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Article ; Online: Activation of disease during therapy with alemtuzumab in 3 patients with multiple sclerosis.

Wehrum, Thomas / Beume, Lena-Alexandra / Stich, Oliver / Mader, Irina / Mäurer, Mathias / Czaplinski, Adam / Weiller, Cornelius / Rauer, Sebastian

Neurology

2018 Volume 90, Issue 7, Page(s) e601–e605

Abstract: Objective: To report 3 patients with multiple sclerosis showing severe activation of disease during immunotherapy with alemtuzumab.: Methods: Retrospective case series.: Results: Patient 1, a 21-year-old woman, developed severe cognitive ... ...

Abstract	Objective: To report 3 patients with multiple sclerosis showing severe activation of disease during immunotherapy with alemtuzumab. Methods: Retrospective case series. Results: Patient 1, a 21-year-old woman, developed severe cognitive impairment, sight deterioration, severe gait ataxia, urinary retention, and extensive progression of cerebral lesion load, including new lesions that exhibited gadolinium ring enhancement and dominance of CD19/20-positive B lymphocytes, 6 months after induction of alemtuzumab. Patient 2, a 28-year-old man, developed left-sided hemihypesthesia and ∼60 new cerebral and spinal lesions including lesions with gadolinium ring enhancement 6 months after induction of alemtuzumab. Patient 3, a 37-year-old woman, developed ataxia and numbness of the left thigh, 16 new gadolinium-positive supratentorial lesions, and partly ring-enhancing and dominance of CD19/20-positive B lymphocytes 6 months after induction of alemtuzumab. Conclusion: This is a case series reporting severe activation of disease during immunotherapy with alemtuzumab. All patients showed onset of symptoms 6 months after induction of alemtuzumab, strikingly similar MRI lesion morphology, and unexpected high total B cell count, which may suggest a B-cell-mediated activation of disease. Whether this is due to different rates of B- and T cell repopulation has to be the subject of further research. Moreover, further effects on the interactions between the adaptive and innate immunity as well as between B and T cell lineages might explain the observed disease activation.
MeSH term(s)	Adult ; Alemtuzumab/adverse effects ; Alemtuzumab/therapeutic use ; B-Lymphocytes/immunology ; Brain/diagnostic imaging ; Brain/immunology ; Female ; Humans ; Immunologic Factors/adverse effects ; Immunologic Factors/therapeutic use ; Immunotherapy/adverse effects ; Male ; Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging ; Multiple Sclerosis, Relapsing-Remitting/immunology ; Multiple Sclerosis, Relapsing-Remitting/therapy ; Retrospective Studies ; Rituximab/therapeutic use ; Young Adult
Chemical Substances	Immunologic Factors ; Alemtuzumab (3A189DH42V) ; Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2018-01-19
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000004950
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Article ; Online: Ocrelizumab Treatment in Patients with Primary Progressive Multiple Sclerosis: Short-term Safety Results from a Compassionate Use Programme in Germany.

Rauer, Sebastian / Hoshi, Muna-Miriam / Pul, Refik / Wahl, Mathias / Schwab, Matthias / Haas, Judith / Ellrichmann, Gisa / Krumbholz, Markus / Tackenberg, Björn / Saum, Kai-Uwe / Buck, Fabian / Leemhuis, Jost / Kretschmann, Anita / Aktas, Orhan

Clinical neurology and neurosurgery

2020 Volume 197, Page(s) 106142

Abstract: Objectives: In January 2018, the European Union (EU) approved ocrelizumab in relapsing multiple sclerosis (RMS) and as the first disease-modifying therapy (DMT) for patients with primary progressive multiple sclerosis (PPMS) with efficacy proven in a ... ...

Abstract	Objectives: In January 2018, the European Union (EU) approved ocrelizumab in relapsing multiple sclerosis (RMS) and as the first disease-modifying therapy (DMT) for patients with primary progressive multiple sclerosis (PPMS) with efficacy proven in a phase 3 randomised controlled trial. Eleven months prior to the European regulatory approval, a compassionate use programme (CUP) made ocrelizumab available to 489 patients with PPMS in Germany, thereby for the first time providing a therapeutic option to patients with PPMS who could not participate in ocrelizumab studies. Here, we report real-world patient characteristics and short-term safety data of patients with PPMS treated with ocrelizumab in this CUP. Patients and methods: This CUP was initiated in February 2017 - shortly before US Food and Drug administration approval in March 2017 - and ended in January 2018, following ocrelizumab approval in the EU. Adult patients (age ≥18 years) with PPMS who had a positive benefit/risk ratio according to the treating physician were eligible for inclusion at German treatment centres. The main exclusion criteria were current/recent treatment with other immune therapies and unresolved/chronic/active infections. Patients received methylprednisolone and an antihistamine before treatment with intravenous ocrelizumab in 6-month cycles. The first ocrelizumab dose was a 300 mg infusion followed by a second 300 mg infusion 2 weeks later; subsequent doses were delivered as a single 600 mg infusion. Adverse events were reported immediately. Results: Of 580 requests received from 104 centres, 525 patients met the eligibility criteria. Thirty-five patients did not participate due to withdrawal by the treating physician, and one due to death prior to treatment. A total of 489 patients received at least one 600 mg dose of ocrelizumab (administered as two 300 mg infusions) and 51 received a second dose. Due to termination of the CUP upon marketing authorisation, the maximum follow-up period was 12 months. Median patient age was 52 years (range: 24-73), and 49% were female. Previous immunomodulatory or immunosuppressive therapies had been received by 41% of patients, with the most commonly used being glucocorticoids, mitoxantrone, interferon-β and glatiramer acetate. Patients with a previous malignancy, serious disease or infection (42 patients, 9%) had recovered from this prior to the CUP. Nine serious adverse events and 70 non-serious adverse events were reported in 40 patients. Adverse event categories were generally consistent with the known safety profile of ocrelizumab; one patient had carry-over progressive multifocal leukoencephalopathy (PML) due to previous natalizumab treatment. Conclusion: This CUP provides first real-world observations of ocrelizumab for the treatment of PPMS in a large patient cohort in Germany, supporting that ocrelizumab is generally well-tolerated in clinical practice. Physicians should be vigilant for early symptoms of PML, as to date, 9 PML cases that were all confounded have been reported in patients treated with ocrelizumab worldwide, with 8 carry-over cases from a prior DMT.
MeSH term(s)	Adult ; Aged ; Antibodies, Monoclonal, Humanized/therapeutic use ; Compassionate Use Trials ; Female ; Germany ; Humans ; Immunologic Factors/therapeutic use ; Immunotherapy/methods ; Male ; Middle Aged ; Multiple Sclerosis, Chronic Progressive/drug therapy ; Treatment Outcome ; Young Adult
Chemical Substances	Antibodies, Monoclonal, Humanized ; Immunologic Factors ; ocrelizumab (A10SJL62JY)
Language	English
Publishing date	2020-08-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	193107-6
ISSN	1872-6968 ; 0303-8467
ISSN (online)	1872-6968
ISSN	0303-8467
DOI	10.1016/j.clineuro.2020.106142
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Article: Frühsommer-Meningoenzephalitis (FSME)

Kaiser, Reinhard / Archelos-Garcia, Juan-Jose / Jilg, Wolfgang / Rauer, Sebastian / Sturzenegger, Mathias

Aktuelle Neurologie

2017 Volume 44, Issue 03, Page(s) 161–169

Abstract: Die Frühsommer-Meningoenzephalitis (FSME) ist eine durch ein gleichnamiges Virus verursachte akute Entzündung des Nervensystems. Reservoir für die FSME-Viren sind Kleintiernager des Waldes und der Wiesen und selten auch Ziegen, was die räumliche ... ...

Abstract	Die Frühsommer-Meningoenzephalitis (FSME) ist eine durch ein gleichnamiges Virus verursachte akute Entzündung des Nervensystems. Reservoir für die FSME-Viren sind Kleintiernager des Waldes und der Wiesen und selten auch Ziegen, was die räumliche Begrenzung von Endemiegebieten erklärt („Naturherde“). Die FSME-Viren werden hauptsächlich durch Zecken übertragen, gelegentlich aber auch durch Produkte aus nicht pasteurisierter Ziegenmilch. Infektionen können das gesamte Jahr über erfolgen, die meisten Erkrankungen treten jedoch in den Hochsommermonaten auf. Mehr als 90 % der Infektionen erfolgen während der Freizeit. Dennoch ist die FSME eine typische Berufserkrankung von Land- und Forstwirten. Bei ca. 70 % der Patienten manifestiert sich die FSME mit einem zweigipfligen Fieberverlauf. Nach einer Inkubationszeit von 5 – 28 Tagen entwickeln die Patienten zunächst ein allgemeines Krankheitsgefühl, Kopfschmerzen und Fieber (Prodromalphase). Nach vorübergehender Besserung markiert dann ein erneuter Fieberanstieg wenige Tage später den Beginn der zweiten Krankheitsphase. Diese manifestiert sich in ca. 50 % der Fälle als isolierte Meningitis, in 40 % als Meningoenzephalitis und in 10 % als Meningoenzephalomyelitis. Häufig finden sich quantitative und qualitative Bewusstseinsstörungen und eine Ataxie. Das frühzeitige Auftreten von Schluck- und Sprechstörungen, Lähmungen der Gesichts- und Halsmuskulatur sowie einer Atemlähmung weist auf eine ungünstige Prognose hin. Die FSME verläuft bei Kindern und Jugendlichen häufig unspezifisch mit den Symptomen eines grippalen Infektes und somit gutartiger als bei Erwachsenen. Mit zunehmendem Alter ist nicht nur der Verlauf gravierender, auch steigt die Zahl der Defektheilungen. Die Diagnose basiert auf der Anamnese mit Aufenthalten in einem Risikogebiet, der neurologischen Symptomatik mit deutlicher Beeinträchtigung des Allgemeinbefindens, dem positiven Nachweis von FSME-spezifischen IgM- und IgG-Antikörpern im Blut und einer Pleozytose im Liquor. Es existiert keine kausale Therapie, die Behandlung erfolgt symptomatisch. Vor der Erkrankung kann man sich durch eine aktive Immunisierung gut schützen. Die Impfung wird allen Personen empfohlen, die sich wiederholt in einem Risikogebiet aufhalten.
Keywords	FSME ; Frühsommer-Meningoenzephalitis ; Meningitis ; Encephalitis ; Myelitis ; Impfung ; TBE ; Tick-borne encephalitis ; Meningitis ; Encephalitis ; Myelitis ; Vaccin
Language	German
Publishing date	2017-04-01
Publisher	© Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	124980-0
ISSN	1438-9428 ; 0302-4350 ; 1431-4886
ISSN (online)	1438-9428
ISSN	0302-4350 ; 1431-4886
DOI	10.1055/s-0043-101424
Database	Thieme publisher's database

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Article: Tick-borne Encephalitis (TBE)

Kaiser, Reinhard / Archelos-Garcia, Juan-Jose / Jilg, Wolfgang / Rauer, Sebastian / Sturzenegger, Mathias

Neurology International Open

2017 Volume 01, Issue 01, Page(s) E48–E55

Abstract: Tick-borne encephalitis (TBE) is an acute inflammation of the nervous system caused by a virus of the same name. Reservoirs for the TBE viruses are small rodents of the forest and meadows and rarely also goats, which explains the spatial limitation to ... ...

Abstract	Tick-borne encephalitis (TBE) is an acute inflammation of the nervous system caused by a virus of the same name. Reservoirs for the TBE viruses are small rodents of the forest and meadows and rarely also goats, which explains the spatial limitation to endemic areas ("natural foci"). TBE virus is transmitted mainly by ticks, but occasionally also by products from non-pasteurized goat's milk. Infections can occur throughout the year, but most of the diseases present during the high summer months. More than 90% of infections occur during leisure time. However, it is a typical occupational disease for farmers and foresters. In approximately 70% of the patients, TBE manifests itself with a two-phase fever course. After an incubation period of 5–28 days, the patients first develop a general feeling of illness, headaches and fever (prodromal phase). After a temporary improvement, a new episode of fever marks the beginning of the second phase of the disease a few days later. This is manifested in about 50% of the cases as isolated meningitis, in 40% as meningoencephalitis and in 10% as meningoencephalomyelitis. Frequently, there are quantitative and qualitative disturbances of consciousness and ataxia. The early onset of swallowing and speech disturbances, paralysis of the facial and throat muscles as well as the need for assisted ventilation indicates an unfavorable prognosis. In children and adolescents, TBE is often unspecific with the symptoms of a flu infection and thus more benign than in adults. With age, not only the course is more serious, but also the number of residual deficits increases. The diagnosis is based on history with stays in a risk area, the neurological symptoms with marked impairment of the general condition, the demonstration of TBE-specific IgM and IgG antibodies in the blood and a pleocytosis in the CSF. No specific treatment for TBE is known so far, but TBE can be successfully prevented by active immunization. Vaccination is recommended for all persons who stay repeatedly in a risk area.
Keywords	tick-borne encephalitis ; TBE ; meningitis ; encephalitis ; myelitis ; vaccine
Language	English
Publishing date	2017-03-01
Publisher	© Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	2878288-4
ISSN	2511-1795 ; 2511-1795
ISSN (online)	2511-1795
ISSN	2511-1795
DOI	10.1055/s-0043-103258
Database	Thieme publisher's database

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Article ; Online: Antiviral CD8 T cells recognize borna disease virus antigen transgenically expressed in either neurons or astrocytes.

Baur, Karen / Rauer, Mathias / Richter, Kirsten / Pagenstecher, Axel / Götz, Jürgen / Hausmann, Jürgen / Staeheli, Peter

Journal of virology

2008 Volume 82, Issue 6, Page(s) 3099–3108

Abstract: Borna disease virus (BDV) can persistently infect the central nervous system (CNS) of mice. The infection remains nonsymptomatic as long as antiviral CD8 T cells do not infiltrate the infected brain. BDV mainly infects neurons which reportedly carry few, ...

Abstract	Borna disease virus (BDV) can persistently infect the central nervous system (CNS) of mice. The infection remains nonsymptomatic as long as antiviral CD8 T cells do not infiltrate the infected brain. BDV mainly infects neurons which reportedly carry few, if any, major histocompatibility complex class I molecules on the surface. Therefore, it remains unclear whether T cells can recognize replicating virus in these cells or whether cross-presentation of viral antigen by other cell types is important for immune recognition of BDV. To distinguish between these possibilities, we used two lines of transgenic mice that strongly express the N protein of BDV in either neurons (Neuro-N) or astrocytes (Astro-N). Since these animals are tolerant to the neo-self-antigen, we adoptively transferred T cells with specificity for BDV N. In nontransgenic mice persistently infected with BDV, the transferred cells accumulated in the brain parenchyma along with immune cells of host origin and efficiently induced neurological disease. Neurological disease was also observed if antiviral T cells were injected into the brains of Astro-N or Neuro-N but not nontransgenic control mice. Our results demonstrate that CD8 T cells can recognize foreign antigen on neurons and astrocytes even in the absence of infection or inflammation, indicating that these CNS cell types are playing an active role in immune recognition of viruses.
MeSH term(s)	Adoptive Transfer ; Animals ; Antigens, Viral/genetics ; Antigens, Viral/immunology ; Borna disease virus/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Flow Cytometry ; Immunohistochemistry ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic
Chemical Substances	Antigens, Viral
Language	English
Publishing date	2008-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02479-07
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Article: Transgenic mice expressing the nucleoprotein of Borna disease virus in either neurons or astrocytes: decreased susceptibility to homotypic infection and disease.

Rauer, Mathias / Götz, Jürgen / Schuppli, Daniel / Staeheli, Peter / Hausmann, Jürgen

Journal of virology

2003 Volume 78, Issue 7, Page(s) 3621–3632

Abstract: The nucleoprotein (N) of Borna disease virus (BDV) is the major target of the disease-inducing antiviral CD8 T-cell response in the central nervous system of mice. We established two transgenic mouse lines which express BDV-N in either neurons (Neuro-N) ... ...

Abstract	The nucleoprotein (N) of Borna disease virus (BDV) is the major target of the disease-inducing antiviral CD8 T-cell response in the central nervous system of mice. We established two transgenic mouse lines which express BDV-N in either neurons (Neuro-N) or astrocytes (Astro-N). Despite strong transgene expression, neurological disease or gross behavioral abnormalities were not observed in these animals. When Neuro-N mice were infected as adults, replication of BDV was severely impaired and was restricted to brain areas with a low density of transgene-expressing cells. Notably, the virus failed to replicate in the transgene-expressing granular and pyramidal neurons of the hippocampus (which are usually the preferred host cells of BDV). When Neuro-N mice were infected within the first 5 days of life, replication of BDV was not suppressed in most neurons, presumably because the onset of transgene expression in the brain occurred after these cells became infected with BDV. Astro-N mice remained susceptible to BDV infection, but they were resistant to BDV-induced neurological disorder. Unlike their nontransgenic littermates, Neuro-N mice with persistent BDV infection did not develop neurological disease after immunization with a vaccinia virus vector expressing BDV-N. In contrast to the situation in wild-type mice, this treatment also failed to induce N-specific CD8 T cells in the spleens of both transgenic mouse lines. Thus, while resistance to BDV infection in N-expressing neurons appeared to result from untimely expression of a viral nucleocapsid component, the resistance to BDV-induced neuropathology probably resulted from immunological tolerance.
MeSH term(s)	Animals ; Astrocytes/metabolism ; Astrocytes/virology ; Borna Disease/immunology ; Borna Disease/pathology ; Borna Disease/virology ; Borna disease virus/genetics ; Borna disease virus/immunology ; Borna disease virus/physiology ; CD8-Positive T-Lymphocytes/immunology ; Disease Susceptibility ; Mice ; Mice, Transgenic ; Neurons/metabolism ; Neurons/virology ; Nucleoproteins/genetics ; Nucleoproteins/metabolism ; Organ Specificity ; Vaccinia virus/genetics ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Replication
Chemical Substances	Nucleoproteins ; Viral Proteins
Language	English
Publishing date	2003-12-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.78.7.3621-3632.2004
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Article: Upregulation of chemokine receptor gene expression in brains of Borna disease virus (BDV)-infected rats in the absence and presence of inflammation.

Rauer, Mathias / Pagenstecher, Axel / Schulte-Mönting, Jürgen / Sauder, Christian

Journal of neurovirology

2002 Volume 8, Issue 3, Page(s) 168–179

Abstract: Infection of adult rats with Borna disease virus (BDV) causes CD8 T cell-mediated meningoencephalitis. Previously, we described a complex pattern of chemokine gene expression in the central nervous system (CNS) of such rats. We now found that expression ... ...

Abstract	Infection of adult rats with Borna disease virus (BDV) causes CD8 T cell-mediated meningoencephalitis. Previously, we described a complex pattern of chemokine gene expression in the central nervous system (CNS) of such rats. We now found that expression of chemokine receptor genes CXCR3, CCR5, CX(3)CR1, and CXCR4 was also upregulated, which is in agreement with the predominance in brains of adult infected rats of T cells and monocytes/macrophages that express these receptors. In contrast to these rats, neonatally infected rats (designated PTI-NB) develop a persistent CNS infection associated with neurodegenerative processes in the absence of inflammation. In brains of PTI-NB rats, sustained expression of chemokines also takes place. We therefore analyzed mRNA expression of selected chemokine receptor genes, as well as of the chemokine fractalkine in brains of PTI-NB rats. We observed a marked increase of CCR5 and CX(3)CR1 transcripts in brains of these rats. CX(3)CR1 expressing cells were predominantly microglia, and upregulation of CX(3)CR1 was mainly due to an increase in the number of CX(3)CR1 expressing microglia. Fractalkine gene expression was found to be reduced to similar extents in brains of adult and newborn infected rats. These findings might be of relevance with respect to the selective neuronal cell loss observed in brains of PTI-NB rats.
MeSH term(s)	Age Factors ; Animals ; Animals, Newborn ; Borna Disease/immunology ; Borna Disease/physiopathology ; Borna disease virus ; Brain/immunology ; Brain/virology ; CX3C Chemokine Receptor 1 ; Gene Expression Regulation/immunology ; Rats ; Rats, Inbred Lew ; Receptors, CCR5/genetics ; Receptors, CXCR3 ; Receptors, CXCR4/genetics ; Receptors, Chemokine/genetics ; Receptors, Cytokine/genetics ; Receptors, HIV/genetics ; Up-Regulation/immunology
Chemical Substances	CX3C Chemokine Receptor 1 ; Cxcr3 protein, rat ; Receptors, CCR5 ; Receptors, CXCR3 ; Receptors, CXCR4 ; Receptors, Chemokine ; Receptors, Cytokine ; Receptors, HIV
Language	English
Publishing date	2002-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1283265-0
ISSN	1538-2443 ; 1355-0284
ISSN (online)	1538-2443
ISSN	1355-0284
DOI	10.1080/13550280290049741
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Zs.A 4426: Show issues

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Article ; Online: Response of atmospheric biomarkers to NO(x)-induced photochemistry generated by stellar cosmic rays for earth-like planets in the habitable zone of M dwarf stars.

Grenfell, John Lee / Grießmeier, Jean-Mathias / von Paris, Philip / Patzer, A Beate C / Lammer, Helmut / Stracke, Barbara / Gebauer, Stefanie / Schreier, Franz / Rauer, Heike

Astrobiology

2012 Volume 12, Issue 12, Page(s) 1109–1122

Abstract: Understanding whether M dwarf stars may host habitable planets with Earth-like atmospheres and biospheres is a major goal in exoplanet research. If such planets exist, the question remains as to whether they could be identified via spectral signatures of ...

Abstract	Understanding whether M dwarf stars may host habitable planets with Earth-like atmospheres and biospheres is a major goal in exoplanet research. If such planets exist, the question remains as to whether they could be identified via spectral signatures of biomarkers. Such planets may be exposed to extreme intensities of cosmic rays that could perturb their atmospheric photochemistry. Here, we consider stellar activity of M dwarfs ranging from quiet up to strong flaring conditions and investigate one particular effect upon biomarkers, namely, the ability of secondary electrons caused by stellar cosmic rays to break up atmospheric molecular nitrogen (N(2)), which leads to production of nitrogen oxides (NO(x)) in the planetary atmosphere, hence affecting biomarkers such as ozone (O(3)). We apply a stationary model, that is, without a time dependence; hence we are calculating the limiting case where the atmospheric chemistry response time of the biomarkers is assumed to be slow and remains constant compared with rapid forcing by the impinging stellar flares. This point should be further explored in future work with time-dependent models. We estimate the NO(x) production using an air shower approach and evaluate the implications using a climate-chemical model of the planetary atmosphere. O(3) formation proceeds via the reaction O+O(2)+M→O(3)+M. At high NO(x) abundances, the O atoms arise mainly from NO(2) photolysis, whereas on Earth this occurs via the photolysis of molecular oxygen (O(2)). For the flaring case, O(3) is mainly destroyed via direct titration, NO+O(3)→NO(2)+O(2), and not via the familiar catalytic cycle photochemistry, which occurs on Earth. For scenarios with low O(3), Rayleigh scattering by the main atmospheric gases (O(2), N(2), and CO(2)) became more important for shielding the planetary surface from UV radiation. A major result of this work is that the biomarker O(3) survived all the stellar-activity scenarios considered except for the strong case, whereas the biomarker nitrous oxide (N(2)O) could survive in the planetary atmosphere under all conditions of stellar activity considered here, which clearly has important implications for missions that aim to detect spectroscopic biomarkers.
MeSH term(s)	Atmosphere/chemistry ; Biomarkers/chemistry ; Cosmic Radiation ; Earth, Planet ; Exobiology ; Extraterrestrial Environment ; Nitrogen Oxides/chemistry ; Oxygen/chemistry ; Ozone/chemistry ; Photochemical Processes ; Planets ; Ultraviolet Rays
Chemical Substances	Biomarkers ; Nitrogen Oxides ; Ozone (66H7ZZK23N) ; Oxygen (S88TT14065)
Language	English
Publishing date	2012-12-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2047736-3
ISSN	1557-8070 ; 1531-1074
ISSN (online)	1557-8070
ISSN	1531-1074
DOI	10.1089/ast.2011.0682
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Article: Biomarker response to galactic cosmic ray-induced NOx and the methane greenhouse effect in the atmosphere of an Earth-like planet orbiting an M dwarf star.

Grenfell, John Lee / Griessmeier, Jean-Mathias / Patzer, Beate / Rauer, Heike / Segura, Antigona / Stadelmann, Anja / Stracke, Barbara / Titz, Ruth / Von Paris, Philip

Astrobiology

2007 Volume 7, Issue 1, Page(s) 208–221

Abstract: Planets orbiting in the habitable zone of M dwarf stars are subject to high levels of galactic cosmic rays (GCRs), which produce nitrogen oxides (NOx) in Earth-like atmospheres. We investigate to what extent these NO(Mx) species may modify biomarker ... ...

Abstract	Planets orbiting in the habitable zone of M dwarf stars are subject to high levels of galactic cosmic rays (GCRs), which produce nitrogen oxides (NOx) in Earth-like atmospheres. We investigate to what extent these NO(Mx) species may modify biomarker compounds such as ozone (O3) and nitrous oxide (N2O), as well as related compounds such as water (H2O) (essential for life) and methane (CH4) (which has both abiotic and biotic sources). Our model results suggest that such signals are robust, changing in the M star world atmospheric column due to GCR NOx effects by up to 20% compared to an M star run without GCR effects, and can therefore survive at least the effects of GCRs. We have not, however, investigated stellar cosmic rays here. CH4 levels are about 10 times higher on M star worlds than on Earth because of a lowering in hydroxyl (OH) in response to changes in the ultraviolet. The higher levels of CH4 are less than reported in previous studies. This difference arose partly because we used different biogenic input. For example, we employed 23% lower CH4 fluxes compared to those studies. Unlike on Earth, relatively modest changes in these fluxes can lead to larger changes in the concentrations of biomarker and related species on the M star world. We calculate a CH4 greenhouse heating effect of up to 4K. O3 photochemistry in terms of the smog mechanism and the catalytic loss cycles on the M star world differs considerably compared with that of Earth.
MeSH term(s)	Astronomical Phenomena ; Astronomy ; Atmosphere ; Biomarkers/analysis ; Cosmic Radiation ; Exobiology ; Extraterrestrial Environment ; Greenhouse Effect ; Methane/radiation effects ; Nitrogen Oxides/radiation effects ; Ozone/radiation effects ; Planets ; Space Simulation
Chemical Substances	Biomarkers ; Nitrogen Oxides ; Ozone (66H7ZZK23N) ; Methane (OP0UW79H66)
Language	English
Publishing date	2007-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2047736-3
ISSN	1557-8070 ; 1531-1074
ISSN (online)	1557-8070
ISSN	1531-1074
DOI	10.1089/ast.2006.0129
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Article ; Online: Importance of cerebrospinal fluid analysis in the era of McDonald 2010 criteria: a German-Austrian retrospective multicenter study in patients with a clinically isolated syndrome.

Huss, André M / Halbgebauer, Steffen / Öckl, Patrick / Trebst, Corinna / Spreer, Annette / Borisow, Nadja / Harrer, Andrea / Brecht, Isabel / Balint, Bettina / Stich, Oliver / Schlegel, Sabine / Retzlaff, Nele / Winkelmann, Alexander / Roesler, Romy / Lauda, Florian / Yildiz, Özlem / Voß, Elke / Muche, Rainer / Rauer, Sebastian /

Bergh, Florian Then / Otto, Markus / Paul, Friedemann / Wildemann, Brigitte / Kraus, Jörg / Ruprecht, Klemens / Stangel, Martin / Buttmann, Mathias / Zettl, Uwe K / Tumani, Hayrettin

Journal of neurology

2016 Volume 263, Issue 12, Page(s) 2499–2504

Abstract: The majority of patients presenting with a first clinical symptom suggestive of multiple sclerosis (MS) do not fulfill the MRI criteria for dissemination in space and time according to the 2010 revision of the McDonald diagnostic criteria for MS and are ... ...

Abstract	The majority of patients presenting with a first clinical symptom suggestive of multiple sclerosis (MS) do not fulfill the MRI criteria for dissemination in space and time according to the 2010 revision of the McDonald diagnostic criteria for MS and are thus classified as clinically isolated syndrome (CIS). To re-evaluate the utility of cerebrospinal fluid (CSF) analysis in the context of the revised McDonald criteria from 2010, we conducted a retrospective multicenter study aimed at determining the prevalence and predictive value of oligoclonal IgG bands (OCBs) in patients with CIS. Patients were recruited from ten specialized MS centers in Germany and Austria. We collected data from 406 patients; at disease onset, 44/406 (11 %) fulfilled the McDonald 2010 criteria for MS. Intrathecal IgG OCBs were detected in 310/362 (86 %) of CIS patients. Those patients were twice as likely to convert to MS according to McDonald 2010 criteria as OCB-negative individuals (hazard ratio = 2.1, p = 0.0014) and in a shorter time period of 25 months (95 % CI 21-34) compared to 47 months in OCB-negative individuals (95 % CI 36-85). In patients without brain lesions at first attack and presence of intrathecal OCBs (30/44), conversion rate to MS was 60 % (18/30), whereas it was only 21 % (3/14) in those without OCBs. Our data confirm that in patients with CIS the risk of conversion to MS substantially increases if OCBs are present at onset. CSF analysis definitely helps to evaluate the prognosis in patients who do not have MS according to the revised McDonald criteria.
MeSH term(s)	Adult ; Austria/epidemiology ; Disease Progression ; Female ; Germany/epidemiology ; Humans ; Kaplan-Meier Estimate ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis/cerebrospinal fluid ; Multiple Sclerosis/diagnosis ; Multiple Sclerosis/mortality ; Oligoclonal Bands/cerebrospinal fluid ; Retrospective Studies ; Severity of Illness Index
Chemical Substances	Oligoclonal Bands
Language	English
Publishing date	2016-10-11
Publishing country	Germany
Document type	Journal Article ; Multicenter Study
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-016-8302-1
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