Acquired Immunodeficiency Syndrome: Jones M

Fisher M, Benn P, Evans B, Pozniak A, Jones M, Maclean S, Davidson O, Summerside J, Hawkins D, Anonymous00359. · Department of Genitourinary Medicine, Royal Sussex County Hospital, Brighton, UK. · Int J STD AIDS. · Pubmed #16464267 No free full text.

Abstract: We present the British Association for Sexual Health and HIV (BASHH) guidelines for post-exposure prophylaxis after sexual exposure (PEPSE) to HIV. This document includes a review of the current data to support the use of PEPSE, considers how to calculate the risks of HIV infection after a potential exposure, and provides recommendations on when PEPSE would and would not be considered. Other areas included are the possible impact on sexual behaviour, cost-effectiveness, and issues relating to service provision. Throughout the document, consideration is given to the place of PEPSE within the broader context of HIV prevention strategies and sexual health.

Jones M. · Eastbourne Downs Primary Care Trust. · Nurs Times. · Pubmed #12929474 No free full text.

This publication has no abstract.

Liu Y, Jones M, Hingtgen CM, Bu G, Laribee N, Tanzi RE, Moir RD, Nath A, He JJ. · Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. · Nat Med. · Pubmed #11100124 No free full text.

Abstract: Neurological disorders develop in most people infected with human immunodeficiency virus type 1 (HIV-1). However, the underlying mechanisms remain largely unknown. Here we report that binding of HIV-1 transactivator (Tat) protein to low-density lipoprotein receptor-related protein (LRP) promoted efficient uptake of Tat into neurons. LRP-mediated uptake of Tat was followed by translocation to the neuronal nucleus. Furthermore, the binding of Tat to LRP resulted in substantial inhibition of neuronal binding, uptake and degradation of physiological ligands for LRP, including alpha2-macroglobulin, apolipoprotein E4, amyloid precursor protein and amyloid beta-protein. In a model of macaques infected with a chimeric strain of simian-human immunodeficiency virus, increased staining of amyloid precursor protein was associated with Tat expression in the brains of simian-human immunodeficiency virus-infected macaques with encephalitis. These results indicate that HIV-1 Tat may mediate HIV-1-induced neuropathology through a pathway involving disruption of the metabolic balance of LRP ligands and direct activation of neuronal genes.

Kruman II, Nath A, Maragos WF, Chan SL, Jones M, Rangnekar VM, Jakel RJ, Mattson MP. · Sanders-Brown Research Center on Aging, Department of Neurology, Lexington, Kentucky, USA. · Am J Pathol. · Pubmed #10393834 links to  free full text

Abstract: Progressive neuronal degeneration in brain regions involved in learning and memory processes is a common occurrence in patients infected with human immunodeficiency virus type 1 (HIV-1). We now report that levels of Par-4, a protein recently linked to neuronal apoptosis in Alzheimer's disease, are increased in neurons in hippocampus of human patients with HIV encephalitis and in monkeys infected with a chimeric strain of HIV-1 and simian immunodeficiency virus. Par-4 levels increased rapidly in cultured hippocampal neurons following exposure to the neurotoxic HIV-1 protein Tat, and treatment of the cultures with a Par-4 antisense oligonucleotide protected the neurons against Tat-induced apoptosis. Additional findings show that Par-4 participates at an early stage of Tat-induced neuronal apoptosis before caspase activation, oxidative stress, and mitochondrial dysfunction. Our data suggest that Par-4 may be a mediator of neuronal apoptosis in HIV encephalitis and that therapeutic approaches targeting the Par-4 apoptotic cascade may prove beneficial in preventing neuronal degeneration and associated dementia in patients infected with HIV-1.

Stephens J, Cosyns M, Jones M, Hayward A. · Departments of Pathology, Pediatrics, Immunology, and the Barbara Davis Childhood Diabetes Center, University of Colorado Health Sciences Center, Denver, CO, USA. · Hepatology. · Pubmed #10385635 No free full text.

Abstract: Patients with acquired immune deficiency syndrome (AIDS) and boys with mutations of the CD154 gene (causing congenital X-linked immunodeficiency with hyper-IgM [XHIM]) are susceptible to chronic infections of the biliary tract with Cryptosporidium parvum (CP) that may lead to biliary sclerosis and ultimately to cholangiocarcinoma. To determine whether the CP infection and the consequent immune response contribute independently to this morbidity, we infected mice with severe combined immunodeficiency (SCID) or with disrupted genes for CD154, CD40, or interferon gamma (IFN-gamma) with CP. Even when CP infection persisted for 16 weeks, the SCID mice developed only mild triaditis, without apoptosis of biliary epithelial cells (BEC). Fifty percent of the CD154 knockout mice developed lobular hepatitis with acute and chronic triaditis. The CD40 knockout mice developed marked triaditis, and the IFN-gamma knockouts either succumbed to enteritis or survived to develop marked triaditis, portal fibrosis, biliary sclerosis, necrosis with dilation of duct-like structures within the porta hepatis, and dysplastic changes. CP-infected SCID mice reconstituted with T cells from IFN-gamma knockout donors either developed severe enteritis or survived to develop triaditis, cholangitis, lobular hepatitis with periductular sclerosis, and scarring. Mice with disruptions of both the CD40 and IFN-gamma genes remained infected by CP and developed bile duct and liver disease, but not enteritis. Our results suggest that T-cell cytokines are required for the inflammatory and sclerosing responses to CP infection in immunodeficient animals. The response of immunodeficient mice to CP infection may model at least the initial steps toward the development of sclerosing cholangitis or bile duct cancers in XHIM patients.