1. No category

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1960 15: 856-862
Effect of Homologous Bone Marrow-Spleen Cell Suspension on Survival of
Swine Exposed to Radiation from a Nuclear Weapon
HARRY W. DANIELL and WILLIAM H. CROSBY
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Copyright 2011 by The American Society of Hematology; all rights reserved.
From www.bloodjournal.org by guest on November 20, 2014. For personal use only.
Effect
of Homologous
Bone
Marrow-Spleen
Suspension
on Survival
of Swine
Exposed
Radiation
from
a Nuclear
Weapon
By
I
T
HAS
BEEN
In
has
most
of
that
x- or gamma
are
results
irradiated
animals’
radiation
and
success
of
cessive
may
well
Available
as
speed
of
in
treatment
of
be
dependent
upon
)
iifldl
of
subsequent
mouse.
t
Commission
at
to evaluate
the
1)Osed
to mixed
paper
reports
therapy
effect
of homologous
neutron
the
and
results
in
gamma
indicate
including
upon
irradiating
the
intensity
of
particles.
casualties
experiments
on
ir-
Eventual
exposed
to
larger
animals
( approximately
organ
completed
by
an
1957,
the
cx-
cn
from
0.15
Atomic
opportunity
suspensions
irradiation
of these
as
smaller
tests
cell
reports
laboratory
conditions.
It is not
organ
of a large
mammal
( per) can regenerate
US readily
after
the
as can
During
the weapons
their
Nevada
Test
Site
heterologous
factors,
well
human
,
Gm.
and
and by many
routes.
Responses
after
other
multiple
strain
and
administration
homologous
upon
( comparable
to man in size ) under
controlled
known
whether
the relatively
hematopoictic
haps
1000 Gm. for a 120 pound
pig or man
exposure
conditions
suspensions
been
used.
has
and
charge
therapy
radiation
isologous,
depend
CROSBY
can prevent
death
in otherwise
of small
animals
can be treated
investigated.
species
weight,
certain
or in cell
being
therapy
size,
similar
from
irradiation
now
of such
under
intact
H.
WILLIAM
suspensions
species
Tissue
administered
exposure
the
that
manner.
been
studies
types
AND
or spleen
cell
animals.7
Several
in this
sources
DANIELL
demonstrated
of bone
marrow
fatally
irradiated
successfully
W.
HARRY
Cell
to
Energy
vas
survival
presented
of swine
a nuclear
cxThis
weapon.
studies.
METHODS
Sixty-nine
35
to
swine
Kg. , were
60
weapon.
this
The
series
of
resulted.
similarly
vival.
Spleen
weight
amined
for
comparison
(table
1).
foil
air
as
with
of
from
well
these
to
as
donor
?IIe(lical
Submitted
Mar.
for
that
pigs
first
(of
of
Center,
1959;
the
Hematology,
Washington,
accepted
4
E
an(I
Similar
l)oses
of
survive.
D.
Reed
17
Army
for publication
856
Oct.
31,
the
Cell
suspensions
to
Kg.
and
Institute
C.
1959.
of
animals
measured
by
rep’s.
35
burns,
the
were
measured
ex-
studied
weapon
upon
sur-
were
were
the
from
irradiation
in
weighing
swine
inflicted
was
compared
ultimate
cellularity
of
in
a hone
intricardiac
and
groups
nuclear
closes
of
were
and
gamma
measured
cells
animals
was
weighing
a
of
intravenous,
received
trauma
of
range’
nucleated
the
and
from
symptoms
Six
F)
age
wide
cytology
air
Walter
a
10
x
signs,
irradiation
stock)
that
I)y
Neutron
close
of
irradiation
Treated
marrow
not
groups.
same
given.
did
(groups
collision
animal
was
hone
irradiation.
dosinwters.
the
Department
20,
animals
these
chemical
Hurst,
and
3 to
terms
months
so
e:tch
in
spleen
groups
“controls”
From
tile
Reed Army
as
addition
Sigoloff
system
obtained
in
to
therapy
6
neutron
controlled
exposure,
animals,
in those
of
both
be
administered
to
and
gamma
not
after
further
untreated
as
mixed
8 hours
No
4
strain,
the
could
were
exposed,
Two
designated
in
to
route.
with
to
irradiation
mixture
or
Hampshire-Landrace
Four
intraperitoneal
wounds
a
exposed
(lose
marrow-spleen
or
of
fissionwere
prepared
Research,
as
Walter
From www.bloodjournal.org by guest on November 20, 2014. For personal use only.
SURVIVAL
FROM
NUCLEAR
WEAPON
857
RADIATION
Table
1
30 day
Group
A
10
10
3 x
10#{176}
IV
100
10
100
B
10
10
3 x
10#{176}
IV
100
10
100
C
725
3
1)
660
715
640
E
435
180
4
IV or IC
IV or IC
10#{176}
IP
F
197
71
4
intravenous;
=
follows:
cardiac
Neutron
rep
Each
scooped
of
out
very
young
much
fat,
through
and
rendering
canal
and
The
vertebral
dropped
sediment
Fig.
easily
were
briefly
a solution
so
that
IP
to
1).
to
a
of
10
per
cent
per
hone
spine
from
incision.
10
10
0
9
0
0
9
0
10
0
13
4
142
65
18
for
split
cent
10
65
those
injection.
fixture
to
serum
fell
donor
to
rod
jack
the
pig.
in
107
was
the
saline,
2)
shaken
bottom.
The
Scalpel
blade
marrow
bones
pigs
contained
removed
through
spine
(fig.
intra-
of
the
Long
older
driven
plane,
means
and
saline.
spine
was
hold
in
by
from
The
steel
a 6 inch
killed
lengthwise,
serum
and
square
autologous
of
animals
N
then
were
bone,
wooden
with
%
milliliters,
animal
prepare
away
particles
1.-Removal
of intact
removed
through
same
the
A 1, 4 inch
ends
10
hundred
control
%
animals
N
intraperitoneal.
=
cancellous
shaved
the
IP
a solution
with
both
of
100
from
difficult
were
x
x
several
(fig.
at
bodies
x
bones
in
each
anchored
into
bled
Long
filled
incision
route*
intracardiac;
=
was
air.
of cells
treated
109
3 X 100
suspended
pigs
a dorsal
No.
IC
donor
injection
Therapy
survivals
Gamma
rep
rigidly
and
the
and
supernatant
indicates
of
intact
the
spinal
in
place.
planings
allowed
was
spleen,
to
re-
From www.bloodjournal.org by guest on November 20, 2014. For personal use only.
(S’th
I) tN Ll;LL
iil:tced
and
the
flask
((ll5
had
ic’eii
shak(I)
(-(Iltrate(l
1)\
isiortar
a
il5
Cell
concentration
LI(l
all
suspension.
tion
of
icll
vss
3.0
No.
1 and
given.
No.
clinical
of
1)100(1
in drawing
X
10”
course
were
1)100(1
Postmortd’In
(table
1). \Tolum,
cells.
after
of
done
irradiation.
all
sampk’s
from
was
pilot
conducted
of solution
therapy
other
than
for
the
cell
but
no
indicated
irradiated
that
pigs
within
animals
8
car
to
ml.
Each
Hog
transfusion
laboratory
the
struggle’
affected
a
10
veins
Pillsbury’s
carefully,
had
tla
in
:111(1 adininistra-
10 to 25
was
offered
each
dqllal
cells
were
all
chamber,
( marginal
followed
solution,
from
)15
supplie(l
pig
a
serum-saline-.
nearly
Aniimmals
on
in
in
(honor
in
handle
syringe
shaken
were
intravenous
stuelies
placed
a
Contributions
)
itiarrow
con-
WaS
henloc-yti)Ineter
a
of
thrombocytopenic
were
c’xaminations
No
animals
becasmse
spleen
donor
nucleated
route
4.0
2 ad libitum
Thc’
(xaminati0ns
adversely.
to
amul
by
thei
in
injection.
(heath
Each
administered
of
suspc’naon
to
lx’teve’en
animals.
was
or mtraperitoneal
cohimmin
passed
screen,
the
of
i-rc’
maus
d-ollliting
Prior
most
stipc’nsion
which
B
.
final
to
by
together
iii’ces.
3 )
tIn
prior
dctcrnined
recipient
large’
( fig.
through
vertebral
suspension
into
itre,
hours
two
to
Cell
forcc’d
niixed
bones,
cut
suspensions,
the
ccli
and
bottom
once
solution
than
its
as
pulp
such
two
fragments.
as
at
screen
( long
hon’
spleen
‘ere’
suspension
received
entailed
e’ach
Le’ss
immiracarehiac
was
in
rigs.
Feast
sI)ld’t’fl
After
the
screen
the
source’s
final
animal
the
suspensions
three
recipient
steel
through
three
tIme
)
1)(’stk’
strained
again.
The
a stainless
and
of
c’ntrifugation.
vith
( II5((I
\vils shaken
loose
from
(;li()5i131
AND
survival
few
hours
of
(lentil.
RESULTS
Approximately
cardiac
minutes.
of cerebral
15 per
injections
One
Fig. 2 (at
of a pointed
short
length
Fig. 3 (at
with stainless
cent
exhibited
animal
died
of
mild
promptly
the
animals
ataxia,
after
by
treatedi
lasting
mtracardiac
from
or
intravenous
a
few
injection,
seconds
intrato
10
apparently
embolism.
left).-Vertebral
column
has been anchored
in wooden
fixture
by means
steel
rod in the spinal
canal
driven
into end
block
and anchored
by
of chain
at the other.
right).-Apparatus
for homogenizing
splenic
tissue
consisting
of mortar
steel
screen
bottom
and syringe
handle.
From www.bloodjournal.org by guest on November 20, 2014. For personal use only.
SURVIVAL
FROM
All
All
ill effects
animals
)
fever
.
course
from
All
fatally
in numerous
treated
and untreated
in cellularity,
differ
during
the
pyknosis
and
of all
cell
Plasma
hihited
cells.
small
Poietic
series.
promimieitly
than
Survival
Bone
irradiation
cx-
diarrhea,
or clinical
a few
smears
intervals
The
few
cells
phagocytes,
and
after
were
many
sections
from
irradiation
cells
the
a few
and
animals
early
cells
occasional
that
dliedl
cxof the myclo-
after
irradiation
all
and
many
marrows
were
either
normocellular
tal)le
1 and
figure
stu(hes
have
summarized
in
phases
lysis,
disappearance
days
are
did not
obtained
by
rapid
and
,
small
specimens
with
of
and
)
many
characterized
reticulum
cells
damage
hemorrhage
demonstrated
exposure
of erythropoietic
data
showed
of radiation
and
marrow
at identical
or cytology.
post-irradiation
days
Thirteen
of
anorexia,
survival
signs
atrophy
of hematopoietic
reappeared
perceiltilar.
prominent
following
fragmentation
By 10
islands
doses
injections
as well.6
days
other
and
therapy.
supralethal
intravascular
swine
dying
composition
four
forms
or
hematopoietic
tissues,
first
survived
or the
revealed
and
received
emboli
radiation
animals.
animals
( lymphoid
had
of
radiation
radiation
illness
( hemorrhage,
did not differ
significantly
in their
control
irradiated
which
swine
the
intermediate
of
untreated
necropsy
on
dOses
either
signs
animals
859
RADIATION
minimal
from
receiving
clinical
Treated
lliI)ited
WEAPON
receiving
animals
other
fl()
NUCLEAR
of hematopoiesis
had
or by-
4.
DIscUsSIoN
The
from
of
of
cell
homogenates
several
marrow,
other
from
our
experience
is similar
same
Most
although
both
reports
indicating
quantities
In
used
sources.
in
animal
the
(10
the
the
that
similar
long
bones
have
and
obtainable
10#{176}
in a 20 Kg.
successfully
number
of
from
pig).
The
We
in
prepared
cells
all
been
obtained
of
the
method
long
bones
TREATED
-J
F
>
(J)
0
30
DAYS
Fig.
4.-Survival
of
POST
irradiated
IRRADIATION
pigs,
treated
and
are unaware
considerable
for
is relatively
GROUP
as a source
from
UNTREATED
>
obtained
served
and ilia have
also been
used.
that
marrow
can
be obtained
column
swine
to
x
ribs
vertebral
with
amount
in pre\Tious
frequently,
untreated.
injection.
this
source
from
simple,
the
and
From www.bloodjournal.org by guest on November 20, 2014. For personal use only.
860
DANIELL
may
very
The
well
be of further
beneficial
irradiated
effect
animals
including
homogenate
has
mice,
rats,
therapy
hematopoietic
use
of
been
and
repopulation
in our
studies
small
mammals,
tissue
be
to
stration
The
type
and
animals,
range,
and
due
to the
the
received
Vogel
of
of
they
may
have
have
previously
therapy
may
Some
rather
injury.
days,
doses
days
the
be
evidence
Mean
may
well
animal,
or a cornanimals
make
demon-
times
F
the
be
cannot
Of
in
our
the
lethal
lethal
dose.
determined,
survival
animals
for such
demon-
range.
below
affected
control
adversely.
group
E,
which
rep of neutron
irradiation,
in which
an effect
is most
to
exposed
survival
in
for
this
the
of
and
by
electrical
death
after
hematopoietic
These
spleens
x-irradiation.
fission
neutrons,
doses
of
where-
Co6#{176} gamma
Repeated
demonstration
after
exposure
Randolph
charge
to
faster
et al.2 indicated
of the bombarding
difference.
was
dying
or
the
of transplanted
therapy
neutron
irradiation,
of
survival.
marrow
same
authors1
to mass
and
time
beta
LD2OO/aO
that
from
effect
doses
to
improvement
that
gamma
gamma,
LDop,’:m
homologous
responsible
indicating
nature
a beneficial
to
mice
suggests
the
than
which
of
of a different
exposed
by
effect
be
in
Mev)
neutrons
by the
the energy,
in addition
particles,
and
evidence
may
a significant
a beneficial
(14
that
the
possible
that
the
mass
of marrow
LDmflo/:so
several
E
reviewed
recently
irradiation
produced
of
marrow
not be optimal
effect
has been
doses
with
and
180
the range
following
just-lethal
exposure
were
unable
to demonstrate
rays
in
of
or
recipient
factors
may
irradiation
fallen
in
death
authors
similar
cellof the
evidence
of therapy
and
of
species
demonstrable.
et al.1-4
mice
differences
beneficial
LD)a/ao
to
burns
cent
neutron
as
no
It seems
increased
study
groups
and
4 per
gamma
of
survival
(lonor
received
by
fission
in
our
probably
of wounds
rep
that
to be
D
number
swine,
technic
of these
irradiated
received
survival
435
suggests
and
on
from
between
in
B were
dosages
presence
However,
likely
C
of the
a
survival
difficult.
radiation
and
animals.
on
improve
the
other
animals
maximal
irradiation
near
the
A
groups
Lethality
of
In
of
groups
to
or a combination
dose
study
improved
survival.
or perhaps
the
effect
experimental
suspensions
on
resulted
similarity
a beneficial
a demonstration.
strated
at doses
our
of therapy,
with
swine,
regenerated,
of such
In
have
CROSBY
Improved
survival
following
to accelerated
repopulation
Failure
type
genetic
has been
closely
correlated
genetic
heterogenicity
of
rabbits.
related
found.
may
the
large
cell
demonstrated
tissues.
was
the quality
of radiation,
bination
of these.
spleen
clearly
lymphatic
repopulation
on other
and
guinea
pigs and
has been closely
accelerated
In
in studies
marrow
AND
irradiation
the
received
by
force
in their
dominant
animals
in
each
experiment
our
animals,
radiati’n
was
6
to
10
the same
period
reported
by Vogel
et al.4 in mice
irradiated
with varying
of fission
neutrons
and in contrast
to the mean
survival
time of 13 to 15
in mice
receiving
equally
lethal
doses
of gamma
rays.
With
survival
as
common
parameter,
trons,
as
compared
these
values
can
RBE
with
certainly
biologic
(relative
gamma
not
rays,
be
is between
transposed
effectiveness)
2 and
to swine,
of
7 in
it
mice.4
seems
fission
neu-
Although
likely
that
From www.bloodjournal.org by guest on November 20, 2014. For personal use only.
SURVIVAL
FROM
neutrons
compared
are
)
Both
peutic
Since
NUCLEAR
more
perhaps
,
spleen
effective
biologically
by a factor
near
4.
and
bone
splenic
marrow
homogenate
radiation
resulted
were
not affected
not
This
have
into
in a fatal
by the
“protective”
fatal
bodies
than
been
doses
reaction
of
was
against
the
F-i
failure
to
The
bone
quate
from
sterility
a
were
perature
tissues.
Time
intervals
genates
cenditions.
cells were
experience7
required
animals
for
and
lack
of
of benefit
are
given
observed
cannot
LDI,o/3
dose
that
on
larger
may
in groups
E and
cells.
cell
homo-
laboratory
),
and
injected
of transfused
genetically
rather
have
tern-
intact
of
25 ml.
numbers
intraperitoneally
factors
excessive
of
under
than
ade-
regarding
injection
in
survival
results
seemed
to
satisfactory
was small
( less
to 4 X 10#{176}).
(3
given.
of anti-
extrapolate
numbers
and
as
been
cells
pig. it is possible
that
is responsible
for the
exposed
animals
of
animals
whether
also
animals.
animals
large
are
thera-
precautions
not
accepted
effect
These
were
donor
limits
indicated
cells
one
contained
has
routes.
an
implanted
reasonable
tissues
a beneficial
when
intracardiac
the
the treated
into
recipient
All
the
sacrifice
within
by
in
injected
Volume
of cell suspension
given
in large
numbers
Previous
are
kept
a beneficial
had
homogenate
Although
homogenates
between
were
we
and
The
rep
been used together.
that
injection
of
given
might
happen
in the
our cell homogenates
viewpoint.
observed,
to have
previously
survival
that
technical
changes.
mice
to formation
improved
homogenate
shown
( when
rays
Rarely
have they
al.3 have
reported
marrow
ascribed
recipient
demonstrate
cell
gamma
reaction
within
8 to 16 days.
Nonirradiated
homogenate,
and
the reaction
occurred
obtained
in mice
to predict
what
the addition
of splenic
tissue
to
or
861
RADIATION
effect in the post-irradiation
period.
our study,
however,
Schwartz
et
parental
or
WEAPON
than
contributed
cells
heterogenous
by
intravenous
significantly
to
the
F.
SUMMARY
1. Swine
weapon
exposed
were
to mixed
treated
by
of homologous
marrow-spleen
2. This therapy
did not
mediate
lation
or supralethal
of
that
or
with
compared
reasons
for failure
3. A new, simple
the
vertebral
lymphatic
tissues
untreated
animals
1. Porcos
un
arma
o
intraperitonee
de
splen.
2. Iste
of large
al irradiation
nucleari
esseva
therapia
non
suspensiones
afficeva
from
a nuclear
receiving
evidence
was
of
found
dying
in
at the
injection
sublethal,
inter-
accelerated
the
repopu-
treated
same
animals
time.
survival
are
of marrow
Possible
discussed.
cells from
is described.
mammals
exponite
de
irradiation
or intraperitoneal
a beneficial
effect
on
obtaining
large
numbers
IN
SUMMARIO
ab
neutron
No
of irradiation.
to demonstrate
method
for
column
and
intracardiac
cell suspensions.
affect
survival
of animals
doses
hematopoietic
died,
gamma
intravenous,
tractate
de
INTERLINGUA
miscite
de
con
injectiones
homologe
Ic superviventia
radios
gamma
e de
intravenose,
cellulas
del
animales,
de
neutrones
intracardiac,
medulla
tanto
ossee
post
doses
e
From www.bloodjournal.org by guest on November 20, 2014. For personal use only.
862
DANIELL
subletal
como
evidentia
de
esseva
etiam
un
trovate
tractate
post
intermediari
repopulation
in le tractate
animales
possibile
(loses
accelerate
que
animales
moriva
nove,
medulla
ab Ic columna
1.
H.
simple
quc
a!
Ic non-obtention
pro
porcos.
3. Un
tin
pro
vertebral
tissus
effecto
obtener
Es
henefic
grande
de grande
Nulle
o lymphatic
c-omparation
in
tempore.
CROSBY
irradiation.
de
hematopoietic
moriva
mesme
de
methodo
c supraletal
del
AND
con
discutite
Ic non-
Ic
rationes
super
Ic longevitate
del
quantitates
de
de
mammiferos
cellulas
es descrihite.
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