14 results on '"Anthony, Peter"'
Search Results
2. Case Studies Discussing the Pathology, Immunogenicity, and Proposed Mechanism of Toxicity of an Inhaled Anti-TGFβ Humanized Fab Antibody in Non-Human Primates and Mice
- Author
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James T. Raymond, Sherri Dudal, Jacquelin Jolette, Annick Cauvin, Petrina Rogerson, and Anthony Peter Hall
- Subjects
Primates ,Pathology ,medicine.medical_specialty ,040301 veterinary sciences ,Inflammation ,Toxicology ,Antibodies ,Pathology and Forensic Medicine ,0403 veterinary science ,03 medical and health sciences ,Mice ,Immune system ,Transforming Growth Factor beta ,medicine ,Macrophage ,Animals ,Molecular Biology ,Lung ,030304 developmental biology ,0303 health sciences ,medicine.diagnostic_test ,biology ,business.industry ,Immunogenicity ,04 agricultural and veterinary sciences ,Cell Biology ,respiratory system ,Bronchoalveolar lavage ,biology.protein ,Lymph ,medicine.symptom ,Antibody ,business ,Bronchoalveolar Lavage Fluid ,CD8 - Abstract
Treatment of nonhuman primates and mice with a humanized antigen-binding fragment (Fab) antibody (UCBFab) inhibiting transforming growth factor β via daily inhalation for up to 13 weeks resulted in low systemic exposure but high local exposure in the lung. Target engagement was demonstrated by reduced levels of signal transducers, phosphoSMAD and plasminogen activator inhibitor-1 in the bronchoalveolar lavage fluid (BALF). Treatment was associated with a high frequency and titer of antidrug antibodies, indicating high local immunogenicity, and local pathology within the lung and draining lymph nodes. Microscopic changes were characterized by perivascular (PV) and peribronchiolar (PB) mononuclear inflammatory cell (MIC) infiltrates that were principally lymphocytic in nature and mixed inflammatory cell infiltrates and/or inflammation within the alveoli. Immunohistochemical investigation revealed a predominantly CD68-positive macrophage and CD3- and CD8>CD4-positive T-cell response in the alveoli, whereas within the airways, there was a variable mixture of CD3-positive T cells, CD20-positive B cells, and CD68-positive macrophages. Increased cellularity of the draining lymph nodes was also noted, indicating the presence of an immune response to the inhaled test article. Morphologic changes did not progress over time, and all changes partially recovered. Increased leukocytes (principally macrophages) in BALF cytology correlated with the changes seen by histopathology.
- Published
- 2020
3. The Rationale and Design of the Reducing Pathology in Alzheimer’s Disease through Angiotensin TaRgeting (RADAR) Trial
- Author
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Yoav Ben-Shlomo, Beth Howden, Jeremy Horwood, Hannah Baber, Ian B. Malone, Athene Lane, Peter S Blair, Lucy E Selman, Ian B. Wilkinson, Clare Clement, Elizabeth Coulthard, Patrick G. Kehoe, Anthony Peter Passmore, Nick C. Fox, and David L. Thomas
- Subjects
Male ,0301 basic medicine ,Pathology ,CRICBristol ,law.invention ,Renin-Angiotensin System ,0302 clinical medicine ,Quality of life ,Randomized controlled trial ,law ,Activities of Daily Living ,Medicine ,Randomized Controlled Trials as Topic ,General Neuroscience ,Brain ,General Medicine ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,Clinical Psychology ,Losartan ,Tolerability ,Centre for Surgical Research ,Disease Progression ,Regression Analysis ,Female ,BRTC ,Alzheimer's disease ,medicine.drug ,medicine.medical_specialty ,Placebo ,BTC (Bristol Trials Centre) ,03 medical and health sciences ,Clinical Trials, Phase II as Topic ,Double-Blind Method ,Alzheimer Disease ,Humans ,Antihypertensive Agents ,business.industry ,medicine.disease ,Blood Pressure Monitors ,Clinical trial ,030104 developmental biology ,Blood pressure ,Multivariate Analysis ,Quality of Life ,Atrophy ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery - Abstract
Background: Anti-hypertensives that modify the renin angiotensin system may reduce Alzheimer’s disease pathology and reduce the rate of disease progression. We report a phase II, two arm, double-blind, placebo-controlled, randomised trial (ISRCTN: 93682878; EudraCT: 2012-003641-15) of losartan to test the efficacy of Reducing pathology in Alzheimer’s Disease through Angiotensin TaRgeting (RADAR). Study population: Men and women aged at least 55 years with mild-to-moderate Alzheimer’s disease (AD) Interventions: Randomly allocated 100mg encapsulated generic losartan or placebo once daily for 12 months after successful completion of a 2 week open-label phase and 2 weeks placebo washout to establish drug tolerability. Outcomes: The primary outcome is the rate of whole brain atrophy as a surrogate measure of disease progression. Secondary outcomes include changes to (i) white matter hyperintensity (WMH) volume and cerebral blood flow (CBF) (also surrogate markers of cognitive decline and disease progression); (ii) performance on a standard series of assessments of memory, cognitive function, activities of daily living and quality of life. Assessments: Major assessments (for all outcomes) and relevant safety monitoring of blood pressure and bloods will be at baseline and 12 months. Additional cognitive assessment will also be conducted at 6 months along with safety blood pressure and blood monitoring. Monitoring of blood pressure, bloods and reported side effects will occur during the open-label phase and during the majority of the post-randomisation dispensing visits. Sample Size: 228 participants to provide at least 182 subjects with final assessments to provide 84% power to detect a 25% difference in atrophy rate (therapeutic benefit) change over 12 months at an alpha level of 0.05. Analysis: Intention-to-treat analysis, estimating between-group differences in outcomes derived from appropriate (linear or logistic) multivariable regression models adjusting for minimisation variables.
- Published
- 2017
4. Alzheimer's disease–like pathology has transient effects on the brain and blood metabolome
- Author
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Xiaobei Pan, Christopher T. Elliott, Stewart F. Graham, Bernadette McGuinness, Patrick G. Kehoe, Muhammad Bin Nasaruddin, Christian Hölscher, Brian D. Green, Paula McClean, and Anthony Peter Passmore
- Subjects
Male ,0301 basic medicine ,Serotonin ,Aging ,medicine.medical_specialty ,Pathology ,Transgene ,Mice, Transgenic ,Biology ,Pathogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolomics ,Alzheimer Disease ,Carnitine ,Internal medicine ,Blood plasma ,Metabolites ,medicine ,Metabolome ,Animals ,Neurotransmitter ,Phospholipids ,APP/PS1 ,General Neuroscience ,Biogenic Polyamines ,Brain ,Alzheimer's disease ,medicine.disease ,Disease Models, Animal ,Blood ,030104 developmental biology ,Endocrinology ,chemistry ,Amino Acids, Essential ,Neurology (clinical) ,Geriatrics and Gerontology ,Amino Acids, Branched-Chain ,030217 neurology & neurosurgery ,Homeostasis ,Developmental Biology - Abstract
The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology affects the metabolome is still not understood nor is it known how disturbances change as the disease progresses. For the first time, we have profiled longitudinally (6, 8, 10, 12, and 18 months) both the brain and plasma metabolome of APPswe/PS1deltaE9 double transgenic and wild-type mice. A total of 187 metabolites were quantified using a targeted metabolomic methodology. Multivariate statistical analysis produced models that distinguished APPswe/PS1deltaE9 from wild-type mice at 8, 10, and 12 months. Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids, branched-chain amino acids, and also in the neurotransmitter serotonin. Pronounced imbalances in phospholipid and acylcarnitine homeostasis were evident in 2 age groups. AD-like pathology, therefore, affects greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood.
- Published
- 2016
5. P3‐076: QUANTITATIVE METABOLOMICS PROFILING OF BRAIN TISSUE FROM PEOPLE WHO SUFFERED FROM MILD AND SEVERE AD REVEALS DISTINCT BIOCHEMICAL DIFFERENCES WHEN COMPARED TO TISSUE HARVESTED FROM NON‐COGNITIVELY IMPAIRED PEOPLE
- Author
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Bernadette McGuinness, Stewart F. Graham, Patrick G. Kehoe, Joseph Kirma, Brian D. Green, Christian Hölscher, Anthony Peter Passmore, Ali Yilmaz, Xiaobei Pan, and Michael Maddens
- Subjects
Pathology ,medicine.medical_specialty ,Epidemiology ,business.industry ,Health Policy ,Brain tissue ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Metabolomics ,Developmental Neuroscience ,Medicine ,Profiling (information science) ,Neurology (clinical) ,Cognitively impaired ,Geriatrics and Gerontology ,business - Published
- 2018
6. Case Studies Discussing the Pathology, Immunogenicity, and Proposed Mechanism of Toxicity of an Inhaled Anti-TGFβ Humanized Fab Antibody in Non-Human Primates and Mice.
- Author
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Hall, Anthony Peter, Cauvin, Annick, Dudal, Sherri, Raymond, James, Rogerson, Petrina, and Jolette, Jacquelin
- Subjects
- *
PATHOLOGY , *TRANSFORMING growth factors , *PRIMATES , *PLASMINOGEN activators , *IMMUNE response - Abstract
Treatment of nonhuman primates and mice with a humanized antigen-binding fragment (Fab) antibody (UCBFab) inhibiting transforming growth factor β via daily inhalation for up to 13 weeks resulted in low systemic exposure but high local exposure in the lung. Target engagement was demonstrated by reduced levels of signal transducers, phosphoSMAD and plasminogen activator inhibitor-1 in the bronchoalveolar lavage fluid (BALF). Treatment was associated with a high frequency and titer of antidrug antibodies, indicating high local immunogenicity, and local pathology within the lung and draining lymph nodes. Microscopic changes were characterized by perivascular (PV) and peribronchiolar (PB) mononuclear inflammatory cell (MIC) infiltrates that were principally lymphocytic in nature and mixed inflammatory cell infiltrates and/or inflammation within the alveoli. Immunohistochemical investigation revealed a predominantly CD68-positive macrophage and CD3- and CD8>CD4-positive T-cell response in the alveoli, whereas within the airways, there was a variable mixture of CD3-positive T cells, CD20-positive B cells, and CD68-positive macrophages. Increased cellularity of the draining lymph nodes was also noted, indicating the presence of an immune response to the inhaled test article. Morphologic changes did not progress over time, and all changes partially recovered. Increased leukocytes (principally macrophages) in BALF cytology correlated with the changes seen by histopathology. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
7. Angiosarcoma Of The Liver In Great Britain, 1963-73
- Author
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Baxter, Peter J., Anthony, Peter P., MacSween, Roderick N. M., and Scheuer, Peter J.
- Published
- 1977
8. No Evidence of Endothelial Dysfunction in Patients with Alzheimer’s Disease
- Author
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G D Johnston, Anthony Peter Passmore, Daniel F. McAuley, and B M McGleenon
- Subjects
Male ,Nitroprusside ,medicine.medical_specialty ,Pathology ,Brachial Artery ,Endothelium ,Vasodilator Agents ,Cognitive Neuroscience ,Hemodynamics ,Central nervous system disease ,Alzheimer Disease ,Internal medicine ,medicine ,Humans ,Infusions, Intra-Arterial ,Vascular Diseases ,Endothelial dysfunction ,Aged ,Aged, 80 and over ,Dose-Response Relationship, Drug ,business.industry ,Middle Aged ,medicine.disease ,Acetylcholine ,Plethysmography ,body regions ,Forearm ,Psychiatry and Mental health ,medicine.anatomical_structure ,Regional Blood Flow ,Case-Control Studies ,Circulatory system ,Cardiology ,Female ,Endothelium, Vascular ,Sodium nitroprusside ,Geriatrics and Gerontology ,Alzheimer's disease ,business ,medicine.drug ,Blood vessel - Abstract
In view of accumulating evidence of vascular pathology in Alzheimer’s disease (AD), we tested the hypothesis that AD patients have impaired endothelial function. This was assessed using the technique of strain-gauge venous occlusion plethysmography, which measures forearm blood flow (FBF). Intra-arterial (brachial) infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) was used to assess local endothelial dependent and independent responses, respectively. There was no difference in the basal FBF of patients and controls. ACh and SNP caused dose-related increases in FBF from baseline, but no difference was recorded between the AD and control group. This study provides no evidence of endothelial dysfunction in the systemic circulation of patients with AD.
- Published
- 2000
9. Plasma chain-breaking antioxidants in Alzheimer's disease, vascular dementia and Parkinson's disease
- Author
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Anthony Peter Passmore, C J Foy, J T Lawson, Ian S. Young, and M D Vahidassr
- Subjects
Male ,Vitamin ,medicine.medical_specialty ,Pathology ,Free Radicals ,medicine.medical_treatment ,Antioxidants ,chemistry.chemical_compound ,Alzheimer Disease ,Internal medicine ,medicine ,Humans ,Dementia ,Vascular dementia ,Aged ,Aged, 80 and over ,Vitamin C ,business.industry ,Dementia, Vascular ,Vitamin E ,Retinol ,Parkinson Disease ,Vitamins ,General Medicine ,Middle Aged ,medicine.disease ,Ascorbic acid ,Carotenoids ,Endocrinology ,chemistry ,Female ,Alzheimer's disease ,business ,Oxidation-Reduction - Abstract
Summary We studied the plasma chain-breaking antioxidants in AD ( p
- Published
- 1999
10. The Rationale and Design of the Reducing Pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR) Trial.
- Author
-
Kehoe, Patrick G., Blair, Peter S., Howden, Beth, Thomas, David L., Malone, Ian B., Horwood, Jeremy, Clement, Clare, Selman, Lucy E., Baber, Hannah, Lane, Athene, Coulthard, Elizabeth, Passmore, Anthony Peter, Fox, Nick C., Wilkinson, Ian B., and Ben-Shlomo, Yoav
- Subjects
ALZHEIMER'S disease ,OXIDATION ,PATHOLOGY ,ANGIOTENSINS ,PLACEBOS ,BRAIN ,COMPARATIVE studies ,ANTIHYPERTENSIVE agents ,MAGNETIC resonance imaging ,RESEARCH methodology ,MEDICAL cooperation ,MULTIVARIATE analysis ,QUALITY of life ,REGRESSION analysis ,RESEARCH ,STATISTICAL sampling ,RENIN-angiotensin system ,ACTIVITIES of daily living ,EVALUATION research ,BLOOD pressure testing machines ,RANDOMIZED controlled trials ,BLIND experiment ,ATROPHY ,DISEASE progression ,LOSARTAN ,PSYCHOLOGY - Abstract
Background: Anti-hypertensives that modify the renin angiotensin system may reduce Alzheimer's disease (AD) pathology and reduce the rate of disease progression.Objective: To conduct a phase II, two arm, double-blind, placebo-controlled, randomized trial of losartan to test the efficacy of Reducing pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR).Methods: Men and women aged at least 55 years with mild-to-moderate AD will be randomly allocated 100 mg encapsulated generic losartan or placebo once daily for 12 months after successful completion of a 2-week open-label phase and 2-week placebo washout to establish drug tolerability. 228 participants will provide at least 182 subjects with final assessments to provide 84% power to detect a 25% difference in atrophy rate (therapeutic benefit) change over 12 months at an alpha level of 0.05. We will use intention-to-treat analysis, estimating between-group differences in outcomes derived from appropriate (linear or logistic) multivariable regression models adjusting for minimization variables.Results: The primary outcome will be rate of whole brain atrophy as a surrogate measure of disease progression. Secondary outcomes will include changes to 1) white matter hyperintensity volume and cerebral blood flow; 2) performance on a standard series of assessments of memory, cognitive function, activities of daily living, and quality of life. Major assessments (for all outcomes) and relevant safety monitoring of blood pressure and bloods will be at baseline and 12 months. Additional cognitive assessment will also be conducted at 6 months along with safety blood pressure and blood monitoring. Monitoring of blood pressure, bloods, and self-reported side effects will occur during the open-label phase and during the majority of the post-randomization dispensing visits.Conclusion: This study will identify whether losartan is efficacious in the treatment of AD and whether definitive Phase III trials are warranted. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
11. Increased oxidative stress in Alzheimer's disease as assessed with 4-hydroxynonenal but not malondialdehyde
- Author
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Stephen P. McIlroy, B M McGleenon, Anthony Peter Passmore, Siobhan Brennan, D McColl, and Lawrence T. McGrath
- Subjects
Male ,medicine.medical_specialty ,Pathology ,Normal Distribution ,Ascorbic Acid ,medicine.disease_cause ,Statistics, Nonparametric ,4-Hydroxynonenal ,Pathogenesis ,Lipid peroxidation ,chemistry.chemical_compound ,Degenerative disease ,Alzheimer Disease ,Internal medicine ,Malondialdehyde ,medicine ,Humans ,Sulfhydryl Compounds ,Chromatography, High Pressure Liquid ,Aged ,Aged, 80 and over ,Aldehydes ,Psychological Tests ,business.industry ,Case-control study ,General Medicine ,Middle Aged ,medicine.disease ,Oxidative Stress ,Endocrinology ,Nutrition Assessment ,chemistry ,Spectrophotometry ,Case-Control Studies ,Linear Models ,Female ,Alzheimer's disease ,business ,Oxidative stress ,Biomarkers - Abstract
Oxidative stress is thought to play a major role in the pathogenesis of Alzheimer's disease (AD). Although there is strong post-mortem and experimental evidence of oxidative damage occurring in AD brains, the use of markers in the peripheral circulation to show oxidative stress is less convincing. We examined plasma from AD patients for markers of increased oxidative stress. We report elevated levels of 4-hydroxy-nonenal (4-HNE) in AD patients compared to controls (median 20.6, IQR 6.0-25.2 vs. 7.8, 3.3-14.5 micomol/l, respectively; p=0.001) but not malondialdehyde (MDA), and lower levels of ascorbate in AD plasma when compared to age-matched controls (9.9, 6.0-33.7 vs. 24.2, 13.9-48.6 micromol/l; p
- Published
- 2001
12. Differences in type II collagen degradation between peripheral and central cartilage of rat stifle joints after cranial cruciate ligament transection
- Author
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R. Clark Billinghurst, Reinout Stoop, Peter M. Van Der Kraan, Anthony Peter Hollander, Pieter Buma, A. Robin Poole, and Wim B. van den Berg
- Subjects
The importance of collagen destruction in irreversible cartilage damage in arthritis and arthrosis ,Pathology ,medicine.medical_specialty ,biology ,Chemistry ,Cartilage ,Immunology ,Pathogenese en behandeling [Chronische arthritis] ,Type II collagen ,Osteoarthritis ,medicine.disease ,Chondrocyte ,Pathogenesis and treatment [Chronic arthritis] ,Cruciate ligament ,Collagen, type I, alpha 1 ,medicine.anatomical_structure ,Het belang van collageenafbraak bij irreversibele kraakbeendestructie in arthritis en osteoarthrose ,Rheumatology ,Proteoglycan ,medicine ,Collagenase ,biology.protein ,Immunology and Allergy ,Pharmacology (medical) ,medicine.drug - Abstract
Objective. Type II collagen degradation is thought to be the key process in cartilage degradation during the development of osteoarthritis (OA). In this study, we investigated the kinetics of type II collagen degradation during surgically induced OA. Methods. Experimental OA was induced in male Wistar rats by transecting the cranial (anterior) cruciate ligament (CCL). Hematoxylin and eosin staining was used to study overall cartilage degradation, while immunostained sections were used to demonstrate denatured type II collagen (Col2-3/4m antibody) and the collagenase cleavage site in type II collagen (Col2-3/ 4Cshort antibody). Results. During the first 3‐4 weeks, cartilage destruction, associated with chondrocyte death, proteoglycan depletion, and a marked increase in the collagenase cleavage neoepitope, was mainly located at the margins of the cartilage. From weeks 3‐4, the central part of the cartilage showed increased surface fibrillation and apparent chondrocyte death. In these areas, increased denatured type II collagen staining but little cleavage-site staining was present. Conclusion. These results indicate that cartilage degradation after CCL transection in the rat consists of 2 phases. An early phase located at the cartilage margins and a late phase located at the central part of the cartilage. In the early phase, collagenase-dependent cartilage damage occurred. During the late phase, the level of type II collagen denaturation increased.
- Published
- 2000
13. Steatorrhoea and pancreatic dysfunction secondary to severe hyperthyroidism
- Author
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A B Stevens, Anthony Peter Passmore, and A. J. Taggart
- Subjects
Adult ,endocrine system ,medicine.medical_specialty ,Pathology ,Malabsorption ,endocrine system diseases ,business.industry ,Pancreatic Diseases ,General Medicine ,medicine.disease ,Gastroenterology ,Hyperthyroidism ,Pathophysiology ,Celiac Disease ,Thyroid dysfunction ,Internal medicine ,Female patient ,medicine ,Humans ,Female ,business - Abstract
Thyroid dysfunction is commonly associated with gastrointestinal abnormalities but the pathophysiology is incompletely understood. We describe a female patient with malabsorption and severe pancreatic dysfunction, both of which improved with the treatment of her hyperthyroidism.
- Published
- 1986
14. Oxford Colour Atlases of Pathology (Book Review).
- Author
-
Anthony, Peter
- Subjects
- *
PATHOLOGY , *NONFICTION - Abstract
Reviews the book 'Oxford Colour Atlases of Pathology. 'Colour Atlas of Liver Pathology,' by R.S., Patrick.
- Published
- 1983
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