A5036652053- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- Vitamin C and Antioxidants Research
- Multiple Sclerosis Research Studies
- Vestibular and auditory disorders
- Neurogenetic and Muscular Disorders Research
- Retinoids in leukemia and cellular processes
- T-cell and B-cell Immunology
- Vasculitis and related conditions
- Cardiac Structural Anomalies and Repair
- Cytomegalovirus and herpesvirus research
- Folate and B Vitamins Research
- Metabolism and Genetic Disorders
- Facial Nerve Paralysis Treatment and Research
- Virology and Viral Diseases
- Vascular anomalies and interventions
- Cardiac electrophysiology and arrhythmias
- Mitochondrial Function and Pathology
- Cardiac Arrhythmias and Treatments
- Acne and Rosacea Treatments and Effects
- Platelet Disorders and Treatments
- Diagnosis and Treatment of Venous Diseases
- Sphingolipid Metabolism and Signaling
- Vitamin D Research Studies
- Autoimmune Neurological Disorders and Treatments
Novartis (Switzerland)
2014-2024
Roche (Switzerland)
2023-2024
Novartis Institutes for BioMedical Research
2013-2022
Ludwig-Maximilians-Universität München
2003-2014
Gold Skin Care Center
2011
Novartis (China)
2011
University of Utah
1999-2008
University College London
2005-2007
Biogen (United States)
2004
Max Planck Institute of Neurobiology
2004
Understanding the mechanisms of immune cell migration to multiple sclerosis lesions offers significant therapeutic potential. This study focused on chemokines CXCL12 (SDF-1) and CXCL13 (BCA-1), both which regulate B in lymphoid tissues. We report that immunohistologically was constitutively expressed CNS parenchyma blood vessel walls. In active chronic inactive protein elevated detected astrocytes vessels. Quantitative PCR demonstrated produced actively demyelinating lesions, but not or...
We report that B cell–activating factor of the tumor necrosis (TNF) family (BAFF) is expressed in normal human brain at ∼10% lymphatic tissues (tonsils and adenoids) produced by astrocytes. BAFF was regularly detected enzyme-linked immunosorbent assay tissue lysates spinal fluid, astrocytes double fluorescence microscopy. Cultured secreted functionally active after stimulation with interferon-γ TNF-α via a furin-like protease-dependent pathway. secretion per cell manifold higher activated...
Vestibular neuritis is the second most common cause of peripheral vestibular vertigo. Its assumed a reactivation herpes simplex virus type 1 infection. Therefore, corticosteroids, antiviral agents, or combination two might improve outcome in patients with neuritis.We performed prospective, randomized, double-blind, two-by-two factorial trial which acute were randomly assigned to treatment placebo, methylprednisolone, valacyclovir, methylprednisolone plus valacyclovir. function was determined...
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset Parkinson's disease (PD), but the underlying pathophysiological mechanisms and normal function of this large multidomain protein remain speculative. To address role vivo, we generated three different LRRK2 mutant mouse lines. Mice completely lacking (knock-out, KO) showed an early-onset (age 6 weeks) marked increase number size secondary lysosomes kidney proximal tubule cells lamellar bodies lung type II cells. expressing a...
Huntington's Disease (HD) is a progressive neurodegenerative disorder caused by CAG trinucleotide repeat expansions in exon 1 of the huntingtin (HTT) gene. The mutant HTT (mHTT) protein causes neuronal dysfunction, causing motor, cognitive and behavioral abnormalities. Current treatments for HD only alleviate symptoms, but cerebral spinal fluid (CSF) or central nervous system (CNS) delivery antisense oligonucleotides (ASOs) virus vectors expressing RNA-induced silencing (RNAi) moieties...
Herpes simplex virus type 1 (HSV‐1) enters sensory neurons and can remain latent there until reactivation. During latency restricted HSV‐1 gene expression takes place in the form of latency‐associated transcripts (LAT). LAT has been demonstrated to be important not only for but also reactivation, which may cause cranial nerve disorders. Tissue sections trigeminal ganglia (TG), geniculate (GG), vestibular (VG) from seven subjects were examined presence using situ hybridization technique. was...
Major human pathologies are caused by nuclear replicative viruses establishing life-long latent infection in their host. During latency the genomes of these intimately interacting with cell nucleus environment. A hallmark herpes simplex virus type 1 (HSV-1) establishment is shutdown lytic genes expression and concomitant induction associated (LAT) transcripts. Although setting up maintenance genetic program most likely dependent on a subtle interplay between viral factors, this remains...
The constitutive androstane receptor (CAR) and the pregnane X (PXR) are closely related nuclear receptors involved in drug metabolism play important roles mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences receptor-dependent mechanisms underlying liver tissue molecular responses PB. Early late transcriptomic sustained PB exposure were investigated from double knock-out...
Abstract Melanocytes of the hair follicle produce melanin and are essential in determining differences color. Pigment cell-specific MELanocyte Protein (PMEL17) plays a crucial role melanogenesis. One critical steps is amyloid-like functional oligomerization PMEL17. Beta Site APP Cleaving Enzyme-2 (BACE2) γ-secretase have been shown to be key players generating proteolytic fragments The β-secretase (BACE1) responsible for generation amyloid-β (Aβ) brain therefore proposed as therapeutic...
In this study we compared the activation of monocytes by different bacterial products via Toll-like receptors (TLR), and proinflammatory mediators. response to TLR-2, -4 -5 engagement, approximately 50% produced TNF-alpha, only 5% after induction with IFN-gamma or GM-CSF. Furthermore, a small proportion IL-10 stimulation TLR, but not cytokines. Both TLR-ligands inflammatory cytokines induced expression CD25, CD69, CD80 and, surprisingly, also CD83, commonly regarded as an marker for mature...
Theiler's murine encephalomyelitis virus (TMEV) infection and relapsing‐remitting experimental allergic (R‐EAE) have been used to investigate the viral autoimmune etiology of multiple sclerosis (MS), a possibleTh1‐type mediated disease. DNA immunization is novel vaccination strategy in which few harmful effects reported. Bacterial oligodeoxynucleotides, contain CpG motifs, reported enhance immunostimulation. Our objectives were two‐fold: first, ascertain whether plasmid DNA, pCMV, widely as...
We examined 103 patients with vestibular neuritis (VN) in a follow-up study (5.7 to 20.5 years, mean 9.8 years). Two (1.9%) had developed second occurrence of VN 29 39 months after the first. affected contralateral ear both and caused less severe distressing vertigo postural imbalance. Unlike Bell's palsy sudden hearing loss, relapse same did not occur.
MicroRNAs are short non-coding RNAs that regulate gene expression at the post-transcriptional level and play key roles in heart development cardiovascular diseases. Here, we have characterized distribution of microRNAs across eight cardiac structures (left right ventricles, apex, papillary muscle, septum, left atrium valves) rat, Beagle dog cynomolgus monkey using microRNA sequencing. Conserved signatures enriched specific these species were identified for valve (miR-let-7c, miR-125b,...
The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the sequence pathological at early stages phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, proteins) mouse 13 weeks PB treatment revealed progressive increases hepatic expression long noncoding RNAs miRNAs originating from...
Retinoic-acid-orphan-receptor-C (RORC) is a master regulator of Th17 cells, which are pathogenic in several autoimmune diseases. Genetic Rorc deficiency mice, while preventing autoimmunity, causes early lethality due to metastatic thymic T cell lymphomas. We sought determine whether pharmacological RORC inhibition could be an effective and safe therapy for diseases by evaluating its effects on functions intrathymic development. inhibitors effectively inhibited differentiation IL-17A...
Multiple sclerosis (MS) can be divided into 4 clinical forms: relapsing‐remitting (RR), primary progressive (PP), secondary (SP), and relapsing (PR). Since PP‐MS is notably different from the other forms of MS, both clinically pathologically, question arises whether immunologically similar to forms. The pathogenesis remains unclear, partly due a lack highly relevant animal models. Using an encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG) 92–106 , we have established models...
Abstract Herpes simplex virus type‐1 latency and CD8+ T‐cell occurrence were investigated in the trigeminal, geniculate, vestibular ganglia from seven deceased humans. The HSV‐1 “latency‐associated transcript” was assessed by situ hybridization quantitative RT‐PCR. Infiltration of T cell detected immunohistochemistry data show that infiltration are not solely confined to trigeminal but can also occur other cranial along neuroaxis. However, transcripts geniculate expressed at a very low...
Immunoglobulin-like transcript (ILT) 3 and 4 are inhibitory receptors that modulate immune responses. Their expression has been reported to be affected by interferon, offering a possible mechanism which this cytokine exerts its therapeutic effect in multiple sclerosis, condition thought involve excessive activity. To investigate possibility, we measured of ILT3 ILT4 on cells from sclerosis patients, post-mortem brain tissue. We also studied the ability interferon beta, alone or combination...
Reactivation of herpes simplex virus type 1 (HSV-1) in the vestibular ganglion (VG) is suspected cause neuritis (VN). Recent studies reported presence HSV-1 DNA not only human VGs but also nuclei, a finding that indicates possibility viral migration to labyrinth. Distribution was determined geniculate ganglia, VGs, semicircular canals, and macula organs 21 randomly obtained temporal bones by nested PCR. Viral detected 48% labyrinths, 62% 57% ganglia. The potential significance this twofold:...
Herpes simplex type 1 (HSV-1) is a neurotropic virus which establishes lifelong latency in human trigeminal ganglia (TG). Currently, two nonexclusive control mechanisms of HSV-1 are discussed: antiviral CD8(+) T cells and viral microRNAs (miRNAs) encoded by the associated transcript (LAT). We investigate here to what extent these may contribute maintenance latency. show that only small proportion LAT(+) neurons surrounded TG. This indicates TG might be controlled other such as miRNAs....