cidp 4

  1. groups in herbal medicine
    TwHF and sulfasalazine
  2. clinical responses in Herbal
    physical global score, pain score, tender joint count
  3. lab réponses in herbal
    • serum levels of ESR (erthyrocyte sedimentation rate)
    • CRP 
    • interleukin
  4. American College of Rheumatology Criteria (ACR20)
    20% of population showed improvement in pain and physical scores
  5. further studies for herbal
    • isolate effects from prednisone
    • extraction of TwHF
  6. which are paranodal and nodal proteins
    • paranode: contactin-1 and neurofascin 155
    • node: neurofascin 186
  7. multifocal motor neuropathy
    • affects peripheral motor nerves 
    • multifocal muscle weakness and conduction block
    • auto-antibodies against neurofascin 186 and gilomedin
    • responds to IVIg
    • IgM auto-antibodies against gangliosides GM1 are present in 50% of the patients
  8. what was the question in contacting and NF study?
    are contacting and NR targets of auto-antibodies in MMN?
  9. ELISA
    measures concentration of antibody in solution using color change
  10. what was a control used in detecting contacting and NF autoantibodies?
    • antibodies to contactin, NR 155/186 showed good binding to transfected cells
    • no detection of binding in patient's or control's sera.
  11. what were the ways in which they measured the role of contactin and NF role in MMN?
    • ELISA
    • cell binding assay
    • binding to murine teased fibers
  12. binding of murine teased fibers
    • patient's sera did not bind to nodal or paranodel region of murine teased fibers or anti-NF 155-186
    • clear detection in CIDP sera
  13. phase 2 how many people
    100-300 people
  14. charcot marie tooth type 1A how many types total, what kind of disease is it, how many percentage of people have it
    • rare inherited peripheral neuropathy
    • caused by autosomal dominant duplication of gene on chromosome 17 (PMP22 protein)
    • 5 types
    • 70-80% of CMT diseases
  15. what does duplication of PMP22 mean?
    • abnormal S.C. myelination
    • affects structure and function, hence axonal loss and muscle wasting
    • weakness in feet and lower legs (foot drop, high foot arch)
  16. what does PXT3003 consists of?
    • baclofen
    • naltrexone
    • sorbitol
  17. baclofen
    • skeletal muscle relaxant
    • treat spasticity (muscles are always contracted)
  18. naltrexone
    opiate receptor antagonist (interferes with and inhibits the action of another), treat opiate addiction
  19. sorbitol
    metabolite in polyol pathway from glucose to fructose, treats intestinal disorders, reduces inflammation
  20. what are the four groups in CMT1A study?
    placebo, low dose, intermediate dose, high dose
  21. measurements for improvement in CMT1A
    • CMTNS (36 point scale based on 9 parameters)
    • ONLS (quality of life)
    • functional measures (walk test, finger dexterity)
    • Electrophysiological parameters
  22. limitations of EMG
    • can only examine distal nerves
    • dependent on target innervation (if your target cannot elicit a response, the extent of distal regeneration cannot be evaluated
    • variability in interpretation
    • longitudinal biopsy not practical and serial
  23. DTI
    diffusion of water in a tensor (direction vector) through an axon measured via imaging (MRI)
  24. what are the sizes of fiber in CNS vs. PNS?
    • CNS (1-2 um)
    • PNS (5-20 um)
  25. fraction anisotropy
    • paths of many protons summed into a scalar value that describes the groups' elliptic diffusion path
    • (lower more disease 0-1)
  26. what was the purpose of DTI experiment?
    to see if DTI can distinguish between healthy and diseased individuals and how FA correlates with traditional evaluations of peripheral neuropathy
  27. conclusion for DTI
    • mean FA provides a valid noninvasive assessment of axon integrity even in proximal regions
    • -correlates with EMG and INCAT (correlates with axonal changes)
  28. for DTI what happens with damages to axonal structure?
    decrease barriers imposing a diffusion tensor
  29. future studies for DTI
    • increase power
    • more sample size
    • correlate longitudinal individual axonal changes with FA
  30. vinculin
    • 117 kDa protein associated with integrin mediated cell matrix adhesion and cadherin-mediated cell cell junctions
    • focal adhesion protein in S.C
  31. difference between active and inactive form of vinculin
    • active localizes to focal adhesions at the membrane
    • inactive form is cytoplasmic
  32. what mediates axon pathfinding through interactions with the extracellular matrix?
    nerve growth cones
  33. what was found in previous studies to be responsible for chemorepulsion
    MAG (myelin associated glycoprotein) stimulates Ca2+ signals in growth cone
  34. where was the proteins where patient antibodies could react with come from?
    pig cauda equina (spinal nerves)
  35. how did they detect vinculin, potential auto-antigen?
    • membrane with proteins from pig caudal equine 
    • membrane reacted with serum from CIDP patients and controls
    • immunoreactive protein bands identified via mass spec
  36. how was it verified that vinculin was in fact in CIDP patient's serum?
    human recombinant vinculin subjected to western blot and reacted with sera from patients
  37. recombinant DNA
    inserting human vinculin gene into E.coli and producing the protein.
  38. igG
    immunoglobulin G, the most common antibody found in human sera
  39. integrin protein
    transmembrane receptors that are the bridges for cell-cell and cell-extracellular matrix (ECM) interactions
  40. what were the MAG studies done in?
    Xenopus spinal neurons
  41. A focal MAG gradient induced
    polarized endocytosis and concomitant asymmetric loss of beta(1)-integrin and vinculin-containing adhesions on the repellent side during repulsive turning
  42. where did Sarah sing in?
    second soprano solo in Gregorio Allegri's Miserere
Card Set
cidp 4