From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
Changes
in
Cellular
Composition
by
T
By
M.
H.
HE
ANEMIA
in mats
Ioss,
Ionizing
PH.D.,
and
atscl
.J.
the
animals
of
Lymph
Caused
Radiations
i’sI.D.
FUIITII,
pathogetsesis
after
the
of the
exposure
H.
AND
BIGEIow,
H.
hemorrhagic
to massive
tetidency
iotsizitsg
ing
studies
msow to be (lescril)ed
indicate
that capillary
fragility
is a major
factor
amsd that
these
changes
may brimsg about
atsemia,
process
death
causing
of the
irradiated
MATERIAL
Preparation
Time
of Exteriorized
operative
Hardemih)ergh
thsoracic
duct,
(polvviumvl
amuot her
exteriorize(l
(fig.
prevent
were
canmnmula
duct
When
sammupliumgs
time loop
cared
was
for
time
as
venuous
Lymph
or
made
were
Experimental
The
either
veimu,
extemuded
by
t horacic
ligatures
musade
time
fist ula
and
the
loot)
was
superior
vemma
canunula,
returmued
aureomycinm
3
I to
the
body.
after
to
was
To
about
inmside
disconumiected,
dog
cava.
fenestrationis
enm(led
ext
places
was
the
anmd
conniectinsg
the
several
Brown
into
the
of the
by
imut roduced
and
camummula
at
1(X) nuug. of
operations
comisecutive
into
at thue tip
ly
was
which
time cage
injected
amsd
thmrough
days.
in Rats
accor(limig
to
tue
techmnie
of
Bollnuami,
(‘aims
amm1 Grindlav.’j
A nimals
(logs
of
jugular
amsd bandaged
After
inudependeumt
cannsula
occurrimug
tip.
The
were
padded,
Preparation
the
of
fastened
stu(Iies
oni three
developed
canniula
above
anuimal.
that
in Dogs
polyethylene)
often
the
was
well
a muornual
cannula
These
just
recomunected,
Fistula
veumous
and
clearamice
ially
bramuchu
isot
METHODS
Anaslamosis
or
*
clots,
1)100(1
i mmthe
AND
essemit
a large
The
b).
by
t hioracic
nmuade
t lie
inuto
la,
obstruction
cmus. ins
320
was
plastic
are
that
these
two
in caitsation
of
a self-aggravat-
amsimals.
Lymph-venous
l)rocedure
A
.
occurring
irradiation
well umsderstood.”4
‘Fhe
problems
are itsterrelated,
postirradiatiomi
M.I).
were
our
momugrels
owmu
iusbred
weigimimig
himse or
24
to
oi)taimue(l
48
pounds.
frons
the
The
W’istar
rats
were
of the
Institute,
Wistar
weighing
stock
from
200
to
Gnu.
Radiation
The
93.7
factors
cmss.,
the
55
of
r/nsin.
proximuual
*
ton,
skins
()btaimmcd
New
We are
mu preparing
Time
For
(logs,
rats
factors
49 r/mimi.
(lose
thsroughu
for
the
The
courtesy
of
were
250
were
anmimals
time
peak
250
were
Irvimugton
kilovoltage,
30
kv.p.,
30 nsa.,
turned
over
Varnish
amid
at
ma.,
mm.
3
3 ml.
Al,
TSD
half-time
Al.
TSD
117
cm.;
exposure.
Imusulator
Compamuy,
Irving-
Jersey.
t
William
x-radiation
indebted
such
techimical
D.
assistance
Cude
Frons
time Biology
Work
performed
Submusitted
to Dr.
fistulas.
October
of
is hmerebv
amud his
Mr.
Knoohuizen,
Mary
Miss
assistant,
E.
John
Hook,
Van
Lamse,
Ira
for
instructions
Campbell
acknowledged.
I)ivision,
uum(ler
Bollnssamu
Oitk
(‘oumtract
1, 1951
Ridge
No.
; :mccepte(l
Nat
iomsal
W-7405-eng-26
for
pul)licat
417
Laboratory,
for
Oak
time
ions December
Atomumic
Ridge,
Emmergv
21 , 1951
Tenn.
Commission.
and
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
418
IONIZING
AND
RADIATIONS
LYM1’tI
.i,,
p
4.
I
FI(.
(a ) (‘omumuected
(b)
hlooil
1001)
Sanse
(lisdomiiueet
lyniphu
collecte(l
of
time exteriorized
(‘(1 Wi tim s\’ringe
from
t
hue
t
horacic
1
lvmuuphi-vemious
coust aiumiuig
duct
/
ammast Omuuosis.
1)100(1
fist ula.
wit hudrawms
fromn
I lie
vci
ii
amid
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
ROSS,
Examination
of Cells
L-n51)h amid blood
The
cell
cells
appear
In
eouumts
ulas
750
r.
Time
motility
of
technic
11 comutrol
cells
were
and
after
to
15 to
those
Fo;.
2.-Erythrocyte
counts
oui which
tue
after
(training
1)100(1
anud
exposed
by
at 37.5
lyniph
lymph
were
irradiation
inscubation
of
re(l
irradiation,
lymnph
after
of 1)100(1
studied.
sinsce
trauma.
10 hours
hourly
were
fistula,
operative
first
amid
of cells
9
7
in the
autopsy
the
20 mssiusutes
‘3
ii
DAYS
oh auminumals
to
30 controls
the
in
amid by the
C.,
ii
to
observimsg
irradiate(1
and
mu rats.
5
3
due
of
time anuimals
before
Exansinationus
similar
rats
durimug
rats,
tested
microscope
of Scisrek.8
(logs
occurring
was
rats ansd from
establishment
of sonic
ins 3 nornial
ins a phiase
419
ISIGELOW
camsnsulated
huours after
of cisamuges
established
viability
safranimie
a few
mm thue lymph
study
were
43 irradiated,
uuuade
transiemutly
a detaile(l
fist
AND
of the Lymph
frons
were
FURTH
lynsph
of rats
findiuugs
5
9
7
IRRADlATOY.
AFTFR
exposed
inudicated
to 650-750
r of x rays.
a biologically
low
dose
Counmts
of
x rays.
RESULTS
The
Lymph
The
of Irradiated
most
of large
of
The
per
tsormal
100
(c)
fatty
white
the
tsuml)er
appearance
lymph
of
blood
cells.
A1)domilmal
viscera
degemierationu
of
X
amid
a musarked
of
The
dyinug
Note
dog
24 days
of lynuphoid
lymph,
and
the
died
after
with
exposure
tissues.
H
of
rapid
predominance
0 to 2 red
of erythrocytes
after
appearance
atsd
of
leukocytes.
hemorrhagic
16 (lays
rats
comstaiuus
tsumher
of the
irradiated
abmiormal
many
increased
(log.
same
liver.
consist
of
its the
is milky-white
The
atrophy
irradiatiots
lymph
nuesenteric
exposure
lymph
to 340
to ams atomnic
& E stain.
AFIP
blood
its the
cells
lymph
nodes
amid
r.
h)omb
showing
Neg.
259084
hensor-
01084.
125
(e)
Erythrophagocytosis
in
macrophage
-
rats
of
tue
by
in the
of lymphocytes
aisd
(d) Lynuphm muode of a nian
rhage
iisduced
of erythrocytes
lymphocytes
large
chatiges
sigmsificamst
numbers
reductioti
Rats
01083.
X
975
nsitosis
i)y
contaimss
macropimages
numerous
in
a lymph
erythrocvtes.
muode
H & E
frons
stain.
the
same
AFIP
man.
Neg.
One
259084
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
420
IONIZING
RADIATIONS
AND
LYMPH
.5
S
S
#{149}
I
a
A
I
S
D
#{149} .#{149}(‘
FIG.
staimsed
(a)
3-Figures
a-i
with
-Giemuisa
Wrighut
Nornsal
lvnspim
X
erythrocvtes.
amid
c)
Multinucleated
and
e)
Lvnuiph
Mitotic
(is)
Numsserous
Note
rats;
figures
predominuamice
lvnsphocvtes
snusear
a 1)immucleate(1
(g) Mitotic
from
k,
I, fromuu
a (log.
All
snuears
are
staiuus.
snsear.
(d
(f)
lvmumphs smears
of
small
lynuphuoeytes
amid
ai)semuee
of
400
(b
amid
are
cell
figure
. )(
at
figure
of the
ii
ervthrocvtes
anminsal
6 hours
after
exposure
at 8 hours
showing
to
75() r.
‘‘lunupimug’’
of
chmromumat;mu
lOOt)
11 (lays.
at
at
sanse
X
(lays.
1000
X 400
amsd
predonsinmausce
(i)
Numerous
ervthrocvtes
and
3 large
(j)
Nunserous
ervthurocvtes
amid 2 abnormally
of
lymphocytes
lobed
large
lymum)hsoeytes
at
large
14
days.
lymssphuoid
at
X
11
ilays.
X
400
400
cells
at 14 days.
X 400
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
ROSS,
was
evideist
unstil
whets
within
the
the
a few
(lays
lysnpls
AND
the
amid
were
98 to 100 per (‘eI5
were
white
cell couist
hi both
but
peak
its
the
I1U(l aim average
was
a marked
reached
(fig.
lymph
of
couiit
did
rise
1
,000,000
of ai)Out
not
occur
9 to 14 (lays,
(fig. 2).
about
its
iieighh)orhoo(l
leukocyte
lympisocytes
1)100(1 ats(l
421
BIGELOW
irra(hation,
after
fourth
or fifth (lay,
erythrorvte
counts
‘Else isormal
FURTH
26,000,
of which
3a). There
was a marked
(lrop its total
svithiis
24 hours
after
irradiatioms,
but
there
was no pralIeiism
1)etweets
total
leukocyte
levels
its blood
atid lymph,
as
the (lisappearal
of lymplsocytes
prece(Ie(l
t hat of gt’at mulocytes.
There
was,
lsowever,
a (‘lose
parallelism
bets-eemm time iiiititil
drop
aml(l sul)se(luemst
rise its
lymphocyte
levels
of blood
atm(l lymph.
‘
I t is i)elieved
their
precursors
cytes
that
the
iii
detaile(l
lymph
study
transient
\‘as
rise
imormal
The
the
after
sequence
precipitous
(Irop.
followed
i)y
No
5.
of
small
iii
largest
‘lttmped”
was
of (lead
mmumbers
occurred
at
S
to
4
At
hours.
the
disappearaisce
after
of
after
irradiatiomi
there
omue-thirtieth
ai)out
vacuoles
(fig.
3d,
cells,
as
10
hours,
lympis
after
duritig
detected
chatiges
At 3 to 4 isours
irradiatiotm.
lime
than
postirradiation.
I to 2 hours
reachitig
drop,
tt severe
irra(liatiOtl
aI1(I
first 12 hours
in the lymph
At 5 to 7 h()urs
in lymphocytes
were
chaisges
figure
iii
chromat
to
its isumbers
of lymphoblood.
Therefore,
a more
of destt’uctiots
i)lasm
of some
cells.
Di- amid multimmucleated
at 3 to 0 hours
after
irradiation.
Omme to
lymphocyte
coumuts
occurre(l
with appearance
the
resistaist
10 hours.
morphologic
illustrated
of the
rebottms(l,
at
ame more
(etuters.
If so, reduction
to pre(e(le
that
of the
atsd lymph
durimig
tise
time lymphocyte
coutst
of
precede(l
a tratssiemst
of
made
its 1)100(1
irra(liatiois
leukocytes
is expected
tss
lymphocytes
A
circulating
its hemopoietic
the
appeared
cells
(fig.
two
hours
its the
miuclei
itudicated
isuclei
atid
(yto-
in lymph
dt-op its
cells its which
(legenerating
were
by
most
are
2 to 3 Isours
3b, c) were
foutsd
later
a precipitous
of matsy
e) ot
irradiation
first
pyknotic
motility
ilmjure(l
or fragmetsted.
aisd
cells
amsd
saframuitme tests,
debris
isad (his-
appeared.
Ilecovery
begaim
tise
lymph
phase
many
large
large
lymphocytes
3a)
-ere
irradiated
an
snts
only
The
absolute
while
after
whose
lvnsph
was
Time
lymphocytes
drained
ami increase
in
in
the
irradiation,
about
much
but normal
cell coumits
Duritsg
the regeneratitsg
(lays.
30
in
as
muunsber
thue
of
irradiatioum
lymph
ins tiue
fourth
large
the
lymusphu
week
imu msormal
mmunsber
there
lymphocytes,
may
i)e
was
the
taken
as
was
900
count
decreased
approached
also
latter
an
reached
in 8 to
irra(liation.
lymphocytes
greatest
was
after
the
large
lynsphocyte
as the total
cell
counuts
comstinuouslv,
large
lympis.
Its isormal
lymph
(fig.
5 per cent of all white
cells; iii
70 per cent.
lynspiuocytes
(lurinmg
day.
Subsequently,
then
increased
again
and
in
even
cu.
num.,
as
of large
ceumt
present
after
after
appeared
in the
omsly about
2 to
3b-j),
relative.
counts,’19
large
per
was
postirra(liatiomm
21 (buys,
and
rats,
only
(fig.
of the
elevations
13(X) per
weeks
two
lymphocytes
numbered
amsimals
peak
Time
but
al)out
approximated
a marked
not
lymph
on the
to
normal.
drop
greater
in(hication
This,
11 (lays,
hmowever,
was
about
fourteemmth
ai)out
In
200
at
normal
in lymphocyte
than
15 per
of regenerative
cent.
efforts
lymphopoiesis.
(k) A vacuolated
(log at 6 days after
(1) Numerous
S days.
X
1000
large lyniphoid
cell
exposure.
X 1000
ervtisrocytes,
a granulocyte
and
a plasma
and
plasma
cell-like
cell-like
leukocyte
leukocyte
in the
lynsph
of sanse
of a
(log
at
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422
IONIZING
Many
highly
of the
large
basophilic
Some
large
lymphocytes
and
lymphoid
cells
The
had
been
character
cytoplasmn.
with
lobed
debated.
We
now
between
the latter
seen,
that
The presence
of neutrophils
and
to 5 to 14 days
after
irradiation.
figures
round
large
by
these
Their
lymph
was
could
ai)normal.
Some
uncommon
(fig.
not
cells,
described
were
pathologic
limited,
was
probably
to
a
g).
with
cells
with
multilarge
lympho-
ago,’#{176}.1’
years
lymusphoblasts.
with
(hue
had
3f,
be identified
an(l large
be abmsornual
to
similar
cells
imu the
presence
not
nuclei
“atypical”
eosinophils
were
were
lymphocytes
assumed
were
transplanstable
believe
LYMPH
animals
Mitotic
or eccentric,
forms
of a leukemia
AND
the irradiated
in
vacuolated
certainty.
Since
all transitional
lobed
nuclei
(fig. 3 h-j) were
cytes.
RADIATIONS
rare
exceptions,
time capillary
fragility
20-
I
I
I
$8-
I
I
I
.9
I
I
/
$6-
I
I
4.
8
I
I
-7
I,
2
012-
i
I
1-
F
A.
I
z
I
Z
I
-53
l0.
Lii
/
LU
\\
8-
.4
I
./
c,’;’
\
4-
-2
2-
-
0-
FIG.
lymph
$
4.-Total
5
leukocyte
of dog S
whicis
permitted
in time blood
durimsg
cent
the
decrease
in erythrocyte
the
relation
of
Lymph
The
same
those
lymph-venous
in
the
total
mast
leukocyte
lymph
count.
couusts
cells
to
of X-Rayed
morphologic
as
of the
16 days
lymph
cells
blood
inuto the
at 5 to
Their
in the
heparims
and
-
$3
and
$5
erythrocyte
counts
of
the
lymph.
15 days
disappearance
lymph.
This
productions1
Tissue
they
frons
mnast
numh)ered
tue
observatiomu
cells
as
1)100(1
were
usoted
niucis
as 5
coincided
is of imuterest
with
because
of
‘
Dogs
changes
An
of rats.
anastomosis
of this
9
II
IRRADIATION
post-irradiation.
the entry
of red blood
5a) 5 days
postirradiation;
(fig.
of the
7
DAYS AFTER
counts
followed
per
The
T-=i”
-
0
dog
in the
lymph
illustrative
was
took
of irradiated
dogs
is that
of the
example
maintained
a sharp
for
upward
16
days.
turn
at
were
dog
The
the
essentially
S (fig.
4),
erytisrocyte
isinth
postirradiation
the
whose
count
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
ROSS,
FUIITH
AND
5
FIG.
(a
A
tissue
(h ) Ervt
(c)
normssal
Time
lmemmuosiderosis.
seen
filling
imave
simiuses
ions.
spleen
of
a
)<
60
of a rat
Time
black
mmmtime
the
fillimug
lymmuphmocytes
irradiat
(e)
hirocvtes
Lrvthroctes
(d) Tue
after
cell
muuast
blood
lvlmml)hi
t he
lvmuupi
snuear
simiuses
beemm replaced
miuesemiterir
at 7 days
st ainim,g
lvnsmphu
simowitig
spots
of a rat
a dog
of
simiuses
by
423
13IGELOW
of
a
plasissa
miode
of
dog
14 (lays
26
at
cells. X
a rat
ams atrophic
corresponud
at
at
filled
follicle,
to
days
13
days
after
irradiatiomu.
after
irradiatiomi.
after
X 1000
X
100
irradiatiomm.
The
at
11 (lays
300
with
diffuse
huemusosiderims
erythrocytes
fibrosis
amu(l moderate
ins musacrophuages.
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
424
IONIZING
day
and
on thesixteenth
in the
rocyte
counts
S,
although
was
reached
The
rats
3k,
In one
cell
count
at
8 hours,
vial)le
this
the
well
has
anatomic
and
set
with
well
rats
liver
85 per
destruction
in
with
and
or
weeks.
knowts
of erythrocyte
to
those
seen
irradiationu.
28,500;
censt
of
at
the
The
in
white
4 hours,
cells
was
12,500;
appeared
sonsewhat
fatty
animals
animal
tw’o
still
slower
in
degetseration
of several
cells
are
highly
presence
lymph
(fig.
isodes
5b-d).
indicated
dogs
gradually,
degree
location.
of erythrocyte
of liver
(fig.
resistant
and
rats
hemorrhagic
of the liver
(fig. ic) have
species,
hut the meaning
of
were
The
every
was
chis-
and occasiomsally
blood
from
the blood
imito the
lymph
nodes
(fig. ic).
The
that
these
occur
of
imsvolvemetst
chamuges
wide-
lymph
lymph
isodes
in lymph
isodes
to he as follows:
hemosiderosis
of the spleets
(fig.
iii
readily
the
durimsg
of differetut
mesenteric
but
are
intermittemstly
destruction
ic) was probably
to radiatiomss
in
duct
fluid
or
The
found
thoracic
The sequetsce
of changes
of lymphoid
organs)
appear
atrophy
The
appreciated.
The
and
dogs
exceptions.
red.
as evidence
degeneration
in the
irradiated
massively
ins lymph
sinuses,
erythrophagocytosis,
moisonuclears.
The hemosiderosis
interpreted
The fatty
eration
after
to coistain
bloody
escape
of erythrocytes
direct
hemorrhage
into
intensely
of erythrocytes
plasia
of large
beets
tiots.
peak
sinsilar
2 hours,
At 8 hours,
here,
the
in abruptly
the
invariably
the
8 hours
at
found
likely,
postirradiation
varied
than
first
lymphocyte
irradiation
was
ins both
may
three
isodes
Chatsges
in eryththe same
pattern
9 to 14 clays).
were
19,500;
chaisges
been
indicated
less
studies
almost
the
hemorrhagic
of massive
or,
and
not
experiments
changes
system
first
the
nodes
and
in irradiated
dogs
These
spread
2,300.
detailed
hitherto
died
in most
clots
The
(in rats,
lymphocytes
was
Thus,
to be
presetst
that
lymph
in
during
anatomical
known
changes
sected
differences.
irradiation
irradiation
test.
lymph
to occur
the
animal
studied
24 hours,
at
of
In
en. mm.
dogs had
Changes
knowis
these
after
per
in rats.
appearance
the
and
characteristic
too
individual
noted
before
safranine
A natomical
been
was
lymph
7,200;
the
than
The
were
abnormalities
immediately
dog
LYMPH
1).
dog
by
are
there
13 to 17 days
morphologic
(fig.
AND
day, it exceeded
one million
lymph
of 6 additional
irradiated
counts
dog
as
RADIATIONS
the
due
emstry
and
Se)
were
(other
hyper-
has
lomsg
greater
circulato anemia
since
undergo
fatty
degen-
of anemia.
DISCUSSION
There
are
of those
of the
numerous
in the
blood
studies
lymph,
with
following
on
one
chaisges
its the
exception.28
irradiation,
noted
by
lymphocytes
Quantitative
several
of
changes
investigators,
blood
but
isot
in lymphocytes
insclude
“clump-
fragmentation
and pykisosis
of nuclei,’3
abnormal
large
lymphoicl
cells, mitotic
lymphoblasts,13
and lymphocytes
with
bibbed
nuclei.’4
The sequence
of changes
following
irradiatiots
of suspensions
of lymphocytes
from
blood,
thymus
and
other
organs
was studied
recently
by Schrek2m
who
ing”
of
observed
after
tive
chromatin
that
atsd
the
irradiation.
phase,
irradiatiots
cytocidal
Thus
effect
as concerns
has
a similar
of irradiation
was
delayed
morphology
and latent
effect on lymphocytes
uistil
3 to
4 hours
period
of the clegeneraits vivo as its vitro.
The
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
ROSS,
present
studies
(‘Olitits
L!’i(l(flC(
for
‘Fhse
tioim have
i)een
#{149}
2 (
capillaries
there
(legenerative
itsterpreted
is preceded
by
a rise
and
S(’quelae
lymph
system
(‘lam.kmu
(‘ompariment
of ervthrocvtes
ins lymph
spaces,
I4Jl/)1i
eVi(letmce
of
mmodes
to itsdicate
of
the
emmtrv
mno gross
presetmt
tissue
phase
limb
that
is
)bservatiomss
ituto
425
ISIGELOW
in
lymph.
indicate
whets
hemosiderosis
hosts.’’
the
AND
of Lr!Jlhrocytcs
studies
evens
massive
the
of
1)ii’ersion
P1e5(11t
occurs
that
suggest
lymphocyte
FURTH
tise
amid
destruction
that
itsdicate
the’
soomm (lie
itsto
the
a hemorrhagic
there
tendency.
excessive
The
bihirubims
excre-
of erytisrocytes
its irradiated
if
escape
ervthrocvtes
amid
emugttlfed
are
from
h)y macro-
pisages.
‘[lie
phemmomemsoms
atid
species
(boursevt7
lymph
Simsce
of 1)r.
Muriel
skitu
durimmg
his
The
autopsy
aplastic
marrow,
the
as
tuot
performed
by
1)rs.
kidlneys.*
the
Among
of the
hemorrhagic
at
Naval
the
Medical
with
who
was
old
soldier
were noted
ots
amsd had h)loody
Hirafuku,
who
of
isoteci
the
bomme
aisd hemorrhages
casualties
petechiae
its the
and
explosioms,
but were
its lymph
isodes
Thsese observatiomms
its mats
activated,f
20
atsd
dogs,
goats,
swimue,
prolomugecl
clotting
presemuted
evidence
platelet
most
were
sing-
is probably
the
sigtuifies
lymph
of
the
other
imudepeimdeimt
of eryt
with
occurretsce
of
the
imsterdepemidemst
informssat ions is reprm
DeCoursey.
into
of this
neede(l
elemetits
and
a proloisged
isrocytes
cotssequetmces
where
spaces
led
clottnug
time
the
to
cotsclusion
of immcreased
‘aswith thrombo-
due
as noted
by Allen3
serum
fihrimuolysiiss
to a circulating
in irradiated
may
have
(logs.
been
levels.
the
erythrocytes
20
of a (omh)itmatiots
This is associated
that
tise hemorrhagic
syndrome
cats develop
its irradiated
rats,
(hickemss
amscl guinea
pigs without
the appearance
of a
time
amid “heparitsemia.”
Very
recemmtly Crotskite
et al.2t, 22
suggest
imsg atm imutimate
relatiotush;p
between
capillary
fra-
diversiots
amsemia,
with
Imsstitute’
result
defect.
with hepariti-like
properties
was
presetutecl
suggesting
that
Thus
its either
amid
courtesy
atrophy
sytsdrome
Research
sytsdrome
is the
a blool
coagulations
amsd itsfrequetstly
*
1)0mb
appreciated
atid
at
pathogenesis
i)e-
of atomic
petechiae
epilated
gastritis
.Japatsese
with
Elbert
isis
year
hemorrhages,
amid hemorrhagic
cytopemmia
1:lbert
a 45
Miyake
with
anticoagulatst
Evidemmce
ent
from
fully
through
autopsy
4 to 14 (lays
after
the
the third
to sixth
weeks.
Hemort-hages
examimmationi
itistil the fout-th
week.’7
seems
the Isemorrisagic
fragility
aiscl
gility
aisd
Although
beets
here
are
ins degree
General
in atsimals.
that
Studies
that
cular
hitherto
omsly
by
as a cotssequetsce
rept-oditced
They
varyimmg
oi)served
died
who
pmseumomsia
atsd
were
that
same
Isas
lse(rotizing
promitient
during
not mmoted ommgross
gest
five
was
omentum,
ecchsymoses
s’ere
the hypocenter.
Widespread
days of life whets he became
isecrotizinig
extetssive
ititestitme,
from
last
utmiversal,
chatiges
e are
Raum.
1 Km.
diarrhea.
focal
amid
id
appears
of mets
chammge
fig.
approximately
the
this
or amiimals,
hselp
tise
Similar
isodes
19
the
iii
explosiomus.
mats
dlescrih)ed
sites.’
luced
tesultaist
of a marked
blood.
chaisges.
frons
lymph
(hiversion
spaces
ate
tissue
anoxia.
Their
capillary
tlamage
Massive
It
irra(liatiots
is
A F I P recor(ls
not
its merely
results
matsifold.
possible
wit is t lie ki n(l
There
presetice
with entry
causes
at
appar-
is a la(k
a variety
present
permmsissionm
of
its lymph
itsto
the
to
of
assess
of Genmeral
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
426
IONIZING
the
relative
is
importance
possible
that
of factors
the
early
different
patho-physiobogic
The anemia
following
for
by
death
to
be
erythrogenesis
AND
already
death
due
LYMPH
known
to
in
causation
overwhelming
death,
of
exposure
erythrocytes.
about
could
120
The
days.23
account
for
life
span
of the
Therefore,
no
more
aging
thais
a loss
by
of dogs
complete
of about
a
be accounted
erythrocyte
in
amid it
is caitsed
disturbance
than that discussed
here.
massive
irradiation
is far greater
than could
of aged
estimated
RADIATIONS
is
ai)setsce
1 per
cemst
of
of the
red cell per day. The lymph
volume
is not known
precisely,
but methods
are isow
known
to approximate
it.24
25 Assuming
that lymph
an(l blood
plasma
are equal
in volume
and the preirradiation
red blood
cell count
is four million,
a red blood
.
cell
count
of one
million
in the
approximately
in the lymph
one-fourth
indicate
the
of their
into
entry
the
lymph.
erythrocytes,25
may prove
capillary
damage,
measuring
and
in gauging
The
Pathogenesis
The
Direct
attempts
latency.
time,
but
Death
is
regenerating
capacity
observations
that
at irradiation
body
irradiation
Numerous
been
is
in excessive
by means
mass
of isotopically
of
labeled
the occurrence
after
irradiations
fragility
multiplying
about
cells
the
to
life
be
irradiation
cellular
by
cells
be
endothelial
The
clinical
to
be
ideistified.
have
an
utsusually
manifest
and
followed
of
liberated
stimulated
by
their
hemorrhages
followimmg
folbowitsg
disintegrating
from
some
and
experimental
by
cells
its sequence
from
for
cells
of endothehial
occur
either
not
of
is not
injury
chatsges
histamine,
amount
may
span
excellent.
direct
remain
if so, this would
of “necrohormones”
and
erythrocyte
means
of timiisg
in relation
to time
capillary
massive
and
an
mass.
The red cell coumits
in the lymph
but isot the rate
cotitrol.
of
known
liberation
26
assayed
is possible;
argue
against
at LD-50
levels.
humoral
The
represent
Damage
known
localized
sites
suggeste&
charged
latter,
at therapeutic
of slowly
nothing
irradiation.
The
cause
or causes
to endothelial
cells
injury
would
originsal
erythroeyte
of erythrocytes
to be an excellent
its iistensity
of Capillary
immediate
long
lymph
of the
number
massive
cells
destroyed
irradiation.26
27
total
has
long
cells
or dis-
The
recent
studies
of Cronkite
et al. present
strong
support
its favor
of the platelet
theory
of
capillary
fragility.21’
22
Whatever
the cause
of the capillary
fragility,
diversion
of erythrocytes
insto
lymph
spaces
causes
anemia;
if this process
is severe,
sudden
shock
follows
with
release
of substances
which
in turn
will increase
the capillary
damage,
thus
initiating
a vicious
cycle
leading
to death.
SUMMARY
Erythrocytes
massive
appear
exposure
the erythrocyte
in rats and the
rocyte
count
Diversion
anemia;
tion
not
couists
eleventh
in
x rays.
large
frequently
into
destruction
to a direct
numbers
The
irradiation
in
peak
in the lymph,
to seventeenth
in the lymph
of erythrocytes
excessive
and
to
of
the
lymph
endothelial
of rats
as
is reached
ots the ninth
day in dogs.
In both
the
exceeds
otse million.
lymph
compartment
of erythrocytes,
injury,
presumably
is responsible
and
fragility,
dogs
to fourteenth
species
the
causes
related
in part
after
itsdicated
a
by
day
erythrelative
to extravasafor
the
absolute
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
ROSS,
anemia.
It
leukemia
The
5
to
is suggested
that
other
ais(l
blood
FURTH
AND
similar
chaisges
diseases
(Irop
in lymphocyte
10 Isoums after irradiation.
427
BIGELOW
associated
may
contribute
to
with
capillary
fragility.
counsts in 1)0th lymph
Durimig the fourths
and
blood
the
anemia
withiti
irradiation,
is precipitous
to eighth
hours
of
after
insjure(l
ing the
audI dead
recovery
increases,
there
lymphocytes
are present
its the lymph
ins large nmumbers.
Durphase,
the per cemst of large
lymphocytes
in the lymph
greatly
are mamsy abtiormal
large
lymphoid
cells atsd mitotic
figures,
mast
cells
and
tissue
It
is
appear
coisclucled
massive
in blood
smears.
that
diversion
of
if severe,
becomes
irra(liation,
erythrocytes
iisto
a self-aggravating
the lymph
caused
process
and leads
by
to
death.
REFERENCES
I
S.,
ScinwkttTz,
time
hensolytic
Rel)ort
effect
Cil-3760,
J. 13.
2 KAHN,
3
1952.
AnmEN, J.
\Vnsti,
L.,
by
BOLLSmAN,
CAIN,
liver,
1948.
R.:
counuts.
10
11
sues,
1$
5:
W. A.
J. Cancer
30:
12 1)uNm.Am’,
18
CLARK,
living
19
Tum.m.ns,
1949.
postirradiation
aniemia.
Nationsal
Blood
Laboratory
7:
404,
Progress
It. H. : Disappearance
Am.
J. Roentgenol.
STOREY,
aninsals.
for
A technique
sampling
lymph
shunt.
Naval
duct-venous
or
J. H.: Techniques
thoracic
M.
C.
duct
of
BIGELOW,
AND
J.:
Lymphocytes
in
A transsmissible
for
the
rate of tagged
In press.
in
unanesthuetized
Medical
R.:
To
the
method
thoracic
leukemia
the
J. Lab.
rat.
R.
of toxicity
of antiseptics
by
Biol.
& Med. 54: 283, 1943.
spleen,
J.,
hepai’in
BARNES,
in
vitro.
Research
collections
& Clin.
Med.
33:
i)e published.
duct,
of unstaimued
intestinal
in mice
of lymnph
with
and
atypical
cell
hepatic
cells.
Am.
E.
R.
F.:
flee.
Thue
Arch.
34: 562, 1942.
Path.
imematological
of
confirnsatiomu
workers.
C.: On
cytoplasmic
specific
effects
of
ionizing
the
origits
particles
a
l)reviousl’
reported
113: 32, 1951.
Science
Vacuolationu
amsd the
104: 45, 1949.
J.
respomuse
E.
anuatonsy
102: 427,
Surgeomu
CLARK,
Am.
nodes.
The
Experinsental
pathologic
Mil.
ANI)
lymph
E.:
of
imeparinu;
an
of nmeoplastic
examination
nsast
cells.
of
J.
1947.
Hunsans
mamnmal.
J. L.:
the
Bmoom,
explosions.
the
of cyclotron
MANGtERI,
amid
107,
and
LORENZ,
1949.
bloo(l
Anat.
E.:
371,
F. AN)
86:
AND
AND
S. W.:
thue
comstent
Med.
in
52:
Bnoosn,
G. H.
time thymus
E. K.
MARKS,
AND
DECOURSEY,
bomb
of
Rel)ort
1937.
finding
Exper.
17
AND
GRINDLAY,
WOODS,
FL’RTH,
75,
0.,
M.
vated
J.,
Ra(liology
utiusual
16 PAFF,
AND
intestine,
tise
L.
INGRAM,
tue
J. C.
Exper.
AND
including
JAcoBSON,
m’ ()Lmva,
: Studies
I)eclassifled
M. R. AND MIDER,
G. B.: Thse identification
of cells from insduced
and spontaneous
of dilute
brown
mice. J. Nat. Cancer
Inst.
2: 115,
1941.
C. E. (Warren,
Shields):
Effects
of radiation
on the blood and the hemapoietic
tis-
radiations.
14
C. J.
WATSON,
1950.
HIGGINs,
G. M.:
177, 1950.
AND
BARNES,
leukoses
31),
FURTH,
Blood
LEWIS,
AND
Consnsission
Amgonune
X-rayed
thoracic
04
012
Soc.
J. D.
lynsph.
of
E.:
Measurement
Proc.
MANN,
C. W.
exteriorized
small
R. H.,
SCnIREK,
of
i)leedimug.
circulation
of an
J. L.,
1349,
abnuormal
ILARDENBERGH,
006
tue
Enuergy
pathogenesis
SHEPPARD,
the
(NM
from
STOREY,
8
J.,
means
Institute
: The
report
FURTIt,
S. AND
(logs
L. 0.
JACOBSON,
Atonsic
1950.
from
BROwN,
J.
FCRTH,
4474,
substances
radiation.
1947.
ANt)
No.
L.,
PORTER,
of
: Progress
Report
6
E. J.,
KATZ,
L.:
Observatiomus
62:
Anat.
of
of
1948,
tissue
59,
release
ionizing
and
on
of Imeparins
radiation
personal
isolated
ins mast
effects
of
cells
tue
cultiatomic
communmications.
lymphatic
capillaries
in
the
1937.
to
total
body
irra(liation.
Am.
J. Path.
25:
829,
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
428
2
IONIZING
E. P.:
CRONKITE,
ins goats
1902,
-‘
22
DILLARD,
ansd
HAHN,
24
UILE,
hemorrhagic
tramusfusion
P. F., Ross,
of
and
to the
platelets.
J. F., BALE,
total)
as
AND
syndronse
by exposure
21, 1950.
C. J., BRECHER,
G. AND
G. H. L., BRECHER,
G.
(circulating
221,
The
swine
December
JAcoBs,
21
23
and
RADIATIONS
of acute
atomic
Proc.
ionizing
bonsb
at
W. F.
Exper.
AND
Biol.
BALFOUR,
deternuined
by
radio
C. L.,
to
LAMSON,
tissue
B. G.,
protein
L. L.
MILLER,
without
AND
evidence
of
by
NP
Ins press.
ions,
dye.
27
28
BROWN,
Research
H. V.:
C.
Institute,
(Discussions)
S., HARDENBERGH,
bacteriologic
changes
Naval
R.:
1055,
Lecture
Am.
Medical
Cytologic
1948.
in the
Research
changes
and
Review
J. Path.
27:
E.
AND
thoracic
J.
eomscenst
rations,
volumes
Exper.
Med.
Inustitute
in thymic
J.
lymph
(NM
glands
1)rocedure
L.:
006
012
The
J.
for
effects
51-2,
of (logs
exl)osed
(‘onuversionu
breakdown.
Ser.
No.
677, 1951.
TULLIS,
duct
G. H.:
WHIPPLE,
cal
Moox,
24:
ansd
proteins
26
tion.
separat
produced
Docutusenst
& Med.
In press.
W. M.: Red
cell amid l)lasmua
irons
539, l95l.
STOREY,
R. H., MOSHMAN,
J. ANt) FURTH,
J.: A simple
approximate
lymph space. Science
114: 665, 1951.
ELLINGER,
F.: The histansine
hypotisesis
of the biologic
SCHREK,
illnsess
AEC
Roentgenuol.
CRONKITE,
Soc.
ions
1946,
75:
1942.
protein
29
radiat
Bikimsi
G. H. L.: Am. J.
E. P.: The
DILLARD,
AND
LYMPH
Me(l.
detemnsimuationm
of radiations.
1951.
biochensical,
exposed
of plasma
Exper.
to
04 29),
1950.
in vivo
to
Naval
93:
of the
Medi-
cellular,
and
total
body
irradia-
X rays.
Am.
J. Path.
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
1952 7: 417-428
Changes in Cellular Composition of the Lymph Caused by Ionizing
Radiations
M. H. ROSS, J. FURTH and R. R. BIGELOW
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