Onchocerca volvulus in putatively immune individuals.

Isotype/subclass-specific antibody responses to adult Onchocerca volvulus extract (OvAg) were assessed by both ELISA and immunoblotting for a group of putatively immune individuals (PIs, n = 29) from a hyperendemic area in Ecuador and for a group of infected individuals (INFs, n = 470) from the same regions. As a group, the PIs have been previously shown to possess lower levels of OvAg specific IgG1, IgG2, IgG3 and IgG4 than INF's but semi-quantitative analysis revealed that the relative proportions of these subclasses differs between the two groups. The IgG of the PI group contained a higher proportion of IgG3 and a lower proportion of IgG4 than the INF group. The frequency distribution of IgG3 responses was similar for the PI and INF groups. The frequency distributions for IgG1, IgG4 and IgE were significantly different between the PI and INF groups. A subgroup of the PIs were identified from frequency distributions and multivariate plots of individual isotype responses as having antibody responses (mainly IgG4) possibly indicative of cryptic infection. High IgE responses were exclusive to INF individuals, and a rare response type of high IgG3 with negligible levels of other isotypes/subclasses was seen only in the PI group. However, the majority of the PIs had negligible responses for all antibody classes. Immunoblots demonstrated no obvious differences in qualitative recognition between the PIs and INFs.

Adult↗

Polymerase chain reaction-based diagnosis of Onchocerca volvulus infection: improved detection of patients with onchocerciasis.

Definitive diagnosis of Onchocerca volvulus (Ov) infection requires the identification of the parasite in either the skin or subcutaneous nodules. These parasitologic approaches suffer from poor sensitivity. To assess the efficacy and utility of a polymerase chain reaction (PCR)-based diagnosis for Ov infection, skin snips were examined from 94 persons in an Ov-endemic region of Ecuador, and results were compared in a blinded fashion with those of a PCR assay based on the Onchocerca-specific repetitive DNA sequence, O-150. All 60 patients microfilaria-positive on skin snip examination were positive in the PCR-based assay. In addition, 13 of 34 who were microfilaria-negative by skin snips were positive in the PCR assay. This suggests that the PCR-based assay is significantly more sensitive than current methods and overcomes many deficiencies of parasitologic and serologic methodologies in diagnosing active onchocerciasis.

Animals↗

Evidence that barbiturates inhibit antigen-induced responses through interactions with a GTP-binding protein in rat basophilic leukemia (RBL-2H3) cells.

Little is known about the mechanism of action of anesthetics at the biochemical level. The present work, however, gives evidence that barbiturates inhibit inositol phospholipid hydrolysis in both intact and permeabilized rat basophilic leukemia (RBL-2H3) cells by an effect on GTP-binding proteins (G-proteins). Inhibition of hydrolysis was observed when intact cells were stimulated with antigen (DNP24 BSA) or with oligomers of IgE. The inhibition was dependent on the concentration and type of barbiturate used with an order of inhibitory action of secobarbital less than S(-) pentobarbital less than pentobarbital less than R(+) pentobarbital less than phenobarbital. The relatively inactive analogue, (1'RS, 3'SR) 3-hydroxypentobarbital caused little (less than 30% at 1 mM) or no inhibition (at 0.1-0.5 mM). In permeabilized cells, the hydrolysis induced by DNP24 BSA and the nonhydrolyzable analogue of GTP, GTP gamma S (2-100 microM), was also inhibited by pentobarbital. The inhibition of hydrolysis was decreased as pH increased, and was no longer apparent at pH 7.8, a possible indication that the inhibitory effect was due to the unionized form of the drug. In permeabilized cells, the inhibition by pentobarbital occurred in the presence or absence of Ca2+ and was uncompetitive in nature (Km = 7.1 microM for GTP in controls vs. 1.6 microM in the presence of 0.5 mM pentobarbital). Taken together, the data suggest that barbiturates alter the activity of G-proteins independently of Ca2+, and the inhibition may depend on both the hydrophobic properties and the stereospecific and structural features of the molecule.

Animals↗

Carbon dioxide laser microsurgical vasovasostomy.

Microsurgical carbon dioxide (CO2) laser vasovasostomy was successfully achieved by fusion coagulation of protein under similar laboratory conditions as those seen in the operating room. Speed of performance, patent lumen, and lack of granuloma formation support the CO2 laser's ability to simplify this technique.

Animals↗

Multiclinic controlled trial of bethanidine and guanethidine in severe hypertension.

One hundred and eight patients with initial diastolic blood pressure in the range of 100-124 mm Hg while taking hydrochlorothiazide were assigned randomly and double-blind to hydrochlorothiazide plus either bethanidine or guanethidine. The average reduction of the fifth and sixth months' diastolic blood pressure was 18.4 mm Hg for guanethidine and 13.6 mm Hg for bethanidine (P less than 0.01). The distribution of the individual values was such that 68.8% of guanethidine treated patients achieved a diastolic level below 90 mm Hg, compared to only 45.5% of the bethanidine treated group (P less than 0.025). The degree of orthostatic fall in blood pressure was greater with bethanidine than with guanethidine (P less than 0.05). The diurnal variation of blood pressure was slightly greater with bethanidine than with guanethidine. The results significantly favor guanethidine. This study failed to demonstrate that the shorter action of bethanidine confers significantly better control of blood pressure than the longer action of guanethidine.

Bethanidine↗

Anesthetic management for tracheobronchial laser surgery.

The use of the laser has become a well-recognized means of treating obstructing lesions of the tracheobronchial tree. Patients with lower airway compromise are in a precarious state of equilibrium. Everything done by the endoscopy-anesthesiology team tends to change this balance. Cooperation and coordination of this well-disciplined team is needed for efficient treatment of difficult cases. This paper outlines our surgical techniques, which have been tempered and modified to an anesthetic technique that provides the greatest safety with comfort. We detail the basic anesthetic methods for drug usage, pulmonary ventilation, and patient monitoring that we now use. A careful analysis of our results is presented to show that this technique does provide relatively safe anesthesia in this difficult setting.

Adolescent↗

Agency advantages.

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Career Choice↗