22 results on '"Lyke K"'
Search Results
2. Erythrocyte CR1 expression level does not correlate with a HindIII restriction fragment length polymorphism in Africans; implications for studies on malaria susceptibility
- Author
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Rowe, J A, Raza, A, Diallo, D A, Baby, M, Poudiougo, B, Coulibaly, D, Cockburn, I A, Middleton, J, Lyke, K E, Plowe, C V, Doumbo, O K, and Moulds, J M
- Published
- 2002
- Full Text
- View/download PDF
3. Homologous and Heterologous Covid-19 Booster Vaccinations.
- Author
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Atmar, R. L., Lyke, K. E., Deming, M. E., Jackson, L. A., Branche, A. R., El Sahly, H. M., Rostad, C. A., Martin, J. M., Johnston, C., Rupp, R. E., Mulligan, M. J., Brady, R. C., Frenck Jr., R. W., Bäcker, M., Kottkamp, A. C., Babu, T. M., Rajakumar, K., Edupuganti, S., Dobrzynski, D., and Coler, R. N.
- Abstract
BACKGROUND Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients. METHODS In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 µg, Ad26.COV2.S (Johnson & Johnson-Janssen) at a dose of 5x1010 virus particles, or BNT162b2 (Pfizer-BioNTech) at a dose of 30 µg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29. RESULTS Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COVZ.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients. CONCLUSIONS Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicaITrials.gov number, NCT04889209.) [ABSTRACT FROM AUTHOR]
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- 2022
- Full Text
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4. Ventriculitis Complicating Use of Intraventricular Catheters in Adult Neurosurgical Patients. (Major Article)
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Lyke, K. E., Obasanjo, O. O., Williams, M. A., O'Brien, M., Chotani, R., and Perl, T.M.
- Subjects
Catheterization -- Complications ,Health ,Health care industry - Published
- 2001
5. Association of HLA alleles with Plasmodium falciparum severity in Malian children
- Author
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Lyke, K. E., Fernández-Viña, M. A., Cao, K., Hollenbach, J., Coulibaly, D., Kone, A. K., Guindo, A., Burdett, L. A., Hartzman, R. J., Wahl, A. R., Hildebrand, W. H., Doumbo, O. K., Plowe, C. V., and Sztein, M. B.
- Published
- 2011
- Full Text
- View/download PDF
6. Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci
- Author
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Cao, K., Moormann, A. M., Lyke, K. E., Masaberg, C., Sumba, O. P., Doumbo, O. K., Koech, D., Lancaster, A., Nelson, M., Meyer, D., Single, R., Hartzman, R. J., Plowe, C. V., Kazura, J., Mann, D. L., Sztein, M. B., Thomson, G., and Fernández-Viña, M. A.
- Published
- 2004
7. Identification of the Kna/Knb polymorphism and a method for Knops genotyping
- Author
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Moulds, J. M., Thomas, B. J., Doumbo, O., Diallo, D. A., Lyke, K. E., Plowe, C. V., Rowe, J. A., and Brimingham, D. J.
- Published
- 2004
8. Protection Against Malaria by Intravenous Immunization with a Nonreplicating Sporozoite Vaccine
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Seder, R. A., Chang, L.-J., Enama, M. E., Zephir, K. L., Sarwar, U. N., Gordon, I. J., Holman, L. A., James, E. R., Billingsley, P. F., Gunasekera, A., Richman, A., Chakravarty, S., Manoj, A., Velmurugan, S., Li, M., Ruben, A. J., Li, T., Eappen, A. G., Stafford, R. E., Plummer, S. H., Hendel, C. S., Novik, L., Costner, P. J. M., Mendoza, F. H., Saunders, J. G., Nason, M. C., Richardson, J. H., Murphy, J., Davidson, S. A., Richie, T. L., Sedegah, M., Sutamihardja, A., Fahle, G. A., Lyke, K. E., Laurens, M. B., Roederer, M., Tewari, K., Epstein, J. E., Sim, B. K. L., Ledgerwood, J. E., Graham, B. S., Hoffman, S. L., DiGiovanni, C., Williams, P., Luongo, N., Mitchell, J., Florez, M. B., Larkin, B., Berkowitz, N., Wilson, B., Clarke, T., Vasilenko, O., Yamshchikov, G., Sitar, S., Stanford, L., Pittman, I., Bailer, R. T., Casazza, J., Decederfelt, H., Starling, J., Williams, E. C., Lau, A., Antonara, S., Brocious, J., Kemp, M., Inglese, J., Dranchak, P., Abot, E. N., Reyes, S., Ganeshan, H., Belmonte, M., Huang, J., Belmonte, A., Komisar, J., Abebe, Y., Getachew, Y., Patil, A., Matheny, S., Nelson, K., Overby, J., Pich, V., Wen, Y., Fan, R., Fomumbod, E., Awe, A., Chakiath, C., King, M., Orozco, M. S., Murshedkar, T., Padilla, D., Jiang, B., Gao, L., Kc, N., Xu, R., Adams, M., Plowe, C., Loblein, H., Renehan, P. Z., Kunchai, M., and Diep, L.
- Subjects
parasitic diseases - Abstract
Malaria Sporozoite Vaccine Each year, hundreds of millions of people are infected with Plasmodium falciparum, the mosquito-borne parasite that causes malaria. A preventative vaccine is greatly needed. Seder et al. (p. 1359, published online 8 August; see the Perspective by Good) now report the results from a phase I clinical trial where subjects were immunized intravenously with a whole, attenuated sporozoite vaccine. Three of 9 subjects who received four doses and zero of 6 subjects who received five doses of the vaccine went on to develop malaria after controlled malaria infection. Both antibody titers and cellular immune responses correlated positively with the dose of vaccine received, suggesting that both arms of the adaptive immune response may have participated in the observed protection. Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine—composed of attenuated, aseptic, purified, cryopreserved PfSPZ—was safe and wel-tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 105 PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards. Intravenous immunization with an attenuated whole malaria sporozoite vaccine protected volunteers in a phase I clinical trial. [Also see Perspective by Good] Intravenous immunization with an attenuated whole malaria sporozoite vaccine protected volunteers in a phase I clinical trial. [Also see Perspective by Good]
- Published
- 2013
9. Blood group O protects against severe Plasmodium falciparum malaria
- Author
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Rowe, J, Deans, A, Thera, M, Lyke, K, Kone, A, Diallo, D, Raza, A, Kai, O, Marsh, K, Plowe, C, and Moulds, J
- Published
- 2007
10. Serum Levels of the Proinflammatory Cytokines Interleukin-1 Beta (IL-1β), IL-6, IL-8, IL-10, Tumor Necrosis Factor Alpha, and IL-12(p70) in Malian Children with Severe Plasmodium falciparum Malaria and Matched Uncomplicated Malaria or Healthy Controls
- Author
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Lyke, K. E., primary, Burges, R., additional, Cissoko, Y., additional, Sangare, L., additional, Dao, M., additional, Diarra, I., additional, Kone, A., additional, Harley, R., additional, Plowe, C. V., additional, Doumbo, O. K., additional, and Sztein, M. B., additional
- Published
- 2004
- Full Text
- View/download PDF
11. A Case of Cutaneous Ulcerative Alternariosis: Rare Association with Diabetes Mellitus and Unusual Failure of Itraconazole Treatment
- Author
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Lyke, K. E., primary, Miller, N. S., additional, Towne, L., additional, and Merz, W. G., additional
- Published
- 2001
- Full Text
- View/download PDF
12. Empirical Treatthent of Febrile Neutropenia: Evolution of Current Therapeutic Approaches
- Author
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Hathorn, J. W., primary and Lyke, K., additional
- Published
- 1997
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13. Serum Levels of the Proinflammatory Cytokines Interleukin-1 Beta (IL-1β), IL-6, IL-8, IL-10, Tumor Necrosis Factor Alpha, and IL-12(p70) in Malian Children with Severe Plasmodium falciparumMalaria and Matched Uncomplicated Malaria or Healthy Controls
- Author
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Lyke, K. E., Burges, R., Cissoko, Y., Sangare, L., Dao, M., Diarra, I., Kone, A., Harley, R., Plowe, C. V., Doumbo, O. K., and Sztein, M. B.
- Abstract
ABSTRACTInflammatory cytokines play an important role in human immune responses to malarial disease. However, the role of these mediators in disease pathogenesis, and the relationship between host protection and injury remains unclear. A total of 248 cases of severe Plasmodium falciparummalaria among children aged 3 months to 14 years residing in Bandiagara, Mali, were matched to cases of uncomplicated malaria and healthy controls. Using modified World Health Organization criteria for defining severe malaria, we identified 100 cases of cerebral malaria (coma, seizure, and obtundation), 17 cases of severe anemia (hemoglobin, <5 g/dl), 18 cases combined cerebral malaria with severe anemia, and 92 cases with hyperparasitemia (asexual trophozoites, >500,000/mm3). Significantly elevated levels (given as geometric mean concentrations in picograms/milliliter) of interleukin-6 (IL-6; 485.2 versus 54.1; P= <0.001), IL-10 (1,099.3 versus 14.1; P= <0.001), tumor necrosis factor alpha (10.1 versus 7.7; P= <0.001), and IL-12(p70) (48.9 versus 31.3; P= 0.004) in serum were found in severe cases versus healthy controls. Significantly elevated levels of IL-6 (485.2 versus 141.0; P= <0.001) and IL-10 (1,099.3 versus 133.9; P= <0.001) were seen in severe malaria cases versus uncomplicated malaria controls. Cerebral malaria was associated with significantly elevated levels of IL-6 (754.5 versus 311.4; P= <0.001) and IL-10 (1,405.6 versus 868.6; P= 0.006) compared to severe malaria cases without cerebral manifestations. Conversely, lower levels of IL-6 (199.2 versus 487.6; P= 0.03) and IL-10 (391.1 versus 1,160.9; P= 0.002) were noted in children with severe anemia compared to severe malaria cases with hemoglobin at >5 g/dl. Hyperparasitemia was associated with significantly lower levels of IL-6 (336.6 versus 602.1; P= 0.002). These results illustrate the complex relationships between inflammatory cytokines and disease in P. falciparummalaria.
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- 2004
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14. Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8+ T Cell Immunity.
- Author
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Epstein, J. E., Tewari, K., Lyke, K. E., Sim, B. K. L., Billingsley, P. F., Laurens, M. B., Gunasekera, A., Chakravarty, S., James, E. R., Sedegah, M., Richman, A., Velmurugan, S., Reyes, S., Li, M., Tucker, K., Ahumada, A., Ruben, A. J., Li, T., Stafford, R., and Eappen, A. G.
- Subjects
- *
IMMUNOLOGY , *MALARIA vaccines , *PLASMODIUM falciparum , *DRUG delivery systems , *INTRAVENOUS injections , *MALARIA prevention , *MOSQUITO vectors , *ANIMAL models in research , *HUMAN experimentation - Abstract
Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8+ T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-speciflc CD8+ IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
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15. Gene expression analyses reveal differences in children's response to malaria according to their age.
- Author
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Tebben K, Yirampo S, Coulibaly D, Koné A, Laurens M, Stucke E, Dembélé A, Tolo Y, Traoré K, Niangaly A, Berry A, Kouriba B, Plowe C, Doumbo O, Lyke K, Takala-Harrison S, Thera M, Travassos M, and Serre D
- Abstract
In Bandiagara, Mali, children experience on average two clinical malaria episodes per season. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, vary dramatically among children. To examine the factors contributing to these variations, we simultaneously characterized the host and parasite gene expression profiles from 136 children with symptomatic falciparum malaria and analyzed the expression of 9,205 human and 2,484 Plasmodium genes. We used gene expression deconvolution to estimate the relative proportion of immune cells and parasite stages in each sample and to adjust the differential gene expression analyses. Parasitemia explained much of the variation in both host and parasite gene expression and revealed that infections with higher parasitemia had more neutrophils and fewer T cells, suggesting parasitemia-dependent neutrophil recruitment and/or T cell extravasation to secondary lymphoid organs. The child's age was also strongly correlated with gene expression variations. Plasmodium falciparum genes associated with age suggested that older children carried more male gametocytes, while host genes associated with age indicated a stronger innate response (through TLR and NLR signaling) in younger children and stronger adaptive immunity (through TCR and BCR signaling) in older children. These analyses highlight the variability in host responses and parasite regulation during P. falciparum symptomatic infections and emphasize the importance of considering the children's age when studying and treating malaria infections., Competing Interests: Competing interests: Authors declare that they have no competing interests.
- Published
- 2023
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16. Bivalent and Monovalent SARS-CoV-2 Variant Vaccine Boosters Improve coverage of the known Antigenic Landscape: Results of the COVID-19 Variant Immunologic Landscape (COVAIL) Trial.
- Author
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Branche A, Rouphael N, Diemert D, Falsey A, Losada C, Baden LR, Frey S, Whitaker J, Little S, Anderson E, Walter E, Novak R, Rupp R, Jackson L, Babu T, Kottkamp A, Luetkemeyer A, Immergluck L, Presti R, Backer M, Winokur P, Mahgoub S, Goepfert P, Fusco D, Malkin E, Bethony J, Walsh E, Graciaa D, Samaha H, Sherman A, Walsh S, Abate G, Oikonomopoulou Z, El Sahly H, Martin T, Kamidani S, Smith M, Ladner B, Porterfield L, Dunstan M, Wald A, Davis T, Atmar R, Mulligan M, Lyke K, Posavad C, Meagher M, Stephens D, Neuzil K, Abebe K, Hill H, Albert J, Telu K, Mu J, Lewis T, Giebeig L, Eaton A, Netzl A, Wilks S, Tureli S, Makhene M, Crandon S, Montefiori D, Makowski M, Smith D, Nayak S, Roberts P, and Beigel J
- Abstract
Vaccine protection against COVID-19 wanes over time and has been impacted by the emergence of new variants with increasing escape of neutralization. The COVID-19 Variant Immunologic Landscape (COVAIL) randomized clinical trial (clinicaltrials.gov NCT05289037) compares the breadth, magnitude and durability of antibody responses induced by a second COVID-19 vaccine boost with mRNA (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2), or adjuvanted recombinant protein (Sanofi CoV2 preS DTM-AS03) monovalent or bivalent vaccine candidates targeting ancestral and variant SARS-CoV-2 spike antigens (Beta, Delta and Omicron BA.1). We found that boosting with a variant strain is not associated with loss in neutralization against the ancestral strain. However, while variant vaccines compared to the prototype/wildtype vaccines demonstrated higher neutralizing activity against Omicron BA.1 and BA.4/5 subvariants for up to 3 months after vaccination, neutralizing activity was lower for more recent Omicron subvariants. Our study, incorporating both antigenic distances and serologic landscapes, can provide a framework for objectively guiding decisions for future vaccine updates.
- Published
- 2023
- Full Text
- View/download PDF
17. Distinct microbes, metabolites, and ecologies define the microbiome in deficient and proficient mismatch repair colorectal cancers.
- Author
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Hale VL, Jeraldo P, Chen J, Mundy M, Yao J, Priya S, Keeney G, Lyke K, Ridlon J, White BA, French AJ, Thibodeau SN, Diener C, Resendis-Antonio O, Gransee J, Dutta T, Petterson XM, Sung J, Blekhman R, Boardman L, Larson D, Nelson H, and Chia N
- Subjects
- Adult, Aged, Aged, 80 and over, Bacteroides growth & development, Bacteroides physiology, Female, Humans, Hydrogen Sulfide metabolism, Male, Middle Aged, Young Adult, Colorectal Neoplasms metabolism, Colorectal Neoplasms microbiology, DNA Mismatch Repair, Metabolome, Microbiota
- Abstract
Background: Links between colorectal cancer (CRC) and the gut microbiome have been established, but the specific microbial species and their role in carcinogenesis remain an active area of inquiry. Our understanding would be enhanced by better accounting for tumor subtype, microbial community interactions, metabolism, and ecology., Methods: We collected paired colon tumor and normal-adjacent tissue and mucosa samples from 83 individuals who underwent partial or total colectomies for CRC. Mismatch repair (MMR) status was determined in each tumor sample and classified as either deficient MMR (dMMR) or proficient MMR (pMMR) tumor subtypes. Samples underwent 16S rRNA gene sequencing and a subset of samples from 50 individuals were submitted for targeted metabolomic analysis to quantify amino acids and short-chain fatty acids. A PERMANOVA was used to identify the biological variables that explained variance within the microbial communities. dMMR and pMMR microbial communities were then analyzed separately using a generalized linear mixed effects model that accounted for MMR status, sample location, intra-subject variability, and read depth. Genome-scale metabolic models were then used to generate microbial interaction networks for dMMR and pMMR microbial communities. We assessed global network properties as well as the metabolic influence of each microbe within the dMMR and pMMR networks., Results: We demonstrate distinct roles for microbes in dMMR and pMMR CRC. Bacteroides fragilis and sulfidogenic Fusobacterium nucleatum were significantly enriched in dMMR CRC, but not pMMR CRC. These findings were further supported by metabolic modeling and metabolomics indicating suppression of B. fragilis in pMMR CRC and increased production of amino acid proxies for hydrogen sulfide in dMMR CRC., Conclusions: Integrating tumor biology and microbial ecology highlighted distinct microbial, metabolic, and ecological properties unique to dMMR and pMMR CRC. This approach could critically improve our ability to define, predict, prevent, and treat colorectal cancers.
- Published
- 2018
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18. Synthesis of multi-omic data and community metabolic models reveals insights into the role of hydrogen sulfide in colon cancer.
- Author
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Hale VL, Jeraldo P, Mundy M, Yao J, Keeney G, Scott N, Cheek EH, Davidson J, Greene M, Martinez C, Lehman J, Pettry C, Reed E, Lyke K, White BA, Diener C, Resendis-Antonio O, Gransee J, Dutta T, Petterson XM, Boardman L, Larson D, Nelson H, and Chia N
- Subjects
- Adult, Aged, Aged, 80 and over, Clostridium perfringens metabolism, Colorectal Neoplasms microbiology, Female, Fusobacterium nucleatum metabolism, Humans, Intestinal Mucosa microbiology, Male, Middle Aged, Young Adult, Colorectal Neoplasms metabolism, Hydrogen Sulfide metabolism, Intestinal Mucosa metabolism, Metabolomics methods, Microbiota physiology, Models, Biological
- Abstract
Multi-omic data and genome-scale microbial metabolic models have allowed us to examine microbial communities, community function, and interactions in ways that were not available to us historically. Now, one of our biggest challenges is determining how to integrate data and maximize data potential. Our study demonstrates one way in which to test a hypothesis by combining multi-omic data and community metabolic models. Specifically, we assess hydrogen sulfide production in colorectal cancer based on stool, mucosa, and tissue samples collected on and off the tumor site within the same individuals. 16S rRNA microbial community and abundance data were used to select and inform the metabolic models. We then used MICOM, an open source platform, to track the metabolic flux of hydrogen sulfide through a defined microbial community that either represented on-tumor or off-tumor sample communities. We also performed targeted and untargeted metabolomics, and used the former to quantitatively evaluate our model predictions. A deeper look at the models identified several unexpected but feasible reactions, microbes, and microbial interactions involved in hydrogen sulfide production for which our 16S and metabolomic data could not account. These results will guide future in vitro, in vivo, and in silico tests to establish why hydrogen sulfide production is increased in tumor tissue., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2018
- Full Text
- View/download PDF
19. Global water fluoridation: what is holding us back?
- Author
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Lyke K
- Subjects
- Animals, Humans, Dental Caries prevention & control, Developmental Disabilities chemically induced, Developmental Disabilities epidemiology, Drinking Water chemistry, Environmental Exposure adverse effects, Fluoridation statistics & numerical data, Fluorides toxicity, Neurotoxicity Syndromes epidemiology, Neurotoxicity Syndromes etiology
- Published
- 2016
20. Ad35.CS.01-RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naïve Adults.
- Author
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Ockenhouse CF, Regules J, Tosh D, Cowden J, Kathcart A, Cummings J, Paolino K, Moon J, Komisar J, Kamau E, Oliver T, Chhoeu A, Murphy J, Lyke K, Laurens M, Birkett A, Lee C, Weltzin R, Wille-Reece U, Sedegah M, Hendriks J, Versteege I, Pau MG, Sadoff J, Vanloubbeeck Y, Lievens M, Heerwegh D, Moris P, Guerra Mendoza Y, Jongert E, Cohen J, Voss G, Ballou WR, and Vekemans J
- Subjects
- Antibodies, Protozoan immunology, Antibody Formation immunology, CD4-Positive T-Lymphocytes immunology, Double-Blind Method, Humans, Immunization, Secondary methods, Immunoglobulin G immunology, Immunologic Tests methods, Interferon-gamma immunology, Vaccination methods, Malaria immunology, Malaria prevention & control, Malaria Vaccines immunology, Sporozoites immunology
- Abstract
Methods: In an observer blind, phase 2 trial, 55 adults were randomized to receive one dose of Ad35.CS.01 vaccine followed by two doses of RTS,S/AS01 (ARR-group) or three doses of RTS,S/AS01 (RRR-group) at months 0, 1, 2 followed by controlled human malaria infection., Results: ARR and RRR vaccine regimens were well tolerated. Efficacy of ARR and RRR groups after controlled human malaria infection was 44% (95% confidence interval 21%-60%) and 52% (25%-70%), respectively. The RRR-group had greater anti-CS specific IgG titers than did the ARR-group. There were higher numbers of CS-specific CD4 T-cells expressing > 2 cytokine/activation markers and more ex vivo IFN-γ enzyme-linked immunospots in the ARR-group than the RRR-group. Protected subjects had higher CS-specific IgG titers than non-protected subjects (geometric mean titer, 120.8 vs 51.8 EU/ml, respectively; P = .001)., Conclusions: An increase in vaccine efficacy of ARR-group over RRR-group was not achieved. Future strategies to improve upon RTS,S-induced protection may need to utilize alternative highly immunogenic prime-boost regimens and/or additional target antigens., Trial Registration: ClinicalTrials.gov NCT01366534.
- Published
- 2015
- Full Text
- View/download PDF
21. Impact of preseason treatment on incidence of falciparum malaria and parasite density at a site for testing malaria vaccines in Bandiagara, Mali.
- Author
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Coulibaly D, Diallo DA, Thera MA, Dicko A, Guindo AB, Koné AK, Cissoko Y, Coulibaly S, Djimdé A, Lyke K, Doumbo OK, and Plowe CV
- Subjects
- Adolescent, Adult, Animals, Child, Child, Preschool, Cohort Studies, Drug Combinations, Humans, Incidence, Infant, Malaria Vaccines, Mali, Plasmodium falciparum isolation & purification, Research Design, Treatment Outcome, Antimalarials therapeutic use, Malaria, Falciparum drug therapy, Malaria, Falciparum epidemiology, Plasmodium falciparum growth & development, Pyrimethamine therapeutic use, Seasons, Sulfadoxine therapeutic use
- Abstract
Treating malaria before immunizing has been standard in malaria vaccine field trials. To assess the impact of this practice on subsequent infection and disease incidence, we conducted a randomized cohort study in Bandiagara, Mali. Subjects received a treatment dose of sulfadoxine-pyrimethamine (SP) or no treatment at the beginning of the transmission season. Cumulative and age-specific incidence of clinical episodes was similar between the 2 groups, but SP treatment delayed the median time to first clinical episode from 38.5 to 68 days, and after this initial period of protection, disease incidence in the SP group quickly surpassed the incidence in the untreated group. Parasite densities during disease episodes were lower in the SP group. SP was chosen as the drug for initial parasite clearance for the following reasons: 1) it has been used in previous vaccine trials; 2) our studies have found it to have >99% efficacy in treating uncomplicated malaria in Mali compared to 85-90% efficacy for chloroquine in this area; 3) SP is the approved second-line antimalarial agent in Mali; and 4) its single-dose regimen ensures compliance when treatment is directly observed.
- Published
- 2002
- Full Text
- View/download PDF
22. Effect of estradiol on accelerated atherosclerosis in rabbit heterotopic aortic allografts.
- Author
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Jacobsson J, Cheng L, Lyke K, Kuwahara M, Kagan E, Ramwell PW, and Foegh ML
- Subjects
- Animals, Aorta, Abdominal pathology, Arteriosclerosis etiology, Arteriosclerosis pathology, Carotid Arteries, Cholesterol, Dietary administration & dosage, Hyperplasia pathology, Lipoproteins blood, Male, Microscopy, Electron, Muscle, Smooth, Vascular pathology, Rabbits, Tunica Intima pathology, Aorta, Abdominal transplantation, Arteriosclerosis prevention & control, Estradiol pharmacology, Transplantation, Heterotopic pathology, Tunica Intima drug effects
- Abstract
Migration and proliferation of vascular smooth muscle cells are early and major events in the formation of atherosclerotic lesions. We report on an aorta transplant model in rabbits wherein myointimal proliferation is inhibited by 17-beta-estradiol. The abdominal aortas of outbred white New Zealand rabbits were harvested and allografted to the carotid artery of the recipient. The animals, which were fed either a normal or a high-cholesterol (0.5%) diet, were killed 3 weeks later. The degree of myointimal proliferation was measured with a digitized system attached to a light microscope. The myointimal hyperplasia was expressed as the cross section area of the intima/the area of the intima + the area of the media x 100. Transmission electron micrographs were obtained for all vessels. Intimal thickening was shown mainly to consist of proliferating smooth muscle cells. The cholesterol diet resulted in significantly higher serum total cholesterol levels compared to animals on a normal diet (p < 0.0001) but did not affect serum high-density lipoprotein-cholesterol or serum triglyceride levels. The cholesterol diet was also associated with a greater but not significant amount of intimal thickening. Treatment with 17-beta-estradiol significantly decreased both serum triglyceride concentration (p < 0.05) and myointimal thickening (p < 0.01) in cholesterol-fed animals. Transmission electron microscopy showed that the endothelial cells appeared structurally normal in the estradiol-treated animals. Further, estradiol prevented the appearance of vacuolized macrophages. Thus estradiol may decrease myointimal thickening by preserving the endothelium and preventing macrophage appearance in the intima.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1992
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