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| 2. |
- Iriemenam, Nnaemeka C., et al.
(författare)
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Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan
- 2009
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Ingår i: Vaccine. - Amsterdam : Elsevier. - 0264-410X .- 1873-2518. ; 27:1, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children <5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in >5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses.
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| 5. |
- Elagib, A A, et al.
(författare)
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Association of the haptoglobin phenotype (1-1) with falciparum malaria in Sudan
- 1998
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Ingår i: Transactions of the Royal Society of Tropical Medicine and Hygiene. - : Oxford University Press (OUP). - 0035-9203. ; 92:3, s. 11-309
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Tidskriftsartikel (refereegranskat)abstract
- The haptoglobin phenotypes of Sudanese patients with complicated and uncomplicated falciparum malaria, and those of uninfected randomly selected individuals, were determined by electrophoresis of sera on polyacrylamide gels followed by benzidine staining of the gels. Among 273 malaria patients, the proportions with haptoglobin phenotypes (1-1), (2-1) and (2-2) were 60.8%, 29.7% and 9.5%, respectively, and in 72 cerebral malaria patients the proportions were 63.9%, 29.2%, and 6.9%. The distribution among 208 control individuals was 26.0%, 55.8% and 18.3%, respectively. The difference between patients and controls was highly significant (P < 0.001). The distribution of the different haptoglobin phenotypes among the randomly selected group of 208 Sudanese individuals was comparable to that in many other populations. The results suggests that the haptoglobin phenotype (1-1) is associated with susceptibility to falciparum malaria and the development of severe complications; alternatively, the other phenotypes may confer resistance.
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| 6. |
- Elbashir, M I, et al.
(författare)
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Antibody response in immunized rabbits measured with bacterial immunoglobulin-binding proteins
- 1990
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Ingår i: Journal of Immunological Methods. - : Elsevier BV. - 0022-1759. ; 135:1-2, s. 9-171
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Tidskriftsartikel (refereegranskat)abstract
- Protein G, an immunoglobulin (Ig)-binding protein isolated from group C or G streptococci, binds to the Fc portion of IgG. Protein L, from the anaerobic bacterium Peptostreptococcus magnus, specifically binds light chains of Ig. In this study, protein G and L were used to measure the production of antibodies in immunized rabbits. Two rabbits were immunized with a mixture of human urinary proteins from a patient with tubular proteinuria, and blood samples were collected regularly from the animals for 6 weeks after the immunization. The antibody levels of the blood samples against six of the proteins in the antigen mixture were then measured by ELISA. Microtiter plates were coated with each of the antigens, incubated with the rabbit serum samples, and the specific antibodies of the IgG class measured by incubation with biotinylated protein G, and antibodies of all Ig classes with biotinylated protein L. Alternatively, Western blotting was employed, where the antibodies which bound to each antigen after separation by SDS-PAGE and transfer to nitrocellulose membranes, were detected by protein G or L. The results showed that antibody production against five of the antigens, albumin, alpha 1 gamma-acid glycoprotein, alpha 1 gamma-microglobulin, Ig light chains, and retinol-binding protein, showed a similar pattern, although the magnitude of the initial IgM response differed somewhat. After 6 weeks, the levels of the protein G-binding antibodies had reached a plateau, while those of protein L-binding antibodies were still increasing. The response to the sixth antigen, beta 2 microglobulin, was considerably different. A dramatic increase of anti-beta 2 gamma-microglobulin antibodies was seen during the 4th week after immunization when protein L was used.
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| 7. |
- Elbashir, M I, et al.
(författare)
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Monoclonal antibodies to the pituitary growth-hormone receptor by the anti-idiotypic approach. Production and initial characterization
- 1990
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Ingår i: The Biochemical journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; 266:2, s. 467-474
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Tidskriftsartikel (refereegranskat)abstract
- We obtained 10/192 and 3/384 antibody-secreting hybrids after immunization of Balb/c mice with either human growth hormone or affinity-purified rabbit anti-(human growth hormone) respectively. Radiolabelled rabbit anti-(human growth hormone) antibodies, but not human growth hormone, were specifically bound by supernatants from the 13 hybrids. The binding was completely inhibited by human-growth-hormone serum binding protein. However, anti-(human growth hormone antibodies) were detected in the sera of all the mice immunized with human growth hormone. In an independent fusion, which was carried out after immunization with fewer doses of human growth hormone, anti-(human growth hormone) antibodies were also obtained. Five hybrids, where the starting antigen was human growth hormone, were selected for ascites production, and the corresponding monoclonal antibodies were partially purified and characterized with respect to their immunoglobulin isotype and their interaction with human-growth-hormone receptors. These antibodies were found to enhance the binding of radioiodinated human growth hormone to human-growth-hormone serum binding protein from human and rabbit plasma by 40%. Scatchard analysis of the effect of one of the monoclonal antibodies showed that this enhancement was due to an increased number of binding sites. All of the partially purified antibodies but one (F12) inhibited the binding of human growth hormone to rat but not rabbit, liver microsomes to various extents, as well as to H-4-II-E rat hepatoma cells. Monoclonal antibody F12 enhanced the binding of radiolabelled human growth hormone to rat liver microsomes and H-4-II-E hepatoma cells. This enhancement was found to be due to an increase in the number of binding sites.
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| 9. |
- Younis, Brima Musa, et al.
(författare)
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Safety and efficacy of paromomycin/miltefosine/liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan : A phase II, open label, randomized, parallel arm study
- 2023
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment for post-kala-azar dermal leishmaniasis (PKDL) in Sudan is currently recommended only for patients with persistent or severe disease, mainly because of the limitations of current therapies, namely toxicity and long hospitalization. We assessed the safety and efficacy of miltefosine combined with paromomycin and liposomal amphotericin B (LAmB) for the treatment of PKDL in Sudan.Methodology/principal findings: An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with persistent (stable or progressive disease for >= 6 months) or grade 3 PKDL, aged 6 to <= 60 years in Sudan. The median age was 9.0 years (IQR 7.0-10.0y) and 64% of patients were <= 12 years old. Patients were randomly assigned to either daily intra-muscular paromomycin (20mg/kg, 14 days) plus oral miltefosine (allometric dose, 42 days)-PM/MF-or LAmB (total dose of 20mg/kg, administered in four injections in week one) and oral miltefosine (allometric dose, 28 days)-AmB/MF. The primary endpoint was a definitive cure at 12 months after treatment onset, defined as clinical cure (100% lesion resolution) and no additional PKDL treatment between end of therapy and 12-month follow-up assessment. 104/110 patients completed the trial. Definitive cure at 12 months was achieved in 54/55 (98.2%, 95% CI 90.3-100) and 44/55 (80.0%, 95% CI 70.2-91.9) of patients in the PM/MF and AmB/MF arms, respectively, in the mITT set (all randomized patients receiving at least one dose of treatment; in case of error of treatment allocation, the actual treatment received was used in the analysis). No SAEs or deaths were reported, and most AEs were mild or moderate. At least one adverse drug reaction (ADR) was reported in 13/55 (23.6%) patients in arm 1 and 28/55 (50.9%) in arm 2, the most frequent being miltefosine-related vomiting and nausea, and LAmB-related hypokalaemia; no ocular or auditory ADRs were reported.Conclusions/significance: The PM/MF regimen requires shorter hospitalization than the currently recommended 60-90-day treatment, and is safe and highly efficacious, even for patients with moderate and severe PKDL. It can be administered at primary health care facilities, with LAmB/MF as a good alternative. For future VL elimination, we need new, safe oral therapies for all patients with PKDL.
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