43 results on '"Louis H. Miller"'
Search Results
2. Plasmodium vivax Infections of Duffy-Negative Erythrocytes: Historically Undetected or a Recent Adaptation?
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Amadou Niangaly, Mahamadou A. Thera, Louis H. Miller, Karthigayan Gunalan, and Ogobara K. Doumbo
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0301 basic medicine ,Erythrocytes ,biology ,Plasmodium vivax ,Disease ,Ligands ,biology.organism_classification ,Adaptation, Physiological ,Virology ,Article ,Blood group antigens ,03 medical and health sciences ,030104 developmental biology ,Infectious Diseases ,Africa ,parasitic diseases ,Vivax infection ,Malaria, Vivax ,Plasmodium vivax infection ,Humans ,Parasite hosting ,Parasitology ,Adaptation ,Duffy Blood-Group System - Abstract
Plasmodium vivax is the main cause of malarial disease in Asia and South America. Plasmodium vivax infection was thought to be absent in African populations who are Duffy blood group antigen negative (Duffy-negative). However, many cases of P. vivax infection have recently been observed in Duffy-negative Africans. This raises the question: were P. vivax infections in Duffy-negative populations previously missed or has P. vivax adapted to infect Duffy-negative populations? This review focuses on recent P. vivax findings in Africa and reports views on the parasite ligands that may play a role in Duffy-negative P. vivax infections. In addition, clues gained from studying P. vivax infection of reticulocytes are presented, which may provide possible avenues for establishing P. vivax culture in vitro.
- Published
- 2018
3. Predictors of Access Site Crossover in Patients Who Underwent Transradial Coronary Angiography
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Jeffrey Le, Binita Shah, Louis H. Miller, Yu Guo, Jinfeng Xu, Sohah N. Iqbal, John Coppola, and Sripal Bangalore
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Crossover ,Coronary Artery Disease ,Coronary Angiography ,Logistic regression ,Article ,Coronary artery disease ,Percutaneous Coronary Intervention ,Internal medicine ,Catheterization, Peripheral ,medicine ,Humans ,reproductive and urinary physiology ,Aged ,Retrospective Studies ,business.industry ,Percutaneous coronary intervention ,Retrospective cohort study ,Odds ratio ,Middle Aged ,Prognosis ,medicine.disease ,Confidence interval ,Quartile ,Radial Artery ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Despite increasing use of the transradial approach (TRA) for coronary angiography, TRA failure and subsequent access site crossover remain a barrier to TRA adoption. The aim of this study was to elucidate patient and procedural characteristics associated with TRA to transfemoral approach (TFA) crossover and examine TRA to TFA crossover by operator experience over time. This retrospective analysis identified 1,600 patients who underwent coronary angiography with possible percutaneous coronary intervention through TRA by operators with varied TRA experience in an urban tertiary care center from October 2010 to August 2013. Univariate and multivariable logistic regression were used to identify independent predictors of access site crossover, from TRA to TFA, and strength of association is presented as odds ratio (OR, 95% confidence interval [CI]). Access site crossover was noted in 166 patients (10.4%). Multivariable predictors of access site crossover included age >75 years (OR 1.90, 95% CI 1.23 to 2.91, p = 0.004) and operator experience (OR 2.98, 95% CI 1.96 to 4.52, p, Link_to_subscribed_fulltext
- Published
- 2015
4. Prognostic Value of Fractional Flow Reserve
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K. Lance Gould, Niels Oud, Josep Rodés-Cabau, Göksel Açar, Gabor G. Toth, Manuel F. Jiménez-Navarro, Michalis Hamilos, Luigi Di Serafino, Yolande Appelman, William F. Fearon, Sinan Altan Kocaman, Chang Wook Nam, Nico H.J. Pijls, Louis H. Miller, Bon-Kwon Koo, Pim A.L. Tonino, Demosthenes G. Katritsis, Ali Metin Esen, Patrick Dupouy, Eric Van Belle, Olivier Muller, Pierfrancesco Agostoni, Bernard De Bruyne, Kohichiro Iwasaki, Fatih Arslan, Jeffrey D. Lorin, Yasuchika Takeishi, Etienne Puymirat, Edoardo Verna, Gilles Rioufol, Hongjian Zhu, Ramón López-Palop, Steven P. Sedlis, Johannes Rieber, Emanuele Barbato, Gerald S. Werner, Dejian Lai, Nils P. Johnson, Antonio J. Domínguez-Franco, Shao-Liang Chen, Lisette Okkels Jensen, and Ozlem Esen
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Hazard ratio ,Fractional flow reserve ,030204 cardiovascular system & hematology ,medicine.disease ,Revascularization ,Confidence interval ,Surgery ,Angina ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Conventional PCI ,Severity of illness ,medicine ,Cardiology ,030212 general & internal medicine ,business ,Cardiology and Cardiovascular Medicine ,Mace - Abstract
Background Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear. Objectives The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization. Methods Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold. Results A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p Conclusions FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.
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- 2014
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5. Long term stability of a recombinant Plasmodium falciparum AMA1 malaria vaccine adjuvanted with Montanide® ISA 720 and stabilized with glycine
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Weili Dai, Kelly M. Rausch, Holly McClellan, Yimin Wu, Darning Zhu, Ruth D. Ellis, Mary Anne Kidwell, Joan Aebig, Elizabeth Gebregeorgis, Louis H. Miller, and Laura B. Martin
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medicine.drug_class ,Drug Storage ,Plasmodium falciparum ,Glycine ,Protozoan Proteins ,Antibodies, Protozoan ,Antigens, Protozoan ,Oleic Acids ,Monoclonal antibody ,Article ,Microbiology ,law.invention ,Mice ,Adjuvants, Immunologic ,Drug Stability ,Western blot ,law ,Lowry protein assay ,Malaria Vaccines ,parasitic diseases ,medicine ,Animals ,Mannitol ,Malaria, Falciparum ,Particle Size ,Apical membrane antigen 1 ,Mice, Inbred BALB C ,Vaccines, Synthetic ,General Veterinary ,General Immunology and Microbiology ,biology ,medicine.diagnostic_test ,Malaria vaccine ,Public Health, Environmental and Occupational Health ,Membrane Proteins ,biology.organism_classification ,Infectious Diseases ,Recombinant DNA ,Molecular Medicine ,Female - Abstract
Plasmodium falciparum apical membrane antigen 1 (AMA1) is an asexual blood-stage vaccine candidate against the malaria parasite. AMA1-C1/ISA720 refers to a mixture of recombinant AMA1 proteins representing the FVO and 3D7 alleles in 1:1 mass ratio, formulated with Montanide ® ISA 720 as a water-in oil emulsion. In order to develop the AMA1-C1/ISA720 vaccine for human use, it was important to determine the shelf life of this formulation. Previously it was found 267 mM glycine stabilized the proteins in Montanide ® ISA 720 formulations for a short period of time at 2–8 °C [25] . We now test the long term stability of AMA1-C1 at 10 and 40 μg/mL formulated with Montanide ® ISA 720 with 50 mM glycine as a stabilizer. Stability of AMA1-C1/ISA720 at different time points following formulation (0, 5, 12 or 18 months) was evaluated by determining the mean particle size (diameter of the mean droplet volume), total protein content by a Modified Lowry assay, identity and integrity using western blot and SDS–PAGE. Our results showed that the mean particle size of these emulsions increased over time, whereas protein content, as determined by an ELISA method using a monoclonal antibody against penta-his, decreased over time. For the 10 μg/mL AMA1-C1/ISA720 vaccine, the protein content was 6.5 ± 2.2 μg/mL, and for the 40 μg/mL AMA1-C1/ISA720 vaccine, the protein content was only 8.2 ± 2.3 μg/mL after 18 months of storage at 2–8 °C. These results suggest that the integrity of the protein was affected by long-term storage. The results of the present study indicate that the AMA1-C1/ISA720 emulsion was unstable after 12 months of storage, after which AMA1-C1 proteins were partially degraded.
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- 2011
6. Immunological responses against Plasmodium falciparum Apical Membrane Antigen 1 vaccines vary depending on the population immunized
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Alassane Dicko, Issaka Sagara, Kazutoyo Miura, Ogobara K. Doumbo, Louis H. Miller, Ruth D. Ellis, Hong Zhou, Carole A. Long, Michael P. Fay, Gregory Tullo, Joan Aebig, Ababacar Diouf, and Samuel E. Moretz
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Adult ,Adolescent ,Plasmodium falciparum ,Population ,Protozoan Proteins ,Antibodies, Protozoan ,Antigens, Protozoan ,Enzyme-Linked Immunosorbent Assay ,Mali ,Article ,Young Adult ,Immune system ,Antigen ,Malaria Vaccines ,parasitic diseases ,medicine ,Humans ,Malaria, Falciparum ,Apical membrane antigen 1 ,education ,Clinical Trials as Topic ,education.field_of_study ,General Veterinary ,General Immunology and Microbiology ,biology ,Public Health, Environmental and Occupational Health ,Infant ,Membrane Proteins ,Middle Aged ,biology.organism_classification ,medicine.disease ,United States ,Immunity, Humoral ,Vaccination ,Infectious Diseases ,Child, Preschool ,Immunology ,biology.protein ,Molecular Medicine ,Antibody ,Malaria - Abstract
Clinical development of malaria vaccines progresses from trials in malaria naïve adults to malaria exposed adults followed by malaria exposed children. It is not well known whether immune responses in non-target populations are predictive of those in target populations, particularly in African children. Therefore humoral responses in three different populations (U.S. adults, Malian adults and Malian children) were compared in this study. They were immunized with 80 μg of Apical Membrane Antigen 1 (AMA1)/Alhydrogel on Days 0 and 28. Sera were collected on Days 0 and 42; antibody levels were determined by ELISA and the functionality of antibodies was evaluated by Growth Inhibition Assay. After immunization, there was no significant difference in antibody levels between the Malian children and the Malian adults, but U.S. adults showed lower antibody levels. Vaccination did not significantly change growth-inhibitory activity in Malian adults, but inhibition increased significantly in both U.S. adults and Malian children. Vaccine-induced inhibitory activity was reversed by pre-incubation with AMA1 protein, but pre-existing infection-induced inhibition was not. This study shows that humoral responses elicited by the AMA1 vaccine varied depending on the population, most likely reflecting different levels of previous malaria exposure. Thus predicting immune responses from non-target populations is not desirable.
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- 2011
7. The TLR9 agonist CpG fails to enhance the acquisition of Plasmodium falciparum-specific memory B cells in semi-immune adults in Mali
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Boubacar Traore, Issaka Sagara, Susan K. Pierce, Louis H. Miller, Ogobara K. Doumbo, Safiatou Doumbo, Younoussou Kone, Peter D. Crompton, Didier Doumtabe, Alassane Dicko, Ruth D. Ellis, Kazutoyo Miura, Kassoum Kayentao, Agnes Guindo, Marko Mircetic, Chiung Yu Huang, and Abdramane Traore
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Adult ,Agonist ,Time Factors ,medicine.drug_class ,Plasmodium falciparum ,Antibodies, Protozoan ,Mali ,Article ,Immune system ,Adjuvants, Immunologic ,Malaria Vaccines ,parasitic diseases ,medicine ,Humans ,Malaria, Falciparum ,B-Lymphocytes ,General Veterinary ,General Immunology and Microbiology ,biology ,Malaria vaccine ,Public Health, Environmental and Occupational Health ,TLR9 ,Flow Cytometry ,biology.organism_classification ,medicine.disease ,Virology ,Vaccination ,Infectious Diseases ,Oligodeoxyribonucleotides ,Immunization ,Toll-Like Receptor 9 ,Vaccines, Subunit ,Immunology ,Molecular Medicine ,Immunologic Memory ,Malaria - Abstract
Antibodies play a key role in controlling blood stage malaria infections, and an effective blood stage malaria vaccine will likely require that it induce vaccine-specific memory B cells (MBCs). Our previous studies showed that the addition of the TLR9 agonist CpG to Plasmodium falciparum protein subunit vaccines greatly increased their efficacy in inducing MBCs in nonimmune U.S. volunteers. Here we show that in contrast the same CpG-containing malaria vaccine did not enhance the acquisition of MBCs in semi-immune adults living in Mali. Understanding the molecular basis of this apparent refractoriness to TLR9 agonist will be of significant interest in vaccine design.
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- 2009
8. Use of o-phthalaldehyde assay to determine protein contents of Alhydrogel-based vaccines
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Louis H. Miller, Laura B. Martin, Allan Saul, Daming Zhu, Kelly M. Rausch, and Shuhui Huang
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Quality Control ,medicine.medical_treatment ,Protozoan Proteins ,Aluminum Hydroxide ,Antigens, Protozoan ,Biology ,Sensitivity and Specificity ,complex mixtures ,Article ,Fluorescence ,Protein content ,O-Phthalaldehyde ,chemistry.chemical_compound ,Adjuvants, Immunologic ,Antigen ,Malaria Vaccines ,parasitic diseases ,medicine ,Bradford protein assay ,Chromatography ,General Veterinary ,General Immunology and Microbiology ,Malaria vaccine ,Alum ,Public Health, Environmental and Occupational Health ,Membrane Proteins ,Reproducibility of Results ,Virology ,Recombinant Proteins ,Infectious Diseases ,chemistry ,Molecular Medicine ,ALUMINUM PHOSPHATE ,Adjuvant ,o-Phthalaldehyde - Abstract
Aluminum based adjuvants (alum), including aluminum hydroxide (Alhydrogel) and aluminum phosphate are the most commonly used adjuvant in the US. In order to ensure quality of vaccines, regulatory authorities require evaluation of antigen content in final vaccine products. Currently, there are no generic methods available for the determination of protein content in alum-based vaccines. Aluminum hydroxide gels exist as particles in solution, which interfere with direct quantitation of protein content in formulations using assays such as Lowry, BCA or Bradford protein assay. The present study adapts a simple fluorescent assay to directly (without the need for antigen extraction) determine antigen content on Alhydrogel with accuracy and sensitivity using the o-phthalaldehyde (OPA) reagent. Malaria vaccine candidates AMA1-C1/Alhydrogel, AMA1-C2/Alhydrogel, MSP1(42)-3D7/Alhydrogel, MSP1(42)-C1/Alhydrogel or BSAM-2/Alhydrogel were used as model formulations. The results of the present study show that the OPA assay is highly accurate (87-100%), reproducible, and simple with a linear detection range of 25-400 microg/mL for Alhydrogel vaccines (except for MSP1(42)-C1, which has a linear detection range of 31.25-500 microg/mL). This assay has proven to be highly useful in our laboratory and been used in routine vaccine quality control processes.
- Published
- 2009
9. Structure of the Plasmodium falciparum Circumsporozoite Protein, a Leading Malaria Vaccine Candidate
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Louis H. Miller, Xiaoyan Zou, Yanling Zhang, Vu Nguyen, Merrit Hickman, Karine Reiter, Raul Herrera, Jacob Lebowitz, Nicholas J. MacDonald, Jacqueline Glen, Matthew L. Plassmeyer, Yimin Wu, David L. Narum, Darrell E. Hurt, Albert J. Jin, Svetlana Kotova, Onyinyechukwu Uchime, Richard L. Shimp, Brent House, and Paul D. Smith
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Models, Molecular ,Protein Folding ,Glycosylphosphatidylinositols ,medicine.drug_class ,Immunoblotting ,Plasmodium falciparum ,Protozoan Proteins ,Antigens, Protozoan ,Monoclonal antibody ,Biochemistry ,law.invention ,Pichia pastoris ,law ,Cell Line, Tumor ,Malaria Vaccines ,parasitic diseases ,medicine ,Animals ,Humans ,Molecular Biology ,Chromatography, High Pressure Liquid ,Binding Sites ,biology ,Heparin ,Malaria vaccine ,Circular Dichroism ,C-terminus ,fungi ,Temperature ,Antibodies, Monoclonal ,Cell Biology ,biology.organism_classification ,Molecular biology ,Recombinant Proteins ,Protein Structure, Tertiary ,Circumsporozoite protein ,Sporozoites ,Protein Structure and Folding ,Hepatocytes ,Recombinant DNA ,Electrophoresis, Polyacrylamide Gel ,Proteoglycans ,Protein folding ,Ultracentrifugation ,Protein Binding - Abstract
The Plasmodium falciparum circumsporozoite protein (CSP) is critical for sporozoite function and invasion of hepatocytes. Given its critical nature, a phase III human CSP malaria vaccine trial is ongoing. The CSP is composed of three regions as follows: an N terminus that binds heparin sulfate proteoglycans, a four amino acid repeat region (NANP), and a C terminus that contains a thrombospondin-like type I repeat (TSR) domain. Despite the importance of CSP, little is known about its structure. Therefore, recombinant forms of CSP were produced by expression in both Escherichia coli (Ec) and then refolded (EcCSP) or in the methylotrophic yeast Pichia pastoris (PpCSP) for structural analyses. To analyze the TSR domain of recombinant CSP, conformation-dependent monoclonal antibodies that recognized unfixed P. falciparum sporozoites and inhibited sporozoite invasion of HepG2 cells in vitro were identified. These monoclonal antibodies recognized all recombinant CSPs, indicating the recombinant CSPs contain a properly folded TSR domain structure. Characterization of both EcCSP and PpCSP by dynamic light scattering and velocity sedimentation demonstrated that both forms of CSP appeared as highly extended proteins (R(h) 4.2 and 4.58 nm, respectively). Furthermore, high resolution atomic force microscopy revealed flexible, rod-like structures with a ribbon-like appearance. Using this information, we modeled the NANP repeat and TSR domain of CSP. Consistent with the biochemical and biophysical results, the repeat region formed a rod-like structure about 21-25 nm in length and 1.5 nm in width. Thus native CSP appears as a glycosylphosphatidylinositol-anchored, flexible rod-like protein on the sporozoite surface.
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- 2009
10. Conjugating recombinant proteins to Pseudomonas aeruginosa ExoProtein A: A strategy for enhancing immunogenicity of malaria vaccine candidates
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Nicholas J. MacDonald, Gregory E. D. Mullen, Louis H. Miller, Lambert Lynn, Guanhong Song, Carole A. Long, Olga Muratova, Yanling Zhang, Feng Qian, David L. Narum, Yimin Wu, Karine Reiter, Allan Saul, Gelu Dobrescu, Hong Zhou, and Peter F. Duggan
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Immunoconjugates ,Immunogen ,Virulence Factors ,Bacterial Toxins ,Plasmodium falciparum ,Protozoan Proteins ,Exotoxins ,Antigens, Protozoan ,complex mixtures ,Article ,Microbiology ,Mice ,Antigen ,Malaria Vaccines ,parasitic diseases ,Animals ,Malaria, Falciparum ,Apical membrane antigen 1 ,ADP Ribose Transferases ,Mice, Inbred BALB C ,General Veterinary ,General Immunology and Microbiology ,biology ,Malaria vaccine ,Immunogenicity ,Public Health, Environmental and Occupational Health ,Antibody titer ,Membrane Proteins ,biology.organism_classification ,Virology ,Recombinant Proteins ,Infectious Diseases ,biology.protein ,Molecular Medicine ,Antibody - Abstract
Conjugation of polysaccharides to carrier proteins has been a successful approach for producing safe and effective vaccines. In an attempt to increase the immunogenicity of two malarial vaccine candidate proteins of Plasmodium falciparum, apical membrane antigen 1 (AMA1) to a blood stage vaccine candidate and surface protein 25 (Pfs25) a mosquito stage vaccine candidate, were each independently chemically conjugated to the mutant, nontoxic Pseudomonas aeruginosa ExoProtein A (rEPA). AMA1 is a large (66kD) relatively good immunogen in mice; Pfs25 is a poorly immunogenic protein when presented on alum to mice. Mice were immunized on days 0 and 28 with AMA1- or Pfs25-rEPA conjugates or unconjugated AMA1 or Pfs25, all formulated on Alhydrogel. Remarkably, sera from mice 14 days after the second immunization with Pfs25-rEPA conjugates displayed over a 1000-fold higher antibody titers as compared to unconjugated Pfs25. In contrast, AMA1 conjugated under the same conditions induced only a three-fold increase in antibody titers. When tested for functional activity, antibodies elicited by the AMA1-rEPA inhibited invasion of erythrocytes by blood-stage parasites and antibodies elicited by the Pfs25-rEPA conjugates blocked the development of the sexual stage parasites in the mosquito midgut. These results demonstrate that conjugation to rEPA induces a marked improvement in the antibody titer in mice for the poor immunogen (Pfs25) and for the larger protein (AMA1). These conjugates now need to be tested in humans to determine if mice are predictive of the response in humans.
- Published
- 2007
11. Plasmodium Biology
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Lakshminarayan M. Iyer, Thomas E. Wellems, Louis H. Miller, and L. Aravind
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Genetics ,Apicoplast ,Biochemistry, Genetics and Molecular Biology(all) ,DNA repair ,ved/biology ,ved/biology.organism_classification_rank.species ,Biology ,Genome ,General Biochemistry, Genetics and Molecular Biology ,Protein structure ,Transcription (biology) ,Phylogenetics ,Model organism ,Malarial parasites - Abstract
The highly A+T rich genomes of human and rodent malarial parasites offer unprecedented glimpses of a lineage that is distinct from other model organisms. Plasmodium is distinguished by the presence of numerous low complexity inserts within globular domains of proteins. It displays several peculiarities in its transcription apparatus, and its DNA repair system appears to favor a certain innate level of mutability. Plasmodium possesses many cell surface molecules with "animal-like" adhesion modules. Potential genetic footprints of the ancestral eukaryotic algal precursor of the apicoplast are also detectable in its genome.
- Published
- 2003
12. Are trials in New World monkeys on the critical path for blood-stage malaria vaccine development?
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Anthony W. Stowers and Louis H. Miller
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Erythrocytes ,Plasmodium falciparum ,Blood stage malaria ,Antigens, Protozoan ,Biology ,Animal model ,Malaria Vaccines ,Vaccine Testing ,medicine ,Animals ,Humans ,Marketing ,Protozoal disease ,Clinical Trials as Topic ,Life Cycle Stages ,business.industry ,medicine.disease ,Malaria ,Vaccination ,Disease Models, Animal ,Infectious Diseases ,Aotus trivirgatus ,Immunology ,New product development ,Parasitology ,business ,Critical path method - Abstract
The development of malaria blood-stage vaccines is gathering momentum: there are several new funding initiatives, one multiantigen formulation is currently being tested and at least one other blood-stage vaccine is expected to begin trials in 2001. However, there is no consensus over the best way to select which form of an antigen to take into clinical testing. There is thus a danger that less-effective vaccines might be tested in the field in the order of their availability, rather than merit. Here, we argue that first proving efficacy in the New World monkey challenge model would accelerate development.
- Published
- 2001
13. Plasmodium falciparum: Invasion of Aotus Monkey Red Blood Cells and Adaptation to Aotus Monkeys
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Sandrine C. Soubes, Louis H. Miller, and Osamu Kaneko
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Erythrocytes ,Plasmodium falciparum ,Immunology ,behavioral disciplines and activities ,Apicomplexa ,parasitic diseases ,medicine ,Cebidae ,Animals ,Humans ,Protozoal disease ,Cells, Cultured ,biology ,fungi ,General Medicine ,medicine.disease ,biology.organism_classification ,Adaptation, Physiological ,Virology ,Red blood cell ,Infectious Diseases ,medicine.anatomical_structure ,Aotus trivirgatus ,Protozoa ,Parasitology ,Adaptation ,Malaria - Abstract
Kaneko, O., Soubes, S. C., and Miller, L. H. 1999. Plasmodium falciparum: Invasion of Aotus monkey red blood cells and adaptation to Aotus monkeys. Experimental Parasitology93, 116–119.
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- 1999
14. Representational difference analysis of cDNA between two Dd2 clones of Plasmodium falciparum
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Xuan Liu, Sandrine C. Soubes, and Louis H. Miller
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Genetics ,DNA, Complementary ,Reverse Transcriptase Polymerase Chain Reaction ,GTPase-Activating Proteins ,Genes, Protozoan ,Molecular Sequence Data ,Plasmodium falciparum ,Protozoan Proteins ,Gene Expression ,Membrane Proteins ,Antigens, Protozoan ,DNA, Protozoan ,Biology ,biology.organism_classification ,Polymerase Chain Reaction ,N-Acetylneuraminic Acid ,GTP-Binding Proteins ,Complementary DNA ,Animals ,Parasitology ,Amino Acid Sequence ,RNA, Messenger ,Representational difference analysis ,Molecular Biology - Published
- 1999
15. Plasmodium gallinaceum:Differential Killing of Some Mosquito Stages of the Parasite by Insect Defensin
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Jules A. Hoffmann, Iesha Fields, Louis H. Miller, Mohammed Shahabuddin, and Philippe Bulet
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Insecta ,Membrane permeability ,Zygote ,Immunology ,Plasmodium gallinaceum ,Aedes aegypti ,Biology ,Plasmodium ,Defensins ,Apicomplexa ,Anti-Infective Agents ,Aedes ,parasitic diseases ,Animals ,Parasite hosting ,Defensin ,Diptera ,fungi ,Blood Proteins ,General Medicine ,biology.organism_classification ,Virology ,Insect Vectors ,Infectious Diseases ,Cecropin ,Parasitology ,Chickens - Abstract
We examined several insect antimicrobial peptides to study their effect on Plasmodium gallinaceum zygotes, ookinetes, oocysts, and sporozoites. Only two insect defensins-Aeschna cyanea (dragon fly) and Phormia terranovae (flesh fly)-had a profound toxic effect on the oocysts in Aedes aegypti and on isolated sporozoites. The defensins affected the oocysts in a time-dependent manner. Injecting the peptide into the hemolymph 1 or 2 days after an infectious blood meal had no significant effect on prevalence of infection or relative oocyst density per mosquito. When injected 3 days after parasite ingestion, the relative oocyst density was significantly reduced. Injection on day 4 or later damaged the developing oocysts, although the oocysts density per mosquito was not significantly different when examined on day 8. The oocysts were swollen or had extensive internal vacuolization. The peptides had no detectable effect on the early stages of the parasite: the zygotes and ookinetes tested in vitro. Both the defensins were highly toxic to isolated sporozoites in vitro as indicated by disruption of the membrane permeability barrier, a change in morphology, and loss of motility. In contrast to the toxicity of cecropin and magainin for mosquitoes, defensin, at concentrations that kill parasites, is not toxic to mosquitoes, suggesting that defensin should be studied further as a potential molecule to block sporogonic development of Plasmodium.
- Published
- 1998
16. Parasitology research in the USA and Japan
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Kiyoshi Kita, Louis H. Miller, Kazuyuki Tanabe, James W. Kazura, and Somei Kojima
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Infectious Diseases ,Geography ,Parasitology ,Library science - Published
- 1997
17. Plasmodium falciparum:A High Proportion of Parasites from a Population of the Dd2 Strain Are Able to Invade Erythrocytes by an Alternative Pathway
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Sandrine C. Soubes, Thomas E. Wellems, and Louis H. Miller
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Infectivity ,education.field_of_study ,Erythrocytes ,biology ,Strain (chemistry) ,Plasmodium falciparum ,Immunology ,Population ,Neuraminidase ,General Medicine ,biology.organism_classification ,Virology ,N-Acetylneuraminic Acid ,Infectious Diseases ,Alternative complement pathway ,biology.protein ,Animals ,Humans ,Protozoa ,Parasite hosting ,Parasitology ,education - Published
- 1997
18. Permeabilization of Eggs of the Malaria MosquitoAnopheles gambiae
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Maria Del Pilar Valencia, Peter Mazur, and Louis H. Miller
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Ethylene Glycol ,Cell Membrane Permeability ,Bleach ,Cryoprotectant ,Sodium Hypochlorite ,Anopheles gambiae ,General Biochemistry, Genetics and Molecular Biology ,Cryopreservation ,chemistry.chemical_compound ,Cryoprotective Agents ,Anopheles ,medicine ,Animals ,Humans ,Dehydration ,Ovum ,Chromatography ,biology ,Isopropyl alcohol ,General Medicine ,biology.organism_classification ,medicine.disease ,Insect Vectors ,Malaria ,Drosophila melanogaster ,chemistry ,Evaluation Studies as Topic ,Sodium hypochlorite ,Ethylene Glycols ,Female ,General Agricultural and Biological Sciences ,Ethylene glycol - Abstract
Although Anopheles gambiae embryos that have developed for 15 h at 17 degrees C are slightly permeable to water, they are impermeable to ethylene glycol, the cryoprotectant used in the cryopreservation of Drosophila melanogaster embryos. Success in cryopreservation requires that they be made permeable to protective solutes. Permeabilization of D. melanogaster was achieved by 1) dechorionation with 50% Clorox (household bleach) followed by 2) a water flush; 3) immersion in isopropyl alcohol to remove most extraembryonic water; 4) 2 min air drying to remove most isopropyl alcohol; 5) 90-s exposure to n-heptane containing 0.3% 1-butanol; and 6) 15-s exposure to pure n-heptane. The permeability of A. gambiae embryos was assessed by determining the times required for the initial dehydration of embryos in 1 M ethylene glycol in 260 mOsm Drosophila culture medium (permeability to water) and the times required for their return to normal volume (permeability to ethylene glycol). Based on these criteria, the above D. melanogaster procedure effectively permeabilizes 15 h/17 degrees C to 19 h/17 degrees C A. gambiae embryos. Nearly all collapsed in
- Published
- 1996
19. Plasmodium gallinaceum: Sporozoite Invasion of Aedes aegypti Salivary Glands Is Inhibited by Anti-gland Antibodies and by Lectins
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Louis H. Miller, Kenneth D. Vernick, C. Barreau, Paulo F. P. Pimenta, and M G Touray
- Subjects
Immunology ,Antibodies, Protozoan ,Plasmodium gallinaceum ,Receptors, Cell Surface ,Binding, Competitive ,Salivary Glands ,Agglutinin ,stomatognathic system ,Aedes ,Lectins ,medicine ,Animals ,Soybean agglutinin ,Fluorescent Antibody Technique, Indirect ,Microscopy, Immunoelectron ,Autoantibodies ,Antiserum ,biology ,Salivary gland ,Immune Sera ,Reproducibility of Results ,General Medicine ,biology.organism_classification ,Molecular biology ,Wheat germ agglutinin ,Insect Vectors ,Kinetics ,Infectious Diseases ,medicine.anatomical_structure ,Microscopy, Fluorescence ,Polyclonal antibodies ,Immunoglobulin G ,biology.protein ,Biological Assay ,Female ,Parasitology ,Basal lamina ,Rabbits - Abstract
There is evidence which suggests that malaria sporozoites recognize mosquito salivary glands by specific receptor-ligand interactions. We are interested in identifying the putative salivary gland receptor(s) for sporozoite invasion. We used an in vivo bioassay for sporozoite invasion of salivary glands. In this assay, purified sporozoites from mature oocysts of Plasmodium gallinaceum were injected into Aedes aegypti mosquitoes and salivary glands were dissected at different time points after injection. One half of the maximum invasion of salivary glands by sporozoites occurred by 6 hr, and salivary gland sporozoite load did not increase further after 24 hr postinjection. This assay was used to determine the effect of experimental treatments with antibodies and lectins at 24 hr postinjection. We raised a rabbit polyclonal antiserum against female Ae. aegypti salivary glands which recognized tissue-specific determinants in the basal lamina of salivary glands. Purified IgG antibody fraction of the immune serum blocked sporozoite invasion in vivo. We tested a panel of 19 lectins and found 7 which bound to salivary glands. Of these 7, succinylated wheat germ agglutinin and wheat germ agglutinin completely blocked sporozoite invasion; Pisum sativum agglutinin and soybean agglutinin partially blocked; and concanavalin A, Dolichos biflorus agglutinin, and Phaseolus vulgaris erythroagglutinin did not block. Our results suggest that sporozoites interact with glycosylated salivary gland surface molecules which serve as receptors for invasion, and which may be in the salivary,oland basal lamina. Because the putative sporozoite receptors contain immunogenic determinants, it is feasible to identify them by an immunological strategy.
- Published
- 1995
20. Plasmodium gallinaceum: Differential Lysis of Two Developmental Stages of Malaria Sporozoites by the Alternative Pathway of Complement
- Author
-
M G Touray, Louis H. Miller, and D.C. Seeley
- Subjects
Hot Temperature ,Lysis ,Complement Pathway, Alternative ,Immunology ,Plasmodium gallinaceum ,Biology ,Salivary Glands ,Microbiology ,chemistry.chemical_compound ,Aedes ,parasitic diseases ,medicine ,Animals ,Humans ,Magnesium ,Saliva ,Egtazic Acid ,Edetic Acid ,Infectivity ,Salivary gland ,Immune Sera ,General Medicine ,biology.organism_classification ,Virology ,Insect Vectors ,Complement system ,EGTA ,Cytolysis ,Infectious Diseases ,medicine.anatomical_structure ,chemistry ,Alternative complement pathway ,Calcium ,Female ,Parasitology ,Chickens - Abstract
During sporogonic development of Plasmodium gallinaceum in the mosquito vector, two developmentally distinct sporozoite stages can be isolated. Sporozoites obtained from oocysts in abdomens of mosquitoes 10 days after an infective blood meal are poorly infectious to the vertebrate host (chicken); days later, sporozoites isolated from mosquito salivary glands are highly infectious. In a first step toward understanding the physiologic basis of this developmentally regulated infectivity to the vertebrate host, we determined the relative resistance of the two sporozoite stages to lysis by the complement system of the vertebrate host. Whereas 86% of oocyst sporozoites were lysed when incubated in fresh chicken serum in vitro, only 24% of salivary gland sporozoites were lysed under identical incubation conditions. Preincubation of oocyst sporozoites in a homogenate of female Aedes aegypti salivary glands did not diminish their susceptibility to lysis by serum, indicating that lysis was mediated by the interaction of serum factors with parasite-specific molecules. The lytic activity of fresh chicken serum was abrogated by incubating for 45 min at 56 degrees C or chelating with EDTA. Fresh chicken serum specifically depleted of Ca2+, by chelating with EGTA in the presence of Mg2+, retained its ability to lyse oocyst sporozoites. The lysis of salivary gland sporozoites mediated by chicken antisporozoite serum is abrogated by EGTA, indicating that the antibody-dependent complement pathway in chicken serum is blocked by EGTA. Because oocyst sporozoite lysis by serum was heat sensitive and Mg2+ dependent, but Ca2+ independent, we conclude that lysis was mediated by the alternative pathway of complement.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
21. Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1)
- Author
-
Mohammed Shahabuddin, Thomas F. McCutchan, Louis H. Miller, and Theodore Roberts
- Subjects
Protozoan Vaccines ,Molecular Sequence Data ,Plasmodium falciparum ,Protozoan Proteins ,Antigens, Protozoan ,Sequence alignment ,Antigenic Diversity ,Animals ,Parasite hosting ,Amino Acid Sequence ,Protein Precursors ,Merozoite surface protein ,Molecular Biology ,Gene ,Alleles ,Merozoite Surface Protein 1 ,Genetics ,Models, Genetic ,Sequence Homology, Amino Acid ,biology ,Point mutation ,biology.organism_classification ,Antigenic Variation ,Antigens, Surface ,Protozoa ,Parasitology - Abstract
Immunization with the first identified Plasmodium falciparum merozoite surface protein (MSP-1) protected monkeys from an otherwise fatal infection. The question of whether the high degree of diversity in MSP-1 among parasite clones will be an impediment to its development as a vaccine candidate needs to be resolved. We have aligned all published sequences, identifying errors, resequencing a portion of one parasite clone, and identifying probable duplicate sequences of four pairs of parasite clones. The sequences are displayed in a fashion that facilitates the study of variation and its potentially diverse origins. The original dimorphic sequences described by Tanabe et al. [22] have been modified to include only common sequences throughout the entire gene. The extension of the dimorphic region to the 5′ end of block 3 brings into question the involvement of intragenic crossover as the major mechanism generating allelic diversity. Additional diversity developed from point mutations and recombination in certain regions of the gene. The regions of variability and conservation should serve as a data base for planning vaccine trials.
- Published
- 1993
22. Binding of Plasmodium falciparum 175-kilodalton erythrocyte binding antigen and invasion of murine erythrocytes requires N-acetylneuraminic acid but not its O-acetylated form
- Author
-
Peter Palese, Roland Schauer, P. A. Orlandi, Russell J. Howard, J. David Haynes, Louis H. Miller, F W Klotz, Gerd Reuter, and Stuart J. Cohen
- Subjects
EBA-175, 175-kDa erythrocyte binding antigen ,Erythrocytes ,Neu5,9Ac2, 9-O-acetyl-N-acetylneuraminic acid ,Plasmodium falciparum ,Red cell ,Protozoan Proteins ,Antigens, Protozoan ,Biology ,Sialidase ,Article ,Mice ,chemistry.chemical_compound ,Antigen ,Cell surface receptor ,parasitic diseases ,medicine ,Animals ,Neu5Gc, N-glycoloylneuraminic acid ,Molecular Biology ,Binding Sites ,Ligand (biochemistry) ,biology.organism_classification ,Sialic acid ,Neu5Ac, N-acetylneuraminic acid ,Mice, Inbred C57BL ,Red blood cell ,medicine.anatomical_structure ,Biochemistry ,chemistry ,Mice, Inbred DBA ,Sialic Acids ,Parasitology ,Carrier Proteins ,Merozoite ,N-Acetylneuraminic acid ,Receptor - Abstract
Sialic acid on human erythrocytes is involved in invasion by the human malaria parasite, Plasmodium falciparum. Mouse erythrocytes were used as a reagent to explore the question of whether erythrocyte sialic acid functions as a nonspecific negative charge or whether the sialic acid is a necessary structural part of the receptor for merozoites. Human erythrocytes contain N-acetylneuraminic acid (Neu5Ac), whereas mouse erythrocytes, which are also invaded by P. falciparum merozoites, contain 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac2) and N-glycoloylneuraminic acid (Neu5Gc), in addition to Neu5Ac. We compared the effects of sialidase and influenza C virus esterase treatments of mouse erythrocytes on invasion and the binding of a 175-kDa P. falciparum protein (EBA-175), a sialic acid-dependent malaria ligand implicated in the invasion process. Sialidase-treated mouse erythrocytes were refractory to invasion by P. falciparum merozoites and failed to bind EBA-175. Influenza C virus esterase, which converts Neu5,9Ac2 to Neu5Ac, increased both invasion efficiency and EBA-175 binding to mouse erythrocytes. Thus, the parasite and EBA-175 discriminate between Neu5Ac and Neu5,9Ac2, that is, the C-9 acetyl group interferes with EBA-175 binding and invasion by P. falciparum merozoites. This indicates that sialic acid is part of a receptor for invasion.
- Published
- 1992
23. Recognition of Red Cells by Malaria Parasites: The Role of Erythrocyte-Binding Proteins
- Author
-
J. David Haynes, Louis H. Miller, and Terence J. Hadley
- Subjects
Male ,Primates ,Plasmodium ,Erythrocytes ,Erythrocyte binding ,Clinical Biochemistry ,Antigens, Protozoan ,Ligands ,Host-Parasite Interactions ,Blood group antigens ,Cell Adhesion ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Cell adhesion ,biology ,Chemistry ,Erythrocyte Membrane ,Biochemistry (medical) ,Membrane Proteins ,Hematology ,medicine.disease ,biology.organism_classification ,Malaria ,Disease Models, Animal ,Erythrocyte membrane ,Biochemistry ,Membrane protein ,Carrier protein ,Blood Group Antigens ,Female ,Carrier Proteins - Published
- 1991
24. The peritrophic membrane as a barrier: Its penetration by Plasmodium gallinaceum and the effect of a monoclonal antibody to ookinetes
- Author
-
Masamichi Aikawa, David C. Kaslow, Motomi Torii, Klaus-Peter Sieber, Marcel Huber, Louis H. Miller, and Steven M. Banks
- Subjects
medicine.drug_class ,Immunology ,Antibodies, Protozoan ,Fluorescent Antibody Technique ,Plasmodium gallinaceum ,Monoclonal antibody ,Aedes ,parasitic diseases ,medicine ,Animals ,Parasite hosting ,biology ,fungi ,Antibodies, Monoclonal ,Midgut ,General Medicine ,biology.organism_classification ,Virology ,Epithelium ,Cell biology ,Microscopy, Electron ,Infectious Diseases ,medicine.anatomical_structure ,biology.protein ,Ultrastructure ,Protozoa ,Parasitology ,Antibody - Abstract
We studied the point at which a monoclonal antibody (mAb C5) to a surface protein (Pgs25) on Plasmodium gallinaceum ookinetes blocked the infection of Aedes aegypti mosquitoes. The antibody did not block the development of zygotes to ookinetes in vitro. Development of ookinetes to oocysts in the mosquito was blocked to the same extent whether zygotes grew to ookinetes in the presence of mAb C5 or the antibody was added after the ookinetes had reached full development. When ookinetes developed in vitro in the presence of mAb C5, antibody remained on the surface of the parasite for the next 50 hr and did not block attachment to the peritrophic membrane. When ookinetes were fed to mosquitoes, two subpopulations of mosquitoes were observed (high numbers of oocysts per midgut and low numbers of oocysts per midgut). mAb C5 reduced the number of oocysts per midgut in the subpopulation that had low numbers of oocysts. The subpopulation that had high numbers of oocysts was unaffected by antibody, indicating that the antibody did not block invasion of the midgut epithelium. When mAb C5 was fed with gametocytes, the parasites invaded the epithelium at the same time (between 30 and 35 hr after the blood meal) as in controls, although at a markedly reduced rate. The ultrastructural observations were consistent with a block of parasites within the peritrophic membrane and not with a block at the epithelium, as parasites were not seen to accumulate within the space between the peritrophic membrane and the epithelium. The mechanism by which mAb C5 to Pgs25 of P. gallinaceum blocks the penetration of the peritrophic membrane remains undefined. We present evidence that the parasite modifies the peritrophic membrane during penetration, an observation first made for Babesia microti during penetration of the peritrophic membrane in Ixodes ticks. Ookinetes in the absence of antibodies appeared to disrupt the layers of the peritrophic membrane, suggesting an enzymatic mechanism for penetration.
- Published
- 1991
25. The duffy receptor family of plasmodium knowlesi is located within the micronemes of invasive malaria merozoites
- Author
-
Motomi Torii, Louis H. Miller, Gary E. Ward, Thomas E. Wellems, John H. Adams, Masamichi Aikawa, and Dlana E. Hudson
- Subjects
Plasmodium ,Erythrocytes ,Molecular Sequence Data ,Restriction Mapping ,Plasmodium vivax ,Protozoan Proteins ,Fluorescent Antibody Technique ,Antigens, Protozoan ,Receptors, Cell Surface ,DNA-binding protein ,General Biochemistry, Genetics and Molecular Biology ,parasitic diseases ,Animals ,Amino Acid Sequence ,Cloning, Molecular ,Binding site ,Microscopy, Immunoelectron ,Peptide sequence ,Gene ,Gene Library ,Base Sequence ,biology ,Binding protein ,Nucleic Acid Hybridization ,DNA ,biology.organism_classification ,Macaca mulatta ,Virology ,Molecular biology ,Blotting, Southern ,Multigene Family ,Plasmodium knowlesi ,Duffy Blood-Group System ,Oligonucleotide Probes - Abstract
Plasmodium vivax and Plasmodium knowlesi merozoites invade human erythrocytes that express Duffy blood group surface determinants. A soluble parasite protein of 135 kd binds specifically to a human Duffy antigen. Using antisera affinity purified on the 135 kd protein, we cloned a gene that encodes a member of a P. knowlesi family of erythrocyte binding proteins. The gene is a member of a family that includes three homologous genes located on separate chromosomes. Two genes are expressed as major membrane-bound products that give rise to soluble erythrocyte binding proteins: the 135 kd Duffy binding protein and a 138 kd protein that binds only rhesus erythrocytes. These different erythrocyte binding specificities may result from sequence divergence of the homologous genes. The Duffy receptor family is localized in micronemes, an organelle found in all organisms of the phylum Apicomplexa.
- Published
- 1990
26. A merozoite receptor protein from Plasmodium knowlesi is highly conserved and distributed throughout Plasmodium
- Author
-
Louis H. Miller, Graham H. Mitchell, Andrew P. Waters, Stanley N. Cohen, A W Thomas, Thomas F. McCutchan, D E Hudson, and J A Deans
- Subjects
Nucleic acid sequence ,Cell Biology ,Biology ,biology.organism_classification ,Biochemistry ,Virology ,Plasmodium ,Molecular biology ,Complete sequence ,Antigen ,Plasmodium knowlesi ,parasitic diseases ,Protozoa ,Apical membrane antigen 1 ,Molecular Biology ,Peptide sequence - Abstract
The 66-kDa merozoite surface antigen (PK66) of Plasmodium knowlesi, a simian malaria, possesses vaccine-related properties that are thought to originate from a receptor-like role in parasite invasion of erythrocytes. We report the complete sequence of PK66 which allowed the demonstration that highly conserved analogues exist throughout Plasmodium including a recently reported gene from P. falciparum (Peterson, M. G., Marshall, V. M., Smythe, J. A., Crewther, P. E., Lew, A., Silva, A., Anders, R. F., and Kemp, D. J. (1989) Mol. Cell. Biol. 9, 3151-3155). These analogues are highly promising vaccination candidates. The distribution of PK66 changes after schizont rupture in a coordinate manner associated with merozoite invasion. The protein is concentrated at the apical end prior to rupture, following which it can distribute itself entirely across the surface of the free merozoite. During invasion, immunofluorescence studies suggest that, PK66 is excluded from the erythrocyte at, and behind, the invasion interface.
- Published
- 1990
27. Transmembrane signaling in P815 mastocytoma cells by transfected IgE receptors
- Author
-
Henry Metzger, N Varin-Blank, G. Alber, Louis H. Miller, and Russell I. Ludowyke
- Subjects
Receptor Aggregation ,biology ,Mastocytoma ,Cell Biology ,Transfection ,medicine.disease ,Immunoglobulin E ,Mast cell ,Biochemistry ,Molecular biology ,medicine.anatomical_structure ,medicine ,biology.protein ,Antibody ,Signal transduction ,Receptor ,Molecular Biology - Abstract
In order to delineate structural-functional relationships of the mast cell receptor for IgE (Fc epsilon RI) by molecular-genetic analysis, a transfectable cell must be identified which resembles mast cells except for being deficient in receptors. We have found that the well known murine mastocytoma P815 is suitable. These cells express no Fc epsilon RI, lack mRNA for the alpha and beta subunits of the receptor, but contain some mRNA for gamma chains. After transfection with the cDNA for each of the subunits, stable clones could be isolated which expressed several hundred thousand normal Fc epsilon RI and synthesized large amounts of mRNA for alpha, beta, and gamma, the last at 3-fold higher levels than in the untransfected cells. Aggregation of the transfected receptors led to opening of presumptive calcium channels and to activation of phospholipase C, phospholipase A2, and protein kinase C. The kinetics and other characteristics of the signals were similar to those observed after stimulation of the rat tumor mast cells from which the receptor genetic material had been derived but were smaller in magnitude. These weaker signals most likely result from an overall reduced reactivity exhibited by the P815 cells since stimulation by other ligands led to weaker or even no responses. The cells failed to degranulate after either receptor aggregation or reaction with ionophores with or without phorbol ester. Both the transfected and untransfected P815 cells express Fc receptors for IgG (Fc gamma RII) which, interestingly, independently triggered similar responses despite their apparently simpler subunit structure.
- Published
- 1990
28. The major merozoite surface protein as a malaria vaccine target
- Author
-
W.R. Ballou, Louis H. Miller, and C.L. Diggs
- Subjects
Geography ,Malaria vaccine ,parasitic diseases ,Parasitology ,Merozoite surface protein ,Virology - Abstract
Experts gathered for two days in the summer of 1992 at the National Institutes of Health and the Walter Reed Army Institute of Research to discuss the potential of a major merozoite surface protein (MSP-1) in malaria vaccine development. The participants came in an exemplary spirit of co-operation, sharing ideas and unpublished data toward the common goal of a malaria vaccine. Their conclusions are presented here by Carter Diggs, Ripley Bollou and Lou Miller.
- Published
- 1993
29. Corrigendum to 'Efficient extraction of vaccines formulated in aluminum hydroxide gel by including surfactants in the extraction buffer' [Vaccine 30 (2012) 189–194]
- Author
-
Laura B. Martin, Gregory E. D. Mullen, Holly McClellan, Elizabeth Gebregeorgis, Daming Zhu, Louis H. Miller, Allan Saul, Carole A. Long, Weili Dai, Najam R. Syed, Patrick E. Duffy, Shuhui Huang, Kelly M. Rausch, and David L. Narum
- Subjects
Infectious Diseases ,Chromatography ,General Veterinary ,General Immunology and Microbiology ,Chemistry ,Aluminum hydroxide gel ,Extraction (chemistry) ,Public Health, Environmental and Occupational Health ,Molecular Medicine ,Buffer (optical fiber) - Published
- 2013
30. Molecular identification of the CR1-related blood group antigens implicated in malarial infection
- Author
-
Dennis E. Hourcade, Louis H. Miller, P Zimmerman, J.P. Atkinson, Issaka Sagara, Ogobara K. Doumbo, M Krych, Lalla Kassambara, Daniel J. Birmingham, and Joann M. Moulds
- Subjects
Pharmacology ,Malarial infection ,business.industry ,Immunology ,Medicine ,business ,Molecular identification ,Blood group antigens - Published
- 2000
31. A genetic cross to identify the Plasmodium falciparium ligands for invasion of erythrocytes
- Author
-
Thomas E. Wellems, Osamu Kaneko, Louis H. Miller, and SC Soubes
- Subjects
Genetics ,Infectious Diseases ,biology ,Parasitology ,biology.organism_classification ,Plasmodium - Published
- 1998
32. Alanine mutagenesis of MGSA identifies specific amino acids that bind to the duffy antigen/chemokine receptor and the IL-8 receptor
- Author
-
Daniel G. Yansura, Beth L. Gillece-Castro, Claire Kotts, Louis H. Miller, Joseph Hesselgesser, Richard Horuk, Wayne J. Fairbrother, Laura C. Simmons, Cindy Wirth, and Chetan E. Chitnis
- Subjects
CCR1 ,biology ,Chemistry ,Chemokine receptor CCR5 ,Immunology ,C-C chemokine receptor type 7 ,Hematology ,C-C chemokine receptor type 6 ,CCR8 ,Biochemistry ,Chemokine receptor ,biology.protein ,Immunology and Allergy ,CCL25 ,Molecular Biology ,CCL21 - Published
- 1994
33. Innate resistance in malaria
- Author
-
Richard Carter and Louis H. Miller
- Subjects
Sickle cell trait ,biology ,Host (biology) ,Mechanism (biology) ,Immunology ,Plasmodium falciparum ,General Medicine ,Disease ,medicine.disease ,biology.organism_classification ,symbols.namesake ,Infectious Diseases ,Immunity ,Mendelian inheritance ,symbols ,medicine ,Parasitology ,Malaria - Abstract
The ability of the host to overcome a malarial infection is determined not only by immunologic mechanisms but also by certain innate characteristics of the host. Innate resistance characteristics are inherited, often as simple Mendelian factors e.g., the sickle cell trait and the Duffy blood group determinants. They are not elaborated as the direct result of an individual's exposure to infection. In evolutionary terms, however, the selective pressures of malarial infection on human populations profoundly affect the distribution and frequency of traits conferring resistance to the disease. Mechanisms of innate resistance to malaria have only been described against the blood stages. As yet nothing is known of the influence of the host upon gametocytogenisis or the establishment of the sporozoite in the liver of the mammalian host in the initial stages of infection. Innate resistance to the asexual stages in the blood may operate by creating conditions at the erythrocyte membrane, within the erythrocyte, or in the plasma, which limit the ability of the parasite to multiply. The demonstration that a surface receptor on the erythrocyte controls the parasite's ability to invade the erythrocyte suggests that such a mechanism may underlie the host specificity in other Sporozoa .
- Published
- 1976
34. Processing of a major parasite surface glycoprotein during the ultimate stages of differentiation in Plasmodium knowlesi
- Author
-
Terence J. Hadley, Louis H. Miller, Peter H. David, and Masamichi Aikawa
- Subjects
Plasmodium ,Immunoprecipitation ,Immunoelectron microscopy ,Schizogony ,chemistry.chemical_compound ,parasitic diseases ,medicine ,Animals ,Parasite hosting ,Molecular Biology ,Glycoproteins ,chemistry.chemical_classification ,biology ,Antibodies, Monoclonal ,Membrane Proteins ,biology.organism_classification ,Trypsin ,Macaca mulatta ,Malaria ,Molecular Weight ,chemistry ,Biochemistry ,Plasmodium knowlesi ,Parasitology ,PMSF ,Glycoprotein ,Protein Processing, Post-Translational ,medicine.drug - Abstract
A monoclonal antibody (13C11) was used to investigate the processing of a Plasmodium knowlesi plasma membrane protein during the late stages of schizogony. 13C11 bound to the surface of merozoites, blocked invasion of erythrocytes and immunoprecipitated a 230 kDa glycoprotein from metabolically labelled schizonts. This protein was a major parasite surface component inserted into the membrane of immature schizonts as shown through the study of saponin-freed schizonts which bound 13C11 to their surface (indirect immunofluorescence and immunoelectron microscopy); in addition, the 230 kDa protein on saponin-freed schizonts was susceptible to trypsin treatment. Cleavage of the protein in pulse-chase experiments was followed by immunoprecipitation with 13C11. As schizogony proceeded, the 230 kDa protein was cleaved to 200, 145 and 110 kDa polypeptides. However, this cleavage did not reflect processing but occurred in vitro during detergent extraction and was due to a proteolytic activity which appeared in the parasite during the later stages of schizogony. As schizonts reached maturity and infected erythrocytes lysed, the 230 kDa protein was processed to 75, 57, 50 kDa and 43 kDa polypeptides which were the surface labelled components on purified merozoites immunoprecipitated by 13C11.
- Published
- 1984
35. Plasmodium berghei: Uptake of clindamycin and its metabolites by mouse erythrocytes with clindamycin-sensitive and clindamycin-resistant parasites
- Author
-
Louis H. Miller, Richard L. Jacobs, Louis C. Koontz, and William L. Lummis
- Subjects
Drug ,Erythrocytes ,Plasmodium berghei ,media_common.quotation_subject ,Immunology ,Drug Resistance ,Microbiology ,Mice ,medicine ,Animals ,Chloroquine resistance ,Active metabolite ,media_common ,biology ,Red Cell ,Clindamycin ,Significant difference ,Phosphate buffered saline ,General Medicine ,biology.organism_classification ,Malaria ,Infectious Diseases ,Parasitology ,medicine.drug - Abstract
Tritiated Clindamycin was used to compare the uptake of Clindamycin in plasma and red cells of mice infected with clindamycin-sensitive or clindamycin-resistant Plasmodium berghei and in uninfected mice. Red cells infected with either sensitive or resistant parasites have a higher concentration of [3H]clindamycin and its active metabolites 1 hr after drug administration than uninfected red blood cells. There was no significant difference in uptake of Clindamycin by red blood cells parasitized by sensitive or resistant parasites. Levels of Clindamycin and its metabolites were consistently higher in red cells than in plasma, both in infected and uninfected mice, but the drug was readily removed by washing red cells with phosphate buffered saline in either case. It is concluded that resistance to Clindamycin is not due to an impaired uptake of the drug by the parasitized red cell as has been shown for chloroquine resistance in P. falciparum and P. berghei.
- Published
- 1979
36. Molecular basis for mutation in a surface protein expressed by malaria parasites
- Author
-
Louis H. Miller, Thomas E. Wellems, and Diana Hudson
- Subjects
Plasmodium ,Restriction Mapping ,Mutant ,Biology ,medicine.disease_cause ,Frameshift mutation ,Structural Biology ,Complementary DNA ,HSPA2 ,medicine ,Animals ,Coding region ,RNA, Messenger ,Molecular Biology ,Gene ,Genetics ,Mutation ,Point mutation ,Membrane Proteins ,Molecular biology ,Molecular Weight ,Blotting, Southern ,Genes ,Chromosome Deletion ,DNA, Circular - Abstract
Plasmodium knowlesi parasites isolated from a rhesus monkey vaccinated with a 143,000/140,000 Mr merozoite surface protein no longer expressed this protein. To study the molecular basis for the mutations, a lambda gt11 cDNA expression library constructed from the original parasite clone was screened with rabbit antiserum specific for the 143,000/140,000 Mr protein. Two cDNA clones that mapped to the 5' and 3' ends of the gene hybridized to two chromosomes of 3.6 x 10(6) kilobases and 1.8 x 10(6) kilobases. The gene on the 3.6 x 10(6) base chromosome was identified as the gene expressing the 143,000/140,000 Mr protein. Since the two cDNA clones also hybridized at high stringency with the 1.8 x 10(6) base chromosome, it appears that the 143,000/140,000 Mr gene was involved in an ancestral duplication and interchromosomal transposition. We have analyzed mutant parasites, using the cDNA clones and a 7000 base fragment of genomic DNA that contains the 143,000/140,000 Mr gene. In one type of mutation, the 143,000/140,000 Mr protein was replaced by a 76,000/72,000 Mr protein. The identical restriction sites and the identical size of the mRNA indicated that a point mutation resulted in premature interruption of translation. Sequence analysis revealed an AT substitution for a C in the middle of the coding region of the gene that created a frameshift and a stop codon. In a second type of mutation, no protein was expressed; a 4000 base deletion encompassed the transcriptional unit of the gene. The rapid mutation under vaccine pressure of an otherwise stable parasite protein emphasizes the need to identify vaccine candidates in which mutations would be lethal.
- Published
- 1988
37. A comparison of Knobby (K+) and Knobless (K−) parasites from two strains of Plasmodium falciparum
- Author
-
Theodore J. Green, Russell J. Howard, Terence J. Hadley, Mats Wahlgren, Louis H. Miller, James H. Leech, and Wendell A. Daniel
- Subjects
Erythrocytes ,Sodium ,Plasmodium falciparum ,chemistry.chemical_element ,Biology ,chemistry.chemical_compound ,parasitic diseases ,Animals ,Cloning, Molecular ,Molecular Biology ,Pathogen ,HEPES ,Gel electrophoresis ,Strain (chemistry) ,Erythrocyte Membrane ,Proteins ,Sodium Dodecyl Sulfate ,Broad band ,biology.organism_classification ,Molecular biology ,Molecular Weight ,chemistry ,Biochemistry ,Aotus trivirgatus ,Protozoa ,Electrophoresis, Polyacrylamide Gel ,Parasitology - Abstract
Erythrocytes infected with Plasmodium falciparum develop knob-like protrusions on their membranes. Knobby (K+) parasites of the FCR-3 (Gambian) strain have been shown to possess a histidine-labelled protein of apparent molecular weight 80 000 which is absent from knobless (K−) variants of the same strain. Here we report similiar findings with K+ and K− parasites of another strain, the Malayan Camp strain, and also with cloned K+ and K− parasites of the FCR-3 strain. A histidine-labelled protein unique to the two K+ parasites was identified as a broad band with an apparent molecular weight of 89 000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The presence of this protein in both K+ Malayan Camp parasites and K+ FCR-3 (Gambian) parasites and its absence from K− parasites of both strains is consistent with this protein being a major component of knobs.
- Published
- 1983
38. Studies on the role of red blood cell glycoproteins as receptors for invasion by Plasmodium falciparum merozoites
- Author
-
J D Haynes, M H McGinniss, Louis H. Miller, and Russell J. Howard
- Subjects
Erythrocytes ,Pan troglodytes ,Plasmodium falciparum ,Acetylglucosamine ,Structure-Activity Relationship ,medicine ,Animals ,Glycophorin ,Glycophorins ,Receptors, Immunologic ,Receptor ,Molecular Biology ,Glycoproteins ,chemistry.chemical_classification ,biology ,GYPB ,Erythrocyte Membrane ,biology.organism_classification ,Molecular biology ,In vitro ,Red blood cell ,medicine.anatomical_structure ,Carbohydrate Sequence ,chemistry ,Biochemistry ,biology.protein ,MNSs Blood-Group System ,Parasitology ,Glycoprotein ,Neuraminidase - Abstract
The mechanism of invasion of human red blood cells by Plasmodium falciparum merozoites has been studied by several indirect methods. Red blood cells of the S+s+U+ and S-s-U- blood group phenotypes were trypsin treated and their susceptibility to invasion measured. Trypsin-treated S+s+U+ cells lack the portion of glycophorin A which bears the MN blood group determinants but possess glycophorin B, whereas trypsin-treated S-s-U- cells lack both the glycophorin A MN determinants and the glycophorin B molecule. Since the treated S-s-U- cells showed an even greater loss in susceptibility to invasion that the treated S+s+U+ cells, we conclude that glycophorin B does have a role In merozoite recognition, although it appears less important than glycophorin A. Attempts to decrease invasion by pretreatment with glycosidases were unsuccessful, except for the previously reported effect of neuraminidase. N-acetyl-D-glucosamine decreases the appearance of ring-stage parasites after in vitro reinvasion of P. falciparum. However, the persistence of intact and lysed schizont-infected cells when N-acetyl-D-glucosamine was present, several hours after disappearance of these cells from control cultures, leads us to conclude that this sugar has a deleterious effect on terminal stages of parasite maturation. It is therefore not possible to conclude that N-acetyl-D-glucosamine inhibits merozoite attachment and reinvasion specifically by competition for the receptor.
- Published
- 1982
39. Involvement of T cells in malaria immunity: implications for vaccine development
- Author
-
Louis H. Miller and Michael F. Good
- Subjects
Cellular immunity ,T-Lymphocytes ,Lymphocyte ,Biology ,Immune tolerance ,Immune system ,Immunity ,parasitic diseases ,Immune Tolerance ,medicine ,Animals ,Antigens ,Vaccines ,General Veterinary ,General Immunology and Microbiology ,Effector ,Public Health, Environmental and Occupational Health ,medicine.disease ,Acquired immune system ,Virology ,Malaria ,Infectious Diseases ,medicine.anatomical_structure ,Immunology ,Molecular Medicine - Abstract
T cells are critical for immunity to malaria, not only because they function as helper cells for an antibody response, but also because they serve as effector cells. Such cellular immunity is directly implicated in protection from sporozoites and plays an important role in protection from blood-stage parasites. It also can block transmission of malaria from mammalian host to the mosquito. Both CD8 and CD4 effector cells have important roles. The parasite's defence from immune attack, however, is designed to minimize activation of T cells. Thus, there appears to be limitation of the number of T sites within many malaria proteins and variation within these limited sites. Homology to host proteins and resultant immune-escape due to tolerance may be another mechanism. These parasite defence mechanisms highlight both the importance of T-cell immunity in malaria and the challenge of designing effective vaccines to stimulate T cells.
- Published
- 1989
40. Localization of the major Plasmodium falciparum glycoprotein on the surface of mature intraerythrocytic trophozoites and schizonts
- Author
-
Russell J. Howard, Stephen B. Aley, Jeffrey A. Lyon, J. David Haynes, James H. Leech, John W. Barnwell, Carter L. Diggs, Louis H. Miller, and Masamichi Aikawa
- Subjects
Erythrocytes ,Plasmodium falciparum ,Epitope ,chemistry.chemical_compound ,Glucosamine ,parasitic diseases ,medicine ,Animals ,Molecular Biology ,Polyacrylamide gel electrophoresis ,Glycoproteins ,chemistry.chemical_classification ,biology ,Erythrocyte Membrane ,Antibodies, Monoclonal ,Membrane Proteins ,biology.organism_classification ,Trypsin ,Primary and secondary antibodies ,Molecular biology ,Malaria ,chemistry ,Biochemistry ,Aotus trivirgatus ,biology.protein ,Parasitology ,Isoleucine ,Glycoprotein ,Subcellular Fractions ,medicine.drug - Abstract
The subcellular location of the major malarial glycoprotein in erythrocytes infected with schizonts of Plasmodium falciparum has been studied by two methods. In the first, glycoproteins were labelled with [3H]glucosamine or [3H]isoleucine during in vitro culture. Trypsin treatment of intact infected erythrocytes caused no major qualitative or quantitative changes in [3H]glucosamine labelled glycoproteins or [3H]isoleucine labelled proteins separated by sodium dodecylsulfate polyacrylamide gel electrophoresis. However, in the presence of Triton X-100 the labelled glycoproteins and proteins were completely cleaved by trypsin. In the second method, two monoclonal antibodies which specifically immunoprecipitate the major 195 kDa glycoprotein failed to react on indirect immunofluoresence with intact non-fixed schizont-infected erythrocytes, but reacted strongly with saponin released schizonts indicating specificity for the surface of mature intracellular parasites. Immunoelectronmicroscopy using ferritin-conjugated secondary antibody confirmed the location of the epitope(s) recognized by these monoclonals on the surface of intracellular parasites. Ferritin particles were not associated with knob-bearing erythrocyte membranes. The results indicate that only a small proportion or none of the 195 kDa glycoprotein is on the surface of the infected erythrocyte and that the largest proportion is expressed on the surface of mature intraerythrocytic parasites.
- Published
- 1984
41. A 60-kDa Plasmodium falciparum protein at the moving junction formed between merozoite and erythrocyte during invasion
- Author
-
Russell J. Howard, Louis H. Miller, Terence J. Hadley, Masamichi Aikawa, James H. Leech, and Francis W. Klotz
- Subjects
Erythrocytes ,biology ,medicine.diagnostic_test ,Immunoblotting ,Plasmodium falciparum ,Antibodies, Monoclonal ,Fluorescent Antibody Technique ,Antigens, Protozoan ,biology.organism_classification ,Immunofluorescence ,Molecular biology ,Epitope ,Mice ,Red blood cell ,medicine.anatomical_structure ,Cell–cell interaction ,Plasmodium knowlesi ,medicine ,Animals ,Protozoa ,Parasitology ,Cytoskeleton ,Molecular Biology - Abstract
Invasion of erythrocytes by malaria merozoites requires the formation of a junction of attachment between erythrocyte and merozoite membranes. The attachment junction initially forms at the apical region of the merozoite. It then moves around to the posterior of the merozoite as invasion proceeds. A monoclonal antibody against a 60-kDa merozoite protein (termed MCP-1 for merozoite capping protein 1) of Plasmodium falciparum reacts in an immunofluorescence pattern resembling the moving junction. By two-color immunofluorescence, MCP-1 was located at the attachment site formed between the merozoite apical region and erythrocyte. During invasion, MCP-1 separated and migrated around merozoites at the orifice of the parasitophorous vacuole. In newly-invaded erythrocytes, MCP-1 persisted at the pole of the young parasite nearest the erythrocyte membrane, suggesting its anterior-to-posterior movement. MCP-1 exhibited no variability in molecular mass among the FCR-3, Camp and 7G8 strains of P. falciparum, and the epitope was invariant in the P. falciparum strains studied. We conclude that MCP-1 may participate in merozoite invasion of erythrocytes by facilitating attachment or movement of the junction along the parasite cytoskeletal network.
- Published
- 1989
42. Surface charge on Plasmodium knowlesi and P. coatneyi-infected red cells of Macaca mulatta
- Author
-
Henry N. Freemount, Louis H. Miller, Shu Chien, and George W. Cooper
- Subjects
Electrophoresis ,Plasmodium ,Erythrocytes ,Density gradient ,Surface Properties ,Iron ,Immunology ,Cell Adhesion ,Centrifugation, Density Gradient ,Methods ,Animals ,Colloids ,Surface charge ,Red Cell ,biology ,Cell Membrane ,Monkey Diseases ,Adhesiveness ,Oxides ,Plasmodium falciparum ,Haplorhini ,General Medicine ,Adhesion ,biology.organism_classification ,Virology ,Malaria ,Electrophysiology ,Microscopy, Electron ,Infectious Diseases ,Membrane ,Plasmodium knowlesi ,Biophysics ,Macaca ,Parasitology - Abstract
Red cells infected by Plasmodium falciparum, P. coatneyi, and P. knowlesi adhere to venous endothelium. The possible role of red cell surface charge in the adhesiveness was investigated. The electrophoretic mobility of red cells from monkeys infected by P. knowlesi and P. coatneyi was not significantly different from mobilities determined before infection. When the infected red cells were concentrated by density gradient, they still showed normal electrophoretic mobility. Surface charge distribution was studied by binding positively charged ferric oxide hydrosols to glutaraldehyde-fixed red cells. Colloid binding was similar between the red cells infected with P. knowlesi and P. coatneyi and the uninfected red cells. Furthermore, knoblike membrane protrusions on red cells infected by P. coatneyi showed similar colloid binding as adjacent membranes. Therefore, neither the net surface charge nor the charge distribution on the red cell surface was altered by these infections. The knoblike protrusions in P. coatneyi-infected red cells have radii of curvature of 28–98 nm. Since these low radii would theoretically allow two similarly curved surfaces to approach within 0.5–1.0 nm of each other, knoblike protrusions may form the basis of adhesion. Knoblike protrusions of P. falciparum-infected red cells have similar dimensions and are the apparent site of attachment to venous endothelium.
- Published
- 1972
43. The main obstacle to a malaria vaccine: the malaria parasite
- Author
-
Louis H. Miller and Michael F. Good
- Subjects
Plasmodium ,T-Lymphocytes ,Plasmodium falciparum ,Protozoan Proteins ,Antigens, Protozoan ,Antigen ,parasitic diseases ,medicine ,Antigenic variation ,Animals ,Vaccines ,General Veterinary ,General Immunology and Microbiology ,biology ,Malaria vaccine ,Public Health, Environmental and Occupational Health ,biology.organism_classification ,medicine.disease ,Antigenic Variation ,Virology ,Circumsporozoite protein ,Infectious Diseases ,Immunization ,Antigens, Surface ,Mutation ,Immunology ,Molecular Medicine ,Protozoa ,Malaria - Abstract
The challenge to development of a malaria vaccine will be the variability of the sequences of target antigens. We discuss the variability in the T cell epitopes on the circumsporozoite protein of Plasmodium falciparum and the rapid selection of mutants after immunization with a protein from the asexual erythrocytic stage of P. knowlesi.
- Published
- 1988
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