Dr. Anders  P Hakansson, PhD - Lund University - Professor

Dr. Anders P Hakansson

PhD

Lund University

Professor

Lund, Skane | Sweden

Main Specialties: Biology, Infectious Disease, Medical Microbiology, Otolaryngology, Pediatric Infectious Diseases, Pulmonary Disease

Additional Specialties: Microbiology

ORCID logohttps://orcid.org/0000-0002-2834-6009

Dr. Anders  P Hakansson, PhD - Lund University - Professor

Dr. Anders P Hakansson

PhD

Introduction

My research interests are in understanding host-pathogen interactions, with emphasis on Streptococcal pathogens, and to develop novel preventive and therapeutic strategies to protect against bacterial infection. My work focuses on both the factors used by bacteria to establish colonization and cause disease and how this is counteracted by the host response to colonization and infection. The main research projects associated with my activity as a principal investigator deal with (A) biofilm formation during bacterial colonization, the role of biofilm formation and colonization for optimal transformation and genetic exchange, and the mechanisms of transition from colonization to infection; (B) applying the information from our pathogenesis studies to develop novel strategies to protect individuals against upper respiratory tract infection through immunization; and (C) to explore the direct bactericidal activity of a human milk protein-lipid complex (HAMLET, human alpha-lactalbumin made lethal to tumor cells) against various bacterial species as well as develop its adjuvant activity in sensitizing bacteria to a broad range of common antibiotics to provide novel therapeutic strategies against infections with antibiotic-resistant bacteria. In all three projects, the focus lays first on better understanding colonization and disease processes using novel in vitro models exploiting factors associated with the colonizing environment, second to apply this knowledge using in vivo models of infection established in the laboratory, and third to develop these findings for potential commercial purposes.

Primary Affiliation: Lund University - Lund, Skane , Sweden

Specialties:

Additional Specialties:

Research Interests:

Education

May 2005
Harvard Medical School
Post-doc
Infectious Diseases
Apr 2002
University of Alabama at Birmingham
Post-doc
Host-pathogen interactions
Sep 1999
Lund University
PhD
Medical Microbiology

Experience

Aug 2014 - Aug 2014
Lunds universitet Medicinska fakulteten
Professor
Translational Medicine
Dec 2006 - Dec 2006
University at Buffalo
Assistant Professor
Microbiology and Immunology
Jun 2005
Harvard Medical School
Instructor
Pediatric Infectious Diseases
Jun 2005
Harvard Medical School
Instructor
Pediatric Infectious Diseases

Publications

114Publications

964Reads

4Profile Views

1011PubMed Central Citations

Chapter 7 – Pathogenesis of otitis media – A review of the literature between 2015 and 2019

International Journal of Pediatric Otorhinolaryngology

Objective: To perform a comprehensive review of the literature from July 2015 to June 2019 on the pathogenesis of otitis media. Bacteria, viruses and the role of the microbiome as well as the host response are discussed. Directions for future research are also suggested. Data sources: PubMed database of the National Library of Medicine. Review methods: PubMed was searched for any papers pertaining to OM pathogenesis between July 2015 and June 2019. If in English, abstracts were assessed individually for their relevance and included in the report. Members of the panel drafted the report based on these searches and on new data presented at the 20th International Symposium on Recent Advances in Otitis Media. Conclusions: The main themes that arose in OM pathogenesis were around the need for symptomatic viral infections to develop disease. Different populations potentially having different mechanisms of pathogenesis. Novel bacterial otopathogens are emerging and need to be monitored. Animal models need to continue to be developed and used to understand disease pathogenesis. Implications for Practice: The findings in the pathogenesis panel have several implications for both research and clinical practice. The most urgent areas appear to be to continue monitoring the emergence of novel otopathogens, and the need to develop prevention and preventative therapies that do not rely on antibiotics and protect against the development of the initial OM episode.

https://portal.research.lu.se/portal/en/publications/chapter-7--pathogenesis-of-otitis-media--a-review-of-the-literature-between-2015-and-2019(19475128-9a3c-4b35-85ec-26bdc7e2872f).html

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December 2019
1 Read

HAMLET, a protein complex from human milk has bactericidal activity and enhances the activity of antibiotics against pathogenic Streptococci

Antimicrobial Agents and Chemotherapy

HAMLET is a protein-lipid complex derived from human milk that was first described for its tumoricidal activity. Later studies showed that HAMLET also has direct bactericidal activity against select species of bacteria, with highest activity against Streptococcus pneumoniae Additionally, HAMLET in combination with various antimicrobial agents can make a broader range of antibiotic-resistant bacterial species sensitive to antibiotics. Here, we show that HAMLET has direct antibacterial activity not only against pneumococci, but also against Streptococcus pyogenes (GAS) and Streptococcus agalactiae (GBS). Analogous to pneumococci, HAMLET-treatment of GAS and GBS resulted in depolarization of the bacterial membrane followed by membrane permeabilization and death that could be inhibited by calcium and sodium transport inhibitors. Treatment of clinical antibiotic-resistant isolates of S. pneumoniae, GAS, and GBS with sublethal concentrations of HAMLET in combination with antibiotics decreased the minimal inhibitory concentrations of the respective antibiotic into the sensitive range. This effect could also be blocked by ion transport inhibitors, suggesting that HAMLET's bactericidal and combination treatment effects used similar mechanisms. Finally, we show that HAMLET potentiated the effects of erythromycin against erythromycin-resistant bacteria more effectively than it potentiated killing by penicillin G of bacteria resistant to penicillin G. These results show for the first time that HAMLET effectively kills three different species of pathogenic Streptococci using similar mechanisms and also potentiate the activity of macrolides and lincosamides more effectively than combination treatment with beta-lactams. These findings suggest a potential therapeutic role for HAMLET in repurposing antibiotics currently causing treatment failures in patients.

https://portal.research.lu.se/portal/en/publications/hamlet-a-protein-complex-from-human-milk-has-bactericidal-activity-and-enhances-the-activity-of-antibiotics-against-pathogenic-streptococci(9235dc1c-0644-49c0-8a41-7e14e6278ced).html

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December 2019
1 Read

Growing and Characterizing Biofilms Formed by Streptococcus pneumoniae.

Methods Mol Biol 2019 ;1968:147-171

Wallenberg Laboratory, Division of Experimental Infection Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden.

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http://dx.doi.org/10.1007/978-1-4939-9199-0_13DOI Listing
August 2019
22 Reads

A Protein Complex from Human Milk Enhances the Activity of Antibiotics and Drugs against .

Antimicrob Agents Chemother 2019 02 29;63(2). Epub 2019 Jan 29.

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA

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http://aac.asm.org/lookup/doi/10.1128/AAC.01846-18
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http://dx.doi.org/10.1128/AAC.01846-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355597PMC
February 2019
29 Reads
4.476 Impact Factor

Bacterial-host interactions

Physiological Reviews

It has long been thought that respiratory infections are the direct result of acquisition of pathogenic viruses or bacteria, followed by their overgrowth, dissemination, and in some instances tissue invasion. In the last decades, it has become apparent that in contrast to this classical view, the majority of microorganisms associated with respiratory infections and inflammation are actually common members of the respiratory ecosystem and only in rare circumstances do they cause disease. This suggests that a complex interplay between host, environment, and properties of colonizing microorganisms together determines disease development and its severity. To understand the pathophysiological processes that underlie respiratory infectious diseases, it is therefore necessary to understand the host-bacterial interactions occurring at mucosal surfaces, along with the microbes inhabiting them, during symbiosis. Current knowledge regarding host-bacterial interactions during asymptomatic colonization will be discussed, including a plausible role for the human microbiome in maintaining a healthy state. With this as a starting point, we will discuss possible disruptive factors contributing to dysbiosis, which is likely to be a key trigger for pathobionts in the development and pathophysiology of respiratory diseases. Finally, from this renewed perspective, we will reflect on current and potential new approaches for treatment in the future.

https://portal.research.lu.se/portal/en/publications/bacterialhost-interactions(895a4ede-e105-4c42-9fdf-e53484f87368).html

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May 2018
2 Reads

Bacterial-Host Interactions: Physiology and Pathophysiology of Respiratory Infection.

Physiol Rev 2018 04;98(2):781-811

Division of Experimental Infection Medicine, Department of Translational Medicine, Lund University , Lund , Sweden ; Department of Microbiology, University of Alabama at Birmingham , Birmingham, Alabama ; and Center for Inflammation Research, Queens Medical Research Institute, University of Edinburgh , Edinburgh , United Kingdom.

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http://dx.doi.org/10.1152/physrev.00040.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966719PMC
April 2018
6 Reads
27.324 Impact Factor

In Vitro and In Vivo Biofilm Formation by Pathogenic Streptococci.

Methods Mol Biol 2017 ;1535:285-299

Division of Experimental Infection Medicine, Department of Translational Medicine, Wallenberg Laboratory, Lund University, 53 Inga Marie Nilsson Street, 20502, Malmö, Sweden.

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http://dx.doi.org/10.1007/978-1-4939-6673-8_19DOI Listing
January 2018
52 Reads
1 Citation

Modulates Biofilm Dispersion and the Transition from Colonization to Invasive Disease.

mBio 2018 01 9;9(1). Epub 2018 Jan 9.

Department of Microbiology and Immunology, State University of New York at Buffalo, Buffalo, New York, USA

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http://dx.doi.org/10.1128/mBio.02089-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760742PMC
January 2018
16 Reads
6.790 Impact Factor

Low NF-κB Activation and Necroptosis in Alveolar Macrophages: A New Virulence Property of Streptococcus pneumoniae.

J Infect Dis 2017 08;216(4):402-404

Division of Experimental Infection Medicine, Department of Translational Medicine, Lund University, SE-20502 Malmö, Sweden.

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http://dx.doi.org/10.1093/infdis/jix161DOI Listing
August 2017
11 Reads
6.000 Impact Factor

Otitis Media Pathogenesis and How It Informs Our Understanding of Vaccine Strategies.

Curr Otorhinolaryngol Rep 2017 20;5(2):115-124. Epub 2017 May 20.

Division of Experimental Infection Medicine, Department of Translational Medicine, Wallenberg Laboratory, Lund University, Inga Marie Nilsson's Street 53, 20502 Malmö, SE Sweden.

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http://dx.doi.org/10.1007/s40136-017-0152-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446555PMC
May 2017
19 Reads
3 Citations

Streptococcus pneumoniae Otitis Media Pathogenesis and How It Informs Our Understanding of Vaccine Strategies.

Current Otorhinolaryngology Report

Purpose of Review This study aimed to review the literature regarding the mechanisms of transition from asymptomatic colonization to induction of otitis media and how the insight into the pathogenesis of otitis media has the potential to help design future otitis media-directed vaccines.
Recent Findings Respiratory viruses have long been shown to predispose individuals to bacterial respiratory infections, such as otitis media. Recent information suggests that Streptococcus pneumoniae, which colonize the nasopharynx asymptomatical- ly, can sense potentially “threatening” changes in the nasopha- ryngeal environment caused by virus infection by upregulating specific sets of genes involved in biofilm release, dissemination from the nasopharynx to other sites, and protection against the host immune system. Furthermore, an understanding of the transcriptional and proteomic changes occurring in bacteria dur- ing transition to infection has led to identification of novel vaccine targets that are disease-specific and will not affect asymptomatic colonization. This approach will avoid major changes in the delicate balance of microorganisms in the respi- ratory tract microbiome due to elimination of S. pneumoniae. Summary Our recent findings are reviewed in the context of the current literature on the epidemiology and pathogenesis of otitis media. We also discuss how other otopathogens, such as Haemophilus influenzae and Moraxella catarrhalis, as well as the normal respiratory microbiome, can modulate the ability of pneumococci to cause infection. Furthermore, the unsatis- factory protection offered by the pneumococcal conjugate vaccines is highlighted and we review potential future strate- gies emerging to confer a more specific protection against otitis media.

https://portal.research.lu.se/portal/en/publications/streptococcus-pneumoniae-otitis-media-pathogenesis-and-how-it-informs-our-understanding-of-vaccine-strategies(45c72669-0d75-4455-8e85-1edc47dc41f3).html

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May 2017
2 Reads

Panel 4: Report of the Microbiology Panel.

Otolaryngol Head Neck Surg 2017 04;156(4_suppl):S51-S62

8 Department of Microbiology and Immunology, Wake Forest University, Winston-Salem, North Carolina, USA.

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http://dx.doi.org/10.1177/0194599816639028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490388PMC
April 2017
10 Reads
1.721 Impact Factor

Panel 6: Vaccines.

Otolaryngol Head Neck Surg 2017 04;156(4_suppl):S76-S87

9 University at Buffalo, The State University of New York, Buffalo, New York, USA.

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http://dx.doi.org/10.1177/0194599816632178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505493PMC
April 2017
15 Reads
1.721 Impact Factor

Panel 6

Otolaryngology - Head and Neck Surgery

Objective: To review the literature on progress regarding (1) effectiveness of vaccines for prevention of otitis media (OM) and (2) development of vaccine antigens for OM bacterial and viral pathogens. Data Sources: PubMed database of the National Library of Science. Review Methods: We performed literature searches in PubMed for OM pathogens and candidate vaccine antigens, and we restricted the searches to articles in English that were published between July 2011 and June 2015. Panel members reviewed literature in their area of expertise. Conclusions: Pneumococcal conjugate vaccines (PCVs) are somewhat effective for the prevention of pneumococcal OM, recurrent OM, OM visits, and tympanostomy tube insertions. Widespread use of PCVs has been associated with shifts in pneumococcal serotypes and bacterial pathogens associated with OM, diminishing PCV effectiveness against AOM. The 10-valent pneumococcal vaccine containing Haemophilus influenzae protein D (PHiD-CV) is effective for pneumococcal OM, but results from studies describing the potential impact on OM due to H influenzae have been inconsistent. Progress in vaccine development for H influenzae, Moraxella catarrhalis, and OM-associated respiratory viruses has been limited. Additional research is needed to extend vaccine protection to additional pneumococcal serotypes and other otopathogens. There are likely to be licensure challenges for protein-based vaccines, and data on correlates of protection for OM vaccine antigens are urgently needed. Implications for Practice: OM continues to be a significant health care burden globally. Prevention is preferable to treatment, and vaccine development remains an important goal. As a polymicrobial disease, OM poses significant but not insurmountable challenges for vaccine development.

https://portal.research.lu.se/portal/en/publications/panel-6(f705ae4e-533a-4009-97af-91cb8a4ddc5b).html

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April 2017
3 Reads

Panel 4

Otolaryngology - Head and Neck Surgery

Objective: To perform a comprehensive review of the literature from July 2011 until June 2015 on the virology and bacteriology of otitis media in children. Data Sources: PubMed database of the National Library of Medicine. Review Methods: Two subpanels comprising experts in the virology and bacteriology of otitis media were created. Each panel reviewed the relevant literature in the fields of virology and bacteriology and generated draft reviews. These initial reviews were distributed to all panel members prior to meeting together at the Post-symposium Research Conference of the 18th International Symposium on Recent Advances in Otitis Media, National Harbor, Maryland, in June 2015. A final draft was created, circulated, and approved by all panel members. Conclusions: Excellent progress has been made in the past 4 years in advancing our understanding of the microbiology of otitis media. Numerous advances were made in basic laboratory studies, in animal models of otitis media, in better understanding the epidemiology of disease, and in clinical practice. Implications for Practice: (1) Many viruses cause acute otitis media without bacterial coinfection, and such cases do not require antibiotic treatment. (2) When respiratory syncytial virus, metapneumovirus, and influenza virus peak in the community, practitioners can expect to see an increase in clinical otitis media cases. (3) Biomarkers that predict which children with upper respiratory tract infections will develop otitis media may be available in the future. (4) Compounds that target newly identified bacterial virulence determinants may be available as future treatment options for children with otitis media.

https://portal.research.lu.se/portal/en/publications/panel-4(a42a0e82-4a48-4583-8c7f-6b976a211a9d).html

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April 2017
1 Read

Structure and Potential Cellular Targets of HAMLET-like Anti-Cancer Compounds made from Milk Components.

J Pharm Pharm Sci 2015 ;18(4):773-824

Faculty of Pharmacy, University of Sydney, Sydney, New South Wales 2006, Australia.

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http://dx.doi.org/10.18433/j3g60cDOI Listing
September 2016
10 Reads
2 Citations
1.681 Impact Factor

Host Physiologic Changes Induced by Influenza A Virus Lead to Staphylococcus aureus Biofilm Dispersion and Transition from Asymptomatic Colonization to Invasive Disease.

mBio 2016 08 9;7(4). Epub 2016 Aug 9.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA

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http://dx.doi.org/10.1128/mBio.01235-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981728PMC
August 2016
29 Reads
9 Citations
6.790 Impact Factor

In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector.

Sci Adv 2016 07 1;2(7):e1600264. Epub 2016 Jul 1.

Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.; Abcombi Biosciences Inc., Buffalo, NY 14260-4200, USA.

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http://advances.sciencemag.org/content/advances/2/7/e1600264
Web Search
http://dx.doi.org/10.1126/sciadv.1600264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942325PMC
July 2016
71 Reads
4 Citations

Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization.

Infect Immun 2016 06 24;84(6):1693-1703. Epub 2016 May 24.

The Department of Microbiology and Immunology, The University at Buffalo, Buffalo, New York, USA

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http://dx.doi.org/10.1128/IAI.01478-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907141PMC
June 2016
23 Reads
4 Citations
3.731 Impact Factor

Directed vaccination against pneumococcal disease.

Proc Natl Acad Sci U S A 2016 06 6;113(25):6898-903. Epub 2016 Jun 6.

Abcombi Biosciences Inc., Buffalo, NY 14260;

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http://dx.doi.org/10.1073/pnas.1603007113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922154PMC
June 2016
30 Reads
7 Citations
9.810 Impact Factor

Halothane modulates the type i interferon response to influenza and minimizes the risk of secondary bacterial pneumonia through maintenance of neutrophil recruitment in an animal model.

Anesthesiology 2015 Sep;123(3):590-602

From the Department of Microbiology and Immunology, State University of New York at Buffalo, Buffalo, New York (B.A. MacDonald, A.P.H., P.R.K.); Department of Anesthesiology, Veterans Administration Western New York Healthcare System, Buffalo, New York (B.A. MacDonald, B.A.D., B.A. Mullan, R.A., P.R.K.); Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland (K.V.C.); and Department of Anesthesiology, State University of New York at Buffalo, Buffalo, New York (B.A.D., B.A. Mullan, R.A., P.R.K.).

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http://dx.doi.org/10.1097/ALN.0000000000000766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678100PMC
September 2015
5 Reads
3 Citations
5.880 Impact Factor

Protective effects of human milk antimicrobial peptides against bacterial infection.

J Pediatr (Rio J) 2015 Jan-Feb;91(1):4-5. Epub 2014 Oct 18.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, United States; The Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, State University of New York, Buffalo, United States. Electronic address:

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http://dx.doi.org/10.1016/j.jped.2014.10.001DOI Listing
July 2015
6 Reads
1 Citation
0.940 Impact Factor

Streptococcus pneumoniae biofilm formation and dispersion during colonization and disease.

Front Cell Infect Microbiol 2014 13;4:194. Epub 2015 Jan 13.

Division of Experimental Infection Medicine, Department of Laboratory Medicine, Lund University Malmö, Sweden ; Department of Microbiology and Immunology, University at Buffalo, The State University of New York Buffalo, NY, USA.

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http://dx.doi.org/10.3389/fcimb.2014.00194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292784PMC
July 2015
8 Reads
26 Citations
2.620 Impact Factor

Mannosylated poly(beta-amino esters) for targeted antigen presenting cell immune modulation.

Biomaterials 2015 Jan 22;37:333-44. Epub 2014 Oct 22.

Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA. Electronic address:

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http://dx.doi.org/10.1016/j.biomaterials.2014.10.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233061PMC
January 2015
77 Reads
7 Citations
8.560 Impact Factor

Dynamic changes in the Streptococcus pneumoniae transcriptome during transition from biofilm formation to invasive disease upon influenza A virus infection.

Infect Immun 2014 Nov 18;82(11):4607-19. Epub 2014 Aug 18.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, New York, USA

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http://dx.doi.org/10.1128/IAI.02225-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249342PMC
November 2014
7 Reads
22 Citations
3.731 Impact Factor

Hybrid biosynthetic gene therapy vector development and dual engineering capacity.

Proc Natl Acad Sci U S A 2014 Aug 11;111(34):12360-5. Epub 2014 Aug 11.

Departments of Chemical and Biological Engineering and

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http://dx.doi.org/10.1073/pnas.1411355111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151754PMC
August 2014
66 Reads
6 Citations
9.810 Impact Factor

A complex of equine lysozyme and oleic acid with bactericidal activity against Streptococcus pneumoniae.

PLoS One 2013 18;8(11):e80649. Epub 2013 Nov 18.

Department of Microbiology and Immunology, University at Buffalo (SUNY), Buffalo, New York, United States of America.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080649PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832479PMC
August 2014
3 Reads
6 Citations
3.234 Impact Factor

Pneumococcal adaptive responses to changing host environments.

J Infect Dis 2014 Jul 6;210(1):1-3. Epub 2014 Feb 6.

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http://dx.doi.org/10.1093/infdis/jiu084DOI Listing
July 2014
4 Reads
1 Citation
6.000 Impact Factor

Small-angle X-ray scattering of BAMLET at pH 12: a complex of α-lactalbumin and oleic acid.

Proteins 2014 Jul 25;82(7):1400-8. Epub 2014 Jan 25.

Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, 2006, Australia.

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http://dx.doi.org/10.1002/prot.24508DOI Listing
July 2014
6 Reads
2 Citations
2.630 Impact Factor

Biofilm formation enhances fomite survival of Streptococcus pneumoniae and Streptococcus pyogenes.

Infect Immun 2014 Mar 26;82(3):1141-6. Epub 2013 Dec 26.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA.

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http://dx.doi.org/10.1128/IAI.01310-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957990PMC
March 2014
5 Reads
17 Citations
3.731 Impact Factor

Monitoring changes in membrane polarity, membrane integrity, and intracellular ion concentrations in Streptococcus pneumoniae using fluorescent dyes.

J Vis Exp 2014 Feb 17(84):e51008. Epub 2014 Feb 17.

Department of Microbiology and Immunology, University at Buffalo, State University of New York; Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, State University of New York; New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, State University of New York;

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http://www.jove.com/video/51008/monitoring-changes-membrane-
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http://dx.doi.org/10.3791/51008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124894PMC
February 2014
7 Reads
3 Citations

Internalization and trafficking of nontypeable Haemophilus influenzae in human respiratory epithelial cells and roles of IgA1 proteases for optimal invasion and persistence.

Infect Immun 2014 Jan 11;82(1):433-44. Epub 2013 Nov 11.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA.

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http://dx.doi.org/10.1128/IAI.00864-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911862PMC
January 2014
7 Reads
14 Citations
3.731 Impact Factor

Sensitization of Staphylococcus aureus to methicillin and other antibiotics in vitro and in vivo in the presence of HAMLET.

PLoS One 2013 1;8(5):e63158. Epub 2013 May 1.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, United States of America.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063158PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641093PMC
November 2013
32 Reads
10 Citations
3.234 Impact Factor

Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease.

mBio 2013 Jul 23;4(4). Epub 2013 Jul 23.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA.

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http://dx.doi.org/10.1128/mBio.00438-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735180PMC
July 2013
29 Reads
61 Citations
6.790 Impact Factor

The human milk protein-lipid complex HAMLET sensitizes bacterial pathogens to traditional antimicrobial agents.

PLoS One 2012 15;7(8):e43514. Epub 2012 Aug 15.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, United States of America.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0043514PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419703PMC
February 2013
12 Reads
10 Citations
3.234 Impact Factor

High levels of genetic recombination during nasopharyngeal carriage and biofilm formation in Streptococcus pneumoniae.

mBio 2012 25;3(5). Epub 2012 Sep 25.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA.

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http://dx.doi.org/10.1128/mBio.00200-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448161PMC
January 2013
22 Reads
59 Citations
6.790 Impact Factor

Pneumococcal interactions with epithelial cells are crucial for optimal biofilm formation and colonization in vitro and in vivo.

Infect Immun 2012 Aug 29;80(8):2744-60. Epub 2012 May 29.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA.

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http://dx.doi.org/10.1128/IAI.00488-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434590PMC
August 2012
19 Reads
53 Citations
3.731 Impact Factor

Oleic acid is a key cytotoxic component of HAMLET-like complexes.

Biol Chem 2012 Jan;393(1-2):85-92

Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow 142290, Russia.

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http://dx.doi.org/10.1515/BC-2011-230DOI Listing
January 2012
21 Reads
9 Citations
3.270 Impact Factor

A novel method for preparation of HAMLET-like protein complexes.

Biochimie 2011 Sep 11;93(9):1495-501. Epub 2011 May 11.

Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.

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http://dx.doi.org/10.1016/j.biochi.2011.05.002DOI Listing
September 2011
6 Reads
5 Citations
2.963 Impact Factor

Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus.

mBio 2011 15;2(1):e00332-10. Epub 2011 Feb 15.

Division of Infectious Diseases, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA.

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http://mbio.asm.org/cgi/doi/10.1128/mBio.00332-10
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http://dx.doi.org/10.1128/mBio.00332-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039441PMC
August 2011
8 Reads
16 Citations
6.790 Impact Factor

Role of dihydrolipoamide dehydrogenase in regulation of raffinose transport in Streptococcus pneumoniae.

J Bacteriol 2011 Jul 20;193(14):3512-24. Epub 2011 May 20.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York 14214, USA.

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http://dx.doi.org/10.1128/JB.01410-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133304PMC
July 2011
5 Reads
20 Citations
2.810 Impact Factor

Apoptosis-like death in bacteria induced by HAMLET, a human milk lipid-protein complex.

PLoS One 2011 Mar 10;6(3):e17717. Epub 2011 Mar 10.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, United States of America.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017717PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053380PMC
March 2011
4 Reads
21 Citations
3.234 Impact Factor

PerR confers phagocytic killing resistance and allows pharyngeal colonization by group A Streptococcus.

PLoS Pathog 2008 Sep 5;4(9):e1000145. Epub 2008 Sep 5.

Division of Infectious Diseases, Children's Hospital Boston, Massachusetts, United States of America.

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http://dx.doi.org/10.1371/journal.ppat.1000145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518855PMC
September 2008
9 Reads
29 Citations

Enzymatic characterization of dihydrolipoamide dehydrogenase from Streptococcus pneumoniae harboring its own substrate.

J Biol Chem 2007 Oct 9;282(40):29521-30. Epub 2007 Aug 9.

Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York 14214, USA.

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http://dx.doi.org/10.1074/jbc.M703144200DOI Listing
October 2007
11 Reads
5 Citations
4.573 Impact Factor

Mg(2+) signalling defines the group A streptococcal CsrRS (CovRS) regulon.

Mol Microbiol 2007 Aug 3;65(3):671-83. Epub 2007 Jul 3.

Division of Infectious Diseases, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.

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http://dx.doi.org/10.1111/j.1365-2958.2007.05818.xDOI Listing
August 2007
9 Reads
40 Citations
4.420 Impact Factor

Capsule does not block antibody binding to PspA, a surface virulence protein of Streptococcus pneumoniae.

Microb Pathog 2006 May 15;40(5):228-33. Epub 2006 Mar 15.

Department of Microbiology, University of Alabama at Birmingham, BBRB, 1530 3rd Ave North, Birmingham, AL 35294, USA.

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http://dx.doi.org/10.1016/j.micpath.2006.01.007DOI Listing
May 2006
36 Reads
9 Citations
2.000 Impact Factor

Enhancement of streptolysin O activity and intrinsic cytotoxic effects of the group A streptococcal toxin, NAD-glycohydrolase.

J Biol Chem 2006 Mar 23;281(12):8216-23. Epub 2006 Jan 23.

Division of Infectious Diseases, Children's Hospital Boston, Massachusetts 02215, USA.

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http://dx.doi.org/10.1074/jbc.M511674200DOI Listing
March 2006
20 Reads
24 Citations
4.573 Impact Factor

PerR contributes to oxidative stress resistance and survival of group a Streptococcus in macrophages

Abstracts of the General Meeting of the American Society for Microbiology

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2005

Extracellular group A Streptococcus induces keratinocyte apoptosis by dysregulating calcium signalling.

Cell Microbiol 2005 Jul;7(7):945-55

Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115, USA.

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http://dx.doi.org/10.1111/j.1462-5822.2005.00525.xDOI Listing
July 2005
9 Reads
26 Citations
4.920 Impact Factor

Cytolysin-dependent evasion of lysosomal killing.

Proc Natl Acad Sci U S A 2005 Apr 28;102(14):5192-7. Epub 2005 Mar 28.

Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115, USA.

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http://dx.doi.org/10.1073/pnas.0408721102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC555683PMC
April 2005
5 Reads
36 Citations
9.810 Impact Factor

Relative roles of genetic background and variation in PspA in the ability of antibodies to PspA to protect against capsular type 3 and 4 strains of Streptococcus pneumoniae.

Infect Immun 2003 Aug;71(8):4498-505

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC166025PMC
http://dx.doi.org/10.1128/iai.71.8.4498-4505.2003DOI Listing
August 2003
7 Reads
21 Citations
3.731 Impact Factor

Regions of PspA/EF3296 best able to elicit protection against Streptococcus pneumoniae in a murine infection model.

Infect Immun 2003 Mar;71(3):1033-41

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC148823PMC
http://dx.doi.org/10.1128/iai.71.3.1033-1041.2003DOI Listing
March 2003
3 Reads
20 Citations
3.731 Impact Factor

Hamlet--a complex from human milk that induces apoptosis in tumor cells but spares healthy cells.

Adv Exp Med Biol 2002 ;503:125-32

Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sweden.

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http://dx.doi.org/10.1007/978-1-4615-0559-4_14DOI Listing
January 2003
9 Reads
4 Citations

Characterization of the dihydrolipoamide dehydrogenase from Streptococcus pneumoniae and its role in pneumococcal infection.

Mol Microbiol 2002 Apr;44(2):431-48

Department of Microbiology, University of Alabama at Birmingham, BBRB-673 Box 10, 658 Bevill Building, 854 19th Street South, 35294, USA.

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http://dx.doi.org/10.1046/j.1365-2958.2002.02883.xDOI Listing
April 2002
17 Reads
18 Citations
4.420 Impact Factor

Bactericidal effects of lactoferrin on Streptococcus pneumoniae

Abstracts of the General Meeting of the American Society for Microbiology

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2001
1 Read

In vivo activation of dendritic cells and T cells during Salmonella enterica serovar Typhimurium infection.

Infect Immun 2001 Sep;69(9):5726-35

Department of Cell and Molecular Biology, Section for Immunology, Lund University, Lund, Sweden.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC98689PMC
http://dx.doi.org/10.1128/iai.69.9.5726-5735.2001DOI Listing
September 2001
1 Read
32 Citations
3.731 Impact Factor

Characterization of binding of human lactoferrin to pneumococcal surface protein A.

Infect Immun 2001 May;69(5):3372-81

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

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http://dx.doi.org/10.1128/IAI.69.5.3372-3381.2001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC98296PMC
May 2001
8 Reads
31 Citations
3.731 Impact Factor

Morphological and functional in vitro and in vivo characterization of the mouse corpus cavernosum.

Br J Pharmacol 2001 Mar;132(6):1333-41

Department of Clinical Pharmacology, University of Lund, Sweden.

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http://dx.doi.org/10.1038/sj.bjp.0703938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1572671PMC
March 2001
7 Reads
12 Citations
4.842 Impact Factor

A folding variant of human alpha-lactalbumin induces mitochondrial permeability transition in isolated mitochondria.

Eur J Biochem 2001 Jan;268(1):186-91

Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden.

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http://dx.doi.org/10.1046/j.1432-1327.2001.01870.xDOI Listing
January 2001
5 Reads
14 Citations

Conversion of alpha-lactalbumin to a protein inducing apoptosis.

Proc Natl Acad Sci U S A 2000 Apr;97(8):4221-6

Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, Sölvegatan 23, S-223 62 Lund, Sweden.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC18203PMC
http://dx.doi.org/10.1073/pnas.97.8.4221DOI Listing
April 2000
8 Reads
41 Citations
9.810 Impact Factor

A folding variant of alpha-lactalbumin with bactericidal activity against Streptococcus pneumoniae.

Mol Microbiol 2000 Feb;35(3):589-600

Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, SE-223 62 Lund, Sweden.

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http://dx.doi.org/10.1046/j.1365-2958.2000.01728.xDOI Listing
February 2000
1 Read
12 Citations
4.420 Impact Factor

Apoptosis induced by a human milk protein complex. Cellular and structural studies in tumour cells and bacteria.

Human milk contains a vast array of bioactive molecules, with nutritional and protective functions. This thesis describes the effects of a human milk protein complex, MAL, on tumour cells and bacteria. During our studies on the anti-adhesive properties of human milk we observed that a milk fraction killed tumour cells. The morphology of the cells indicated apoptotic cell death and this was verified by DNA fragmentation analysis (Proc Natl Acad Sci U.S.A 1995; 92: 8064-8068). The effect of MAL was selective for tumour cells and immature embryonic cells while mature differentiated cells were resistant. MAL bound to the surface of both sensitive and resistant cells but was internalised only in sensitive cells. MAL was shown to co-localise with mitochondria and this interaction caused a disruption of the mitochondrial membrane potential, which caused release of cytochrome c and caspase activation (Exp Cell Res 1999; 249: 260-268). The caspase activation was functional as shown by the cleavage of intracellular substrates. In parallel MAL was also transported via active nuclear transport to the nuclei of sensitive cells. MAL exerted a direct effect on isolated nuclei causing the induction of apoptotic DNA fragmentation without involvement of mitochondrial activation pathways (Exp Cell Res 1999; 2246: 451-460). MAL was purified from the casein fraction of human milk and was shown by N-terminal amino acid sequencing to contain alpha-lactalbumin. Native alpha-lactalbumin had no bactericidal or tumouricidal activity, suggesting that the alpha-lactalbumin of the active fraction had different structural properties. By spectroscopic techniques MAL was shown to have a more flexible tertiary structure with exposure of hydrophobic surfaces like the molten globule form of alpha-lactalbumin (J Biol Chem 1999; 274: 6388-6396). Native alpha-lactalbumin was inactive, but could be converted to the active form by a folding change combined with a fatty acid to stabilise this fold. These studies verified that alpha-lactalbumin was the active component and that the conformational change was required for the apoptosis-inducing activity. MAL was also shown to be bactericidal against S. pneumoniae, but had little effect against gram-negative and other gram-positive bacteria. In S. pneumoniae MAL was shown to induce identical DNA fragmentation as seen in tumour cells, suggesting apoptosis-like features of bacterial death. The bacterial death did not involve cytochrome c and caspase-activation but the bacteria had sequence homologies in three open reading frames of the pneumococcal genome with a caspase-independent effector molecule in eukaryotic cells, apoptosis inducing factor (AIF). These sequences are currently investigated.

https://portal.research.lu.se/portal/en/publications/apoptosis-induced-by-a-human-milk-protein-complex-cellular-and-structural-studies-in-tumour-cells-and-bacteria(b1ec70ec-7e8d-4016-b3dc-df86ef56b9d5).html

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1999

Protease activation in apoptosis induced by MAL.

Exp Cell Res 1999 Jun;249(2):260-8

Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, S-171 77, Sweden.

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http://dx.doi.org/10.1006/excr.1999.4472DOI Listing
June 1999
11 Reads
8 Citations
3.250 Impact Factor

Molecular characterization of alpha-lactalbumin folding variants that induce apoptosis in tumor cells.

J Biol Chem 1999 Mar;274(10):6388-96

Institute of Laboratory Medicine, Section of Microbiology, Immunology, and Glycobiology (MIG), Lund University, Sölvegatan 23, S-223 62 Lund, Sweden.

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http://dx.doi.org/10.1074/jbc.274.10.6388DOI Listing
March 1999
12 Reads
19 Citations
4.573 Impact Factor

Multimeric alpha-lactalbumin from human milk induces apoptosis through a direct effect on cell nuclei.

Exp Cell Res 1999 Feb;246(2):451-60

Department of Laboratory Medicine, Lund University, Sölvegatan 23, Lund, SE-223 62, Sweden.

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http://dx.doi.org/10.1006/excr.1998.4265DOI Listing
February 1999
9 Reads
11 Citations
3.250 Impact Factor

Apoptosis of renal cortical cells in the hemolytic-uremic syndrome: in vivo and in vitro studies.

Infect Immun 1998 Feb;66(2):636-44

Department of Medical Microbiology, University of Lund, Sweden.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC107951PMC
http://dx.doi.org/10.1128/IAI.66.2.636-644.1998DOI Listing
February 1998
3 Reads
37 Citations
3.731 Impact Factor

DNA fragmentation characteristic of apoptosis and cell loss induced by kainic acid in rabbit retinas.

Neurochem Int 1997 Aug;31(2):251-60

Department of Ophthalmology, University Hospital of Lund, Sweden.

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http://dx.doi.org/10.1016/s0197-0186(96)00156-8DOI Listing
August 1997
2 Reads
1 Citation
3.092 Impact Factor

Aspects on the interaction of Streptococcus pneumoniae and Haemophilus influenzae with human respiratory tract mucosa.

Am J Respir Crit Care Med 1996 Oct;154(4 Pt 2):S187-91

Department of Medical Microbiology, Lund University, Sweden.

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http://dx.doi.org/10.1164/ajrccm/154.4_Pt_2.S187DOI Listing
October 1996
3 Reads
11 Citations
13.000 Impact Factor

Antibodies to pneumococcal polysaccharides in human milk: lack of relationship to colonization and acute otitis media.

Pediatr Infect Dis J 1996 Jun;15(6):498-507

Department of Medical Microbiology, Lund University, Sweden.

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http://dx.doi.org/10.1097/00006454-199606000-00006DOI Listing
June 1996
2 Reads
3 Citations
2.723 Impact Factor

Apoptosis induced by a human milk protein.

Proc Natl Acad Sci U S A 1995 Aug;92(17):8064-8

Department of Medical Microbiology, Lund University, Sweden.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC41287PMC
http://dx.doi.org/10.1073/pnas.92.17.8064DOI Listing
August 1995
19 Reads
44 Citations
9.810 Impact Factor

Binding of Haemophilus influenzae to purified mucins from the human respiratory tract.

Infect Immun 1995 Jul;63(7):2485-92

Department of Medical and Physiological Chemistry, Lund University, Sweden.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC173332PMC
http://dx.doi.org/10.1128/IAI.63.7.2485-2492.1995DOI Listing
July 1995
4 Reads
18 Citations
3.731 Impact Factor

Adenovirus infection enhances in vitro adherence of Streptococcus pneumoniae.

Infect Immun 1994 Jul;62(7):2707-14

Department of Medical Microbiology, Lund University, Sweden.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC302872PMC
http://dx.doi.org/10.1128/IAI.62.7.2707-2714.1994DOI Listing
July 1994
4 Reads
28 Citations
3.731 Impact Factor

A prospective cohort study on breast-feeding and otitis media in Swedish infants.

Pediatr Infect Dis J 1994 Mar;13(3):183-8

Department of Medical Microbiology, Lund University, Sweden.

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http://dx.doi.org/10.1097/00006454-199403000-00003DOI Listing
March 1994
5 Reads
25 Citations
2.723 Impact Factor

Top co-authors

Laura R Marks
Laura R Marks

University at Buffalo

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Anders P Håkansson
Anders P Håkansson

Lund University

11
Anders Hakansson
Anders Hakansson

Lund University

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Michael R Wessels
Michael R Wessels

Boston Children's Hospital

6
Emily A Clementi
Emily A Clementi

University at Buffalo

5
Ryan M Reddinger
Ryan M Reddinger

State University of New York at Buffalo

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M Svensson
M Svensson

Lund University

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Charles H Jones
Charles H Jones

University at Buffalo

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David E Briles
David E Briles

University of Alabama at Birmingham

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