Eustachian Tube and Middle Ear Diseases

1 Regulation of the Eukaryotic Cell Cycle.- Mitosis-Promoting Factor.- The cdc2 Gene.- Histone H1 Kinase.- Activation of Mitosis-Promoting Factor.- Cyclins.- Phosphorylation and Dephosphorylation of p34cdc2.- cdc25 and the Timing of MPF Activation.- Dependence of Mitosis on DNA Synthesis.- The wee1 and niml Genes.- The sucl Gene.- Calcium.- Why Two Classes of Cyclin?.- Exit from Mitosis.- Cyclin Degradation.- Regulation of Cyclin Destruction by the Mitotic Spindle.- Cytostatic Factor and c-mos Proto-oncogene.- Cell Cycle Initiation.- Role of cdc2.- G1 Cyclins.- Conclusion.- 2 Growth Factors, Oncogenes and Tumour Suppressor Genes.- Growth Factors and Growth Factor Receptors.- Cytoplasmic Signal Transduction Pathways.- Immediate Early Genes.- The los and jun Genes.- The myc Genes.- Other Immediate Early Genes.- Steroid Receptors.- Tumour Suppressor Genes.- The p53 Gene.- Retinoblastoma Protein.- Conclusion.- 3 The Kinetic Organisation of Tissues.- The General Organisation of Tissues.- Evidence for the Existence of Stem Cells.- Regulation of Stem Cells and the Lineages Derived from Them.- Regulation by Position.- Regulation by Intercellular Communication.- Negative Regulators of Cell Proliferation.- Control of Cell Number and Heterochrony.- Regulation by Growth Arrest.- Regulation by Cell Death.- Do Stem Cells Exist in Conditional Renewal Tissues?.- Cellular Heterogeneity in Tumours.- Conclusion.- 4 Basic Methods for Assessing Cellular Proliferation.- The Cell Cycle.- Growth Fraction.- Cell Loss.- Growth Curves.- Age Distribution.- State Measurements.- Thymidine Incorporation.- Non-Autoradiographic Method of Detecting Incorporated Thymidine.- Mitotic and Labelling Indices.- The Fraction Labelled Mitoses Method.- The Continuous Labelling Method.- Thymidine Labelling - Clinical Applications.- Flow Cytometry.- Summary.- Rate Measurements.- The Rate of Entry into S Phase.- The Rate of Entry into Mitosis.- Summary.- Conclusion.- 5 Mitosis Counting.- Mitosis Counting - Methods.- Mitotic Count.- Mitotic Index.- Mitotic Rate.- Mitosis Counting - Applications.- Uterine Smooth Muscle Tumours.- Gastrointestinal Smooth Muscle (Stromal) Tumours.- Endometrial Stromal Sarcomas.- Placental Site Trophoblastic Tumour.- Ovarian Neoplasms.- Lymphomas.- Other Applications.- Mitosis Counting - Advantages.- Mitosis Counting - Limitations.- Tumour Heterogeneity.- Delay in Fixation.- Inter-Observer Variation.- Cell Size Variation.- Variation in the Area of High-Power Fields.- Conclusion.- 6 Flow Cytometry.- Development and Properties of Flow Cytometers.- General Advantages and Disadvantages of Flow Cytometry.- DNA Flow Cytometry.- Intrbduction.- Methodology.- Clinical Value.- Multiparameter Flow Cytometry.- Conclusion.- 7 Measurement of Cell Proliferation Using Bromodeoxyuridine.- The Parameters of Tumour Cell Proliferation.- Flow Cytometric Methods.- Tissue Preparation and Staining.- Data Acquisition.- Data Analysis.- The Relative Movement Method.- Modifications of the Single Relative Movement Calculation.- Comparisons of Analytical Methods in the Context of Solid Tumours.- Intra- and Inter-Tumour Heterogeneity.- Immunohistochemical Localisation of BUdR.- Staining Procedure.- Clinical Correlations.- Conclusion.- 8 The Application of Immunohistochemistry in Assessment of Cellular Proliferation.- Cell Cycle Associated Antigens.- Ki-67 Antigen.- Proliferating Cell Nuclear Antigen.- DNA Polymerase 0 and a.- p125/6.5 Antigen.- K 112 Antigen.- Transferrin Receptor.- Mitosis-Associated Changes.- Bromodeoxyuridine.- Markers of Quiescent and non-Proliferating Cells.- Markers of Transition from the Quiescent to the Proliferative State.- Quantification and Interpretation of Results.- Conclusion.- 9 Nucleolar Organiser Regions.- Nucleolar Organiser Regions and Nucleoli.- Argyrophilic NORs.- Demonstration of NORs.- AgNOR Staining Techniques.- Enumeration of AgNORs.- Tissue Sampling.- Section Thickness.- NOR Aggregation and Segregation.- NOR Numbers and Ploidy.- Transcriptional Activity.- Assessment of AgNORs in Interphase Nuclei.- Sample Size.- Effect of AgNOR Superimposition and Aggregation.- AgNOR Number per Nucleus.- AgNOR Area.- AgNOR Assessment by Image Analysis.- Significance of High AgNOR Counts.- Proliferation or Ploidy?.- Correlation with Other Indices of Proliferation.- Non-Hodgkin's Lymphoma.- Breast Carcinoma.- Lung Carcinomas.- Applications in Histopathology.- Conclusion.- 10 Clinical Aspects of Assessing Cell Proliferation.- Methods Used to Assess Cell Proliferation.- Clinical Applications.- Diagnosis.- Prognosis.- Predicting Response to Treatment.- Conclusion.- 11 Cell Proliferation and the Principles of Cancer Chemotherapy.- Evolution of the Principles.- The Principles in Practice.- Application to Particular Neoplasms.- Application in Choice of Treatment for Individuals.- New Approaches to Estimating Resistance and Growth Rates.- Mathematical Model Description and Development.- Model Applications.- Conclusion.