Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Molecular Basis of Disease > Muscular dystrophy > Flashcards

Muscular dystrophy Flashcards

1
Q

What type of muscle is skeletal muscle?

A

Voluntary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How many muscles are found in the body?

A

640

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the main functions of muscles?

A

Posture

Locomotion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Muscles are able to regenerate

TRUE or FALSE

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the stem cell found in muscle called?

A

Satellite cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the smallest unit of muscle?

A

Myofibrils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is a collection of myofibrils called?

A

Fascicles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the layer of connective tissue that surrounds the fascicles called?

A

Perimysium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the layer of connective tissue that surrounds each individual muscle fibre?

A

Endomysium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the plasma membrane of the muscle fiber called?

A

Sarcolemma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the cytoplasm of the muscle fiber called?

A

Sarcoplasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the name of the endoplasmic reticulum of the muscle fiber called?

A

Sarcoplasmic reticulum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the role of the endoplasmic reticulum?

A

Stores, releases and retrieves calcium ions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the name of the functional unit of a skeletal muscle fibre?

A

Sarcomere

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the divisions of muscle

A

Sarcomere

Myocytes

Fascicles

Muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What type of nuclei are found in cells composing skeletal muscle?

A

Post-mitotic nuclei

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Is skeletal muscle innervated?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Is skeletal muscle vascularised?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is muscular dystrophy?

A

Inherited disorder where strength and muscle bulk gradually decline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the different conditions of muscular dystrophy?

A

Duchenne muscular dystrophy

Becker muscular dystrophy

Emery-Dreifuss muscular dystrophy

Limb-girdle muscular dystrophy

Facioscapulohumeral muscular dystrophy

Myotoic dystrophy

Oculopharyngeal muscular dystrophy

Congenital muscular dystrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What characterises the different muscular dystrophies?

A

Different mutations to the gene coding for the protein complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the differences in presentation between the different muscular dystrophy types?

A

Different types of muscle affected

Different severity in symptoms

Different onset

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe the appearance of normal muscle

A

Fibres are polyglonal

Fibres are tightly packed

Fibres show little variation in size

Nuclei of muscle cells are found on the edge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe the appearance of muscle in MD patients

A

Cells are characterised by necrosis and fibrosis

Diffuse variation in size

Deposition of adipose tissue

Inflammation

Regeneration observed as small cells with large nuclei

More nuclei internally

Abnormal cells with whorled appearances

Split fibres

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

You can diagnose the type of MD by muscle biopsies

TRUE or FALSE

A

FALSE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What cells do MD pathologies affect?

A

Muscle fibres

Satellite cells

Extracellular matrix

Inflammatory cells

Fibroadipogenic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the consequence of extracellular matrix defects in MD?

A

Dysfunction in the extracellular matrix consequently affects

  • satellite cell niche
  • signalling
  • physical barrier to stem cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the dystrophin-associated complex?

A

Protein that spans the cell membrane and whose mutations at different parts of the complex cause different MD pathologies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Which part of the dystrophin-associated complex is affected in DMD?

A

Dystrophin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Which part of the complex is affected in Becker MD?

A

Dystrophin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Which part of the complex is affected in Emery-Dreifuss MD?

A

Emerin

Lamin

32
Q

Which part of the complex is affected in Limb-girdle MD?

A

Sarcoglycans

33
Q

What does DMD stand for?

A

Duchenne Muscular Dystrophy

34
Q

What is DMD?

A

Progressive, muscle-wasting neuromuscular disorder

35
Q

What proportion of the population is affected by DMD?

A

1 in 5000 newborn boys

36
Q

Describe the pathogenesis of DMD

A

Deficit in dystrophin causes muscle cell death upon contraction

Muscle undergoes successive rounds of degeneration and regeneration

Eventually the muscle tissue is replaced by fibrotic tissue

37
Q

Why is muscle replaced by fibrotic tissue in DMD?

A

The muscle regeneration cannot keep up with the degeneration

38
Q

At what age do patients with DMD lose ambulation?

A

10-12 years

39
Q

At what age do patients with DMD die?

A

Early adulthood (25-30 years)

Advances in treatment have increased the survival in patients

40
Q

What is the best way to monitor a treatment for MD patients?

A

Ambulatory assessment

41
Q

What is an ambulatory assessment?

A

6 minute walking test

42
Q

What is fibrotic tissue composed of?

A

Fat

Connective tissue

43
Q

What causes the loss of stem cells in muscle of DMD patients?

A

Not known

Are they lost via apoptosis

Does the pathological environment cause them to not work correctly

44
Q

What is the main difference between Becker MD and DMD ?

A

Becker is a milder variant of DMD

45
Q

What makes Becker MD a milder condition than DMD?

A

Later onset

Progression of the disease is variable

Loss of walking ability is only seen in 18% of cases

Scoliosis is very uncommon

46
Q

What mutation causes Becker MD?

A

Deletion mutations that lead to misshapen dystrophin

Still maintains the reading frame

Loss of amino acids that are not essential to dystrophin function

Dystrophin produced is functional but still semi-functional

47
Q

What mutation cause DMD?s

A

Frameshift mutation that cause translation to end earlier on the gene

Loss of amino acids that are essential to dystrophin function

No functional dystrophin is produces

48
Q

What is the role of dystrophin?

A

Attaches the dystrophin associated protein complex to the actin of the ECM

Prevents the myocyte cell membrane from ripping apart during the contraction of muscles

49
Q

What makes the discovery of the dystrophin gene unique?

A

The gene was discovered before the protein

50
Q

Where is the dystrophin gene localised?

A

xp21

51
Q

What causes the different isoforms of dystrophin found around the body?

A

Different promoter sequences

Code for different lengths of dystrophin needed in different parts of the body

52
Q

What happens to the muscle following a lack of dystrophin?

A

Myofiber degeneration

Satellite cell activation

Muscle regeneration

Altered composition and stiffness of ECM

53
Q

What are current treatments for DMD patients?

A

Corticosteroids

Ventilation

Cardiac care

Psychological management

Skeletal management

54
Q

What are potential therapies for DMD?

A

Gene therapy through AAVs

Readthrough of stop codons

Antisense oligonucleotides

Stem cells

55
Q

How does gene therapy through AAVs alleviate DMD presentation?

A

They lessen the severity of the symptoms by changing the condition from DMD to Becker

Since AAVs are not able to carry the whole gene

The protein is too large

56
Q

What is the main issue in treating MD?

A

It is a condition with multi-organ presentation

Many aspects of MD need to be tackled

57
Q

Which molecules are used in exon skipping?

A

Antisense oligonucleotides

58
Q

Describe the process of exon skipping in DMD

A

Open reading frame disrupted in DMD forms truncated, non-functional dystrophin

Exon responsible for the frameshift mutation is skipped

This restores the reading frame

Forms an internally deleted, partly functional dystrophin

59
Q

What is the most common mutation that causes DMD?

A

Out-of-frame deletions

Out-of-frame duplications

Occurs to 70-75% of DMD patients

60
Q

What is an outcome measure?

A

Indicates a measure of the result of a system relative to the aim

Used as a measure of the success of a trial

61
Q

What is normally the primary OM of a clinical trial?

A

Safety

62
Q

Why are biochemical OMs of dystrophin patient not good measures of the improvement of a patient?

A

Tells you if the treatment increases dystrophin levels

Does not necessarily correlate to the functional improvement of a patient

63
Q

What type of OM is used to assess functional improvement?

A

Clinical OM

6 minute walk

64
Q

Why is dystrophin quantification at protein and RNA levels difficult?

A

Low levels of a very large protein

65
Q

What are ways to carry out biochemical OMs of treatment modalities used for DMD?

A

Can asses the exon skipping and dystrophin quantifications by immunohistochemistry and western blotting

66
Q

What is a disadvantage of AONs?

A

Ineffectively target the heart

90% of DMD patients suffer cardiac complications

67
Q

How can we increase the efficacy of AONs targeting the heart?

A

Conjugate AONs with cell penetrating peptides to enhance cell delivery

68
Q

What is a disadvantage of using modified AONs?

A

Increased toxicity

69
Q

What are targets of DMD therapy?

A

Premature stop codons

Out of frame deletions or insertions

Absence of functional dystrophin

Loss of regenerative capacity

Loss of muscle mass

Disruption of signalling, inflammation and ROSs

70
Q

What is a therapy that targets premature stop codons?

A

Aminoglucoside antibiotics

Read through stop codons

71
Q

What is a therapy that targets out of frame deletions or insertions?

A

Exon skipping with antisense oligonucleotides

72
Q

What is a therapy that targets the absence of functional dystrophin?

A

Dystrophin gene therapy

Utrophin upregulation

73
Q

What is a therapy that targets the loss of regenerative capacity?

A

Stem cell therapy

74
Q

What is a therapy that targets the loss of muscle mass?

A

Myostatin blockade

75
Q

What is a therapy that targets that targets the disruption of signalling, inflammation and reactive oxygen species?

A

Pharmacological intervention

76
Q

Examples of drugs used to aid the disrupted signalling, inflammation and ROSs seen in MD

A

Steroids

Immunosuppressants

Calcium buffering

NF-kB blockade

Anti-oxidants

Molecular Basis of Disease (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions