A5023432955- HIV Research and Treatment
- HIV-related health complications and treatments
- HIV/AIDS Research and Interventions
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Cytomegalovirus and herpesvirus research
- Alzheimer's disease research and treatments
- HIV/AIDS drug development and treatment
- Stress Responses and Cortisol
- Infectious Encephalopathies and Encephalitis
- Neurological and metabolic disorders
- Multiple Sclerosis Research Studies
- Pharmacological Effects and Toxicity Studies
- Peripheral Neuropathies and Disorders
- Polyomavirus and related diseases
- Bipolar Disorder and Treatment
- Neurological Complications and Syndromes
- Syphilis Diagnosis and Treatment
- Long-Term Effects of COVID-19
- CNS Lymphoma Diagnosis and Treatment
- Mosquito-borne diseases and control
- Nanocluster Synthesis and Applications
- T-cell and Retrovirus Studies
- Palliative Care and End-of-Life Issues
- Herpesvirus Infections and Treatments
UNSW Sydney
2016-2025
St Vincent's Hospital Sydney
2016-2025
St Vincent's Hospital
2016-2025
St Vincent's Clinic
2015-2025
The University of Notre Dame Australia
2017-2025
St Vincent's Health
2019-2025
St. Vincent's Birmingham
2010-2024
St. Vincent's Hospital
2008-2024
Saint Vincent's Catholic Medical Center
2009-2024
St Vincents Institute of Medical Research
2009-2023
In 1991, the AIDS Task Force of American Academy Neurology published nomenclature and research case definitions to guide diagnosis neurologic manifestations HIV-1 infection. Now, 16 years later, National Institute Mental Health Neurological Diseases Stroke have charged a working group critically review adequacy utility these definitional criteria identify aspects that require updating. This report represents majority view, unanimity was not reached on all points. It reviews our collective...
This study examined the validity of four standard psychological paradigms that have been operationally defined within CogState brief computerized cognitive assessment battery. Construct was determined in a large group healthy adults. measures processing speed, attention, working memory, and learning showed strong correlations with conventional neuropsychological these same constructs (r's = .49 to .83). Criterion by examining patterns performance on tasks groups individuals mild head injury,...
Abstract Quinolinic acid is an “excitotoxic” metabolite and agonist of N ‐methyl‐ D ‐aspartate receptors. Of patients infected with human immunodeficiency virus type 1 (HIV‐1) who were neurologically normal or exhibited only equivocal subclinical signs the acquired syndrome (AIDS) dementia complex, concentrations quinolinic in cerebrospinal fluid (CSF) increased twofold early stages disease (Walter Reed 2) averaged 3.8 times above later‐stage 4 through 6). However, either clinically overt...
There is good evidence that the kynurenine pathway (KP) and one of its products, quinolinic acid (QUIN), play a role in pathogenesis neurological diseases, particular AIDS dementia complex. Although QUIN has been shown to be produced neurotoxic concentrations by macrophages microglia, astrocytes production controversial. Using cytokine-stimulated cultures human astrocytes, we assayed key enzymes products KP. We found lack hydroxylase so large amounts antagonist kynurenic were produced....
Abstract There is good evidence that the kynurenine pathway (KP) and one of its end products, quinolinic acid (QUIN) play a role in pathogenesis several major neurological diseases. While QUIN has been shown to be produced neurotoxic concentrations by macrophages microglia, capacity astrocytes neurons produce controversial. Using interferon gamma (IFN‐γ)‐stimulated primary cultures human mixed brain cells, we assayed expression KP regulatory enzyme indoleamine 2,3‐dioxygenase (IDO)...
Objectives: To determine the protective efficacy of highly active antiretroviral therapy (HAART) against AIDS dementia complex (ADC) relative to other initial AIDS-defining illnesses (ADIs), Australian notification data over recent years were examined. Methods: All ADIs in Australia period 1992-1997 included. Three ADI groups established: ADC; predominantly central nervous system (CNS) (toxoplasmosis and cryptococcosis); non-CNS ADIs. For each grouping, proportion total ADIs, median CD4 cell...
Abstract Astrocyte infection with human immunodeficiency virus (HIV) is considered rare, so astrocytes are thought to play a secondary role in HIV neuropathogenesis. By combining double immunohistochemistry, laser capture microdissection, and highly sensitive multiplexed polymerase chain reaction detect DNA single vivo, we showed that astrocyte extensive subjects HIV‐associated dementia, occurring up 19% of GFAP+ cells. In addition, frequency correlated the severity neuropathological changes...
The kynurenine pathway is a major route of L-tryptophan catabolism producing neuroactive metabolites implicated in neurodegeneration and immune tolerance. We characterized the human neurons SK-N-SH neuroblastoma cell line found that enzymes were variably expressed. Picolinic carboxylase was expressed only primary some adult but not cells. Because this difference, cells able to produce excitotoxin quinolinic acid, whereas produced neuroprotectant picolinic acid. net result induction therefore...
Identifying infectious causes of subacute or chronic meningitis can be challenging. Enhanced, unbiased diagnostic approaches are needed.To present a case series patients with diagnostically challenging using metagenomic next-generation sequencing (mNGS) cerebrospinal fluid (CSF) supported by statistical framework generated from mNGS control samples the environment and who were noninfectious.In this series, data obtained CSF 94 noninfectious neuroinflammatory disorders 24 water reagent used...
Abstract Activation of the kynurenine pathway (KP) tryptophan metabolism results from chronic inflammation and is known to exacerbate progression neurodegenerative disease. To gain insights into links between inflammation, KP multiple sclerosis (MS) pathogenesis, we investigated metabolomics profile MS patients. Most significantly, found aberrant levels two key metabolites, kynurenic acid (KA) quinolinic (QA). The balance these metabolites important as it determines overall excitotoxic...
The present immunohistochemical study provides evidence that the kynurenine pathway is up‐regulated in Alzheimer's disease (AD) brain, leading to increases excitotoxin quinolinic acid (QUIN). We show regulatory enzyme of QUIN synthesis, indoleamine 2,3 dioxygenase (IDO) abundant AD compared with controls. In hippocampus, both IDO‐ and QUIN‐immunoreactivity (‐IR) was detected cortical microglia, astrocytes neurones, microglial astrocytic expression IDO highest perimeter senile plaques....
Abstract To evaluate the presence and distribution of central nervous system infection by human immunodeficiency virus type 1 (HIV‐1), we used immunohistochemical methods to map HIV‐1 p24 core protein in brains 55 autopsied patients with acquired syndrome (AIDS). In a subset 40 these who had undergone antemortem neurological evaluation AIDS dementia complex (ADC), analyzed relation between severities viral clinical dysfunction. Viral antigen was detected macrophages cells morphological...
The relationship between the presence and severity of AIDS dementia complex (ADC) levels human immunodeficiency virus type 1 (HIV-1) RNA in cerebrospinal fluid (CSF) were assessed. Nineteen patients with ADC (stages 1–3), 6 without (group 1), 10 2) but cryptococcal meningitis or progressive multifocal leukoencephalopathy studied. There was a significant increasing CSF burden ADCseverity (P = .0006) not plasma severity. In group 2, HIV-1 elevated. These results show that concentrations...
Objective: To determine the effect of introduction highly active antiretroviral therapy (HAART) on survival following AIDS dementia complex (ADC). Methods: Australian notification data in period 1993–2000 were examined. In order to examine impact HAART, two periods diagnoses chosen: pre-HAART (1993–1995) and HAART (1996–2000). Median was based Kaplan–Meier estimates, with examination factors influencing a Cox proportional hazards model. Results: Australia, 5017 initial illnesses diagnosed...
Objective: To determine the efficacy of low-dose trimethoprim-sulfamethoxazole (trimethoprim, 160 mg plus sulfamethoxazole, 800 mg; one tablet twice daily, 2 days per week) as primary prophylaxis against toxoplasmic encephalitis in patients with human immunodeficiency virus (HIV) infection and previous Pneumocystis carinii pneumonia. Design: A retrospective study. Setting: Tertiary referral teaching hospital. Patients: During a 3-year period after episodes P. pneumonia, 60 received...
Some of the tryptophan catabolites produced through kynurenine pathway (KP), and more particularly excitotoxin quinolinic acid (QA), are likely to play a role in pathogenesis Alzheimer's disease (AD). We have previously shown that KP is over activated AD brain QA accumulates amyloid plaques within dystrophic neurons. hypothesized pathophysiological concentrations affects tau phosphorylation. Using immunohistochemistry, we found co-localized with hyperphosphorylated (HPT) cortical neurons...
The kynurenine pathway (KP) of tryptophan metabolism is linked to antimicrobial activity and modulation immune responses but its role in stem cell biology unknown. We show that human mouse mesenchymal neural cells (MSCs NSCs) express the complete KP, including indoleamine 2,3 dioxygenase 1 (IDO) IDO2, it highly regulated by type I (IFN-β) II interferons (IFN-γ), transcriptional depends on interferon, species. IFN-γ inhibited proliferation altered MSC neural, adipocytic osteocytic...
This review will discuss emerging evidence for the possibility that AIDS dementia complex (ADC) has changed in era of highly active antiretroviral therapy (HAART). The consequences not considering these possibilities at patient level and research are considerable. Data be discussed derived from epidemiological studies, neuropsychological positron emission tomography as well analyses abacavir ADC trial. These then assessed to develop concept there now different forms ADC: an inactive form, a...