A5086179668- Neuroinflammation and Neurodegeneration Mechanisms
- Bladder and Urothelial Cancer Treatments
- Urological Disorders and Treatments
- Multiple Sclerosis Research Studies
- interferon and immune responses
- Reproductive System and Pregnancy
- MicroRNA in disease regulation
- Urinary and Genital Oncology Studies
- Bone health and treatments
- Systemic Lupus Erythematosus Research
- Prostate Cancer Treatment and Research
- Macrophage Migration Inhibitory Factor
- Cytokine Signaling Pathways and Interactions
- Extracellular vesicles in disease
- Healthcare Policy and Management
- Diverticular Disease and Complications
- Ureteral procedures and complications
- RNA Research and Splicing
- Pediatric Urology and Nephrology Studies
- RNA regulation and disease
- Immunotherapy and Immune Responses
- Cancer-related molecular mechanisms research
- Animal Behavior and Welfare Studies
- Nuclear Receptors and Signaling
- Neurogenesis and neuroplasticity mechanisms
Cleveland Clinic Lerner College of Medicine
2019-2025
Cleveland Clinic
2020-2024
Corgenix (United States)
2024
Emory University
2022-2024
Kent State University
2020-2024
University of Bristol
2019-2024
Lucile Packard Children's Hospital
2024
The Ohio State University
2008-2023
Case Western Reserve University
2023
University of North Carolina at Chapel Hill
2023
Th cell programming and function is tightly regulated by complex biological networks to prevent excessive inflammatory responses autoimmune disease. The importance of microRNAs (miRNAs) in this process highlighted the preferential Th1 polarization Dicer-deficient T cells that lack miRNAs. Using genetic knockouts, we demonstrate loss endogenous miR-29, derived from miR-29ab1 genomic cluster, results unrestrained T-bet expression IFN-γ production. miR-29b regulates via a direct interaction...
Multiple sclerosis (MS) is characterized by episodes of inflammatory demyelination with progressive failure remyelination. Prior studies using murine models MS indicate that remyelination within the adult central nervous system (CNS) requires expression and activity TNFR2 CXCR4 oligodendrocyte progenitor cells (OPCs), promoting their proliferation differentiation into mature oligodendrocytes. Here, we extend these examining role in ligand, CXCL12, corpus callosum (CC) during cuprizone (CPZ)...
Type I IFNs promote cellular responses to viruses, and IFN receptor (IFNAR) signaling regulates the of endothelial cells blood-brain barrier (BBB) during neurotropic viral infection. However, role astrocytes in innate immune BBB infection CNS remains be fully elucidated. Here, we have demonstrated that type IFNAR permeability protects cerebellum from immunopathology. Mice with astrocyte-specific loss showed decreased survival after West Nile virus Accelerated mortality was not due expanded...
Summary— Several indirect biochemical indices of bone resorption are increased in patients with carcinoma the prostate and skeletal metastases. We have examined histological biopsies from affected patients. Bone‐forming surfaces active osteoblast numbers were sites adjacent to tumour tissue significantly at tumour. Contrary expectation, also distant These findings suggest that prostatic cancer induces generalised loss trabecular which may minimise disturbances plasma calcium homeostasis but...
Abstract Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that associated with clinical worsening and relapses in multiple sclerosis (MS) patients. The mechanism through which MIF promotes MS progression remains undefined. In this study, we identify critical role for regulating CNS effector mechanisms necessary the development of inflammatory pathology mouse model MS, experimental autoimmune encephalomyelitis (EAE). Despite ability to generate pathogenic myelin-specific...
Patients with a terminal illness, identified by palliative care teams working in Manchester, and patients attending heart failure clinic, were asked to participate prospective survey determine their main concerns. Data collected from 213 (PC) (mostly cancer) 66 (HF). The median ages of the two patient groups similar, but HF more likely be male living partner; 13% PC 7% reported that they had no carer. district nurse, hospice, social work physiotherapy input. most frequently troublesome...
A randomised control trial of intravesical instillation mitomycin C was conducted in 457 patients with cancer the bladder that confined to submucosa on histological examination. The events studied were recurrence free rate, rate/year, and number new tumours developing/year. At initial cystoscopy completely resected have no C, a single 40 mg ml water at cystoscopy, or then four further instillations. All had follow up cystoscopies every three months for first year, twice second yearly...
167 patients with T1 bladder transitional cell tumours treated by transurethral resection or cystodiathermy are reviewed. The overall crude survival was 83.2% in 3 years and 71.8% 5 years. 7.8% of the developed an invasive tumour these had unfavourable initial moderate poor differentiation high mitotic rate. High pleomorphism particularly unfavourable. Multiple did as well single ones but more them invasion lamina propria a larger number were either radiotherapy cystectomy.
Current treatment modalities for the neurodegenerative disease multiple sclerosis (MS) use disease-modifying immunosuppressive compounds but do not promote repair. Although several potential targets that may induce myelin production have been identified, there has yet to be an approved therapy promotes remyelination in damaged central nervous system (CNS). Remyelination of axons requires generation new oligodendrocytes from oligodendrocyte progenitor cells (OPCs). OPCs are detected MS...
Abstract During multiple sclerosis (MS), an inflammatory and neurodegenerative disease of the central nervous system (CNS), symptoms, outcomes are determined by location lesions. While we others have shown that T cell cytokines differentially regulate leukocyte entry into perivascular spaces regional parenchymal localization in murine models MS, molecular mechanisms this latter process poorly understood. Here, demonstrate astrocytes exhibit region‐specific responses to promote hindbrain...
Highlights•Astrocytes upregulate BATF2 in response to IFNγ•BATF2 binds chromatin sites upstream of IRF1 regulate its expression astrocytes•BATF2-deficient mice exhibit exacerbated clinical experimental autoimmune encephalomyelitis•The core chronic active multiple sclerosis lesions is enriched for astrocytic BATF2SummaryAstrocytic interferon (IFN)γ signaling associated with reduced neuroinflammation; however, downstream effectors responsible regulating this protection are unknown. Here, we...
Summary— Analytical flow cytometry was used to study circulating prostate specific antigen (PSA)‐positive cells in 40 consecutive patients with newly diagnosed, untreated cancer; 25 (63%) had metastatic disease confirmed by a positive bone scan. Cell suspensions were prepared for each patient from both the primary tumour and peripheral blood samples. The stained monoclonal antibody against PSA, analysed cytometry; PSA‐positive sorted according their immunofluorescence light scatter...
Abstract Background In early autoimmune neuroinflammation, interferon (IFN)γ and its upregulation of the immunoproteasome (iP) is pathologic. However, during chronic multiple sclerosis (MS), IFNγ has protective properties. Although dysregulation iP been implicated in neurodegeneration, function remains to be fully elucidated. Here, we demonstrate that signaling regional astrocytes induces promotes protection CNS autoimmunity. Methods a (MS) brain, evaluated mRNA expression labeled postmortem...