Situs inversus was diagnosed at birth. Since infancy, she had had chronic cough with ... pregnant for three years. There was no historyofsalpingitis. The findings.
Ciliary Ultrastructure of Respiratory and Fallopian Tube Epithelium in a Sterile Woman with Kartagener’s Syndrome A Quantitative Miriam
M.D.;*
Lurie,
Ido Katz, Shulamit
Estimation han
M.D.;Jaron Goldenberg,
Tur-Kaspa,
M.D.;t
Rabinovici, B. Sc. *
Shoshana
M.D.;t
esticomplete KS. Ciliated epithelium was obtained from both nasal mucosa and a fallopian tube. Cilia from both locations were devoid of DA. Various MT abnormalities were found in 16 percent ofrespiratory epithelial and 21 percent of fallopian tube ciliary cross-sections. The abnormality related to radial spoke defect was frequently seen. The findings in the mated
C
was studied and quantitatively sterile woman suffering from
ultrastructure in a 27-year-old
Ciliary
ilia ofrespiratory KS have
tract
been
studied
examination of these cilia, mation of ciliary defects, diagnostic
procedure
ICS; however, of the genital KS
.
These
epithelium
ofpatients
extensively.
Ultrastructural
with
and
other
patients
are
at
high
risk
for
It is not absoin ciliary
motility or ultrastructure (or both) affect We report the ultrastructural findings
fertility. of respiratory
placed
on
tube epithelium complete KS.
quantitative
MT abnormalities. tuba!
For
epithelium
of DA
comparison,
of three
fertile
and
we also
findings
KS Kartageners DAdynein arms;
x-ray
films,
Ciliary
A
27-year-old
diagnosed copious
osmium
5). Mucosal
All
of
shortness
At the of
breath.
complete
age of five years,
of 18 years, Sinusitis,
to become
historyofsalpingitis.
From the *Dep.tment
The
pregnant findings
the
patient
Situs
inversus
chronic she
identified. for
seven
underwent and
for three years. from routine physical
of
with nasal
to complain ciliary and There
had
beat tried was
no
examination,
Pathology, Carmel Hospital, Technion Medical School, Haifa, and the tDepartments of Obstetrics and Gynecology and of tRespiratory Diseases, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Manuscript received March 30; revision accepted July 18. Reprint requests: Dr. Lurie, Car’mel Hospital, Michal St,et, P0 Box 7222, Ha(fa, Israel 34362
578
Downloaded From: http://173.193.11.217/ on 02/20/2013
and
sections
way
for electron
visible
cilia
which
were
times.
from
the basal
cut cilia
were
used
and
inner
with
cross-sections
normal
acetate Oem
were
100-
obtained
by
biopsy,
were
and
at an original was
details
of DA.
found
excluded.
DA
Cross-
Only
ideally
a mean
are
DA
were
number
Typical
was calculated.
or missing
enable
cilia.
and inner
and
were
magnifito
of the
Outer
cross-section,
cross-section
per
uranyl
transversely
part or the tips were
for each DA
cut
magnification
for evaluation
separately
1
microscopy.
were
of axonemal
sections
with
in
in epoxy
endocervical
photographed
This
visualization
postfixed
microscope which
then
and
hours
embedded
stained
and
electron
in 2 percent
hours,
and
measured
For
eight
two
tract,
the same
50,000
for
genital
endometrial
and
of was
Respiratory medial nasal
fixed
on an electron
of the
satisfactory
counted
was
brush.
for
were
examined
portion biopsy
epithelium
acid
in
of
were
fimbrial
METHODS
buffer
the
satisfactory
outer
significant
Nasal years
was
cough
began
bronchiectasis,
reversible airway obstruction were frequency was found to be zero. The patient had been married unsuccessfully
KS.
she had had
infancy,
At the age
cation
syndrome;
An endometrial
dehydrated,
Ultrathin
biopsy
the
immediately
tannic
specimens
prepared
women.
phosphate
tetroxide,
citrate
from
bronchoscopic were
1 percent
(Epon).
and lead
cilia
hysterosalpingography
of respiratory
specimens in
percent
95:578-81)
of an optical photoelectric system.2 were obtained by brushing the a fiberoptic
the in
resin
AND
frequency
immersed
and
MATERIALS
1989;
immotile
a biopsy performed.
using
fimbrial
examined
clear.
was
by means specimens
glutaraldehyde
REPORT
had
Since
expectoration.
polypectomy. of
woman
at birth.
tube
beat
in vitro
studies,
laparoscopy,
the left fallopian done.
microscopy
various
is not
syndrome; ICS MT microtubular
laboratory
During
technically CASE
to fertility
(Chest
turbinate
of a sterile woman Special emphasis was
estimation
these
mucus
sterility,
although pregnancy is not impossible.’ lutely clear to what extent abnormalities
and fallopian suffering from
fallopian tubes were compared to three normal control cases. In these, DA were visible, and MT defects were mainly of excess or missing microtubules. The relevance of
with
are few reports dealing with cilia of female subjects suffering from
patients
M.D.;*
normal.
including quantitative estiis considered an essential
in these
there tract
Weill,
and
shown
of
ciliary
in Figures
1
and 2. A larger
number
configuration. to
of cilia
Microtubular
conform
to
the
classified
as follows:
decrease
in the
outside
the
of ciiary
central
doublets;
classic
peripheral
ring;
microtubules
as defined
(3) radial
spoke
defect’ by
inner
singlets
accompanied
outer
doublets;
(4) total
Ciliary
or doublets, by
disarray:
Uftrastructure
totally
disorganized
in Kartagenes
or
inside
or
transposition al,
Ic,
one
of
as eccentric
displacement
were
increase either
et of
visualized central
as failure and
defect:
Sturgess
displacement
of MT
defined
microtubules:
(2) transposition
central
evaluation
arrangement
or missing
of singlets
for were
nine-plus-two
(1) extra
and
examined
abnormalities
number
singlets
were
missing
the
outer
position of one
of
pair of
microtubules;
Syndrome
(Lurie
et a!)
j
sections of normal cilia magnification x 83,000).
1 . Cut original
FIGURE
citrate,
(uranyl
acetate
and
lead FIGURE 5. Transposition Central singlets are toward center (uranyl x66,000).
I4
2. Cut citrate,
FIGURE
and
lead
section original
of cilia with magnification
DA
deficiency x 83,000).
(uranyl
defect (two cut sections in upper field). missing, and outer doublets are displaced acetate and lead citrate, original magnification
acetate #{149}L
\‘OQ11. -‘.
,‘
G,V?
‘i. sl
/‘sh.
! 6. Radial spoke defect (cut section in center of field). position of central singlets and central displacement doublets (uranyl acetate and lead citrate, original X 66,000).
FIGURE
FIGURE
ring
and
3. Cilia with extranumerary missing DA (uranyl
FIGURE
arms cation and
Cilia are visible X 66,000).
with missing external (tiranyl acetate and
4.
(5) compound
cilia
arrangement
malformations The
of the
accurate
women
Radial sections
was
control were
hysterectomy
in a similar
cases
for
of three
Respiratory Two
hundred
mean
one
nine-plus-two
Typical
med
Dynein inagnifi-
examples
of
in 384 found frequent
tubules percent).
aged
37, 39, during
for fibromyoma
and tubal
as well
from
spokes
were
not
considered ciliary fertile
40 years, ligation (case
the
ciliary
for
for
to
most MT
thirty-one
number
were
MT
Epithelium
suitable
identical
microtubules,
healthy
way.
Tract
considered
than
calculated
tubal
of mag-
RESULTS
DA
outer inner
to
DA
was
DA.
have
cross-sections
evaluation 0.4
per
MT
cross-section,
63 (16
abnormalities was
followed
exam-
percent)
(Table
extra by
1). The
were
of which
abnormality
were
(Table
Microtubules
cross-sections,
(9 percent),
not
the total
evaluated good
as of each
number
2).
or missing
radial
The
micro-
spoke
defect
(3
because enough
the to
Fallopian
Tube
of give
In the no outer
structure, women
specimens were
respectively, (cases
3). These
used.
and 1 and
specimens
from These
the biopsies
2) and
during
were
treated
were
208
cross-sections
or inner
sections
biopsy performed
examined
Note
3 to 6.
malformed
were
and
of microtubules. citrate, original
axoneme.
in Figures
outside peripheral citrate, original
results.
fimbrial were
separately,
cross-sections.
quality As
ofall
pair lead
more
a single
are shown
percentages
malformation ciliary
containing
within
lead
_,_ (:)
x 66,000).
magnification
microtubules acetate and
eccentric peripheral nification
DA
were
for
MT
evaluated found
to show
abnormality
in
abnormality
considered
defect
in the
examined
the
respiratory
visible.
103
abnormalities.
The
cilia
epithelium
of tubal characteristic tract
DA,
Of the
structure,
CHEST
Downloaded From: http://173.193.11.217/ on 02/20/2013
for
492 (21
most for
almost cross-
percent) prevalent was
radial
(9 percent),
I 95 I 3 I MARCH,
the spoke
followed
by
1989
579
Table
DA in a Case
1-Ciliary
ofKartagener
Table
Syndrome*
3-Ciliary
DA ofFallopian Tube Epithelium Healthy Women#{176}
from
Three Data No.
ofcross-sections
Outer
Nasal
F allopian
Mucosa
Tubes
231
examined
208
No.
DA
95
per
Inner
cross-section
25
DA
No.
89
per
*DA,
cross-section
dynein
0.4
metrium
were
estimation.
too
The
Fallopian
tube
showed 3.6, 2.8,
section
poor
very
between frequent
(8 percent). uterine cervix
in cilia few
to enable
TotalNo.
0.01
No.
endo-
cilia
in the
of DA. The findings from of these were normal.
epithelium
taken
from
three
control
8.6, and 8.7 outer DA, DA per ciliary cross-
3). Microtubular
6.2 and 15.7 ones being
and
abnormalities
ranged
per 100 cross-sections, the most extra or missing microtubules
4).
The
ICS
gener’s
as defined
syndrome,
Characteristic definition.
since
included
1933,
malities have been described The importance of quantitative
are part ciliary
in the respiratory estimation
dynein
471
535 8.7
8.6
counted (mean, 3.7
280
2.8
arms. In a survey conditions from
between 44), with
9 and a mean
4.5
and
per cross-section data). Other ICS are
in
of our
18 cases laboratory,
cross-sections result of 6.9 outer
four
in 14 cases DA and 0.05 cases
of
KS
with
we
per case DA and
200
DA per cross-section less than 0.5 outer
inner
KS,
156
3.6
arms.
other inner
than DA
(unpublished
abnormalities which have been related to the defective radial spokes5 and transposition of
ciliary been
microtubules. considered
recent
quantitative
These two nonpathognomonic studies.8”
is another
in
patients
abnormalities for ICS
Disorientation
abnormality
with
have in more of the
which
ICS,7”#{176}but
also
has
been
in
other
8,10
Secondary
tract. of their
342
cross-section
Kataof this abnor-
or nonspecific
compound
cilia,
with
extra
or
the
normal
and
large
MT
disorganized missing with
pattern), excess
include
and
microtubules
nine-plus-two cilia
abnormalities
axonemes
axonemes
(deviations
from
internalized
cilia,
cytoplasm.7’9”8”9
average higher
frequency in patients
chronic
respiratory
DA.7’8”5”6
ports.9”#{176}”4’#{176} Others found a wide range of abnormalities in patients with ICS’8 or no statistical difference in MT abnormalities between patients with or without
rae
with ultrastructurally described.”7 The difficulties DA are well known, and only syndrome
cut The
ciliary outer
profiles can be arms are usually
Table
used more
cases
of
Katagener’s
normal DA have been in the visualization of perfectly transversely for their evaluation. easily demonstrable
2-Ciiary MT Abnormalitie8 Kartagener’s Syndrom&’
in a Case
KS.’ Whereas Table
men
has been found with KS than
Their
relative incidence has often been stressed.8’ The most common and reliable primary ciliary abnormality related to ICS is missing or shortened Nevertheless,
conditions
with
ICS
are
in
Nasal
Fallopian
Mucosa
Tubes
No.
Case
ofcross-sections
Normal
microtubules
Extra
and
missing
Transposition Radial spoke Total
examined
defect defect
384
321 microtubules
36
MT abnormalities
*MT,
microtubular.
Downloaded From: http://173.193.11.217/ on 02/20/2013
389 40
(100)
Normal
(79)
Extra
(8)
0
microtubules and
missing
9 (2)
Complex
(16)
(9)
103 (21)
Case
2
(100)
204
(100)
210
(94)
172
(84)
Case
3
defect
microtubules
Total MT abnormalities *MT
280 236
(100) (84)
micro-
defect
1 (0.3)
46
1
8 (4)
Transposition
Radial spoke Total disarray
(3)
(percent)
224
tubules
8 (2)
63
580
492
2 (0.5)
13
microtubules
Total
(9)
11 (3)
disarray
Complex
(100) (84)
Tube
Women*
of cross-sections examined
No.
with
(percent)
Data Data
re-
sterile,
ofFallopian
Healthy
Three
several
usually
MT Abnormalities
4-Ciliary Epitheliumfrom
of
to be significantly in various other
No. No.
3
62
8.3
than the inner various respiratory
as a subgroup.
ultrastructural defects A variety of ultrastructural
Case
54
154
per
found
by Afzelius,6’7
known
2
41
cross-section
microtubules DISCUSSION
Case
DA
3
quantitative
well-preserved
a mean of 8.3, and 4.5 inner
(Table
(Table
per
*DA,
endometnum showed lack routine histologic examination
and
:
arms.
extra or missing microtubules Mucosal specimens of the
cases
No. Inner
TotalNo.
examined
1
DA
TotalNo.
0.12
0.4
Case
ofcross-sections
Outer
TotalNo. No.
Data
18
(9)
34
(12)
0
8 (4)
6 (2)
2 (1)
1 (0.5)
0
2 (1)
1 (0.5)
2 (1)
2 (1)
4 (2)
14
(6)
32
(16)
2 (1) 44
(16)
microtubular.
Ciliary
Ultrastructure
in Kartagener’s
Syndrome
(Lone
et a!)
very
few
exceptions,
are
less
the
findings
There of the
.
few
found
and
fallopian
Pederson
earlier
of whom report’ of only three
concluded
of ciliary
tract cilia
in ICS.
devoid
6 Afzelius
BA.
A human
Science
1976;
193:317-19
tubes’’
found
a lack
of
study,
had
of cilia
found from
DA
woman Hando
MT
BA.
Immotile
cilia
syndrome
by
infection
and
injury.
cilia
report,2”
reproductive been
tracts
ofan
investigated
of both
sites
cilia
of the
infertile
with
nasal
and 10
for motility
were
found
immotile
or totally lacking DA. We are not aware of any previous of abnormalities fallopian tube the influence noteworthy
These
in
the
three
of fertile women, 6.2, 15.6, and
defects
were
microtubules. lack
with
a high
of DA
defects.
Nielsen
The
practical
Cilia
study
and
MT
to ICS
and
influence
the
Dis
Biopsy
ofthe
spoke
tube
ACKNOWLEDGMENT: reviewing the manuscript work.
We thank Professor and Mrs. K. Lutvak
of
18
in the
BA,
19
immotile
cilia
K. Male
JR,
with an
Ducket
optical
KE.
20
J,
Dewes
studies
analysis
A, Cox
4 Sturgess
JM,
tubules:
J,
Chao
another 1980;
T, Cole
J
ultrastructure. cause
Clin
Turner
Fox
D,
Christensen
chronic
Jouannet
B,
of
cilia
from
Ermini
Mygind from
N.
Blind
patients
with
subjects.
normal
C.
Abnormalities
bronchitis:
Lung
1983;
Eur J
of bronchial
an ultrastructural
and
161:147-56
P. David
complex
B,
Bull
C.
in children:
Abnormalities
an
B,
Makey
AB,
of the
ultrastructural
Rawbone
abnormalities
Pedersen
M, Morkassel
R.
of human
E, Nielsen
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Chest
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a spectrum Dis
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64(suppl
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24
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Afzelius
female fertility in this syndrome important but
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Jean
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