1. No category

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1950 5: 623-647
STUDIES ON THE HISTAMINE CONTENT OF BLOOD, WITH SPECIAL
REFERENCE TO LEUKEMIA, LEUKEMOID REACTIONS AND
LEUKOCYTOSES
WILLIAM N. VALENTINE, MORTON LEE PEARCE and JOHN S. LAWRENCE
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Copyright 2011 by The American Society of Hematology; all rights reserved.
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
STUDIES
ON
THE
HISTAMINE
REFERENCE
TO
CONTENT
LEUKEMIA,
OF
BLOOD,
LEUKEMOID
WITH
SPECIAL
REACTIONS
AND
LEUKOCYTOSES
By
N.
WILLIAM
M.D.,
VALENTINE,
MORTON
LEE
AND
S.
JOHN
REVIEW
H
ISTAMINE,
the
in a wide
role
since
variety
of animal
even
anaphylaxis
significance.
blood
of various
problem
from
from
of
years.
the
general
standpoint
or
of this
clinical
pharmacologic
and
investigations
mine
content
of mammalian
studies
types
of disease
the
tween
it and
“blood
the
in
applied
in
activity
is
in this
as
by
paper
with
into
to
to
some
methods
leukemia,
The
well
leukemoid
the
The
or
of
be-
unequivocal
term
identity
The
of the
term
will
agent
experimental
reactions,
selected
correlations
“histamine-like”
an evaluation
to present
significance
the
substantiated.
to
purhista-
with
any
though
the
employed.
confined
of
is not
is the
(2.)
possible
are
use
It
the
to man;
the
or of the
it
in subjects
if there
with
be largely
Rather
and
criticism,
reasonably
synonymous
the
will
nature
determine
allergy.
concerning
reference
the
from
attention
problem
data
of blood
presented.
open
appears
assayed
subjects
inquire
picture
studies
available
particular
or
than
the
histamine
little
histamine
of histamine.
the
content
and
is perhaps
question
reported
to
hematologic
these
with
histamine
of blood,
histamine”
substance
blood
()
content
action
to review
the
entities;
histamine
physiologic
a conof
physiologist
other
of the
for
in the
relatively
in fields
in the
recognized
interested
received
a review
physiologic
investigation
and
It has
attempt
its
phar-
possible
activity
been
to those
been
of its
of its
of
exceptions,
pharmacologist
allergy.
(I)
regarding
few
confined
character
studies
has
has
1910,
demonstration
histamine-like
man,
with
in
Its
realization2
intensive
investigators
to
early
possessing
been
to
report
of these
to
Dale’
dramatic
the
including
of the
relationship
pose
clinical
has
and
literature.
and
and
However,
substance
Barger
diverse
contributed
species,
of its
purpose
the
mammalian
hematologists
the
all
by
controversial
dilution,
of a substance
of this
standpoint
tissues,
presence
number
significance
in ergot
and
in high
have
The
siderable
detection
of a voluminous
actions
in
its
subject
macologic
on
M.D.,
PEARCE,
M.D.
LAWRENCE,
be
whose
investigations
of results
of studies
leukocytoses
of
varying
etiologies.
Methods
for
tatively
the
the
one
This
Measuring
employed
consists
without
stasis
in this
From
the
paper
Energy
after
acid
for
Medical
laboratory
noting
and
on
the
have
is Code’s
following
the
thirty
School,
is based
Commission
of blood
of the
and,
A number
Histamine.
content
essentially
trichloroacetic
This
Blood
histamine
to sixty
volume
or modifications
The
modification5
The
of the
minutes
performed
University
of methods
employed.3’
procedure.
University
work
been
sample,
in order
of California
under
of the
blood
placed
at Los
of California
at Los
613
method
is removed
directly
Angeles,
No.
without
the
protein.
Los
Angeles,
AT-o4-I-GEN-Il
Angeles.
for determining
in most
quanti-
common
of Barsoum
to be studied
to precipitate
Contract
method
and
use and
Gaddum.6
by venipuncture
anticoagulants
This
into
trichloroacetic
Calif.
between
the
Atomic
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
64HISTAMINE
acid
CONTENT
extract
maining
is filtered
tions
of
than
water
ml.,
four
pine
assay
resulting
from
Results
tamine.
solutions
frigerator
temperatures.5
how
much
kept
in this
thus
far shown
must
occasion
The
to date.
to refer
merit,
in biologic
actually
substance
haves
the
rather
to the
to that
salt
demonstrated
added
in vitro
extracts
evidence
of the
the
is not
by Sumner
diamines.
blood
dence
give
favors
any
of free
can
be said
the
presence
information
a strong
body
As with
histamine
by
only
bound
guinea
provides
have
category
concentrations
strips,
we have
is subject
a very
on
to the
sensitive
Ing8
later
effect
Much
of
have
and
the
that
(i)
the
(2.)
exposure
to
more
recently,
amplified
exhibited
the intra-
those
guinea
from
pig
of the
Urbach
pure
similar
in
crystalline,
and
in plasma
ileum
while,
Code5
with
isolation
histamine
pig
solution
and that
virgin
the
guinea
histamine,
blood.
histamine
cat,
identical
to have
extracts
the activity
of the
substance
assayed
be-
of the
of laked
it desir-
seem
hydrolyzed
exposure
of the
of its pharmathought
would
that
out
reported
blood.
in terms
approach
pig
uterus
other
points
to histamine
situations
in which
Histaminase,
proposed
of histamine
method
action
appearance
to be specific
to represent
as to the
The
ml.
()
and
of the
of evidence
certain
incriminating.
therefore
active
subsequent
in the
of
the
last
Giscafr#{233}9
when
antigen
is
rabbits.
Somers#{176}’) not
He has
demonstration
tized
that
with
cautious
to the
it
and
quantities
of sensitized
completely
and
Code
large
of blood.
dogs
responses
chromatography
blood
conceded
in the
(quoted
from
Histamine
and,
investigators
to the
to the
a contraction
extracts
temperature
finding.
gas.
Smirk7
have
pointed
containing
histaminase,
desensitize
by histamine.
by paper
to the
caused
to determine
in this
and
is assayed
many
exists
it
exhibit
in any
at room
tested
and equivalent
amounts
of standard
pressure
of the etherized,
atropinized
produced
extracts
produced
It is generally
assayed
this
of extract
the
of histamine
have
of evidence
of histamine
of activity
technic
This
desensitizes
that extract
on the blood
are in progress
histamine
identity,
in anesthetized
blood
at re-
experience
no
kept
standard
even
of blood.
as “histamine-like.”
amount
with
of his-
The
Studies
per
careful
Since
Is Histamine.
histamine
concentrations
with
in our
loss
guinea
of extract
blood.
as
of atro-
concentration
overnight
is a consistent
of feces
microgram
content
of its chemical
impressive
like
Further,
dipicrate
but
addition
2.
blue
on terminal
results
of samples
measured,
as .oo
histamine
Assayed
of laked
this
be free
thymol
of whole
extracts
number
be satisfactorily
as low
the
assayed
administration
character
must
been
similar
The
the
times
with
micrograms
standard
of blood
weeks.
has
or not
ileum
histamine
itself.
Barsoum
and
is destroyed
by a preparation
high
histamine.
weeks.
in general,
substance
this evidence
by showing
virtually
identical
effects
venous
assays
in terms
concentrations
conversely,
values
Material
pharmacologically
high
often
than
a rather
contain
assayed
can
of determining
that
although
pig
extracts
there
on
from
to less
four
times
using
assayed
of activity
as three
since
NaOH
re-
addi-
is reduced
three
o.-i.o
ml.
of the
with
is extracted
with
per
loss
acid
whether
guinea
measured
method
activity
be known
the
for
minutes
in vacuo
is then
a known,
of histamine
day,
washings
to dryness
N/5
extract
resulting
for as long
two
with
acid
ninety
of solution
residue
containing
observations
after
per ml.
readily
freeze
dry
solution
trichloroacetic
Preliminary
will
it
The
contractions
each
be extended
of activity
assays
Argument
cologic
to
can
before
inherent
able
in deep
microgram
reproducible
fresh
volume
solution
solution
for
brought
ofTyrode’s
in micrograms
the
kept
no loss
found
whims
expressed
period
manner
as .oi
by matching
of Tyrode’s
be prepared
the
residue
of io ml. This
ml.
1-3
HCI
period,
the
of Tyrode’s
volume
containing
this
satisfactory
as low
alcohol.
when
longer
be extended
For
ethyl
However,
no loss of activity
of this
absolute
pH
trichloroacetic
concentrated
and
addition
must
end
BLOOD
filtered
with
bath,
is conducted
are usually
histamine
At the
up to a final
the
boiled
to the
in a bath
subsequent
then
to a water
of io ml.
brought
per ml. The
those
are
neutralized
suspended
added
are
desiccation.
water,
and
ileum
it
transferred
additions
an indicator,
to
filtrates
prevent
flasks
of distilled
pig
The
to
the
following
ml.
and
precipitate.
OF
that
paper
for
enzyme
but
set
after
in the
material
assayed.
form
in which
has
the
not,
as will
may
indicted,
shown
by
oxidase.”
addition
histamine
material
been
Zeller1#{176}
of attacking
several
Similarly,
of antigen
Nonetheless,
It does
this
active
has
been
‘diamine
of circumstances.
inactive
as the
to be capable
be renamed
chromatography9
a special
example,
for histamine,
this
itself
histamine
the
to
weight
sensiof evi-
be discussed
presently,
exist
the
within
blood
ells.
The
believed
Partition
that
of Histamine
the
erythrocytes
in Blood.
contained
In some
the
of the
larger
early
part
investigations6’
of the
histamine
it
present
was
in
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
VALENTINE,
blood.
Code,
the
goat,
whole
blood
This
observation
as
the
histamine
in
and
tained
from
blood.
fragments
small
found
the
was
further
to
be
leukemia2’
cytic
is not
pleural
The
of the
the
leukocyte
drop
rabbit,
in
blood
administration
histamine
Graiia
and
from
while
in
per
of
in the
platelets
histamine
rabbit,
tend
to
during
is,
same
fundamental
example,
leukocytes.
from
implicate
the
blood
process
then,
some
in
differences
infrequently
and
likely
also
to
been
when
platelets
in this
platelets,
that
thrombocytopenia
in the
to
24
since
rabbits,
the
there
was
This
in the
rabbit,
hista-
naturally
platelets
re-
drawn
amounts
in the
was
a sharp
therefore
in large
clots.’3’
in the
platelets.
injected
that,
that
nearly
evidence
was
a sig-
and
histamine
there
reported
the
in
and
be present
species,
results
reside
similarly
that
affecting
may
conclusion
blood
in the
reported
in nonanesthetized
circumstances,
is more
would
are
largely
of coagulation.
that
species.
in
fluid
The
in
presented
both
to serum
evidence
all
has
of blood
urethane
blood.
the
challenged
removes
leukopenia
of
It has
cells
the
partition
not
content
attain
hand,
in a mono-
without
reduction
of hydatid
may
in monocytic
have
serum
plasma
observed
In
histamine
in the
the
Minard23
with
the
is liberated
There
anesthetized
thrombocytopenia.
mine
destroyed
have
been
antiplatelet
activity
injection
and
than
with
histamine
intravenous
rabbits
along
and
authors
depressed
of
view
of blood
in histamine
has
markedly
removed.
of the
#{233}
Silva24
the
be
This
other
and
or
cow
conclusion
content
the
red
and
rabbit.
These
platelet-containing
platelets
cent
Rocha
leukocytosis
duction
of
to the
97-98
result
for
the
centrifugation
in proportion
the
may
the
granulocytes
co-workers.22
horse
Code’s
1921
an increase
in
the
in blood.
leukemia’7’
to find
the
dog,
On
ob-
contained
of
elevated
172o
was
likewise
histamine
markedly
produced
his
the
by
contaminated
content
It was
of
exhibited
been
of histamine
non-
source
activity
have
cat,
of blood.’4
range.’3’
failed
rabbits
that
rabbit,
that
exact
are
glands
pig,
in platelets
and
the
variable
histamine
lymphatic
within
and
effects
source
normal
in chronic
Zon
histamine
lymph
is frequently
Code’3
of
content,
nificant
observations
of histamine
count
fractional
the
experimentally
by
that
major
the
elevated.
rabbit
histamine
than
of histamine
is rich
as to
the
co-
properties
granulocytic
may
his
in crystalline
the
rabbit
blood.
and
to isolate
blood
latter
dog,
from
unclotted
continued
in the
the
guinea
the
able
both
of rabbit
arc
beyond
exudate
localization
case
that,
by
of blood
of
that
in the
leukemia
content
chemical
However,
higher
leukocytes
times
and
the
by Code
unclotted
that
felt
marrow
myelocytic
histamine
and
He
uniformly
ioo-ioo
were
little
horse,
extractable
of centrifuged,
Ing8
has
Extracts
strengthened
chronic
values
platelets,
the
investigations
and
that
of histamine.
granular
layer
leukocytes
found
material.
of bone
rabbit,
histamine
coat
discussion
of leukocytes.
portion
that
since
Codei3
amounts
in the
of the
of centrifuged,
present,
blood
that
subsequent
Code
62.5
LAWRENCE
cent
pharmacologic
layer
and
platelet
only
was
the
are
horse
with
cellular
16
buffy
series
buffy
others)5’
leukocytes,
granulocytic
human
in the
in
by
per
70-100
confirmed
having
Since
well
in
and
14
AND
evidence
man,
contained
a substance
as
and
was
13,
dipicrate.
produced
1937,
bullock
was
workers8’
form
in
12
the
PEARCE
the
There
histamine
histamine
is also
metabolism
exhibits
blood
content
other
evidence
in different
histamine
of blood
that
species.
activity
may
there
The
2.5-50
not
have
may
rabbit,
times
be
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
6i6
greater
than
the
is excreted
ora
in
cates
that
highly
within
had
the
factor
blood.
in this
The
amount
plasma
under
detected
In the
case
in the
various
histamine
-io
per
least
part
since
found
value.
of
as
the
centrifuged,
an
important
blood
certain
not
that
small
amounts
may
represent
chronic
myelocytic
to
have
rule
they
that
of
the
to at
must.
in amounts
probable
out
contributed
at times
amounts
tremen-
small
this
histamine
it seems
that
since
of plasma,
with
may
is
it
products.
by an elevation
It is difficult
blood
been
employed
is present,
individuals
contains
plasma,26
and
case
and
have
breakdown
accompanied
found.19
is virtually
amounts
methods
if any
In individuals
fluid
artefact,
the
not
normal
the
monocytes,
Small
or their
in the
In
is usually
it
with
are
of handling
In fact,
but
wonder
histamine.
cerebrospinal
assess.
well
Similarly,
fraction
in normal
to
correlate
particular
with
mine,
the
and
have
in
How-
very
the
similar
content
histamine
were
were
In view
histamine
of
the
the
as contrasted
content
in
mild
wide
exists
that,
with
histamine
content
and
in
the
eosinophile.
the
may
above
2.
of
of the
are
normal
the
instances
normally
eosinophilia
have
Code’3
source
and
Code
in a few
blood
eosinophilia.
blood
29
is most
the
histamine
the
to
the
are
allergy
of the
were
ob-
of allergic
of eosinophilia
to interpret.
values
equivaelevated
Both
samples
values
correlation
difficult
elevated
related
blood
and
hista-
instances
Slightly
of eosinophilia.
time
and
made
of blood
histamine
cases
met
been
range
the
or
far
conditions
attempts
blood
subjects,2S
are
in allergic
be one
member
thus
normal
in the
where
one
have
normal
at
subjects
any
found
additional
asthma
fluctuations
in allergic
possibility
to
eosinophile
degrees
observed
having
seen
several
Rackemann27
high
with
leukocytes
frequently
elevations
and
having
values
individuals
some
of blood
myeloid
to allergy,
of blood
that
Randolph
patients
tained.
content
reported
the
eosinophilia
suggested
6 patients
histamine
latter
content
of
of histamine
histamine
have
of eosinophilia.
lents
of the
relationship
McDonald17
histamine
of development
In view
probable
relate
the
stage
failure.
the
still
defibrina-
in plasma.
Attempts
any
blood
to
leukemia
detectable.
processes
entirely
con-
was
leukemia,
layer
eliminated
granulocytes
can
of blood.
total
normal
is not
present
one
with
smaller
the
of this
to those
latter
with
normally
of the
that
ever,
components,
associated
a much
possibility
cellular
content
cent
leukemia,
myeloid
and
myeloid
buffy
be
the
subjects
lymphocytes,
is difficult
lymphocyte,
are
to
in erythrocytes,
contamination
of the
histamine
of
present
circumstances
lymphocytoses
appear
the
by
indi-
further
clotting
with
in
and
in man
within
after
diet,
released
brought
in human
subjects
be
clotting.
of histamine
out
from
would
can
recently
in serum
in carniv-
the
of evidence
histamine
not
histamine
while
on
is contained
quantitatively
platelets
after
normal
to rule
of blood
almost
The
layer
in these
difficult
case
recovered
weight
have
and
form,
histamine
the
blood
components
free
chiefly
which
histamine
of the
in herbivora,
in the
depending
laboratory’9
most
In the
was
dejibrinated
since
Further,
5
from
blood
in this
BLOOD
and
differences,
of the
cellular
occurred.
form
of species
view
for
amounts,
inactive
all,
OF
amounts
variable
and
if not
to this
value
in small
Investigations
histamine
to
in
most,
firmation
dous
only
Irrespective
leukocytes.
found
normal
urine
a conjugated
hydrolysis.’5
tion
average
in the
is excreted
it
only
and
CONTENT
HISTAMINE
A reasonable
found,
but
both
independent
the
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
VALENTINE,
of
each
other.
histamine
Jackson
content
blood
of the
tions
on
anemia,
and
entertained,
outside
performed.
no
no
The
Nature
or Form
normal
within
the
hospital
T.)
had
an
had
elevation
of
of blood
in Blood.
and
it
is bound
leukocytes.
Since
also
to the
certainty.
content
with
histamine
i.-Histam:ne
in some
Content
of Blood
has
in
Hodgkin’s
L. T.
Subjects
with
\VBC
R. M.
W.
78
? Etiology.
G.
Periarteritis
of cell
tained
membranes
histamine
of
into
their
only
pharmacologically
The
nature
but
certain
from
its
lactic
shock,
whole
may
Katz33
to
have
and
sensitized
allergic
within
human
the
blood
the
was
been
liberated
subjects
from
mere
;er cent
eoio-
rr
mechanical
p
Total
--
1 es
Histamine
ar
ml. blood
mm.
cu.
iooo
41.0
6300
0.03
50.0
5975
0.10
2.3600
2.7.5
6490
o.i8
662.5
37.0
1451
0.069
5175
11.0
1139
0.10
i68oo
57.0
9576
0.053
14415
6.o
2.6650
4.5
more
866
0.02.4
a part
of the
disrupted
histamine
membrane
0.040
1199
than
thus
still
in freely
to
permit
cells
conretain
diffusible
its
of
has
been
either
who
blood
in the
release
in
plasma.
a
the
subjected
shown
That
in vitro
that
sensitized
prompt
transfer
part
the
in
anaphy-
increase
many
per
cent
of the
of this
free
79-91
by
state
to
to
known
be liberated
active
dogs
is suggested
experimentally
by
is not
may
in dogs,
cells
showed
cell
to a pharmacologically
and
blood
the
Histamine
pigs
free
from
is followed
within
available.
concentration
found
Cohen34
histamine
In guinea
of maximal
histamine
blood
that
form
Eosinophilia
cells
contain
cell
are
content
period
and
not
of bound
histamine
of Katz
do
outer
of mechanisms.
the
blood
mine
the
of
is capable
follows
11950
to bring
fragments
of speculation
state
the
During
sufficient
then
to
combination
a number
could
state.3’
worthy
inactive
by
fold.32
of the
facts
plasma
Cells
active
infection.
The
damage
I
disease.
is not
solution.
histamine.
awaiting
tract
Hodgkin’s
2.5
disruption
much
nodosa.
Urinary
P. H.
indi-
inactive
mm.
?Etiology.
K. A.
S. G.
form
disease.
?Etiology.
F. B.
was
table
form
it
indicated,
Trichinosis.
6o+
free
pharmacologically
Diagnosis
R. S.
W.
process
eosinophilia
in the
Total
C.
observation.
The
inactivated,
Cu.
R.
a macrocytic
leukemic
with
is rapidly
As Trethewie3#{176}
Age
Subject
histamine
and
atypical
established
of observa-
z.
subsequent
an
the
in the
results
splenomegaly
months
of histamine
symptoms
circumstances
TABLE
in table
in
of eosinophiles
determinations.
of Histamine
myeloid
The
shown
also
ever
changes
intervals.
a few
was
parallel
time
possibility
correlation
profound
under
(L.
show
percentage
are
subject
The
in these
producing
subject
diagnosis
to
in the
laboratory
This
62.7
LAWRENCE
unable
at different
ml.
the
significant
demonstrated
of
per
was
were
in this
a single
died
but
that
be
that
AND
variations
taken
made
microgram
autopsy
cates
patient
be seen
o.io
No
same
Rose26
marked
eosinophilia
It can
above
and
with
PEARCE
the
hista-
observations
addition
animals
of histamine
of
of antigen
or
clinically
from
cells
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
6L8
HISTAMINE
to
plasma.
These
Dragstedt
wise
and
capable
needing
usual
animal
plasma.42
may
be due
in
rabbits,
has
also
Such
has
The
of certain
ability
to proteolytic
has
show
paralleled
amide
arginine
plain
or
capacity
The
as the
blood
cells
from
cells
cells
in vitro
for
to plasma
with
peptone
or by
any
capable
of attacking
cifically
capable
acid
state
It has
been
of hydrolysing
At
to
Rocha
its
the
cell
by
the
there-
and
toxic
example,
phar-
in plasma
such
cathepsins
likewise
Cathepsin
would
must
only
an
remain
ex-
its
of attacking
that
an
either
would
it
state
capable
by
being
from
and
it
They
fact
arginine-amide46
however,
hista-
acid
release
free
and
release
is bound
amino
intracellular
for
#{233}
Silva
to
linkage.
in
enzymes
shown,
corresponding
capacity
histamine
activate
benzoyl-l
present,
its
attractive
cell
would
acids.
the
but
proximal
proteolytic
which
it.
the
Thus,
the
amino
of the
arginine-amide
is rendered
within
and
group
histamine.
that
histamine
residues,
external
process
category.
the
that
of histamine
carboxyl
of pure
felt
attacking
observations.
by either
the
activity
papain
hypothesis
inactive
with
pharmacologic
conclusion
experimental
be mediated
requisite
just
rabbit
from
is mixed
like-
a vegetable
histamine
of compounds
activity
to amino
lysine.
linkages,
no
with
provisional
macologically
could
liberate
by
are
acid
from
of histamine
blood
bonds
characteristic
of linkage
many
or
experiments
its
the
type
the
peptide
little
the
in their
made
to
and
type
ascorbic
histamine
release
when
Browne35
trypsin
Papain,
and
poisons
a number
forming
show
hydrolysates
mine
to release
The
rats
and
the
to plasma.34’
cysteine,
animal
synthesized
histamine
compounds
fore
and
Rose
of
demonstrated.43’
#{233}
Silva45
Andrade42
found
enzymes.38
pigs,
cells
as HCN,
been
by
enzymes
from
such
BLOOD
confirmed
histamine
cathepsins,
been
the
been
OF
Proteolytic
37
activators
guinea
Rocha
acids,
have
co-workers.36’
of liberating
cathepsin,
to
findings
CONTENT
II
is spe-
into
fit
the
attractive
hy-
pothesis.
Histamine
is readily
histamine
in
man
pharmacologically
within
the
blood
Origin
myeloid
per
cent
in
rather
than
with
by
paper
when
added
when
to
pure
cultures
in the
There
the
urine
injected
are
many
gastrointestinal
reasons
but
for
to
not
within
belief
have
form
histamine
it
is
form
the
cells
of
to
that
nothing
grown
in urine
exogenous
only
and
negligible
this
sources
do
with
recently
been
Histamine
are
conproduced
in histamineis excreted
amounts
is in free
of
form.
of histamine,
the
major
is
diet
is effectively
substance
are
up
urine
with
subcutaneously
while
to
has
feces,
latter
aerogenes
administered
appear
chiefly
histamine.47
autoclaved
of the
hours,
varies
acetyl
Orally
in the
compound
be
known.
in amounts
excreted
amount
or Aerobacter
a few
histamine
the
and
form
in similar
is not
its
amounts
coli
within
contents,
existence
histamine
conjugated
histamine
free
its
flora,
in which
in conjugated
the
and
This
small
Conjugated
subcutaneously
as
form,
feces,
and
of Escherichia
media.
quantitatively
of blood
urine
the
methods
human
intestinal
of histamine
origin
factors.
histamine,
for
in
conjugated
fresh
by
conjugate,
nature
In man,
chromatographic
to acetyl
containing
The
endogenous
tract
acetyl
as uncertain.
administered.25
inactive,
shown
exact
is excreted
of that
an
The
Histamine.
intestinal
is no evidence
be regarded
histamine
entirely
verted
only
the
as the
There
leukocytes.
can
of Blood
administered
to
in
in urine
inactive.47
at present
The
acetylated
is excreted
part
such
of
the
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
VALENTINE,
histamine
content
that
both
the
the
histamine
It
has
been
and
equivalent
of
there
is no
kocytes.
There
to selectively
blood
plasma.
by
bone
marrow
myelocytic
an
myeloid
inherent
authors
have
presence
of
also
and
Segesser.52
Fate
for
intravenous
pears
The
leukocytes
of the
most
the
accounts
the
erythro-
form
to any
leu-
significant
content
of
blood
to
that
in
rapidly
This
origin
of
of
finding
histamine
in
histamine
in
render
1720
im-
it
present
histamine
of course,
within
cells.
Little
part,
destroyed
very
are
the
to
the
supply
and
potential
rich
source
about
fifteen
the
56
be
as
of blood
latter
as to
in
the
as
urine,
a wide
man.
and
injected,
period
to
with
or
of
it
administered
histamine
According
by
histamine
leukocytes
rapidly
of parenterally
liberated
the
as well
Continuously
injected
detoxification
of
Edlbacher
information
a considerable
deaminization
can
fate
myeloid
about
minutes.48
by way
by
but
factual
is excreted
intravenously
occur
denied
a
in the
in man.
body.31’
over
that
acid
acid,
no
the
histamine
others
ascorbic
lymphocytes54’
then,
within
involving
been
in ascorbic
is,
inactivated
by
may
has
of leukocytes
in the
among
in vitro
transformation
There
little
out,
rapid
an attractive
histamine-poor
be maintained
of leukocytes
The
relative
plentiful
Credner5’
claim
is known
concentration
the
this
content
be
certain
lhistidine.Ilb
The
it
by
The
of blood
within
for
and
50
amine.
myeloid
process
make
in some
that
information
marrow.
to histamine
in
pointed
blood
Holtz49’
amounts
can
specific
its origin
established
tissues.
the
must
has
well
decarboxylating
bone
to Holtz,49
to
effects
previously
a chemical
in
its
histamine
from
any,
Histamine.
constant
probably
as are
blood.’4
histamine
to locate
histamine
of
blood
unable
parenterally,
the
that
of
by
imine
of Blood
injected
be,
man,56
to
in
histamine
subjects’3’
capable
According
significance
as
exposed
present
free
up
the
in
and
be in contact
in the
related
enzyme
be converted
and
origin
relatively
rats,
normal
It appears
may
histamine-rich
exact
then,
claimed
in substantial
as in the
must
might
values
of myelopoiesis.
in mammalian
been
acid
is present
When
unable,
exogenous
high
is significantly
of histidine,
of oxygen.
imino
the
are
picked
own.
conjugated
ever
that
they
that
when
their
is detectible
are
to
shown
only
substance,
blood
of peripheral
than
with
none
equal
histamine
extremely
decarboxylase
of histidine
the
Since
been
histidine
availability
has
an
to date
of histamine
The
the
selectively
rather
the
of
threshold
which
that
exceeds
urine,
a low
is evidence
than
exists,
contain
material
of
in the
of
have
histamine
amounts
leukocytes
is not
histamine
process
universal
the
large
with
comparison
probability
tissues
presence
when
remotely
there
endogenous
Fourtbly,
metabolic
animal
It
serum
administered
hence
co-workers’6
leukocytes.
A reasonable
portion
or
that
higher
in
plasma
elements
histafline
and
exogenous
up
plasma
Thirdly,
leukemia
that
the
parenterally
leukocytes.
and
take
excreted
evidence
blood,
Anrep
therefore,
formed
in
leukocytes.48
suggests
being
6L9
LAWRENCE
of blood
periods
is,
the
is consistently
obviously
probable
are
moreover,
the
the
myeloid
origin
concentrate
from
degree
place,
surrounding
during
that
Secondly,
disappears
the
histamine
is,
cytes,
first
conjugate
suggestion
of
the
AND
erythrocytes
even
Histamine
concentrations
the
that
of exogenous
blood.25
In
leukocytes
found
histamine
the
of blood.
PEARCE
since
of time.
largely
Goodman
subsequent
injected
variety
In
disapand
Gil-
oxidation
histamine.
of agents,
it
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
630
HISTAMINE
seems
quite
mate
possible
fate.
to have
This
during
life
the
destruction,
require
requirements
tient
with
mine
values
for
total
preciable
The
blood
indicate
The
gradually
with
histamine
blood.
of
large
during
the
destruction
the
normal
in addition
to
to
testinal
tract.
Best55
of
the
and
Best
tissues,
histaminase,
kidneys,
is capable
twenty-four
Normal
Values
human
part
blood.
to
the
included
Such
individuals.
with
cluded
in any
series
a role
in
variations
gators
are
tions
tained
in
the
the
laboratory
in normal
or
in Man.
or
paid
factors
histamine
to collecting
It
by
is pertinent,
this
laboratory
be
that
The
each
allergic
of
at
in
29
in-
to
be
have
different
and
they
24,
normal
occasional
may
report
least
do
expected
by
that
close
content
subjects
that
stasis
to
MAN
individual
than
be
reported
without
in order
of hista-
IN
attributed
conceivably
therefore,
role
and
slowly,
reasonably
blood
can
values
animal
but
BLOOD
is so widespread
blood
acts
that
of their
which
in-
in
histamine
certainty
manifestations
in
the
mucosa
in general,
normal
is known
it
OF
can
content
forms
Other
is,
the
with
example,
of normal
individuals
There
body,
evaluation.
CONTENT
as to
the
enzyme
56
in the
suggest
from
enzyme
future
probably
histamine
allergic
of normals.
technic.
exist
another
atypical
attention
field
do
For
in the
in one
mild
of activity.
await
of establishing
“normal.”
fluctuations
assay
must
in
pa-
in urine
diet,25
intestinal
this
be the
a single
quantities
an
the
of
liberated
elevation
absorbed
In vitro,
usual
in the
as
in
normal
realm
only
on
occurs
that
amounts
HISTAMINE
Histamine
difficulty
Allergy
dividuals
THE
variations
inherent
wider
histamine
in the
investigators
is actually
exhibit
leukocytes
demonstrated
on
the
with
ap-
implica-
present
any
91.5
any
agent
of large
myeloid
in vivo
at
histamine
acetylated
or
outside
to show
of
found.
possess
all
laboratory
presence
been
have
toxic
pahista-
others35-37
can
from
histamine.
ON
of Blood
among
the
largest
required
STUDIES
failed
adult
blood
catastrophic
is not
this
hours.
In one
of
and
their
leukemia,
would
have
cells
in
of urine
have
in
destruction
EXPERIMENTAL
agreement
McHenry3
being
would
this
despite
histamine
myeloid
of a potentially
correlation
of
of
blood
Cohen34
have
range
the
of destroying
in histamine
and
leukemia
present
hours
minase
form
is liberated
twenty-four
individual
ulti-
shown
mg.
liberation
of leukemic
excretion
and
free
its
time
laboratory,
whole
sudden
b:
been
the
greater.
this
an
observations
histamine
urinary
The
quantities
Preliminary
beyond
ml.
such
circumstances,
of such
in each
in chronic
in
per
ml.,
at
0.5-1.0
be appreciably
Katz
special
or
source
observed
toxic,
role
detoxification
this
leukocytes
also
have
If histamine
‘
body
of
for
5000
Katz,33
under
myelocytic
contrast
the
the
from
histamine.
chronic
This,
that
of
into
of speculation.
tient
micrograms
observations
possibility.
subject
18.3
may
leukocytes
blood.
in
might
volume
of this
that,
in the
leukemia
circulating
portion
tions.
as
blood
detoxification
neighborhood
span
detoxification
high
milligrams
the
life
myelocytic
as
a total
even
similar
chronic
Assuming
in
BLOOD
myeloid
activities
detoxification
a somewhat
of
The
hours
their
somewhere
normally
Assuming
of a few
of
OF
method
a certainty.
span
course
then
would
a similar
is by no means
a probable
either
the
that
CONTENT
investi-
minor
the
may
in-
played
findings
serve
variaobas a
1
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
VALENTINE,
standard
data
of reference
are
also
and
to
mine
assayed
per
0.07
micrograms
tion
was
made
with
normal
0.071
micrograms
own
histamine
of
pressed
in terms
of the
in
tion
also
with
have
subjects
the
were
therefore
an
are
are
have
normal
average
ing
ties,
below.
as the
in
upper
a few
as
and
to
co-workers2#{176}
values
in man,
out
of normal
Code5
has
histamine
values
than
more
assay
the
to exhibit
beyond
of
lack
was
ex-
histamine
Since
this
reference
per
for
similar
mm.
fasting
filtrates
clear.
of
correla-
on both
are
the
latter
Cu.
obvious
cloudy
which
usual
the
are
felt
of any
that
slight
our
by
report,
individual.
Observations
those
in table
certified
the
eosinophiles
reported
likely
this
it
standard
blood.
values
each
subjects
indicated
In addition,
cells,
total
again
content
in
for
The
human
are
equipment
these
a rough
included.
nonfasting
blood.
computed
to point
the
ml.,
blood
with
a range
and
tend
to
In nonfasting
turbidity,
and
in our
experi-
normal
range.
Both
group-
observed.
o.io
The
vast
majority
total
and
the
exceptions,
value
of o.uo
limit
individuals,
microgram
individuals
per
however,
of subjects
with
leukocyte
histamine
per
normal,
ml.
has
will
had
values
been
values
with
fast-
only
au
disease
enti-
consistently
per
arbitrarily
slightly
In
with
nonfasting
micrograms
laboratory
have
ml.,
of
is normal,
o.uo
ml.
in the
2.
miscellaneous
therefore
in this
in the
while
to
0.030
per
per
ml.,
count
values
from
micrograms
0.140
Three
subjects,
as determined
ostensibly
to
to range
micrograms
0.075
micrograms
differential
blood
of normal
2.
found
of
0.057
was
latter
was
value
over
The
few
average
of from
micrograms,
ml.
histamine
an
likewise.
whom
The
marked
micrograms
0.019
as elsewhere
within
disease.
values
per
with
and
examina-
individuals
2.0
histamine
using
of whole
been
value
histamine
did
micrograms
have,
here,
ml.
with
subjects
of o.o86
showed
group
of
subjects
per
normal
group
that
histamine
micrograms
nonfasting
two
o.o5
studied.
In fasting
0.110
o.o8o
into
to any
in
of assay
obtained
resides
merely
filtrates
occasionally
per
has
prove
higher
ence
base
individuals
subjects
somewhat
hista-
and
one
vary
Shimkin
and
method5
values
histamine
recorded
the
nonfasting
followfor
fall
than
not
blood
fasting
Code’s
were
leukocytes
might
between
from
blood.
on
(i)
histamine
to range
literature
to
more
did
blood
of whole
of both
by
reported
free
blood
computations
ml.
of the
Histamine
computation
content
the
counts
per
of blood
studies
of
histamine
eosinophile
laboratory
myeloid
part
in whom
o.oio
tended
and
in
and
the
between
ml.
blood
students
values
per
found
some
Standards.
million
are
whom
elements
MacDonald59
vary
most
of
formed
university
to
individuals
the
base
content
hematologic
blood
on
I
observations.
in this
Bureau
per
and
found
that
the
and
micrograms
0.04
times
summarized
as determined
greater
disease
content
in
normal
felt
8 normal
histamine
ml.
Haworth
were
Rackemann27
leukocyte
their
All
In
and
recently
The
with
histamine
per
supposedly
It was
and
ml.
normal
in plasma.
103
blood.
at different
Randolph
including
ml.
0.02.
per
the
obtained
of
between
(i)
degree.
in subjects
micrograms
of
values
ml.
found
1936
blood
The
micrograms
groups:
63
LAWRENCE
determinations
o.o5-o.ii
per
the
content.
have
in
be
micrograms
year
2..
Smirk7
subjects
O.002.-.OIO
ing
similar
AND
presented.
Barsoum
human
for
PEARCE
ml.
or
accepted
the
realization
in
excess
of
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
632.
HISTAMINE
CONTENT
1.-Blood
TABLE
Histamine
Fasting
OF
Values
Normal
BLOOD
in
Normal
Subjects
Subjects
Histamine
J. F.
J. L.
M.
E.
W.
L. P.
A.
N.
V.
3
148
0.035
.0113
5000
0
0.077
.0154
4450
2.850
2.67
0.100
.0350
662.5
3 100
5475
32.50
million
0.091
.0191
0.100
.0309
0.074
.0143
0.063
.oi88
5150
532.5
3350
i6o
M.
68oo
3950
S. H.
2092.5
6400
J. B.
7150
3800
E. M.
602.5
3100
F. K.
82.2.5
5700
R. D.
4450
D. H.
6375
0. S.
68
383
72.
0.067
.0169
0.077
.0110
0.030
.0079
12.1
0.042.
.0135
0
0.069
.0111
2.300
0
0.067
.02.89
4450
2.55
0.110
.02.47
6300
3350
2.52.
0.092.
.02.75
N. R.
6o
4400
‘3’
0.070
.0159
R. D.
8o
6oo
‘7’
0.110
.0181
6669
4194
151
0.075
.0196
Normal
Subjects
D. P.
62.50
4300
88
0.057
.0131
C. S. G.
6450
3850
193
0.090
.02.32.
J. F.
5,00
i8oo
2.04
0.093
.0332.
M.
6o5o
3450
12.1
0.
110*
.0348
D. T.*
6950
4450
2.09
0.
140*
.0314
R. H.
6io
3900
i8
0.057
.0146
F. S.
4350
2.900
87
0.075
.02.58
M.
H.*
L. P.
6450
4450
0
0.100
L. P.
5000
3050
50
0.
W.
6ioo
3900
366
0.084
.0115
.02.2.9
N. V.
.02.2.5
110*
.0115
E. A.
5550
3150
444
0.072.
L. C.
6ioo
4500
12.2.
0.059
.0131
C. K.
5700
3550
2.2.8
0.075
.0111
R. D.
5050
2.350
101
o.o88
.0372.
H. G.
5375
2.650
i6i
0.089
.0336
5900
2.03
o.o6i
.0103
6047
3697
179
o.o86
.02.49
6o8
3710
0.077
.02.2.5
10115
..
less
figure.
66
8450
Average
the
100
L. B.
V.
nelcdd
6775
R. H.
A. F.
this
per
in micrograms
Total
eosinophiles
per Cu. mm,
492.5
Nonfasting
in
myeloid
cells
Cu. mm.
55
42.3
Average
Average,
Total
Total
WBC
per Cu, mm.
Subject
*
There
non-fasting
myeloid
..
determination
may
be somewhat
state
leukocytes
but
this
ranged
greater
variability
variability
from
-
is not
0.0113
in determinations
large.
to
0.0350
The
total
micrograms
obtained
histamine
in
per
fasting
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
VALENTINE,
subjects,
and
group
from
are
of value
subjects
chiefly
with
Blood
I tO
leukocytoses
conditions
Values
most
indicated
that
almost
present
in Leukemia.
interest
within
and
In
been
the
in the
former
These
figures
similar
to
and
leukocytes.
the
in
Count
in
values
the
data
Subjects
in Absolute
with
older
literature’3’
in
Acute
Myelo.
1164
9700
P.
2.08500
Stabs.
I067
195990
138750119650
M.
Mc.
md.
blasts
Segs.
57750
38115
1932.5
13044
D. P.
D.
W.
M.
A.
Average,
4600
1761
and
values
leukemia.2’
is
Since
leukemia.
and
little
with
peripheral
Table
by
in micrograms
r
perIO6
l
bl
myeloid
cells md.
blasts
d
2.06415
7372.
7,631
11938
2.16813
7163
306
55li
4104
7656
918
578
14438
41580
3382.
15750
1353i
.0136
1.0117
o.o6I.oool8
0
1733
0.10
10415
16170
.00575
0.011
.000093
.002.93
0.C2.0
.002.6
.0118
.002.7
.0155
0,0181.00067
2.706
peri0’
‘myeloid
cells less
blasts
.0017
0.042.
0
89
979
3940
446
1408
690
2.99440
12.83
3568
1111
1111
95
0
0
94560
3940
390
704
io68
1157
117
1186
1141
1840
7471
138639
io68
0.02.7
.02.53
.02.53
7880
0.110
.0007
.02.66
1341
o.o6o
.oo8o
.02.56
0.2.60
.0019
.0072.
0.02.5
.0315
.o66
0.017
.0077
.
35891
794
382
1108
1931
68I78
oo88
.0195
76l00.074)00844
only.
not
country
by
generally
data
et
are
in
and
in
recently
Shimkin
histamine
or
19-21
histamine
by
blood
leukemia’7’
on the
have
Lawrence’9
elevation
content
in
monocytic
of blood
published
their
and
above
in acute
findings
on
leukemia.
regarding
the
in leukemia,
blood
and
that
lymphatic
available
al.,2#{176}however,
subacute
acute
Valentine
agreed
customary
is known
of leukocytes
patients
and/or
l085
determinations...
much
Shimkin
of acute
0
0
is also
Not
leukemia.
0
95
in this
It
20
normal
on
*
values
co-workers.
0
Ill
413
Approximate
series
578
2.8854
3175
Thiersch,’8
this
17
Australia
Histamine
Less
blasts
8536
4170
1063
5119
excluding
cases
0
0
11150,
K.
*
0
578
I40750I0l748
Mrs.
0
6i
394000191560
E.G.
that
0.02.0
1115
MM.
is
to
Leukemia
575
M.
G.
4ol6H76
1746
0
6738
11150
S. M.
have
blood
relative
Total myeloid
cells
per
mm.
blood
Terms
of
reported
of
normal
studies
content
tremendous
reports
in cases
under
Numerous
histamine
additional
Values
that
00
A. D.
in
Cu.
Blasts
M.
values
of blood
observations
Total
WBC
per Cu.
mm.
Subj.
with
content
the
attains
addition
Leukocyte
histamine
of
myeloid
Histamine
Differential
comparison
leukemia
reviewed
3.-Blood
TABLE
It averaged
micrograms.
0.02.49
for
view
frequently
subjects.
recently
subjects.
group
The
in
myelocytic
elevated,
633
LAWRENCE
leukemia.
chronic
in normal
more
latter
of reference
of it resides
in
always
in the
and
is of particular
AND
in nonfasting
0.0394
and
as a standard
Histamine
leukemia
has
0.013
micrograms,
0.0196
PEARCE
it
leukemia
and
picture,
3 summarizes
partition
was
data
as data
thus
histamine
pertinent
a predominantly
as well
the
of
considered
within
blastic
on
obtained
subjects
the
to collect
type
with
in cases
of bone
chronic
of acute
myeloid
further
data
marrow
myeloid
leukemia.
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
634
HISTAMINE
The
total
cate
determinations.
leukocyte
subjects
on
those
the
For
series
basis
the
tions
been
myeloid
be noted
of blood
grams
per
ml.
This
was
uo,ooo
per
cu.
mm.
in eight
were
micrograms
per
ml.
was
present.
than
blasts
were
than
blast
of
blood.
of the
the
blastic
of the
It is not
cases
tents
observed
myeloblastic
such
were
included,
more
differentiated
to the
doubtful
values
with
the
arbitrary
blast
cells.
The
those
in
stances
for
the
latter
the
plasma
terms
noted
that
tion
of
conclusion
is apparent
eral
must
with
chronic
those
per
ml.
highest
Cu.
that
mm.
the
in normal
whole
blood
18.3
micrograms
blast
in the
results
a very
low
Chronic
leukemia
are
histamine
The
a subject
ml.
values
lowest
with
in
an
individual
is,
3, the
ways:
(i)
exclusion
the
normal
of
range;
subjects.
per
total
In
ml.,
in-
values
histamine
It should
blood,
the
low
blasts
in
also
be
computa-
values.
in the
The
periph-
content.
Leukemia.
obtained
value
arbitrary
the
of
some
in table
extremely
in table
41,950
least
leukemia
normal
studied,
histamine
at
cases
in two
of
con-
any
in histamine.
significance.
in
Myelocytic
presented
that
peripheral
of leukemia
of
below
in
in any
histamine
poor
expression
counts
cases
low
micrograms
of little
usually
in
subjects.
those
lympho-
certainty
reported
far
0.03
and
leukemia
with
the
are
to
is probably
in the
per
group
in acute
and
computed
with
(i)
is below
cells
possessed
in
former
approached
cells
blood
and
cases
number
peripheral
myeloblastic
been
comparable
being
of Blood
myelocytic
on inspection
with
have
Content
cells
data
disease,
in the
have
a large
likely
in acute
chronic
cells
cells
histamine
million
cell
the
other
in the
exclusion
more
normal
leukocytes
myeloblastic
generally
much
the
o.i6o
leukocytes
included
fortuitous
blast
blast
in the
roughly
that
the
the
of
and
myeloid
be made
above
numbers
beyond
of the
micro-
0.2.10
numerous
with
could
in
of blast
of high
per
the
of the
blood
in instances
evaluation
It seems
myeloid
myeloid
histamine
blood
that
are
million
Histamine
and
to
these
micro-
0.03
was
large
of
35,891
very
that
progeny
group
total
histamine
of per
due
series.
values
and
were
distinction
the
million
average
mm.,
cells
fact
myeloid
(E.G.)
o.o6
count
values
7880
of subjects
been
inclusion
where
cu.
in the
this
origin
per
second
were
below
elevation
only
It is conceivable
in
its
Due
that
have
leukemia
histamine
per
blast
separation
cases
unlike
In the
problems
here.
could
mm.
present
felt
reported
a distinct
(MM.)
in subcalcula-
however.
were
the
with
and
in the
leukocyte
despite
were
myeloid
table
cells,
cent
total
In 2. subjects,
instances
pertinent
per
the
and
of these
cu.
were
both
fact
respectively,
first
morphologic
types.
the
determinations,
per
cells
In
One
despite
of blood
In the
myeloid
determinations
o
counts
included
all
most
particularly
neutrophilic
in this
been
106
than
in
cases,
differential
values
have
per
more
observed.
found
myelocytes.
involves
true
cell
of dupli-
computed
few
of the
differential
basophiles
and
uoo
average
were
In some
only
exceptions,
or below,
the
types
members
histamine
three
frequently
range
other
and
with
ml.
low,
only
in the
and
cells
that,
per
cells
very
included
represent
cell
count.
space
eosinophiles
grams
blast
was
BLOOD
instance
individual
differential
of conserving
The
of total
It will
count
OF
every
for
cell
2.00
total
have
tables.
values
of a
purposes
of cells
sequent
in almost
The
in which
made.
counts
CONTENT
The
data
4. It will
are
determined
leukocytes
with
very
large
was
per
2.35,2.50
on
subjects
be readily
noted
in comparison
0.17
Cu.
micrograms
mm.,
leukocytes
and
the
per
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
VALENTINE,
It
will
dividual
also
be
noted
that
to individual
W.
C. G.
Blasts
164000
j.
R.
0
2.560
118000
36000
0
2.03500
0
92.50
F. T.
M.
H.
414500
36450
138100
78600
M.
F.
J. T.
65900
in
per ml
blood
per 106
myeloid
cells
193700
1.50
.0119
i6oooo
1.31
.0083
2.3500
2.7500
4I600
17900
4480
111300
8.oo
.0653
,6oo
1610
1.10
.062.8
51900
1017
11910
1010
935o
1980
30500
59000
910
463
I7l0
92.5
555
2.4800
536
983
32.2.0
68
2.5400
I.’
.0413
1.0
I 150
6.6
.032.6
116100
3.0
.02.58
2.2.5750
18.3
3080
11550
44150
6i6oo
6oo
2.979
2.0840
17170
39300
31575
442.50
15300
35300
54100
1176
40500
11910
2.02.50
51100
1191
110100
3050
2.34
.02.76
0.44
.035!
872.0
2.02.500
596
.0117
14.00
6 8
2.055
1046
0.90
399500
1710
5790
1010
I .90
3.75
15900
11410
10100
1095
86oo
171800
93
.05
11.00
i88oo
1430
10610
2.630
52.
101100
3540
80750
140800
33400
463
5550
382.00
532.00
39350
70400
104
119100
Lymphs.
Histamine
micrograms
32.80
2.63
135150
Segs.
Total
myeloid
cells
per
Cu. mm,
3990
0
P. E.
Stabs.
Terms
Leukemia
57400
0
500
in Absolute
Myelocytic
45900
10415
2.05
Chronic
insub-
40900
2.6300
C. E.
with
from
in
33900
43500
2.0700
example,
11100
89
17850
E. A.
Count
1010
1771
markedly
For
2.9600
0
177100
vary
42.900
47900
2.02.00
values
leukemia.
Subjects
MetaMyelo,
4860
8140
in
635
LAWRENCE
histamine
Leukocyte
Myelo.
998
199500
AND
myelocytic
Values
Differential
WBC
per Cu,
mm.
blood
chronic
Histamine
Total
‘ubj.
the
with
4.-Blood
TABLE
PEARCE
.0811
5.5
.02.50
.0115
13415
0
79590
0
13415
0.2.8
41950
0
5870
7340
13810
14150
0
41900
0.17
732.50
0
62.2.5
6590
11980
31100
32.975
39550
I .40
.03
9500
0
475
760
0.55
.o66i
0
1140
832.0
1140
52.30
0041
54
I.W.
115750
6465
44150
11610
67850
6ooo
32.30
110100
.8o
.02.76
B. D.
141500
4830
41050
42.2.50
78450
6io
1108
2.40000
7.60
.0316
J. C.
J. A.
M.
0.
70000
0
2.450
7700
8750
2.8700
350
47950
0.43
62.000
0
12.40
8o6o
8370
15715
930
44650
0.52.
.0,
74500
0
ioo6o
70800
1.70
.0382.
i6iooo
9.50
.05
187750
9.00
.0480
82.00
13810i
2.4580
3350
169100
2.538
2.7900
2.62.00
43I50
49050
762.6
45750
13810
46700
49550
176500
3530
42.400
2.6500
37956
51100
883
173900
6.70
.0385
153100
3833
2.3780
2.0700
5o6oo
42.2.00
766
146400
5.34
.0364
416
5830
78100
3.75
.0480
4.14
.0352.
8330
3Il40
0
2.080
17715
Average*
*
Averages
this
table
where
more
than
in
one
determination
vidual
have
been
averaged
mean.
The
averages
are,
then,
number
of determinations.
leukocyte
jects,
whose
histamine
(J.R.)
with
are
the
of
the
entire
made
on
the
same
considered
count
leukocyte
means
was
as
in terms
content
a total
not
and
of total
blood
i6
190650
83300
42.35
0090
ranged
of the
varied
determination
number
between
from
count
one
5.5
of
set
in
of individuals
ioo,ooo
tO
ui8,ooo
of
18.3
per
determinations.
individual,
the
the
and
Cu.
mm.
rather
per
2.50,000
per
had
for
computation
studied
micrograms
In
values
ml.
histamine
of
instances
that
indi-
the
total
in
terms
than
Cu.
One
90
mm.,
the
subject
values
of
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
636
HISTAMINE
8.o
micrograms
( W.C.G.)
per
ential
cell
counts
ations
in
histamine
stages
of the
elevation
any
are not
is eliminated
elevated
sometimes
values
unit
histamine
edly
when
the
average
the
different
more
the
within
determined
on
to
rises
of these
most
with
given
individual.
will
not
counts
drop
It fails
proto
em-
content
leukocyte
in capacity
in
levels.
to incorporate
leukemia
may
be cannot
of histamine
myeloid
be
my-
total
do
differential
of chronic
The
mark-
chronic
in histamine
and
from
This
histamine
correlation
or course
change
with
variations
No
therapy.
range.
values
in unit
reduced
ray
in subjects
myelocytic
data.
prognosis
to
histamine
total
interesting
are
roentgen
variability
same
of chronic
of existing
the
great
or mod-
variations
physiologic
in any
the
the
leukocytes
and
cell
cells,
normal
counts
that
in
in total
myeloid
io6
marked
of blood
unit
of
the
out
correlation
that
feature
basis
to
point
of the
relationship
per
studied,
van-
terminal
of variations
of
of
instances
close
count
if any,
the
Rather
wide
the
to be high,
leukocyte
To
say
leukocyte
the
in terms
a result
the
of magnitude
factor
content
total
few
order
if the
count.
as
for
consistent
total
the
at approximately
in myelopoiesis
be
metabolism
leukemia
has
been
as yet.
Shimkin
content
to
pertinent
the
is rough
meaning,
histamine
possible
there
the
when
164,ooo
in differ-
excepting
a roughly
histamine
approaches
presently.
way,
is to say,
normal
numbering
Thevariations
explanation
that
bear
histamine
of the
striking
subjects
What
the
unit
in
any
a general
That
the
detail
the
to
however,
is merely
as
phasize
for
count
leukocytes
to afford
experience
disease.
appear,
total
portionately
our
approximately
leukemia
the
the
values
total
In
tends
irrespective
in more
elocytic
been
occur,
BLOOD
of blood.
large
by expressing
to
discussed
has
tendency
content
with
observed.
histamine
with
is a rough
high
sufficiently
it
blood
erately
another
OF
microgramsperml.
content
individual
count
there
while
1.32.
disease,
in
one
on
ml.,
possessedonly
CONTENT
and
his
fall
in
to this
blood
collaborators2#{176}
the
terminal
point
has
histamine
months
total
This
leukocyte
of blast
count
cells
in histamine
A second
terminal
but
per
(M.F.)
million
myeloid
This
subject
The
data
offered
in
as any
The
the
line
subjects
normal
of
to state
the
cases
a few
lowest
total
and
Shimkin’s2#{176}
cell
in
death
histamine
observation,
but
reduction
histamine
comparison
hospitalization.
values
are
noted.
the
in
in
number
of reduction
terminal
two
variations
in some
degree
his
(P.E.)
than
of increased
before
to
unit
on
reduction
weeks
prior
either
to result
the
of data
patient
lower
presence
three-fold
months
this
histamine
range
content
from
terms
of
in chronic
series
three
this
relatively
myelocytic
to
incorporate
per
essentially
approximately
In
that
in
They
values
subject.
fair
almost
In one
too
in our
series.
inadequate
to
be
confirmation.
interest.
to
three
with
computations
siderable
explained
leukocytes
made
exhibited
are
an
The
histamine
amount
considerably
be expected
have
for
a small
explained
count.
might
not
showed
a determination
was
be adequately
picture
a tendency
Only
laboratory.
death
differential
could
reported
disease.
in this
before
not
or in the
in the
recently
of the
collected
days
could
content,
patient
content
with
been
a few
previously.
have
phase
million
the
times
myeloid
same
greater
crude
than
standard
leukemia
the
histamine
in
cells
as those
are
observed
those
observed
of reference,
of
con-
in normal
in
it
capacity
exists
in virtually
normal
amounts
within
any
appears
all
each
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
VALENTINE,
myeloid
cell
capacity
exceeds
pen
irrespective
million
presented
cells
4 include
This
million
little
computation
This
chronic
the
next
of
this
is no
leukocytes
gen
been
most
nearly
been
below
oo
micrograms
per
cation
in
all
trophilic
cell
normal
subjects
unit
will
or,
cases
when
granulocytes
necessarily
contained
was
high.
within
It
to
more
nearly
cases
in
not
appear
does
the
by
not
the
would
while
the
manifest.
of
abnormal
cell
9.5
The
impliseries
that
the
the
neu-
in most
are
factors
that
the
when
in total
were
the
existent
may
percentage
mature
cell
the
types
total
count
histamine
cells,
true,
It
together
content
while
cells
counts
indicated.
of incorporating
more
hista-
reduction
of
aberration
this
decreasing
histamine
while
leukocyte
histamine
and
However
capable
2.00
was
leukemia.
cell
an
on
of histamine
unit
If this
has
histamine,
these
mean
make
values.
of all
reduction
cells.
high
fall
burden
of blood
(based
therapy
immature
the
the
histamine
differential
approached
than
more
alter
3, the
are
ap-
of
blood
blood
of irradiation
parallel
an
mm.
is made
of
carriers
This
values
to
suggestion
and
histamine
twelve
In
Cu.
at
merely
polymorphonuclear
myelocytic
individual
irradiation,
of the
chronic
when
myelopoiesis
roentgen
the
quota
a. and
that
normal
eosinophiles
important
reduced
in
no
latter,
of total
histamine
per
has
values
in
not
types.
with
counts
mean
cell
roent-
differential
and
more
be a roughly
is greatly
count
The
a result
is increasing.
incorporated
does
in
in the
of myeloid
aberration
count
their
in figures
more
be
duction,
may
leukocyte
can
that
as
the
disease,
cells
relationships
content
presented
metabolism
of
seen
histamine
the
micrograms-quite
subjects
variable
mine
interest
cases
that
receiving
cell
and
that
the
of the
contain
the
unit
lowest
in
instances,
probably
merely
was
in histamine.
in most
there
may
of major
in
development
the
eosinophile
7.6
may
are
granulocytes
mine
absolute
in another
physiologic
of mature
from
in subjects
differentiated
and
the
as in the
rise
less
In one
histamine
that
of
determinations
and
be noted
is not
to be discussed
of
andJ.T.)
one
in these
stage
Indeed,
argument
in four
basophile
1-4,
cell
strong
rich
any
count
observed.
that,
series
In figures
to
is
the
likelihood
and
total
were
clear
eosinophile
which
obtained.
leukocytes
reactions
of blood.
E.A.
presence
and
ml.
is quite
were
the
cells,
counts)
blasts,
alteration
difference
between
the
This
reported,
differential
of
figures
histamine
is, of course,
important
leukemoid
in the
The
When
exclusion
average
this
content
normal.
cells.
in
and
is a fundamental
to
determinations
the
instances
histamine
times
incorporation
an
content
when
normal.
due
the
some
the
myeloid
by
since
as PatientsJ.R.,
greatest
one
in
furtherelevation
represents
correlation
observed
parent
of two
the
is corrected
histamine
histamine
(such
metabolism
that
average,
report.
the
irradiation
and
the
among
included
for
obvious
and
times
been
leukocytoses
section
There
not
cells,
On
a slight
leukemia
physiologic
blasts
cells
capacity
myelocytic
of
fold.
637
LAWRENCE
neighborhood
the
histamine,
has
significance.
is in the
myeloid
contain
AND
number
by several
table
per
probably
the
normal
myeloid
in
content
of
the
PEARCE
in
may
be,
it
over-all
cell
metabolism
cell
hista-
in
is of
pro-
certain
of leukemia.
Blood
Histamine
recognized
that
although
Values
histamine,
there
is no
in
Leukocytoses
the
close
and
granulocytes
correlation
in
Leukemoid
contain
under
normal
Reactions.
the
majority
circumstances
It
of
has
the
between
been
blood
the
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
638
HISTAMINE
total
number
of
blood
moid
of granulocytes
histamine
reactions
(quoted
to
by
a normal
the
although
was
he
has
has
20)
reported
blood
no
been
histamine.
mention
in which
of a leukemoid
the
was
point,
of leukeGingold6#{176}
reaction
increase
in which
in granulocytes.
has
presented
a concomitant
FIG.I
relationship
and
evaluated.
a marked
of
there
The
leukocytoses
adequately
a case
with
O.2O
2
w3
not
associated
makes
leukemia
of
BLOOD
of physiologic
in leukemia
et al.
OF
level
myelopoiesis
histamine
of monocytic
4
and
the
that
Shimkin
blood
Thiersch,2’
cases
in
CONTENT
J.R.
data
on
increase
in cells
of
FIG.2
E.A
O.I5
(I)
_1
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‘C
w
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)
0
i
ig
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z
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KEYS
CELLS
MYELOID
HISTAMINE
PER
MATURITY
separate
courses
relationship
To
this
per
each
The
end
i
the
have
and
cytic
presence
likewise
other
discussion
without
and
in
leukocytoses
of the
reported
blood
myeloid
index.
figure
whether
type
Increasing
of those
(these
Stabs,
1;
per
two
,
or not
of maturity
cell
such
that
the
differences
leukemoid
histamine
normal
granulocytic
leukocytoses
or
to each
degree
histamine
In
to indicate
the
z; Metamyelocytes,
as a maturity
of nine
suggested
metabolic
and
cells,
therapy.
any
cells.
numbers
are
3; Segments,
4.
index
values
indicate
see text.
predominantly
laboratories
myeloid
irradiation
is designed
cells
assigned
expressed
have
mention
index
total
in
received
myeloid
106
elevation
Lawrence’9
CELLS
2.
o; Myelocytes,
and
MYELOID
relationships
arbitrarily
Blasts,
106
who
maturity
per
totaled
series
of
The
are
cells):
are then
made
leukemia
with
weights
myeloid
For
and
to fundamental
jects
histamine
maturity.
myeloid
the
shown.
the
values
Valentine
in
are
between
cent
cell
maturity
of therapy
following
per
weighted
cell
and
I
of the changing
in four subjects
Illustration
and
exists
increasing
the
graphic
I0
INDEX
FIGS.
Fios. i-4.-A
myeloid
cells,
X
of
blood
leukocytoses
instances.
blood
two
histamine
reactions
levels
are
Forty
analyzed
values.
Shimkin
observations
origin
states.
normal
determinations
and
These
nonleukemic
in the
above
histamine
et
in chronic
might
serve
table
this
myeloas
observations
in
al.2#{176}
from
a clue
on
.
sub-
Where
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
VALENTINE,
more
than
peated
determination
determinations
The
on
leukemoid
cytic
the
In
mm.
absolute
different
blood
the
are
data
was
82.2.3
myeloid
cell
count
in
and
with
the
the
,
highest
lowest
per
data
FIG.3
JT.
3/22
6/15
re-
leukocytoses
value
mm.;
for
in chronic
of
In only
Cu.
are
leukocytosis.
found
50,063.
io,ooo
the
of
nonleukemic
to those
table
below
0.20
levels
contrast
U)
4
subject,
different
in subjects
reported
639
LAWRENCE
a given
and
in sharp
of blood
AND
after
dates
histamine
reactions
leukemia.
Cu.
appears
at
observations
or with
per
one
PEARCE
six
in
myelo-
myeloid
cells
instances
was
twenty-nine
FIG.4
de-
PLO.
400
Id
0
0I5
300
x
w
0
2
200
0.I0
>-
0%
I-
I
0.05
I00
I4
0
(dO
z
8/16
10/2
4
IU)
z
KEY
MYELOID
CELLS
X
HISTAMINE
PER
io6
MATURITY
INDEX
Fios,
terminations
in
the
the
a.5,ooo
cells
series
The
dicated
myeloid
remaining
and
per
slightly
Cu.
of normal
clinical
in
five
the
cells
was
and
ranged
than
the
5o,ooo
17,362.-more
per
than
CELLS
4
between
determinations,
more
mm.
MYELOID
L I
F%J
Io,000-a.5,ooo
per
leukocyte
count
myeloid
Cu. mm.
four
The
times
average
the
cu.
number
average
mm.;
fell
and
between
of myeloid
values
in
the
are
in-
subjects.
diagnoses
table.
associated
They
cover
with
a fairly
the
wide
elevated
range
leukocyte
of etiologies
counts
from
infection
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
-Blood
TABLE
Histamine
Values
in Sedjects
with
Differential
Subj.
Total
WBC
per cu.
Diagnosis
mm.
Carcinoma
AK.
with
Hodgkin’s
CT.
I
AM.
bladder
Leukocyte
Count
Absolute
Terms
ta
Stabs.
Leukemoid
in
Reactions
Total
Histamine
myebid
cells
micrograms
mm.
blood
per 10,
myeloid
cells
0.088
.00540
per
Segs.
in
Cu.
20550
0
0
0
2466
13152
2877
16440
15000
0
0
0
300
5700
1650
12300
11950
0
0
0
120
3824
1434
9919
15800
0
0
0
948
12482
1264
per
ml.
infection
Trichinosis.
R.S.
R.C.
F.D.
PH.
P.Hu.
of
Blasts
and
Leukocytoses
disease.
Pneumonia.
Type
Chronic
alcoholism.
I.
0.030
.00244
0.10
.01008
13588
0.050
.00368
Histiocytic
leukemia.
34200
15048’
1368
1539
5643
5130
4446
14364
0.037
.00258
Histiocytic
Histiocytic
Leukemia.
leukemia.
53250
27158’
1331
3994
6922
7721
4793
21300
0.048
.00225
112500
54563’
3375
10688
18563
14625
7875
50063
0.042
26650
0
0
4264
16790
3465
225 19
0.024
.00107
Hodgkin’s
disease.
267
00084
Sickle
cell
anemia.
15175
0
0
10016
3642
10547
0.100
.00948
Sickle
cell
anemia.
20425
0
0
102
2247
13481
1838
15932
0.140
.00879
27600
0
0
276
4140
19872
2208
25116
0.2S0
.01150
16800
0
0
672
8316
5964
9660
0.070
.00725
16800
0
0
16425
0
0
17000
0
0
24250
0
0
0
46100
0
0
0
17125
0
0
257
4538
10018
14725
0
0
74
3313
10475
0
0
52
14425
0
0
144
11175
0
0
0
1285
7878
17800
0
0
89
1246
12015
bladder.
41025
0
1026
14154
22769
bladder.
16125
0
0
161
3144
Subacute
cirrhosis
of
0
152
liver.
W.G.
?
Leukocytosis.
Eti.
0
ology.
W.K.A.
Periarteritis
L.A.
Hodgkin’s
J.C.R.
Rheumatic
nodosa.
disease.
heart
ease.
T.D.
dis-
tailure.
Mediastinal
malignancy.
Postoperative
appen-
dectomy.
A.E.
ES.
S.G.
170
1092
3696
1932
14532
0.053
.0036.5
1807
11333
1643
13551
0.045
.00332
3655
11305
765
15470
0.025
.00162
4001
16733
1698
2766
42182
21098
0.033
.00156
45178
0.029
.00064
1113
14984
0.065
00434
10308
589
13989
0.020
.00143
367
7123
1571
8223
0.077
.00936
1298
9376
1803
11684
0.040
.00342
0
? Abscess.
Pneumonia.
toid
0
Congestive
Etiology.
W.H.W.
168
Rheumaarthritis.
pain.
? Eti.
ology.
Bilateral pyelonephritis.
Abdominal
Bilateral
nephros.
tomies.
G.P.
Chronic
arthritis
urethritis.
CT.
Carcinoma
of
Infected
A.B.
and
? Etiology.
410
9164
0.045
00491
13528
0.085
.00626
205
39179
0.067
10965
403
14593
0.072
.00493
14706
1397
3204
0171
wound.
Carcinoma
of
Urinary
tract
infec-
tion.
J.W.H.
AS.
Cirrhosis
19350
0
0
0
1548
1451
17125
0.200
.01170
ruptured
13950
0
0
0
2302
9765
767
12137
0.029
.00239
ruptured
14775
0
0
0
3915
9899
591
13815
0,034
.00246
10385
.00287
of liver.
Postoperative
appendix.
R.P.
Postoperative
appendix.
J.P.L.
Fever.
J.L.S.
J.C.
Pneumonia.
? Etiology.
Fever.
Pleural
effusion.
? Etiology.
AD.
Portal
0
0
0
1816
1525
12201
0.035
11525
0
0
0
2881
7 88
1325
9969
0.063
00632
17850
0
0
0
4105
5266
6605
9728
0.110
.01130
20936
0
0
0
6490
11934
628
18424
0.025
.00136
14500
0
0
0
1740
9353
942
11310
0.065
.00575
16325
0
0
0
1469
9550
3183
11019
0.082
.00744
4295
6232
847
10527
0.033
.00313
Postsple-
nectomy.
Rheumatic
pericarditis.
Pulmonary
AR.
14525
infarct.
cirrhosis.
operative
Post-
renal-lienal
shunt.
R.T.
Arteriosclerotic
heart
disease.
T.E.H.
? Pneumonia.
PyeLonephritis.Uretero-
12100
0
0
0
17200
0
0
0
9804
1462
14620
0.075
.005
51500
0
0
0
10815
3759
1545
48410
0.015
.00031
17632
348
21228
0.005
.00023
79
14782
0.012
.00081
12243
0.074
17362
0.063
lithotomy.
W.E.M.
Pyelonephritis.
Tabes
dorsalis.
C.P.R.
Carcinoma
MG.
Hodgkin’s
NW.
Uremia.
drome.
of
bladder.
disease.
Nephrotic
syn-
4730
1
23200
0
0
0
3596
15725
0
0
0
blOb
13602
15900
0
0
79
636
9620
13
Splenomegaly.
Hepatomegaly.
J.G.
Pulmonary
malignancy.
Average
*
Histiocytic
blast
cells.
640
1590
00604
H00449
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
VALENTINE,
and systemic
disease
invasion.
In only four
above
the
accepted
these,
one
a patient
PEARCE
AND
to malignancies
with
of forty determinations
normal
range
with
of o.
sickle
cell
and without
made was
micrograms
10
641
LAWRENCE
anemia
(P.
the
per
Hu.)
probable
bone
marrow
total blood
histamine
ml
and
.
of blood
the
In two
.
U.
other
C.)
of
a pa-
tient
whose
diagnosis
is not established,
the values
were only slightly
elevated.
In two others
(A. M. and J. W. H.),
both with
severe
liver disease,
distinct
dcvations
above
normal
were observed
In twenty-one
of the assays,
blood
histamine
values
of 0.050
micrograms
or less per ml. were obtained,
and in eight
instances
.
assays
kin’s
of 0.030
micrograms
disease
(M. G., not
per
in
ml. or less were found.
In one subject
with
Hodgterminal
stage)
a particularly
active
assay prepara-
tion permitted
the determination
micrograms
per ml. This existed
per Cu. mm. of blood,
and could
of a total
blood
histamine
level of only 0.005
in spite of the presence
of a.i,a.a.8 myeloid
cells
only signify
that the granulocytes
were extremely
poor
total
in histamine.
The
average
histamine
ml.
per
of blood
micrograms,
actually
The failure
of histamine
contrast
to the observations
somewhat
lower
than the average
values
to rise with
the myeloid
in chronic
myelocytic
leukemia
flected
in histamine
computation
in this
is
0.063
fasting
myeloid
in the
less
value
million
per
0.00449
myeloid
as compared
cells. The
to 0.0196
subjects.
In other
words,
in the determinations
cells contained
only about
one-fourth
as much
average
normal
subject
and roughly
one-eighth
the average
three of the
was
content
group
of subjects
with
forty determinations
than
was
lowest
value
approximately
individuals.
It should
cytosis
the
in any
normal
one-twentieth
be expressly
is invariably
chronic
myelocytic
recorded,
the
mentioned
associated
that
with
these
figures
with
no elevation
in total blood
in the present
report
have
total
histamine
beyond
blood
histamine
normal
pendent
range.
solely
It is, of course,
on myelopoiesis.
not true
Allergy
ditions,
as yet
inadequately
normality
of histamine
explored,
metabolism.
Histamine
presented
Values
published
distinctly
in
their
Subjects
elevated
obtained
on 9 such subjects
the myeloid
leukocyte
count
total
myeloid
count
The total histamine
with
blood
do
the
may
likewise
the
not
imply
unit
histamine
values.
was i6,a.a.a. per cu. mm. of blood.
per ml. in individuals
exhibiting
leuko-
histamine
Two
values
pathologic
with
present
or
subjects
above
the
are
decon-
some
ab-
differences
and leukemoid
reactions
series
suggest
some
funda-
Shimkin
i8 subjects
with
in this laboratory.
In this
was elevated
in all except
this
fasting
that
cell
be associated
consistently
Erythremia.
on
instances,
in normal
that
all blood
histamine
is a case in point.
Other
However,
observations
In five
that
the normal
range.
values
substantially
between
the great
majority
of subjects
with
leukocytoses
and those
with
chronic
myelocytic
leukemia
in our
mental
metabolic
difference
in the two groups.
recently
in our series.
In thirtyper million
myeloid
cells
subject.
in
was
average
value
for this
micrograms
in normal
one-ninetieth
a reduction
group
in this group,
each unit of
histamine
as the same unit
to one-tenth
as much
as
leukemia
histamine
fasting
to
in this
for the normal
group.
leukocyte
count
in
is dramatically
re-
and co-workers2#{176}
erythremia.
Over
In table
6 are
have
half
recorded
data
particular
series of patients
one individual.
The average
leukocytosis
in association
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
642.
HISTAMINE
with
erythremia
is, like
that
CONTENT
in chronic
OF
myelocytic
trast
to the findings
in the series
of nonleukemic
In only one subject
in this group
was the total
grams
per ml. In 4 subjects
it was only
slightly
not
beyond
that
it was
above o.io
per ml. The latter
seen
patient
veloped
with
frank
erythremia.
in an occasional
have thus
erythremia
the highest
myelocytic
There
Cu.
6.-Blood
that
any
M.
18750
Count
in Absolute
Myebo.
0
0
MetaMyebo.
Stabs.
H.
C.
i88
2.344
A.
D.
I
5 S.
S.
0
III
0
0
0
1781
9850
C. R.
2.7000
L. F.
16550
less
Probably
*
196
88o
66o
io6o
518
691
5701
0
0
0
0
0
in chronic
group
0
myelocytic
figures
have
is expressed
of subjects
only
6, the
Terms
I
T
otab
myeboid
cells per
Lymphs.
13406
Cu.
1781
968
13978
‘955
with
like-
I
ml.
blood
mm.
per
rier 106
myeboid
cells
162.19
0.400
.02.47
14996
0.130
.00867
17302.
0.2.30
.0133
o.,o6
.02.18
0.040
.00308
11115
1140
12.968
1782.0
2.860
37180
0.58*
.0,56*
31959
0.48
.0150
0.13
.0136
‘555
7388
8x8
leukemia
done
Histamine
in micrograms
4868
2.360
2.3149
192.1
0
14674
4499
4455
135
I
have
dein
Erythremia
I
9555
148
18900
io8o
2.4975
I 0.13
.0052.1
11999
32.2.7
13157
0.33
.02.51
6xxx
0.2.2.
.0145
determination
wise.
The average
data
on S. S.
When
histamine
in this
0
173
34550
R. G.
*
0
00
44000
.444
98
142.50
subjects
0
98
7375
In
patients
with
Segs.
i6ix
19550
con-
above 0.30
micrograms
in other inadequately
degree
of consistency
leukemia.
In table
other
in Subjects
I
Average,
of the
Values
Histamine
mm.
Blasts
T. M.
sharp
of other
etiology.
below
o.io microthe variation
was
individual.
Total
\‘BC per
Subj.
M.
in quite
total
blood
histamine
content
(S. S.) has probably
leukemia
which
is a not infrequent
terminal
event
Differential Leukocyte
M.
normal
and in 4 subjects
was
occasionally
attained
far been seen with
any
and chronic
myelocytic
is no indication
TABLE
leukemia,
leukocytoses
blood
histamine
elevated,
and
ostensibly
micrograms
per ml.,
values,
while
perhaps
explored
conditions,
in the subjects
with
BLOOD
stage.
therefore
been
in terms
of per
erythremia
are
computed
with
million
myeloid
not
from
far
the
omission
cells,
normal.
the
Most
of the
findings
values
fall within
the normal
range,
though
the average
is somewhat
below
that
of
normal
subjects.
No extreme
elevation
in values
such as is seen in some cases of
chronic
myelocytic
leukemia
have yet been observed.
The difference
from the very
low average
figure
for the leukocytotic
group
analyzed
in table
is, however,
very
striking.
DIScussIoN
The significance
is incorporated
and
into
mechanisms
of the
myeloid
leukocytes
metabolic
remain
processes
a mystery.
by which
histamine
Many
observations
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
VALENTINE,
such
as those
of Shimkin
after
epinephrine
more
is understood
histamine
content
PEARCE
AND
et al.,’#{176}
who
643
LAWRENCE
reported
a rise
in corpuscular
histamine
injection,
are without
adequate
explanation
at present.
Until
of the basic physiology
involved,
the striking
differences
in
of blood
in the leukocytoses
of chronic
myelocytic
leukemia
and some cases of erythremia
as compared
with
the great majority
of other
leukocytoses
studied
here can only remain
a subject
for speculation.
The observations,
however,
suggest
the possibility
that
the incorporation
of histamine
within
the
myeloid
leukocytes
chronic
myelocytic
may
be
a fundamental
leukemia
metabolic
it appears
that
at
process
least
of myelopoiesis.
a normal
amount,
In
and
some-
times
a greatly
increased
amount,
of histamine
is incorporated
as a rule into each
cell regardless
of the total cell count.
The result
is a variable
and often tremendous
increase
in total
corpuscular
histamine,
and a normal
or increased
unit
cell histamine
content.
In
dramatic,
pattern
Whether
this
terminating
many
cases
in total
blood
affords
with
the
any
clue
event,
this
metabolic
close
respect
bone
marrow.
In over
emphasizes
per
total
cent
individuals
and
the
histamine
histamine
as judged
of at least
chronic
kinship
somewhat
proportion
cannot
myelocytic
of other
danger
of
be stated.
In
leukemia
two
in
disturbances
etiologies
elevated
and
the abnormally
less
of cases.
in potential
of these
is not
among
of myeloid
cells in the peripheral
blood.
The
cell content
of histamine.
Of considerable
interest
with
debilitating
disease
such
as malignancy
stimulation
or irritation
dence of a total depression
are
leukemia
of leukocytoses
blood
of total
though
in a fair
myelocytic
of erythremia
again
o
a similar,
is observed
to frank
similarity
on the other
hand,
the
have been a redistribution
erythremia
as to which
a transition
any
of
histamine
in our
of
series,
there
appears
to
large
numbers
result
is a markedly
reduced
unit
to us have been those
individuals
in whom,
despite
myelopoietic
by the peripheral
blood,
this particular
metabolic
there
is actually
evicomponent
of myelo-
poiesis.
One individual
with
Hodgkin’s
disease,
a young
man in fair general
condition
and nutrition
and without
obvious
bone marrow
involvement,
is a striking
illustration
of this point.
The total
blood
histamine
was down
to levels
usually
thought
to be present
present,
was
chronic
myelocytic
in plasma
of necessity
alone.
extremely
leukemia,
graphically
leukemia
illustrated
and erythremia
quantitative
significance
The
small.
unit
cell
The
erythremia,
histamine,
if indeed
relationship
and
of
nonleukemic
they
will
of necessity
vary
widely,
in
is
in chronic
rather
than
.
since
was
factors
leukocytoses
in figure
The average
total
blood
histamine
as indicated
in this figure
are of qualitative
same direction,
in different
series of cases.
The suggestion
is tentatively
advanced,
process
of incorporation
of histamine
into
any
these
though
in the
then,
that an aberration
in the metabolic
myeloid
leukocytes
may in some manner
be an inherent
component
of chronic
myelocytic
thremia,
whereas
in the majority
of leukocytoses
different
etiology
this is not the case. This may,
leukemia
and
in some
and some cases of cryleukemoid
reactions
of
instances,
be of value
in
their
only
the
stance
practical
differential
diagnosis.
However,
in which
a diagnostic
point
of view.
Again,
it
would
test of this nature
the determination
would
might
be
exceptional
prove
necessary
be inconclusive
circumfrom
a
in those
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
6
HISTAMINE
situations
in which
ble,
for
example,
not
the
its successful
on
aberrations
possible
which
further
investigation.
of
might
HISTAMINE
early
manifest
is not
value.
before
Of much
difference
to their
more
in
pathogenesis.
BLOOD
PER
are
other
106
or
important
interest
to us is the
between
This
IN
availa-
Whether
physiology
HISTAMINE
03
figures
leukemia.
distinctly
known.
as a clue
No
or incipient
itself
MICROGRAMS
ML.
BLOOD
be of most
very
a fundamental
serve
IN
PER
to
occur
implication
groups
with
begins
OF
use would
individuals
abnormality
hematologic
CONTENT
these
is deserving
of
MICROGRAMS
MYELOID
CELLS
.04
0.2
0.1
0
KEY
NORMAL
ERYTHREMIA
CHRONIC
Fio.
tamine
5.-A
per
erythremia,
comparison
,ot
and
The
problem
of the
is also
nificance
cannot
cells
cells
now
increased
be
function,
stated.
and
It
has
contributes
granulocytes
the
so-called
to
per
with
ml.
chronic
the
other
the
former
of histamine
it plays
previously
of blood
myelocytic
been
are
a major
signs
hand,
in the
a physiologic
cardinal
mononuclear
is the principal
invading
cell
SCold abscesses”
are an example.
Whether
granulocytes
in micrograms
in subjects
if any,
or not
the
On
histamine
subjects
Whether
by
etc.
for
LEUKEMIA
and
his-
leukemia,
etiologies.
normal
in which
heat,
values
fasting
of other
characterized
local
MYELOID
average
normal
of interest.
processes
are
in
leukocytoses
of blood
matory
the
of
myeloid
LEUKOCY1OSES
pointed
situation
cells
of any
that
of the
sig-
inflaminvading
inflammation-redness,
inflammatory
are usually
or not the
out’9
component
of
myeloid
role
processes
devoid
release
is unknown.
in which
the
of these
features.
of histamine
from
From www.bloodjournal.org by guest on November 19, 2014. For personal use only.
VALENTINE,
PEARCE
AND
645
LAWRENCE
SUMMARY
The
literature
evidence
concerning
that
the
blood
incorporation
histamine
has
of histamine
been
within
reviewed,
the
including
myeloid
the
leukocytes
may
be one
tamine
chronic
of the metabolic
functions
of myelopoiesis.
Data
are presented
on the hiscontent
of blood
in normal
subjects
and in subjects
with
acute
leukemia,
myelocytic
leukemia,
erythremia,
and with
leukocytoses
or leukemoid
reactions
to unit
of other
etiologies.
myeloid
cell histamine
myelocytic
leukemia
are
The data
indicate
is usually
very high
a definite
leukocytoses
but
histamine
per
jects
with
The changing
in subjects
also
relationships
of total
blood
histamine
receiving
irradiation
therapy
for chronic
presented.
that
total
in comparison
blood
histamine
to normal,
less marked
tendency
in the same direction,
while
the values
in
of other etiology
are, with few exceptions,
normal
or low. The blood
million
chronic
in erythremia,
myeloid
cells
myelocytic
and
very
is, on the
leukemia,
low
on the
ponent
of chronic
myelocytic
reactions
average
is not
normal
in the
group
whereas
the
about
the
twice
normal
range
or a little
in sub-
of leukocytoses
an aberration
leukocytes)
leukemia,
this
average,
within
The suggestion
is tentatively
made
that
(histamine
incorporation
within
myeloid
leukemoid
in chronic
myelocytic
leukemia
the values
in erythremia
show
that
in this metabolic
may be an inherent
in physiologic
low
studied.
process
com-
leukocytoses
and
case.
ACKNOWLEDGMENTS
The
authors
assistance
ter,
in
Dr.
Henry
to express
the
H.
Hospital,
General
from
wish
performing
suitable
Dr.
Henstell,
Veterans
clinical
their
grateful
histamine
appreciation
determinations.
Myron
material,
and
and
Prinzmetal
to them
the
were
authors
John
Fuschetti
cooperation
of many
Angeles
Los
Administration,
to Mr.
The
wish
and
for valuable
aid
members
of Dr.
of the
invaluable
staff
their
E. Carpen-
of Wadsworth
in obtaining
to express
technical
Gurth
blood
sincere
specimens
thanks.
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