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Aberrant cell cycle reentry in human and experimental inclusion body myositis and polymyositis.
[inclusion body myositis]
Inclusion
body
myositis
(
IBM
)
,
a
degenerative
and
inflammatory
disorder
of
skeletal
muscle
,
and
Alzheimer
's
disease
share
protein
derangements
and
attrition
of
postmitotic
cells
.
Overexpression
of
cyclins
and
proliferating
cell
nuclear
antigen
(
PCNA
)
and
evidence
for
DNA
replication
is
reported
in
Alzheimer
's
disease
brain
,
possibly
contributing
to
neuronal
death
.
It
is
unknown
whether
aberrant
cell
cycle
reentry
also
occurs
in
IBM
.
We
examined
cell
cycle
markers
in
IBM
compared
with
normal
control
,
polymyositis
(
PM
)
and
non-
inflammatory
dystrophy
sample
sets
.
Next
,
we
tested
for
evidence
of
reentry
and
DNA
synthesis
in
C
2
C
12
myotubes
induced
to
express
β-amyloid
(
Aβ
42
)
.
We
observed
increased
levels
of
Ki-
67
,
PCNA
and
cyclins
E
/
D
1
in
IBM
compared
with
normals
and
non-
inflammatory
conditions
.
Interestingly
,
PM
samples
displayed
similar
increases
.
Satellite
cell
markers
did
not
correlate
with
Ki-
67
-
affected
myofiber
nuclei
.
DNA
synthesis
and
cell
cycle
markers
were
induced
in
A
β-bearing
myotubes
.
Cell
cycle
marker
and
cyclin
protein
expressions
were
also
induced
in
an
experimental
allergic
myositis
-like
model
of
PM
in
mice
.
Levels
of
p
21
(
Cip
1
/
WAF
1
)
,
a
cyclin-dependent
kinase
inhibitor
,
were
decreased
in
affected
myotubes
.
However
,
overexpression
of
p
21
did
not
rescue
cells
from
Aβ-induced
toxicity
.
This
is
the
first
report
of
cell
cycle
reentry
in
human
myositis
.
The
absence
of
rescue
and
evidence
for
reentry
in
separate
models
of
myodegeneration
and
inflammation
suggest
that
new
DNA
synthesis
may
be
a
reactive
response
to
either
or
both
stressors
.
Diseases
Validation
Diseases presenting
"first report"
symptom
achondroplasia
alexander disease
aniridia
cadasil
canavan disease
child syndrome
cohen syndrome
congenital toxoplasmosis
cowden syndrome
cushing syndrome
cutaneous mastocytosis
cystinuria
dedifferentiated liposarcoma
dentinogenesis imperfecta
dracunculiasis
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
esophageal squamous cell carcinoma
fabry disease
familial mediterranean fever
focal myositis
harlequin ichthyosis
hirschsprung disease
hodgkin lymphoma, classical
holt-oram syndrome
homocystinuria without methylmalonic aciduria
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kindler syndrome
krabbe disease
lamellar ichthyosis
liposarcoma
lymphangioleiomyomatosis
monosomy 21
neonatal adrenoleukodystrophy
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
omenn syndrome
pendred syndrome
pleomorphic liposarcoma
primary hyperoxaluria type 1
pyomyositis
pyruvate dehydrogenase deficiency
scrub typhus
severe combined immunodeficiency
sneddon syndrome
triple a syndrome
typhoid
waldenström macroglobulinemia
werner syndrome
wiskott-aldrich syndrome
x-linked adrenoleukodystrophy
zellweger syndrome
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