Lecture 12 disturbances in growth and differentiation
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Lecture 12 disturbances in growth and differentiation

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  • In humans 70% of spina bifida cases have a latex allergy

Lecture 12 disturbances in growth and differentiation Lecture 12 disturbances in growth and differentiation Presentation Transcript

  • Disturbances in Growth and Differentiation
    • Embryology
    • Teratology
    • Oncology
  • Embryology
  • Coordinated events
    • Physiologic Stimuli
      • Hormones
      • Growth factors
      • Nutrients
    • Blood Supply
    • Tissue/Cell interactions (cell-cell communication)
  • Cell Differentiation and Regeneration
    • The capacity for tissue repair following injury depends on the ability of the terminally differentiated cells to replicate and the presence of tissue stem cells
  • Renal Dysplasia vs. Chronic Renal Failure
  • Teratology
  • Teratology Study of Developmental Anomalies
    • 2% of live births have major abnormality
    • Up to 5% if minor abnormalities included
    • Cultural differences
  • Etiologies of Birth Defects
  • Cyclopia
    • Veratrum californicum
      • 14th day of gestation
        • protruding lower jaw, underdeveloped upper jaw, proboscis-like nose, cyclopia, hydrocephaly, other ocular defects
        • prolonged gestation
          • hypothalmic-pituitary-adrenal axis
      • 17-19 days of gestation
        • tracheal stenosis
      • 28-31 days of gestation
        • shortened metatarsal and metacarpal bones
  • Errors of Morphogenesis Developmental Syndrome
  • Developmental Syndrome
    • Aborted minature foal
    • Hydrocephalus
    • Brachygnathia superior
    • Metacarpal-digital and metatarsal-digital varus
  • Errors of Morphogenesis Deformation
  • Arthrogryposis
    • Cache Valley Virus
    • oligoamnios
    • Lupinosis
    • CNS malformation
    Errors of Morphogenesis Deformation
  • Spina Bifida
  • Spina Bifida
  • Cleft Palate
  • Relationship Between Genotype and Phenotype Epigenetic Events
    • Histone de-acetylation
    • DNA methylation
    • Micro RNA
      • Downregulation
  • Interplay Between Environment and Genotype
    • Carcinogens
      • Chemical
      • Radiation
    • Oncoviruses
      • Papilloma
      • Lymphoma
      • Sarcomas
    • Inflammation
    • DNA repair defects
    • Tumor suppressor gene defects
  • Mutations
    • Genome mutations ( gain/loss of whole chromosomes)
    • Chromosome mutations (altered structure)
    • Single gene mutations
  • Cytogenetics
  • Types of Chromosome Mutations
  • Spectral Karyotyping
  • Molecular Diagnostics FISH- Interphase nucleus- Green probes for Chr 13, and Red for Chr 21 (trisomy 21) FISH- Multicolor FISH- Shows portion of chromosome 22q to chromosome 9
  • Microarray- Gene Chip (left) – used to sequence thousands of base pairs of DNA. Close up view of hybridization pattern of the microarray.
  • Single Gene Mutations
    • Target genes
      • Enzymes
      • Receptors
      • Structural proteins
      • Cell growth regulators
    • Different mutations may have vastly different effects
  • Mechanisms of Single Gene Mutations Amino Acid Substitution Premature Termination Frameshifts
  • Diagnosis of Single Gene Mutations “ Molecular Pathology ”
  • Errors of Morphogenesis Sensitivity to Teratogenic Agents
  • Errors of Morphogenesis Agenesis vs. Aplasia
  • Errors of Morphogenesis Hypoplasia vs. Abiotrophy
  • Errors of Morphogenesis Dysraphism Spinal bifida and menigomyelocoele
  • Errors of Morphogenesis Ectopia
  • Errors of Morphogenesis Dystopia
  • Errors of Morphogenesis Dysplasia
  • Neoplasia
  • Disturbances of Cell Proliferation Epithelium Reversible Reversible Reversible
  • Cell Cycle G1/S Checkpoint- Cyclin D/CDK4, Rb, P53 G2/M Checkpoint- Cyclin A/CDK2
  • Cell Cycle-Stages
    • G0- Resting Cells
    • G1-preparation for division(G for growth)
    • S- DNA synthesis
    • G2- Preparation for cell division
    • M- Actual mitosis
  • Cell types
    • Non-Dividing
      • Permanent G0
        • Neurons, Cardiac muscle, Skeletal muscle
    • Quiescent (Stable tissues)
      • G0-G1 transition when stimulated
        • Liver, kidney, pancreas, mesenchymal tissues, vascular
    • Continuously Dividing (Labile)
      • Never in G0
        • Epithelia, Bladder, glands
        • Arise from tissue stem cells
  • Cell Cycle- Regulation
    • Proto-Oncogenes
      • Growth Factors, Transcription factors stimulated by growth factors or involved in signaling by growth factors
      • Necessary for progression through cell cycle checkpoints
        • Cyclins, CDK’s, c-fos, c-jun- c-myc, PDGF, RAS
    • Tumor Suppressor Genes
      • Monitor DNA damage and lead to arrest of cell cycle or apoptosis
        • P53, Rb
    • DNA repair genes
    • Apoptosis genes
  • Cell Cycle
  • Cancer Genetics
  •  
  • THE END!