Midterm Flashcards

Question

Describe CNS tumours

Answer 1

Can occur in supratentorium (gluons and ependydmoma) or infratentorium (posterior fossa and brain stem) Account for 20% of all childhood cancers Second most common group Frequently occur in young children <3 years with worse prognosis but can occur with all kids

Answer 2

``` Sustaining proliferation signalling Resisting cell death Inducing angiogenesis Enabling replicative immortality Activating invasion and metastasis Evading growth suppressors ```

Answer 3

Programmed cell death The death of cells that occurs as a normal and controlled part of an organisms growth or development Cell suicide Hallmarks: morphological (cell shrinkage, chromatic condensation, cell budding) and biochemical (DNA fragmentation, activation of caspases, protéolytic cleavage of key proteins)

Answer 4

Needed for proper development in tissue remodeling, organ formation, formation of synopses Needed to destroy cells that represent a threat to the integrity of the organism

Answer 5

ER mediated Death-receptor mediated Mitochondria mediated All lead to formation of caspases by cleavage of subunits and combination of large and small

Answer 6

Extrinsic: death receptors indice signalling complex with activates initiator caspase 8 and pro-apoptopic BID protein (which goes to mitochondria). 8 activiste executioner caspases Intrinsic: mitochondria releases cytochrome c which causes conformation change in caspases leading to activation of initiator caspase 9

Answer 7

Indirect: regulation of mitochondria and ER permeability Direct: caspase inhibitors

Answer 8

Closing and opening of channels Opening: proapoptotic bid binds to pro-survival Bcl-2, removing it from the opening and allowing the releases of pro-spoptotic factors leading to apoptosis

Answer 9

Targeting the Bcl-2 family to allow apoptosis in cancer cells to occur using agents such as ABT-737

Answer 10

Baculorviral protein that blocks defensive apoptosis (direct inhibition) Contains a broad range of inhibitors, inhibiting caspase-1,3,6,7,8,10 Also inhibits C. Elegans Once bound, p35 undergoes conformational change and is therefore irreversible

Answer 11

Inhibitors of apoptosis protein Are often implicated in neurofegenerative diseases and cancer Inhibit cell death induced by various triggers

Answer 12

1. BIR domains: are involved in the direct binding and inhibition of cell-death professes, specifically caspases 3,7,9 2. RING domains: function as E3 ligase that médiate the ubiquitination of binding proteins to target them either for proteasomal degradation or for signaling complex formation

Answer 13

Promising new anti-cancer drugs Stable and bio available small molecule compounds Designed against the AVPI tetrapeptide sequence of SMAC that antagonizes IAP function Potency has been shown t greatly increase dimerization Pan-IAP antagonists that mainly target cIAP1 and cIAP2 and to a lesser extent XIAP Kills through multiple mechanisms

Answer 14

1. Chromosomal abnormalities 2. Gêne abnormalities 3. Intra-utérine injury 4. Environmental factors

Answer 15

Structural: clubfoot, congenital dislocated hip, gear defects, spina bifida, cleft palate Metabolic: phenylketonuria, yay-Sachs disease, galactosemia, maple syrup urine disease

Answer 16

Abnormality of the hip joint where the femoral bead slips out of the normal position that becomes noticed in the first months Symptoms: asymmetrical folds of the affected thigh, difference in leg length, positive Ortolanis (clicking) Étiology: unknown ex improper position prior to or during birth or relaxation of joint due to maternal hormones Diagnosis: x Ray Treatment: cast/splint for 3 months (maybe surgery) Prevention: prenatal care

Answer 17

Frequent deformity of foot or ankle Symptoms: fixation of the foot Etiology: unknown ex. Fetal positioning, genetics Diagnosis: physical exam and X-ray to assess severity Treatment: successful if caught early by using splint or cast depending on severity Prevention: none

Answer 18

Neurological tube effect where the vertebrae fail to close over the spinal cord, generally in the low back Symptoms: skeletal malformation, deformed joints, paralysis of legs, bowel incomtinence Etiology: unknown risk factors are maternal radiation, obesity, diabetes, lack of folate, genetic factors Diagnosis: x Ray and prenatal screening, look for skin defect over spinal area and muscle abnormalities Treatment: surgery in first 24 hours w/ addition support depending on severity Prevention: folic acid level maintenance

Answer 19

Occulta: most coming, a symptomatic, dumpling of skin, dark hairy patch Mengingocele: meninges of spinal cord peptide though the opening in vertebrae, fluid filled sack, nerve tissues not involved therefore no neurological issues Myelomengocele: most severe form, spinal cord protrudes, neurological problem

Answer 20

Failure of segregation: aneuploidy (one less) or polyploidy (one more), can occur in first of second division Breaks and rearrangement: deletions, translocations (balanced or unbalanced), inversions (paracentric:long part, or pericentric:middle part), or duplication

Answer 21

Trisomy 13, 18, or 22 Turners syndrome Klinefelters 47 XYY syndrome

Answer 22

Patau syndrome Typically not compatible with life, most dying in first days or weeks Only 10% live past first year Symptoms: severe intellectual disability and physical abnormalities (also see heart defects, brain and spinal cord abnormalities, very small or poorly developed eyes, extra digits, cleft lil, and hypotonia

Answer 23

Edwards syndrome 1/5000 births but frequently fatal before and after birth (6-10% past first year) Symptoms: severe intellectual disability (other system abnormalities, growth delay, low birth weight, small abnormally shaped head, small jaw and mouth, clenched fist, club feet

Answer 24

Down syndrome 1 in 800 but goes up with age Symptoms: mild to moderate intellectual disability (facial appearance, hypotonia, heart defects, GI tract abnormalities) Increased risk of reflux, celiac disease, hearing an vision problems, leukemia and hypothyroidism Can be very productive members of society

Answer 25

Missing or partially X chromosome 1 in 25000 newborn girls Symptoms: impaired devlopment (short stature, loss of ovary function, don’t undergo puberty without hormone therapy, may also see webbed neck, low hairline on back, swelling in lower extremities, and heart defects)

Answer 26

Extra copy of X chromosome in males 1/500-1000 but usually not diagnosed until puberty Symptoms: failure of normal male sexual development (sterility, small penis and tests, large breasts, minimal or absent body hair, decreased muscle development)

Answer 27

Extra Y chromosome on males 1/1000 Symptoms: not physically obvious, may be taller, normal sexual development, can have kids (complications: risk of learning disabilities, delayed language development and skills and motor skills, hypotonia, motor ticks, behavioural and emotional difficulties, autism)

Answer 28

In an organism, one metabolic step is catalyzed by one enzyme One gene = one enzyme Genetic input in each metabolic step in an organism

Answer 29

PKU in 1934 by folling He found 2 children with severe mental retardation and noticed that the urine had an unusual odor. He found it had an unusual chemical reaction with FeCl and discovered it was phenylpyruvic acid. Found that 8 of 430 children shared the same reaction. He found it was chased by a blocking of tyrosine formation from phenylalanine, resulting in a build-up of phenylalanine and resulting in the formation of phenylketones

Answer 30

Substrates: acylcarnitines (MCAD) Products: glucose (GSD I-glycogen storage disease) Byproducts: succinylacetone (type I tyrosinemia) Enzyme: hexosaminidase (Tay-Sachs disease) Gene: aldolase B (HFI)

Answer 31

Bickel found that restriction of dietary phenylalanine intake prevents mental retardation. He found the diet must be instituted before any significant symptoms are evident.

Answer 32

Biopterin: allows more tolerance of Phe in diet as a chaperone therapy but very expensive Large natural amino acid supplements: Phe enters the brain via LNAA transporters so LNAA act as competitive inhibitors Enzyme replacement therapy: give enzyme that breaks down Phe either orally in intestines of parenterally in blood Gene therapy

Answer 33

Tertiary; treatment of affected individuals to prevent séquelae (presenting clinically) Secondary: early diagnosis and treatment prevent morbidity, trying to find the disease before an individuals expresses it Primary: intervention to prevent disease, stop smoking

Answer 34

Guthrie test Put a drop of blood on agar that contains a bacteria that is Phe dépendant in growth. Blood diffusés out radial, the concentration dropping as it goes. The larger the bacterial circle the higher the Phe and the higher the chance they have PKU Also used tandem mass spectronomy

Answer 35

Disease characteristics: serious, natural history understood, preclinical stage (high prevalence, period before overt disease) Screening test: sensitive and specific, simple and cheap, safe and acceptable, reliable Diagnosis and treatment: facilities are adaquste, effective acceptable and safe treatment available

Answer 36

Results from the disruption in the sequential degradation of by-products or cellular turnover Most are autosomal recessive disorders excepts for Danon, fabry, and hunter syndrome Results in storage of hndegraded substrate

Answer 37

Small molecule disease: carbs, amino acids, organic acids, purines/pyrimidines Organelle disease: lysosomal, peroxisomal, mitochondrial, golgi/ER

Answer 38

As fatty acids are shortened via fatty acid oxidation, enzymes don’t work as well with smaller chains resulting multiple enzymes overlapping in the cycle in normal bêta oxidation Occurs when one enzyme defect blocks remaining chain Risk factor: infancy (30% risk of death due to severe fasting hypoglycaemia, 30% risk of beurocognitive disability) Treatment is highly effective/simple using intravenous glucose and avoiding fasting

Midterm Flashcards

(62 cards)