The role of herpesviruses in brain tumor development [Elektronische Ressource] / eingereicht von Sabine Poltermann

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• Gesundheit

Informations

• Publié par: justus-liebig-universitat_giessen
• Publié le: 01 janvier 2006
• Nombre de lectures: 19
• Langue: Deutsch
• Poids de l'ouvrage: 4 Mo

Extrait

The Role of Herpesviruses
in Brain Tumor Development









INAUGURAL-DISSERTATION
zur Erlangung des Grades eines
Dr. med. vet.
beim Fachbereich Veterinärmedizin
der Justus-Liebig-Universität Gießen






Sabine Poltermann

Aus dem
Institut für Veterinär-Pathologie
der Justus-Liebig-Universität Gießen
Betreuer: Prof. Dr. M. Reinacher
und dem
Deutschen Krebsforschungszentrum, Heidelberg
Abt. Umweltepidemiologie
Betreuer: Prof. Dr. J. Wahrendorf
Abt. Tumorvirologie
Betreuer: Prof. Dr. J. R. Schlehofer



The Role of Herpesviruses
in Brain Tumor Development



INAUGURAL-DISSERTATION
zur Erlangung des Grades eines
Dr. med. vet.
beim Fachbereich Veterinärmedizin
der Justus-Liebig-Universität Gießen


Eingereicht von
Sabine Poltermann

Tierärztin aus Lichtenfels/Bayern

Gießen 2006






Mit Genehmigung des Fachbereichs Veterinärmedizin
der Justus-Liebig-Universität Gießen






Dekan: Prof. Dr. M. Reinacher





Gutachter:
Prof. Dr. M. Reinacher
Prof. Dr. J. R. Schlehofer






Tag der Disputation: 05. Juli 2006









Meiner Omi,
in Liebe






I
Table of Contents
Introduction .............................................................................................................................. 1
Study Intention ......................................................................................................................... 3
1 Background and State of the Art................................................................................... 4
(A) Clinical Background....................................................................................................... 4
1.1 Primary Brain Tumors in Humans.......................................................................................................... 4
1.2 Glioma......................... 11
1.3 Meningioma.......................................................................................................................................... 15
1.4 Acoustic Neurinoma ............................................................................................................................. 18
(B) Virological Background ............................................................................................... 20
1.5 The Family of Herpesviruses................................................................................................................ 20
1.6 Human Cytomegalovirus ...................................................................................................................... 24
1.7 Herpes Simplex Virus........................................................................................................................... 29
1.8 Varicella-Zoster Virus .......................................................................................................................... 33
1.9 Epstein-Barr Virus................... 37
2 Material and Methods .................................................................................................. 41
2.1 Study Design and Recruitment of the Study Population....................................................................... 42
2.2 Questionnaire........................................................................................................................................ 43
2.3 Laboratory Material.............................................................................................................................. 44
2.4 Methods ................................................................................................................................................ 51
3 Results............................................................................................................................ 72
(A) Questionnaire Data....................................................................................................... 72
3.1 Characteristics of Participants Completing the Questionnaire.............................................................. 72
3.2 Medical History .................................................................................................................................... 76
3.3 Assessment of Occupational History.................................................................................................... 88
3.4 ent of High-level Contact to Animals and/or Humans............................................................ 89
(B) Laboratory Results ....................................................................................................... 92
3.5 Characteristics of Participants Providing Biological Samples.............................................................. 92
3.6 Analyses of the Presence of HCMV DNA Sequences in Blood Samples of the Brain Tumor
Patients................................................................................................................................................. 92
3.7 Polymerase Chain Reaction in Brain Tumor Tissues ........................................................................... 95
3.8 Prevalence of HCMV Proteins in Primary Brain Tumors .................................................................... 98
3.9 Summary of Analyses for the Detection of HCMV Macromolecules in Brain Tumor Tissues and
Blood Samples.................................................................................................................................... 100
3.10 Prevalences of IgG and IgM Antibodies in Serum Samples............................................................... 101


II
4 Discussion .................................................................................................................... 106
4.1 Ethical Justification for the Part-time Anonymous Sample Collection .............................................. 106
(A) Questionnaire Data..................................................................................................... 107
4.2 Characteristics of Participants Completing the Questionnaire............................................................ 107
4.3 Association between Medical History and Primary Brain Tumors..................................................... 109
4.4 Assessment of Occupational History.................................................................................................. 128
4.5 Contact to Animals and/or Humans and Primary Brain Tumors ........................................................ 130
(B) Laboratory Analyses................................................................................................... 134
4.6 HCMV and Primary Brain Tumors..................................................................................................... 134
4.7 Herpesvirus Infections in Brain Tumor Patients................................................................................. 137
(C) Strengths and Limitations of the Study .................................................................... 144
4.8 Limitations.......................................................................................................................................... 144
4.9 Strengths ............................................................................................................................................. 145
5 Conclusion ................................................................................................................... 147
6 Summary 148
Bibliography ......................................................................................................................... 149
Schedular Annexes ............................................................................................................... 168
List of Tables 176
List of Figures....................................................................................................................... 179
Acknowledgement ................................................................................................................ 181
Presentations and Publications ........................................................................................... 182
Declaration of Compliance with Good Scientific Practice ............................................... 183
III
List of Abbreviations
Ab Antibody
ACN Acoustic neurinoma
AEC 3-amino-9-ethylcarbazol
approx. Approximately
bp Base pairs
BSE Bovine spongiforme encephalitis
°C Degrees Celsius
CBTRUS Central Brain Tumor Registry of the United States
cf confer
Chap. Chapter
CI Confidence interval
CID Cytomegalic inclusion disease
CJD Creutzfeld-Jacob
CNS Central nervous system
CO Carbon dioxide 2
CSF Cerebrospinal fluid
CT Computed tomography
D DNA ladder
DAE Deutsche Arb