A5024147491- Prion Diseases and Protein Misfolding
- Acute Kidney Injury Research
- Alzheimer's disease research and treatments
- Tracheal and airway disorders
- Neurological diseases and metabolism
- Lung Cancer Diagnosis and Treatment
- Dialysis and Renal Disease Management
- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Trace Elements in Health
- Congenital Diaphragmatic Hernia Studies
- Asthma and respiratory diseases
- Sepsis Diagnosis and Treatment
- Alcoholism and Thiamine Deficiency
- Cystic Fibrosis Research Advances
- Medical Imaging and Pathology Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neurotransmitter Receptor Influence on Behavior
- Pneumonia and Respiratory Infections
- Mosquito-borne diseases and control
- Pleural and Pulmonary Diseases
- Renal function and acid-base balance
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Infectious Diseases and Tuberculosis
- Mycobacterium research and diagnosis
University College London
2007-2024
MRC Prion Unit
2007-2024
Medical Research Council
2008-2023
OpGen (United States)
2018
Monash Medical Centre
1994-2017
Monash Health
1999-2017
Monash University
2015-2017
Austin Hospital
2015
The University of Melbourne
2015
Prince Charles Hospital
2015
Critically ill patients with acute renal failure are traditionally treated low-protein diets to help control uremia. This dietary approach may be deleterious the patient's nutritional status and unnecessary, especially if continuous placement therapies (CRRT) used. However, optimal amount of protein supplementation during CRRT is unknown. In receiving CRRT, a high intake result in positive nitrogen balance absence uncontrolled Accordingly, we studied metabolism two consecutive cohorts equal...
Prion diseases are fatal neurodegenerative conditions for which there is no effective treatment. propagation involves the conversion of cellular prion protein, PrP C , to its conformational isomer, Sc accumulates in disease. Here, we show therapeutic knockdown expression using RNAi mice with established A single administration lentivirus expressing a shRNA targeting into each hippocampus disease significantly prolonged survival time. Treated animals lived 19% and 24% longer than given an...
Mutations in the charged multivesicular body protein 2B (CHMP2B) gene cause frontotemporal lobar degeneration. The mutations lead to C-terminal truncation of CHMP2B protein. We generated Chmp2b knockout mice and transgenic expressing either wild-type or C-terminally truncated mutant CHMP2B. have decreased survival show progressive neurodegenerative changes including gliosis increasing accumulation p62- ubiquitin-positive inclusions. inclusions are negative for TAR DNA binding 43 fused...
Bronchiectasis is a heterogeneous disorder with large number of etiologic factors. The main symptom chronic productive cough. aim this study was to describe the phenotypes patients bronchiectasis who had developed cough in childhood (before 16 years age) compared those as adults. One hundred and eighty-two subjects diagnosed by computed tomography scanning were studied. Subjects all detailed clinical review assessment potential factors performed investigators. There 107 (59%) 75 (41%)...
Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in variety of chronic respiratory diseases. The role this the pathogenesis lung inflammation not well defined. In study we examined effect NTHi on two important inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils 15 human-lung fibroblast epithelial cell lines 16 subjects. Cells stimulated with to measure reactive...
Alzheimer's disease (AD) is associated with pathological assembly states of amyloid-β protein (Aβ). Aβ-related synaptotoxicity can be blocked by anti-prion (PrP) antibodies, potentially allowing therapeutic targeting this aspect AD neuropathogenesis. Here, we show that intravascular administration a high-affinity humanized anti-PrP antibody to rats prevent the plasticity-disrupting effects induced exposure soluble brain extract. These results provide an in vivo proof principle for such strategy.
Potentially therapeutic monoclonal antibodies do not kill neurons.
Endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) is an important diagnostic procedure for the interrogation of mediastinal lymph nodes. There limited data describing accuracy & safety this technique diagnosis tuberculous lymphadenitis.A multi-centre retrospective study all EBUS-guided TBNA procedures that referred samples mycobacteriology was performed. Results were correlated with post-procedural diagnoses after a period surveillance and cross-checked against relevant...
It is unknown whether continuous renal replacement techniques result in diminished morbidity and mortality when compared to conventional dialytic techniques. To investigate this issue a previously described, retrospectively studied group of critically ill patients with severe acute failure treated by dialysis (CD) was prospectively similar hemodiafiltration (ACHD). A combined retrospective prospective clinical laboratory investigation carried out for 234 consecutive the intensive care unit...
Abstract Background Overcoming β-lactam resistance in pathogens such as Pseudomonas aeruginosa is a major clinical challenge. Rapid molecular diagnostics (RMDs) have the potential to inform selection of empiric therapy patients infected by P. aeruginosa. Methods In this study, we used heterogeneous collection 197 that included multidrug-resistant isolates determine whether 2 representative RMDs (Acuitas Resistome test and VERIGENE gram-negative blood culture test) could identify...
Our aim was to investigate if deoxyribonuclease (DNase) 1 is a potential therapeutic agent reduce pathogenic effects of cigarette smoke exposure in the lung. Cigarette causes protease imbalance with excess production proteases, which key process pathogenesis emphysema. The mechanisms responsible for this effect are not well-defined. studies demonstrate both vitro and vivo that significantly increases expression neutrophil macrophage extracellular traps coexpression elastase matrix...
Endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA) is an established, minimally invasive way to sample intrathoracic abnormalities. The EBUS scope can be passed into the oesophagus perform endoscopic with bronchoscope-guided fine-needle (EUS-B-FNA). In cases of suspected lung cancer, a combination two techniques now recommended by consensus guidelines. TBNA usually performed pulmonologists; however, learning curve for EUS-B-FNA, which may during same procedure, has not...
Abstract Alzheimer’s disease (AD) is defined by the accumulation of neurofibrillary tangles containing hyperphosphorylated Tau and plaques Amyloid-β (Aβ). The aggregation these two proteins considered central to disease. lack animal models that can recapitulate Aβ tau pathologies without overexpressing has hindered AD research. Accelerating pathology inoculating seeds helped understand their prion-like propagation in brain. Previous studies failed characterise both vivo upon brain...
Syntaxin-6, a SNARE protein involved in intracellular trafficking, is proposed risk factor for sporadic prion disease, progressive supranuclear palsy and Alzheimer's disease. However, no study has validated its functional role these diseases, explored the disease stage at which it acting nor mechanism of action. Here, we show that syntaxin-6 acts early stages experimental mice by increasing transmission following inoculation with low doses. Conversely, does not affect propagation kinetics or...
The syndrome of sepsis-associated severe acute renal failure is a frequent component sepsis-induced multiorgan failure. Continuous hemofiltration techniques are often used in its dialytic management but little known about their impact. aim this study to define the biochemical and clinical impact continuous hemodiafiltration (CHD) retrospectively compare it that conventional dialysis. A prospective, cohort retrospective comparison with historical controls was conducted at an intensive care...
Background: Transesophageal introduction of the endobronchial ultrasound (EBUS) videobronchoscope allows pulmonologists to perform endoscopic fine-needle aspiration (EUS-B-FNA) mediastinal lesions. Safety, diagnostic accuracy, and feasibility EUS-B-FNA in evaluation pulmonary parenchymal lesions are not established. Methods: All patients undergoing pulmonologist-performed lung at 2 tertiary centers were included this prospective observational cohort study. Results: sampling was performed 27...
Continuous renal replacement therapy is increasingly used in the management of acute failure critically ill patients. The advantages continuous (CRRT) over intermittent hemodialysis (IHD), however, are not yet fully documented. In particular, it unknown whether veno-venous hemodiafiltration (CVVHDF) provides better control azotemia than IHD.To study effect on azotemic changing treatment from IHD to CVVHDF.Tertiary intensive care unit.Forty seven consecutive patients with multiorgan and...
Summary Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells have a key role in host defence against infectious pathogens, but their response to bacteria is not well characterized. Non-typeable Haemophilus influenzae major cause of respiratory tract infection including otitis media, sinusitis, tonsillitis chronic bronchitis (especially obstructive pulmonary disease bronchiectasis). This bacterium also present the pharynx most healthy adults. The primary factor that may determine...
Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is thought to occur when cellular protein (PrPC) spontaneously misfolds and assembles into fibrils, culminating in fatal neurodegeneration. In a genome-wide association study of sCJD, we recently identified risk variants around gene STX6, with evidence suggest causal increase STX6 expression disease-relevant brain regions. encodes syntaxin-6, SNARE primarily involved early endosome trans-Golgi network retrograde...
Summary Non-typeable Haemophilus influenzae (NTHi) is a major cause of respiratory but rarely systemic infection. The host defence to this bacterium has not been well defined in patients with chronic airway aim study was assess the effect humoral immunity NTHi. Responses were measured control and bronchiectasis subjects who had recurrent bronchial Antibody complement-mediated killing assessed by incubating NTHi serum role membrane–attack complex classical/alternate pathways complement...
Background: Bronchoalveolar lavage (BAL) is a commonly used diagnostic and research tool. Currently, there limited evidence regarding standardizing this technique. The type of suction method number aliquots as well the anatomic lung segment sampled are not standardized nor studied. Our primary aim was to compare quantity quality BAL specimens using 2 methods, hand-held syringe versus wall suction. secondary assess which yields greatest results how many required. Methods: A prospective...