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

Le téléchargement nécessite un accès à la bibliothèque YouScribe
Tout savoir sur nos offres
193 pages
Deutsch

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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 ITable of Contents Introduction .............................................................................................................................. 1 Study Intention .........................................................................................................................

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Publié par
Publié le 01 janvier 2006
Nombre de lectures 19
Langue Deutsch
Poids de l'ouvrage 4 Mo

Exrait








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 Arbeitsgemeinschaft Epidemiologie
dATP Deoxy adenosine triphosphate
dCTP cytosine
ddHO Double distilled water 2
dGTP guanosine triphosphate
DKFZ Deutsches Krebsforschungszentrum
DMEM Dulbecco’s Modified Eagle Medium
DNA Deoxyribonucleic acid
dNTP Deoxy nucleoside triphosphate
dTTP thymidine
EA Early antigen
EB Electrophoresis buffer
EBMT European Group for Blood and Marrow Transplantation
IV
EBV Epstein-Barr virus
EDTA Ethylenediaminetetraacetic acid
e.g. Exempli gratia
ELISA Enzyme Linked Immunosorbent Assay
et al. et alii (and others)
EtBr Ethidium bromide
FCS Fetal calf serum
FH Fachhochschule
Fig. Figure
FSME Frühsommer-Meningoenzephalitis (tick-borne
encephalitis)
GAPDH Glyseraldehyde-3-phosphate dehydrogenase
gB Glycoprotein B
GBM Glioblastoma multiforme
GI Gastrointestinal
h Hour (s)
HCMV Human cytomegalovirus
HHV Humaherpesvirus
HIV an immunodeficiency virus
HRP Horseradish peroxidase
HSV Herpes simplex virus
IARC International Agency for Research on Cancer
ICD-9 International Statistical Classification of Diseases and
thRelated Health Problems, 9 version
ICD-10 InternClassificatiod
ths, 10 version
ICD-O-3 International Classification of Diseases for Oncology,
rd3 version
IE Immediate early antigen
i.e. Id est
Ig Immunoglobulin (IgA, IgG, IgM)
IHC Immunohistochemistry
IHV Industrieverband Heimtierbedarf e. V.
V
ISCO International Standard Classification of Occupation
kbp Kilo base pairs (1 kbp=1000 bp)
LA Late antigen
M Molar
MgCl Magnesium chloride 2
min Minute (s)
ml Milliliter
MMR Measles, mumps rubella combined immunization
MOI Multiplicity of infection
MRI Magnetic resonance imaging
NC Negative control
NF Neurofibromatosis
nm Nanometer
OR Odds ratio
PBS Phosphate buffered saline
PC Positive control
PCR Polymerase chain reaction
PNET Primitive neuroectodermal tumor
POD Peroxidase
Pp65 Phosphoprotein 65
RKI Robert Koch Institute
RNA Ribonucleic acids
rpm Rotations per minute
RR Risk ratio
RT Room temperature
SE Standard error
sec Seconds
SES Socioeconomic status
SP Seroprevalence
STIKO Ständige Impfkommission des RKI
SV40 Simian virus 40
Tab. Table
TBS Tris buffered saline
VI
TMB Tetramethylbenzidine
Tris Tris(hydroxymethyl)aminomethane
U Unit
UK United Kingdom
USA States of America
UV Ultraviolet light
v/v (%) Percent by volume
VZV Varicella-zoster virus
WHO World Health Organization
W Wat
w/v (%) Percent by weight per volume
y years