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Brian Wigdahl

Bio: Brian Wigdahl is an academic researcher from Drexel University. The author has contributed to research in topics: Virus & Long terminal repeat. The author has an hindex of 41, co-authored 215 publications receiving 5987 citations. Previous affiliations of Brian Wigdahl include Thomas Jefferson University & Pennsylvania State University.


Papers
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Journal ArticleDOI
TL;DR: Cell populations of the monocyte-macrophage lineage, which originate in the bone marrow, are of particular importance in HIV-1 persistence due to their ability to cross the blood-brain barrier and spread HIV- 1 infection in the immunoprivileged central nervous system (CNS).
Abstract: A major obstacle in human immunodeficiency virus type 1 (HIV-1) eradication is the ability of the virus to remain latent in a subpopulation of the cells it infects. Latently infected cells can escape the viral immune response and persist for long periods of time, despite the presence of successful highly active antiretroviral therapy (HAART). Given the appropriate stimulus, latently infected cells can reactivate and start producing infectious virions. The susceptibility of these cell populations to HIV-1, their life span, their proliferative capacity, and their ability to periodically produce infectious virus subsequent to alterations in cellular physiology and/or immunologic controls are critical issues which determine the contribution of these cells to viral persistence. Memory CD4+ T cells due to the long life span, which may be several years, and their ability to reactivate upon encounter with their cognate antigen or other stimulation, are considered a critical reservoir for maintenance of latent HIV-1 proviral DNA. Cells of the monocyte-macrophage lineage, which originate in the bone marrow (BM), are of particular importance in HIV-1 persistence due to their ability to cross the blood-brain barrier (BBB) and spread HIV-1 infection in the immunoprivileged central nervous system (CNS). Hematopoietic progenitor cells (HPCs) are also a potential HIV-1 reservoir, as several studies have shown that CD34+ HPCs carrying proviral DNA can be found in vivo in a subpopulation of HIV-1-infected patients. The ability of HPCs to proliferate and potentially generate clonal populations of infected cells of the monocyte-macrophage lineage may be crucial in HIV-1 dissemination. The contribution of these and other cell populations in HIV-1 persistence, as well as the possible strategies to eliminate latently infected cells are critically examined in this review.

325 citations

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TL;DR: Potential antiviral properties of medicinal plants against a diverse group of viruses are described, and screening the potential of plants possessing broad-spectrum antiviral effects against emerging viral infections is suggested.

305 citations

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TL;DR: The results indicate that CD4 is not the receptor for HIV-1 infection of the glioblastoma line U373-MG, medulloblastomas line MED 217, or primary human fetal neural cells.
Abstract: A number of studies have indicated that central nervous system-derived cells can be infected with human immunodeficiency virus type 1 (HIV-1). To determine whether CD4, the receptor for HIV-1 in lymphoid cells, was responsible for infection of neural cells, we characterized infectable human central nervous system tumor lines and primary fetal neural cells and did not detect either CD4 protein or mRNA. We then attempted to block infection with anti-CD4 antibodies known to block infection of lymphoid cells; we noted no effect on any of these cultured cells. The results indicate that CD4 is not the receptor for HIV-1 infection of the glioblastoma line U373-MG, medulloblastoma line MED 217, or primary human fetal neural cells.

285 citations

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TL;DR: It is proposed in this review that the dysregulation of the BBB during and after neuroinvasion is a critical component of the neuropathogenic process and that Dysregulation of this protective barrier is caused by a combination of viral and host factors including secreted viral proteins, components of the inflammatory process, the aging process, therapeutics, and drug or alcohol abuse.

184 citations

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TL;DR: Changes in the growth and differentiation process of HPCs may be involved in the generation of monocyte populations that are more susceptible and/or permissive to HIV-1, and have potentially altered trafficking profiles to several organs, including the CNS.
Abstract: Patients with HIV-1 often present with a wide range of hematopoietic abnormalities, some of which may be due to the presence of opportunistic infections and to therapeutic drug treatments. However, many of these abnormalities are directly related to HIV-1 replication in the bone marrow (BM). Although the most primitive hematopoietic progenitor cells (HPCs) are resistant to HIV-1 infection, once these cells begin to differentiate and become committed HPCs they become increasingly susceptible to HIV-1 infection and permissive to viral gene expression and infectious virus production. Trafficking of BM-derived HIV-1-infected monocytes has been shown to be involved in the dissemination of HIV-1 into the central nervous system (CNS), and it is possible that HIV-1 replication in the BM and infection of BM HPCs may be involved in the early steps leading to the development of HIV-1-associated dementia (HAD) as an end result of this cellular trafficking process. In addition, the growth and development of HPCs in the BM of patients with HIV-1 has also been shown to be impaired due to the presence of HIV-1 proteins and changes in the cytokine milieu, potentially leading to an altered maturation process and to increased cell death within one or more BM cell lineages. Changes in the growth and differentiation process of HPCs may be involved in the generation of monocyte populations that are more susceptible and/or permissive to HIV-1, and have potentially altered trafficking profiles to several organs, including the CNS. A monocyte subpopulation with these features has been shown to expand during the course of HIV-1 disease, particularly in HAD patients, and is characterized by low CD14 expression and the presence of cell surface CD16.

139 citations


Cited by
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Journal ArticleDOI
TL;DR: This paper presents a meta-analysis of the chiral stationary phase transition of Na6(CO3)(SO4)2, a major component of the response of the immune system to Na2CO3.
Abstract: Ju Mei,†,‡,∥ Nelson L. C. Leung,†,‡,∥ Ryan T. K. Kwok,†,‡ Jacky W. Y. Lam,†,‡ and Ben Zhong Tang*,†,‡,§ †HKUST-Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China ‡Department of Chemistry, HKUST Jockey Club Institute for Advanced Study, Institute of Molecular Functional Materials, Division of Biomedical Engineering, State Key Laboratory of Molecular Neuroscience, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China Guangdong Innovative Research Team, SCUT-HKUST Joint Research Laboratory, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China

5,658 citations

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TL;DR: This Review discusses neuroimaging studies in the living human brain and post-mortem tissue as well as biomarker studies demonstrating BBB breakdown in Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic encephalopathy.
Abstract: The blood-brain barrier (BBB) is a continuous endothelial membrane within brain microvessels that has sealed cell-to-cell contacts and is sheathed by mural vascular cells and perivascular astrocyte end-feet The BBB protects neurons from factors present in the systemic circulation and maintains the highly regulated CNS internal milieu, which is required for proper synaptic and neuronal functioning BBB disruption allows influx into the brain of neurotoxic blood-derived debris, cells and microbial pathogens and is associated with inflammatory and immune responses, which can initiate multiple pathways of neurodegeneration This Review discusses neuroimaging studies in the living human brain and post-mortem tissue as well as biomarker studies demonstrating BBB breakdown in Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic encephalopathy The pathogenic mechanisms by which BBB breakdown leads to neuronal injury, synaptic dysfunction, loss of neuronal connectivity and neurodegeneration are described The importance of a healthy BBB for therapeutic drug delivery and the adverse effects of disease-initiated, pathological BBB breakdown in relation to brain delivery of neuropharmaceuticals are briefly discussed Finally, future directions, gaps in the field and opportunities to control the course of neurological diseases by targeting the BBB are presented

1,507 citations

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TL;DR: Preclinical and clinical experience gained during the development of polymeric excipients, biomedical polymers and polymer therapeutics shows that judicious development of dendrimer chemistry for each specific application will ensure development of safe and important materials for biomedical and pharmaceutical use.

1,083 citations

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TL;DR: This review examines molecular and cellular mechanisms underlying the establishment of the blood-brain barrier, and examines how BBB dysfunction relates to neurological deficits and other pathologies in the majority of sporadic AD, PD, and ALS cases, multiple sclerosis, other neurodegenerative disorders, and acute CNS disorders.
Abstract: The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At the same time, the BBB regulates transport of molecules into and out of t...

1,033 citations