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ABSTRACT: The genesis and appropriate treatment of neuroinflammation in various infectious and non-infectious disorders of the central nervous system is still a matter of debate. We introduce an alternative and simple experimental model for the investigation of the cellular inflammatory response to bacterial antigens by stereotactic intracerebral injection of heat-inactivated Staphylococcus epidermidis (HISE). HISE-injection resulted in well-circumscribed intraparenchymal deposits encompassed by an early micro- and astroglial response and a selective but sustained opening of the blood-brain barrier (BBB). After 24h, the HISE collections were densely infiltrated by granulocytes and few circumjacent macrophages that became the predominating immunocompetent cell type from day 4 on. CD8a+ lymphocytes peaked at day 4, whereas CD4+ and CD20+ lymphocytes increased gradually in number, developing a scattered infiltrate until day 17, indicating the initiation of an adaptive immune response. MHC class II presenting cells were abundantly recruited from day 1 and eventually shaped an increasingly dense accumulation within the lesion. Intracerebral HISE administration provides a controlled, highly reproducible and well defined influx of immunocompetent cells across the BBB leading to a distinct and condensed inflammatory reaction. The technique is straightforward, easily feasible and may significantly enable further investigations of the initiation, maintenance and therapeutic modulation of acute neuroinflammation.
Journal of neuroscience methods 09/2011; 203(1):89-95. · 2.30 Impact Factor
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ABSTRACT: Using TNF receptor 1 knock out (TNFR1KO) mice, we investigated the role played by TNFR1 in immune regulation during neonatal listeriosis. Induction of protective immune response in wild type pups resulted in the prompt control of infection with an attenuated DeltaactA mutant Listeria monocytogenes, accompanied by enhanced hepatic expression of mRNA for IFN-gamma, TNF-alpha, and IL-10. Conversely, the lack of TNFR1 signalling in TNFR1KO neonatal mice resulted in substantial changes in the profile of inflammatory mediators and ultimately fatal outcome of the infected pups. Despite remarkable increase in indoleamine 2, 3-dioxygenase (IDO) and inducible nitric oxide synthase (iNOS) mRNA detected in the liver of TNFR1KO mice, bacterial proliferation was unrestrained. Increased mRNA expression of IDO, iNOS, TNF-alpha, IFN-gamma, MCP-1, and MIP-1alpha was found in the spleens of infected KO mice, and in the brains mRNA encoding iNOS, IDO, IFN-gamma, IL-12p40, IL-10, and RANTES was also upregulated. Large necrotic lesions consisting of granulocytes and macrophages were scattered throughout the liver of these mice. TNFR1KO neonates were unable to clear neutrophils and switch from the innate immune response to a specific reaction mediated by T cells. These results prove that TNF-alpha signalling is crucial and irreplaceable in antilisterial protection during the neonatal period.
Microbial Pathogenesis 10/2010; 49(4):186-95. · 1.94 Impact Factor
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ABSTRACT: Despite the significance of hypertrophy of the ligamentum flavum (HLF) in the disease progress of neurogenic claudication, the cellular mechanisms underlying the gradual fibrotic thickening of the ligamentum flavum remain poorly understood. The aim of our study was to get insight into the contribution of inflammatory mechanisms to the development of hypertrophy.
Specimens of hypertrophied ligamenta flava were obtained at surgery from 20 patients with acquired lumbar osteoligamentous spinal canal stenosis from the central part of the ligament. Paraffin sections were stained with hematoxylin and eosin and Elastica van Gieson to evaluate extracellular matrix architecture, and immunohistochemistry was performed to characterize the inflammatory reaction and the sources of transforming growth factor beta (TGF-β) expression. Sections of normal ligamenta flava obtained from corresponding anatomical sites and stained in parallel served as a control.
HLF was characterized by a considerable distortion of the elastic matrix and fibrotic transformation by extracellular collagen deposition. All specimens showed highly inflammatory cellular infiltrates confined to regions exhibiting marked degeneration of the elastic matrix composed mainly of macrophages, scattered T lymphocytes, and neovascularization, thus representing a chronic inflammation. Surprisingly, macrophages as well as vascular endothelial cells but not fibroblasts showed a strong expression of TGF-β, a strong inducer of extracellular collagen deposition.
Macrophages were identified as a major cellular source of TGF-β in advanced HLF and may perpetuate further hypertrophy. This finding suggests that modulating the immune response locally or systemically could prove to be effective for impeding the disease progress.
Acta Neurochirurgica 10/2010; 153(1):134-41. · 1.52 Impact Factor
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ABSTRACT: The objective of this work was to present possible, though rare, complications of Neuro-Patch implantation after brain surgery.
Two patients, aged 62 and 63 years, who had a partial dural substitution with an artificial polyurethane graft after neurosurgical resection of a gross tumour, are presented.
In the two patients, the a-vital tissue was infiltrated by either inflammatory or neoplastic tissue respectively.
This report demonstrates a new pathological point of view in using synthetic materials for the reconstruction of dural defects.
Acta Neurochirurgica 04/2009; 151(7):833-5. · 1.52 Impact Factor
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Marek Molcanyi,
Peter Riess,
Nadia Nabil Haj-Yasein,
Kristine Bentz,
Mario Loehr,
Johannes Kuchta,
Jozef Zivcak, Werner Stenzel,
Hrvoje Miletic,
Jurgen Hescheler,
Edmund Neugebauer,
Jurgen Anton Hampl,
Ralf-Ingo Ernestus,
Ute Schafer
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ABSTRACT: Although engraftment of undifferentiated pluripotent embryonic stem cells (ESCs) into the injured central nervous system (CNS) may lead to targeted cell replacement of lost/damaged cells, sustained proliferative activity combined with uncontrolled differentiation of implanted cells presents a risk of tumor formation. As tumorigenic potential is thought to be associated with pluripotency of embryonic stem cells, pre-differentiation may circumvent this problem. Recently, it has been demonstrated that tumorigenesis occurs despite pre-differentiation if the neural precursor cells are implanted into the brain of a homologous animal (e.g., mouse to mouse). However, xenotransplantation (e.g., mouse to rat) without pre-differentiation, lead to the development of healthy neuronal cells, in absence of tumor formation, suggesting that tumor-suppressive effects of host tissue on engrafted ESCs may play a role in transplant tumorigenesis. We critically investigated tumorigenesis and possible mechanisms of anticipated tumor-suppressive effect under conditions analogous to previously published studies. Xenotransplantation of D-3 murine ESCs into uninjured adult rat brains lacking any preliminary inflammatory potential was found to lead to tumor formation in 5 out of 8 of animals within 2 weeks postimplantation. Tumor-suppressive effects, reflected by Erdo et. al could possibly be ascribed to immunomodulatory activity of macrophages scavenging the tumorigenic fraction of the implanted cells. The importance of number of engrafted cells, implantation site and immunosuppressive effects are discussed as possible variables determining tumorigenic outcome after ESC transplantation.
Cellular Physiology and Biochemistry 02/2009; 24(1-2):87-94. · 2.86 Impact Factor
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Brain Pathology 11/2008; 18(4):598-601. · 3.99 Impact Factor
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ABSTRACT: To identify basic mechanisms of how infections may induce a neuron-specific autoimmune response, we generated mice expressing OVA as neuronal autoantigen under control of the neuron-specific enolase promoter (NSE-OVA mice). Intracerebral, but not systemic, infection with attenuated Listeria monocytogenes-secreting OVA induced an atactic-paretic neurological syndrome in NSE-OVA mice after bacterial clearance from the brain, whereas wild-type mice remained healthy. Immunization with attenuated Listeria monocytogenes-secreting OVA before intracerebral infection strongly increased the number of intracerebral OVA-specific CD8 T cells aggravating neurological disease. T cell depletion and adoptive transfer experiments identified CD8 T cells as decisive mediators of the autoimmune disease. Importantly, NSE-OVA mice having received OVA-specific TCR transgenic CD8 T cells developed an accelerated, more severe, and extended neurological disease. Adoptively transferred pathogenic CD8 T cells specifically homed to OVA-expressing MHC class I(+) neurons and, corresponding to the clinical symptoms, approximately 30% of neurons in the anterior horn of the spinal cord became apoptotic. Thus, molecular mimicry between a pathogen and neurons can induce a CD8 T cell-mediated neurological disease, with its severity being influenced by the frequency of specific CD8 T cells, and its induction, but not its symptomatic phase, requiring the intracerebral presence of the pathogen.
The Journal of Immunology 06/2008; 180(12):8421-33. · 5.79 Impact Factor
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ABSTRACT: Toll-like receptors (TLRs) play central roles in the innate reaction to bacterial products and transmit specific immune responses against these pathogens. TLRs are expressed on numerous cell types, including innate immune cells, and on astrocytes, neurons, and microglial cells of the central nervous system (CNS). Lipoproteins and lipopolysaccharides are specifically recognized by TLR2 and TLR4, respectively. We examined the in vivo role of TLR2 and TLR4 in Staphylococcus aureus-induced brain abscess. Phenotypically, 87% of TLR2(-/-) mice and 43% of TLR4(-/-) mice died whereas all wild-type (WT) mice recovered. Clearance of bacteria from the CNS was significantly delayed in TLR2(-/-) mice compared with TLR4(-/-) and WT animals. Recruitment of granulocytes and macrophages to the CNS, as well as microglial activation and expansion, was up-regulated in TLR2(-/-) mice. Although inflammation persisted especially in the CNS of TLR2(-/-) mice, but also of TLR4(-/-) mice, WT mice terminated the infection more effectively. Collectively, these data show that the immune response to experimental S. aureus-induced brain abscess depends crucially on the recognition of S. aureus by TLR2 but that TLR4 is also required for an optimal intracerebral immune response in this disorder.
American Journal Of Pathology 02/2008; 172(1):132-45. · 4.89 Impact Factor
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ABSTRACT: Lentiviral vectors pseudotyped with glycoproteins of the lymphocytic choriomeningitis virus (LCMV-GP) are promising candidates for gene therapy of malignant glioma, as they specifically and efficiently transduce glioma cells in vitro and in vivo. Here, we evaluated the therapeutic efficacy of LCMV-GP and vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped vectors.
Therapeutic efficacy was tested for unmodified (9L) and DsRed-modified (9LDsRed) gliomas using the suicide gene thymidine kinase of the herpes simplex virus type 1 (HSV-1-tk). Positron emission tomography (PET) and magnetic resonance imaging were done to analyze transduction of tumors and monitor therapeutic outcome.
LCMV-GP pseudotypes mediated a successful eradication of 9LDsRed tumors with 100% of long-term survivors. Before initiation of ganciclovir treatment, a strong HSV-1-tk expression within the tumor was detected by noninvasive PET using the tracer 9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine. Therapeutic outcome was successfully monitored by magnetic resonance imaging and PET imaging and correlated with the histopathologic data. In the 9L model, LCMV-GP and VSV-G pseudotyped lentiviral vectors displayed similar therapeutic efficacy. Further studies revealed that normal brain cells transduced with VSV-G pseudotypes were not eliminated by ganciclovir treatment and contributed significantly to the bystander killing of tumor cells.
Suicide gene transfer using pseudotyped lentiviral vectors was very effective in the treatment of rat glioma and therefore is an attractive therapeutic strategy also in human glioblastoma especially in conjunction with an imaging-guided approach. In addition, high selectivity of gene transfer to tumor cells may not always be desirable for therapeutic genes that exert a clear bystander effect.
Clinical Cancer Research 12/2007; 13(22 Pt 1):6761-8. · 7.74 Impact Factor
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Brain Pathology 08/2007; 17(3):333-4. · 3.99 Impact Factor
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Hrvoje Miletic,
Yvonne Fischer,
Sara Litwak,
Tsanan Giroglou,
Yannic Waerzeggers,
Alexandra Winkeler,
Huongfeng Li,
Uwe Himmelreich,
Claudia Lange, Werner Stenzel,
Martina Deckert,
Harald Neumann,
Andreas H Jacobs,
Dorothee von Laer
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ABSTRACT: Adult stem cells are promising cellular vehicles for therapy of malignant gliomas as they have the ability to migrate into these tumors and even track infiltrating tumor cells. However, their clinical use is limited by a low passaging capacity that impedes large-scale production. In the present study, a bone marrow-derived, highly proliferative subpopulation of mesenchymal stem cells (MSCs)-here termed bone marrow-derived tumor-infiltrating cells (BM-TICs)-was genetically modified for the treatment of malignant glioma. Upon injection into the tumor or the vicinity of the tumor, BM-TICs infiltrated solid parts as well as the border of rat 9L glioma. After intra-tumoral injection, BM-TICs expressing the thymidine kinase of herpes simplex virus (HSV-tk) and enhanced green fluorescent protein (BM-TIC-tk-GFP) were detected by non-invasive positron emission tomography (PET) using the tracer 9-[4-[(18)F]fluoro-3-hydroxymethyl)butyl]guanine ([(18)F]FHBG). A therapeutic effect was demonstrated in vitro and in vivo by BM-TICs expressing HSV-tk through bystander-mediated glioma cell killing. Therapeutic efficacy was monitored by PET as well as by magnetic resonance imaging (MRI) and strongly correlated with histological analysis. In conclusion, BM-TICs expressing a suicide gene were highly effective in the treatment of malignant glioma in a rat model and therefore hold great potential for the therapy of malignant brain tumors in humans.
Molecular Therapy 08/2007; 15(7):1373-81. · 6.87 Impact Factor
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ABSTRACT: Early clinical trials for gene therapy of human gliomas with retroviral packaging cells (PC) have been hampered by low transduction efficacy and lack of dissemination of PC within the tumor. In the current approach, these issues have been addressed by creating a stable packaging cell line for retroviral vectors pseudotyped with glycoproteins of lymphocytic choriomeningitis virus (LCMV) based on tumor-infiltrating progenitor cells.
Tumor-infiltrating progenitor cells, which had been isolated from adult rat bone marrow (BM-TIC), were modified to stably express Gag-Pol proteins of moloney murine leukemia virus (Mo-MLV) and glycoproteins of LCMV. Packaging of a retroviral vector was measured by titration experiments on human fibroblast cells as well as on mouse and human glioma cell lines. Additionally, gene transfer was tested in a rat glioma model in vivo.
The BM-TIC-derived packaging cell line (BM-TIPC) produced retroviral vectors with titers between 2-8 x 10(3) transducing units (TU)/ml. Extended culturing of BM-TIPC over several weeks and freezing/thawing of cells did not affect vector titers. No replication-competent retrovirus was released from BM-TIPC. In a rat glioma model, BM-TIPC infiltrated the tumors extensively and with high specificity. Moreover, BM-TIPC mediated transduction of glioma cells in vivo.
This proof-of-principle study shows that primary adult progenitor cells with tumor-infiltrating capacity can be genetically modified to stably produce retroviral LCMV pseudotype vectors. These BM-TIPC may be a useful tool to enhance specificity and efficacy of gene transfer to gliomas in patients.
The Journal of Gene Medicine 06/2007; 9(5):335-44. · 2.48 Impact Factor
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ABSTRACT: Lymphomatoid granulomatosis (LYG) is a rare systematic lymphoproliferative disorder of uncertain etiology. We present a rare case of isolated cerebral LYG developing in an HIV-1-infected patient after initiation of highly active antiretroviral therapy (HAART).
The Journal of infection 04/2007; 54(3):e175-8. · 4.13 Impact Factor
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ABSTRACT: Extensive epidural fibrosis after lumbar spine surgery might be an important underlying cause of failed-back syndrome. Based on previously obtained data, the effect of mitomycin C (MMC) in a concentration of 0.1 mg/ml on spinal epidural fibrosis in a rat laminectomy model was investigated in a large series.
Eighty adult Wistar rats underwent lumbar laminectomy. In 40 rats, MMC in a concentration of 0.1 mg/ml was locally applied to the laminectomy sites. No similar treatment was performed in the other 40 rats. At intervals from one to 12 weeks after laminectomy, both macroscopic and histological evaluations were performed. For radiological investigation, 10 rats underwent magnetic resonance (MR) imaging at 6 weeks postoperatively. Furthermore, the concentration of MMC in cerebrospinal fluid (CSF) and serum was determined 12 hours postoperatively in seven rats. Due to ease of absorption, high levels of MMC were rapidly detectable in serum, whereas the values obtained from the CSF were markedly lower. In the majority of MMC-treated laminectomy sites, epidural scarring was significantly reduced and dural adhesions were absent, in comparison with control sites (p < 0.001), as confirmed by MR images. Accordingly, the macroscopic dissection of epidural fibrous tissue to reexpose the dura mater was performed more easily and without severe bleeding in these rats. The healing of skin and the lumbar fascia was not affected, and dural leakage was not observed. All control sites showed dense epidural fibrosis with marked dural adherence.
In this experimental model, it was shown that locally applied MMC in a concentration of 0.1 mg/ml effectively reduces epidural fibrosis and dural adherence without side effects in rats that underwent lumbar laminectomy.
Journal of Neurosurgery Spine 07/2006; 5(1):53-60. · 1.53 Impact Factor
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ABSTRACT: Extensive peridural fibrosis after lumbar spine surgery may contribute to poor outcome and recurrent symptoms leading to repeated operation. Secondary procedures are considerably hampered by the presence of scar tissue. Moreover, after excision of the peridural scar, the fibrous tissue may recur, leading to unsuccessful surgical outcome. Mitomycin C (MMC), an alkylating antibiotic substance isolated from Streptomyces caespitosus, potentially suppresses fibroblast proliferation after surgical intervention. The authors investigated the effect of MMC on the reformation of epidural fibrosis in a laminectomy model in rats.
Twenty-four Wistar rats underwent a repeated lumbar laminectomy 3 months after the first operation. In 12 rats, MMC in a concentration of 1 mg/ml was locally applied to the laminectomy site. No treatment was performed in the control group of the other 12 rats. All rats underwent clinical evaluation. Mobility ratings and any evidence of neurological deficit were recorded. Twelve weeks after the second operation, the animals were killed for histological examination. The extent of epidural fibrosis and dural adherence was evaluated. All MMC-treated animals showed reduced epidural scarring, compared with the control group. In nine MMC-treated rats (75%), dural adhesions were moderate. In contrast, all control sites showed dense epidural fibrosis with marked dural adherence. No side effects of the treatment were observed.
In this experimental study, MMC in a concentration of 1 mg/ml locally applied significantly reduced recurrence of epidural fibrosis and dural adhesions without any side effects after repeated spinal surgery in a laminectomy model in rats.
Journal of Neurosurgery Spine 05/2006; 4(4):329-33. · 1.53 Impact Factor
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Hrvoje Miletic,
Yvonne Fischer,
Tsanan Giroglou,
Sara Litwak,
Sandra Winkeler,
Uwe Himmelreich, Werner Stenzel,
Martina Deckert,
Andreas H. Jacobs,
Harald Neumann,
Dorothee von Laer
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ABSTRACT: Molecular Therapy (2006) 13, S25|[ndash]|S25; doi: 10.1016/j.ymthe.2006.08.074
59. Targeted Gene Therapy of Malignant Glioma with Adult Stem Cells
Hrvoje Miletic1, Yvonne Fischer2, Tsanan Giroglou2, Sara Litwak3, Sandra Winkeler4, Uwe Himmelreich5, Werner Stenzel1, Martina Deckert1, Andreas H. Jacobs4, Harald Neumann3 and Dorothee von Laer21Abteilung f|[uuml]|r Neuropathologie, Universit|[auml]|t zu K|[ouml]|ln, K|[ouml]|ln, Germany2Georg-Speyer-Haus, Frankfurt am Main, Germany3Neural Regeneration Unit, Institute of Reconstructive Neurobiology, Bonn, Germany4Labor f|[uuml]|r Gentherapie und Molekulares Imaging, Max-Planck-Institut f|[uuml]|r Neurologische Forschung, K|[ouml]|ln, Germany5Labor f|[uuml]|r Kernspintomographie, Max-Planck-Institut f|[uuml]|r Neurologische Forschung, K|[ouml]|ln, Germany
Molecular Therapy 04/2006; · 6.87 Impact Factor
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ABSTRACT: A characteristic of brain abscess is a localized suppurative infection leading to substantial damage of the adjacent central nervous system tissue. The orchestrated interplay of pro- and antiinflammatory cytokines released by leukocytes as well as resident cells of the central nervous system is crucial for both an effective host defense and for limiting tissue damage in brain abscess. To study the regulatory role of interleukin (IL)-10 in brain abscess in vivo, IL-10-deficient (IL-10(0/0)) mice were stereotaxically infected with Staphylococcus aureus-laden agarose beads. Increased numbers of intracerebral (IC) granulocytes, macrophages, CD4+ and CD8+ T cells, and higher levels of TNF, IL-1beta, and iNOS were observed in IL-10(0/0) mice than in wild-type mice, whereas chemokines were induced earlier and more pronounced in wild-type mice. Together with prominent microvascular hemorrhage, necrotic vasculitis, severe brain edema, and markedly increased abscess size, these alterations led to an increased morbidity of IL-10(0/0) mice. Nevertheless, the hyperinflammatory response of IL-10(0/0) mice did not improve bacterial elimination. Collectively, these data outline the important role of IL-10 in vivo for the regulation of the IC host immune response in experimental S. aureus-induced brain abscess.
Journal of Neuropathology and Experimental Neurology 01/2006; 64(12):1046-57. · 4.26 Impact Factor
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Manuel Montesinos-Rongen,
Roland Schmitz,
Cornelius Courts, Werner Stenzel,
Dörte Bechtel,
Gerald Niedobitek,
Ingmar Blümcke,
Guido Reifenberger,
Andreas von Deimling,
Berit Jungnickel,
Otmar D Wiestler,
Ralf Küppers,
Martina Deckert
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ABSTRACT: Primary lymphomas of the central nervous system (PCNSLs) were investigated for their capacity to perform further maturation steps. We studied a series of 11 PCNSLs derived from immunocompetent patients for immunoglobulin (Ig) class switch recombination (CSR) by performing reverse transcriptase-polymerase chain reaction (RT-PCR) for transcripts of Ig constant region gene segments (IGHC). This analysis revealed exclusive transcription of IgM and IgD mRNA in the absence of IgG, IgA, or IgE transcription. This finding was corroborated at the protein level by the immunohistochemical demonstration of IgM on the surface of the tumor cells. The unexpected lack of CSR may be due to internal switch mu region deletions, which were detected in 7 of 11 cases. We also found that expression of activation-induced cytidine deaminase (AID), which is required for CSR and somatic hypermutation, was detectable by RT-PCR in 4 of 10 cases and by immunohistochemistry in one of three cases analyzed. This may indicate that ongoing somatic mutation, which is often observed in PCNSL, could be due to sustained AID expression in a fraction of cases and that intraclonal V gene diversity may occur in other cases at an earlier phase of tumor clone expansion, when AID may have been expressed.
American Journal Of Pathology 07/2005; 166(6):1773-9. · 4.89 Impact Factor
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ABSTRACT: Cerebral cavernous malformations (CCMs) are congenital vascular anomalies that can cause seizures, intracranial hemorrhages, focal neurological deficits, and migrainelike headaches. Magnetic resonance (MR) imaging has substantially facilitated diagnosis of CCM. It is now widely accepted that familial clustering with an autosomal dominant inheritance pattern should be suspected in cases of multiple lesions.
To determine by MR imaging the penetrance of cavernous malformations in a 3-generation family that included 5 members with typical clinical signs and diagnostic findings.
All family members underwent routine MR T1-weighted and T2-weighted spin-echo sequences in addition to MR T2-weighted gradient-echo sequences.
Four family members had been symptomatic with either brainstem bleeding, headaches, or focal neurological signs. The gradient-echo sequences yielded a dramatically higher sensitivity with regard to lesion number and distribution. As in previous reports of familial CCM, an increase in lesion number with increasing age, changes in lesion characteristics, de novo occurrence in serial MR imaging over time, and the phenomenon of anticipation could be confirmed in this family.
Magnetic resonance gradient-echo sequences should be considered the method of choice for diagnosis of familial CCM.
Archives of Neurology 05/2005; 62(4):653-8. · 7.58 Impact Factor
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ABSTRACT: The present study describes a new model of autoimmune neuritis in C57BL/6 mice induced by immunization with the novel neuritogenic epitope P0(106-125), derived from mouse peripheral myelin protein P0. Immunization with this peptide in combination with pertussis toxin induced high levels of peptide-specific CD4+ T cells in spleen and popliteal lymph nodes. Clinical symptoms of autoimmune neuritis started with a flaccid tail at day 10 postimmunization (p.i.), progressed to moderate paraparesis at day 15 p.i., declining thereafter with undetectable symptoms at day 40 p.i. Clinical disease activity paralleled decreased sciatic nerve motor conduction and histopathologic alterations of sciatic nerves. These included inflammatory infiltrates, mainly consisting of inducible nitric oxide synthase (iNOS)+ macrophages and CD4+ T cells. These data fit into the pathogenetic concept of murine autoimmune neuritis as a CD4+ TH1 cell-mediated disease. Our new mouse model provides an attractive tool to identify critical factors that regulate the severity of autoimmune responses in the peripheral nervous system.
Journal of Neuropathology and Experimental Neurology 02/2005; 64(1):66-73. · 4.26 Impact Factor
