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ZINC
THE
CONTENT
AND
By
W
L.
BERT
E HAVE
OF WHOLE
IN
M.D.,
VALLEE,
previously
whole
concentrations
BLOOD,
ERYTHROCYTES
AND
described
blood,
plasma,
in micrograms
PLASMA,
THE
G.
JOHN
our
findings
leukocytes
(gammas)
LEUKOCYTES
ANEMIAS
II, M.D.
GIBSON,
of the
zinc
and erythrocytes.’
were
found
to
content
of normal
The following
represent
the
zinc
normal
pattern:
Amis.
Whole
Blood
3
.
2.
X
,2
Erythrocytes
,
.34
X
‘0
eral
blood
Out,
No measurements
.
No
however.
blood
components
in
reported
was
attempt
to elucidate
of the
quantitative
conducted
with
on
the
zinc
content
million
I
on
with
cells
cells
ffllllion
I CC.
the
are
afflicted
of zinc
I0
i
zinc to rats and
in the cytology
of
anemia
patients
role
X
of red and
measurements
patients
cr2
±1.7
Larson4
fed
as reflected
cc.
i
X
±0.2.
14.4
and Smith
and
and leukopoiesis
I CC.
±i.6
3.0
Leukocytes
and Nelson,2’
on erythropoiesis
Unit
S.D.
±1.0
Plasma
Erythrocytes
Sutton
effect
in pg
8.8
white
zinc
observed
the
of the periph-
cells
were
carried
concentrations
record.
The
various
of
study
types
of
the
herewith
anemia,
in
an
in erythrocytes.
METHOD
The
hematologic
viously.’.
.
technics
The
6
small
cal analysis.
The
values.
concentrations
Zinc
standard
mean
deviations
and
number
method
of the normal
lying
one
of
of patients
would
series
was
outside
expect
measuring
which
taken
of two
I out
blood
was
studied
Nine
of
patients
with
following
while
time
A second
to have
so-called
cell
tious
under
anemia
of liver
maintenance
group
therapy
with
‘refractory
anemia.
‘
Four
patients
i
mononucleosis,
were
patient
and
were
therapy.
of patients
anemia,
2.000/miD.3
sickle
pernicious
institution
‘ ‘
anemic
each
Cooley’s
liver
types
Three
been
described
internal
in the evaluation
were
normals
of
secondary
considered
fall
to
was
prestatisti-
of individual
abnormal.
outside
patients
was
iron
a total
prior
followed
For
of these
two
limits.
of 34 blood
had
2.
had
cell
period
analyzed.
splenic
found
were
counts
below
of infection,
anemia,
of 2.3 blood
was
patients
blood
an anemia
a few
a prolonged
samples
Five
white
deficiency
to or within
over
investigated.
hemorrhage,
anemia,
obtained
were
A total
anemia
these
to
There
were
patients
extract.
of
had nutritional
anemia.
Samples
of these
with
on
have
precluded
STUDIED
studied.
Five
various
of reference
deviations
observations
MATERIAL
days
content
category
as a point
standard
of o
zinc
in each
2.
anemia,
had
infec-
samples.
RESULTS
Table
leukocytes
Hospital,
Cambridge,
*
i
summarizes
the
and erythrocytes
the Department
From
Brigham
This
i
zinc concentrations
in patients
with
of Medicine,
Boston;
and
Harvard
the
Medical
Department
found
anemias
School
of Physics,
and
in whole
other
than
the Medical
Massachusetts
Clinic
Institute
Mass.
study
was supported
by a grant-in-aid
cc.
of erythrocytes
packed
by centrifuging
from
the National
at ;ooo r.p.m.
455
Institute
for 30
of Health.
minutes.
blood,
plasma,
pernicious
aneof the
Peter
of Technology,
Bent
a
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
456
ZINC
mia.
Table
The
values
plasma,
WHOLE
BLOOD
presents
similar
data obtained
from
for the zinc concentrations
contained
calculated
and
erythrocytes
as previously
abnormal
pernicious
red
anemia
to other
forms
i-The
TABLE
OF
patients
with
pernicious
in i ml. of whole
blood
2.
leukocytes
The
CONTENT
cell
findings
possibly
of anemia,
Values
sickle
of Zinc
Content
are
cell
in which
3 and
than
Blood,
Leukocytes
Unit
Irllc7
Content
Plasma
____________
74.5
5.5
3.2.4
2.4.2.
Anemia
3.65
2.0.0
17-2.
“Refractory”
Anemia
;.6o
31.6
88.o
.6
1.1
17-3
“Refractory”
Anemia
3.42.
2.9.9
87.5
4.2.
1.3
i8-i
“Refractory”
Anemia
;.66
36.6
100.0
11.5
62.-I
“Refractory”
Anemia
95-I
“Refractory”
Anemia
8i-
55.0
36.7
90.5
3.2.2.
30.0
93.2.
Hemorrhage
2.68
2.4.0
90.0
zo6-i
Hemorrhage
3.52.
36.2.
88.6
zi8-,
Hemorrhage
2.92.
2.4.0
81.1
153-I
Hemorrhage
2.93
2.5.5
87.0
23.5
by
Dithizone
‘
Erythrocytes
_____________________
__________________________
-3
Zn/cc.
XlO
3.3
i6.i
,6.8
per 1 X
l0’cells
e re
17.7
1.49
-
-
10.0
9.5
1.09
.6o
16.4
2.9.0
1.33
13.6
z.8
2.06
2.1.3
3.7
5.7
Extraction
19.0
4.4
8.2.
1.3
1.1
1.69
18.9
9.1
2.6
2.92.
i8.8
7.1
1.5
3.9
1.2.6
15.4
6.8
3.0
1.4
1.45
i6.8
2.1.7
16.4
ii.8
Nutritional
3.32.
33.0
90.5
4.1
1.61
Iron
4.76
37.5
79.0
6.7
1.2.
-*
1.01
12.8
Uremia
3.2.5
30.6
94.5
7.0
2.7
4.0
1.43
15.2.
Uremia
1.95
2.8.7
97.0
5.9
1.6
4.4
1.63
16.7
Sickle Cell
31.0
78.0
4.2.
i.6
1.01
2.5.8
Deficiency
17.8
98-2.
Sickle
Cell
34.0
88.o
Sickle
Cell
3.2.9
31.0
97.5
6-i
Splenic
3.99
31.6
79.0
66-,
Infection
3.96
39.0
99.0
11.1
107-I
Infection
3.78
36.9
97.5
10.4
101-I
Inf.
3.40
35.0
103.0
3.46
36.0
104.0
Monon.
Cooley’s
normal
nificantly
in Anemias
0.92.
2.8
8.
‘33-I
Sample
‘.5
3.0
3.95
3.85
*
to be in the
-2
XlO
per 1 X
lO’cells
ml.
Anemia
97-I
found
- ------
“Refractory”
98-I
with
in contrast
}11k
“Refractory”
3.73
patients
Erythrocytes
---_______________
17-I
Ill-I
to
and
24-2.
39-I
lost
to
were
anemia,
were
‘I, per
49-I
due
values
Anemia
M.C.V.
in
Hct
per
mm.2
limited
Plasma,
:
RBC
139-I
4. These
In pernicious
concentrations
Pernicious
t
Diagnosis
essentially
anemia.
zinc
of Whole
other
Exp.No.
in tables
described.’
blood
and
Unit
are shown
anemia.
12.5
1.4
-*
1.50
17.0
4.2.
i.6
2.92
29.6
4.6
6.4
1.52.
29.3
4.5
z.6
1.93
19.8
4.3
6.6
i.86
19.2.
6.
2.6
i.6
1.30
12.5
4,7
1.2.
4.8
2.2.5
22.0
7.2.
16.3
8.4
in processing.
range,
the
increased,
unit red blood
cell zinc concentration
but returns
to within
normal
limits
prior
with
to therapy
is sigsuccessful
therapy.
DISCUSSION
The
over-all
tology)
The
have
direct
limitations
been
found
measurements
of the
technics
to be defined
for
whole
employed
(chemical
analysis
by an error of about
±15
per
cent.’
blood,
plasma,
red cells and white
and
hemacells,
in
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
BERT
the
group
figure
of secondary
L.
VALLEB
AND
anemias,
given
JOHN
in
G.
GIBSON,
table
i
II
, are
457
graphically
depicted
in
I.
..-Tbe
TABLE
Unit
Values
of
Zinc
Content
of
Whole
Blood,
Pernicious
Plasma,
Unit
Days
of
RBC
per
Observa-
No.
Exp.
Hct
in
mm.’
tiont
Content
Plasma
M.c.v.
o
Leukoc,ytes
and Erjthrocytes
in
Anemia
by Dithizone
Extraction
Leukocytes
Erythrocytes
‘
7 X 10’
per 1 X 10’
cells
7 per ml.
X
10
cells
‘9-I
I
.
8o
2,7.2.
152.
7S
1.2.
19-2.
I
.94
2.7.1
‘43
6.7
1.7
2..
4.7
4.I
I
3.4
7.9
2..
‘9-3
20
3.70
37.0
I00
II.
40
3.13
35.’
io8
-*
‘9-4
3.77
I
3.38
6
Zn v/cc.
packed
2..
6
7S
35
for M.C.V
2.2..
‘7,5
2.1.6
39’ 7
‘Os
7.0
“9
‘5
2..
50
30.3
‘LI
8.7
0.9
“4
i.6
4.7
4.2.
2..
3.6
i.6
I .72.
‘7,7
1.4
5.3
3.14
2.3.7
3SS
2.9.7
366
2.1-2.
2.2.
2..
78
32..
i6
8.6
2.1-3
30
2..
96
34.1
‘Is
9.3
2.1-4
369
45.1
104
10.6
2.1-5
369
57-I
6
57-2.
3
45.0
I .2.2.
15.0
S9
2.1.9
‘3’
10.0
3.8
2.6.2,
“5
I0.0
3’’
I
99
573
‘3
57-s
2,2
2..
48
2.9.0
“7
57-6
2.7
2..
94
31.
107
57-7
4’
3.66
35
57-8
55
3 88
37S
57-9
2.08
4.4’
44.8
57-10
2.57
4.33
43.0
9’-’
-7
1.47
2.7.1
2.6.
2.43
91-2.
I’
115-I
2..
4
118-I
118-1
8
118-3
6o
2,
‘47
‘57
2.07
2.6.
2.35
32..
it8-6
66
4.2.8
4’.o
118-7
8o
4.87
4’
i.6
131-1
132-3
*
Sample
t
Withrefcrence
lost
Seventeen
within
±2.
0
.0
2.6.
i
17.
I
2..
30
2.1,0
2.3.8
5
2..
52.
2.4.1
,_.
10
2.1.0
109
19.0
.69
2..
9.3
14.7
I
78
II0
1.00
2,9.6
2..
2..
‘53
3.44
2.. 8i
-*
7.2.
14.r
2.5.6
6
8.o
‘4’ 3
i6
‘.5
.49
3.10
2,.
2..
99
2.3
I
1.0
99
2..7
118-5
131-I
10.
2.8
7.2.
I0I
0.94
1.42.
6.4
15.0
4.9
138
2.1
2..
5
I.,
2.2. .0
.
-*
97
118-4
119-I
97
‘.59
I
9.3
12.3
I
I. I
43S
4S4
2. . 2.0
104-I
1.9
19.1
5
.6o
‘.9
I
.
8o
3.2.
I
.
2.1
12.3
3.1
3.0
2..
8o
2,.4
8.1
1.8
2.. 2.
2,, 47
6.7
“9
3.6
2..
64
6.8
4.2.
“7
2..
36
o.8
3.50
2..
10.4
0
4
3.7
2..
18.7
2.2. .2.
2.6.7
‘7.
5
49S
34.0
*
7.2.
46.0
0.7
12.8
0.7
3.67
30.0
136
9’ 6
3.0
4.0
2.9.3
96
7,5
1.2.
‘.4
“59
84
9.0
3.2.
1.2.
I
1I0
4.0
1.2.
8.6
*
8
1.81
2,3.3
12.8
‘5
69
1.76
2.6.
96
7.0
2,, 4
2,, I
4.92.
44.0
89
6.4
I.0
i6.
.41
x6.8
2.. 2.4
2.0.4
53
96
2.0.0
*
2..
2.. 2.
2..
‘‘3
I
I
2.3.0
5,3
6.
*
4
19.0
2,-I
‘9-5
red
1 X ‘#{176}‘cellsCorr.
per
.42
30.7
‘5.9
in processing.
toinstitution
of the
standard
2.3
of therapy.
whole
blood
zinc measurements
deviations
of the mean
of our
(fig.
normal
iA) are shown
to fall
series.
Case 49 had a
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
458
ZINC
high
whole
zinc
was
just
above
blood
zinc
normal.
of error.
lower
limit
TABLE
3.-Zinc
due
Case
the
limit
range
of
the
of normal.
z ml.
of
Whole
Erythroc,ytes
Exp.
No.
series
zinc,
while
within
samples
observation,
Blood
Calculated
in Anemias
from
the
were
Unit
red
blood
cell
zinc
was
blood
possible
technical
consistently
was
Values
Pernicious
Plasma
Column
the
whole
no diagnosis
other than
Diagnosis
The
though
consecutive
under
BLOOD
to all therapy.
normal
While
of
WHOLE
plasma
refractory
three
17,
OF
to an increased
was
14
In Case
Content
CONTENT
of
below
the
established,
Plasma,
and
Leukocytes
and
Anemia
Leukocytes
Total Zn in I
ml, of
Whole
Blood
Erythrocytes
1
2
3
4
14-2.
“Refractory”
Anemia
4.1
0.14
4.9
9.1
17-I
“Refractory”
Anemia
1.2.
0.14
1.5
1.9
17-2.
“Refractory”
Anemia
1.4
o.6I
3,3
5.3
‘7-3
“Refractory”
Anemia
0.9
0.15
3.7
4.8
18-I
“Refractory”
Anemia
,.8
0.37
6.o
8.2.
61-I
“Refractory”
Anemia
i.8
0.52.
5.0
8.3
95-I
“Refractory”
Anemia
7.6
0.2.3
6.7
9.5
8,-,
Hemorrhage
1.0
0.04
4.5
106-I
Hemorrhage
.8
o,,6
6.8
1,8-I
Hemorrhage
1.9
o.x6
‘53-I
Hemorrhage
2.3
0.15
49-’
Nutritional
139-I
Iron
3,7
.8
4.3
6.8
0.31
5.4
o.8
0.07
4.8
17.8
Deficiency
#{149}
5.5
ii,8
10.1
5.7
39_I
Uremia
1.9
0.31
4.7
6.9
‘Il-I
Uremia
i.8
0.37
4.8
7.0
98-I
SickleCell
2.9
o.6
8.o
,,.6
98-2.
SickleCell
0.9
-
.8
-
SickleCell
2.9
o.,8
6.3
9,4
3.1
0.14
6.
Infection
1.8
0.31
7.7
11,0
107-I
Infection
2.7
0.39
7.1
10,1
101-I
Inf,
1.7
0.19
4.4
6.3
4.3
5.3
‘33-I
1
6-x
Splenic
66-,
Monon.
Cooley’s
97-I
o.8
9.3
0.19
*
Sample
lost in processing.
Explanation
we
I
Zn
2.
Total
3
Zn
4
Sum
are,
of Columns:
per
ml.
Zinc
per
X
#{247}ml,
million
of Columns
therefore,
conclusions
Figure
of plasma
in Sample
from
iB
red
cells
I, 2.
Figure
million
iC
is a plot
kukocyts.
and
because
shows
of Whole
X red
these
limits
of normality
apparent
cause.
Hematocrit
100
the
except
of Whole
Blood
cell count
from
of Whole
Blood.
which
leukocytes
Blood
X
‘
X
obtained.
I0.
3.
of the singularity
of the
data.
plasma
zinc concentrations,
Case
of leukocyte
It is apparent
4,
previously
zinc
that
all
referred
content
Cases
observation,
in terms
17,
i8 and
unable
of which
to,
of
and
i
are
Case
X
6i have
Icr2
to draw
within
io6,
gamma
a leukocyte
the
for
no
per
zinc
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
BERT
elevated
concentration
considered
‘
VALLEE
from
to
‘refractory’
AND
JOHN
three
to ten
all therapy.
‘
Content of z ml.
4.-Zinc
TABLE
L.
of
Whole
Blood
G.
GIBSON,
II
459
times above
normal.
These
They
all had leukocyte
Calculated
from
Unit
Values
of Plasma,
patients
counts
were
below
Leukocytes
and
Erythrocytes in Pernicious Anemia
Exp.
No.
Days
Total
of Observationf
Plasma
Leukocytes
Erythrocytes
Zn
Column
1
in
Blood
2
3
4
‘9-I
0.9
0.7.1
6.x
7.2.
19-2.
‘.3
0.2.6
5.2.
6.8
‘9-3
2.0
3.0
0.44
6.
‘9-4
40
1.2.
0.51
7.6
9,9
10.3
‘9-s
366
1.2.
015
2.I-I
‘5
o.6
o.66
7.8
9’
2.1-1
7.2.
I.0
0.09
9.6
10.7
7.0
I
30
1.0
0.50
8.4
10.4
2.1-4
369
1.3
0.2.6
10.3
11-5
369
2.0
0.2.0
7,7
8.o
2.0
0.11
3.8
6.o
11-3
57-’
b
2.
3.0
0.43
5.7
9.
2.3
0.14
5.’
7.5
2.2.
‘‘5
0.14
6.9
8.
2.7
1.0
0.
7.4
8.
4’
4.7
o.8
11.4
9.1
6
57-2,
57-3
‘3
57-s
57-6
57-7
*
57-8
55
0.2.4
7.7
6.2.
57-9
2.08
I.’
0.13
8.o
57-10
2.57
I. I
0.14
5.2.
6.
9,-I
-7
2.3
0.13
6.9
7.2.
2.0
0.11
5.9
II
‘.4
0.11
6.9
8.4
4
3.2.
0.11
3.8
7’’
1.1
0.03
3.3
3.’
0.
12.5-I
118-I
I
9.3
8.o
91-1
104-I
-5
118-1
o8
5.4
8.i
5.2.
*
o.6
8
12.8-3
*
8.7
*
*
118-4
x6
0.5
118-5
2.3
2..0
0.09
118-6
66
0.7
0.17
9,4
6.8
II’S
118-7
8o
i.8
o. o8
6.9
8.8
‘‘I
0.07
3’’
4.6
4.3
015
8,i
9.8
0.09
7.0
7,7
119-I
I32.-2.
Is
131-3
69
*
t
Sample
With
Explanation
lost
therapy
This
12.,75o/mm’.
but
‘‘5
o.6
7,7
in processing.
reference to institution
of columns
the
2.000/mm’.
7.7
*
x.8
8
131-I
1
ml. of
Whole
was
of therapy.
same
as in table
in contrast
had
a normal
We
are
not
to Case
zinc
at
3.
present
5,
which
concentration
prepared
was
of
to
also
found
leukocytes
interpret
refractory
which
the
to
numbered
significance
and
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
460
ZINC
physiologic
implications
contrast
to our
the
concentration
zinc
of
findings
CONTENT
these
the
WHOLE
WHOLE
findings
in leukemic
of
OF
cells.
BLOOD
which,
however,
In myelogenous
circulating
leukocytes
PLASMA
was
appear
and
lymphatic
found
to
ERYTHR
LEUCOCYTES
striking
in
leukemia,
he
about
io
per
OCYTES
BLOOD
1,1
ZII.j
GAMMA
GAMMA
PER
PER
PER
L.
MILLION
7
GAMMA
GAMMA
PER
MILLION
CELLS
XIO
CELLS
110
1*
50
II
“-1
14
4.ij
20’
II
IS
I
It
Id’
“
5
0
1
1
:
MEAN
2
_____
3
3
(3’
‘
4,
A
FIG,
anemia
values
Cent
tration
cyte
i-Distribution
other
arc
B
of
than
zinc
in
blood,
whole
pernicious
anemia.
Under
effective
C
The
mean
leukocytes
plasma,
and
2.
standard
D
and
deviations
erythrocytes,
of the
in patients
comparable
with
normal
indicated.
of normal.
returned
picture
to
are
normal
apparent.
levels.7
therapy
with
x-ray
and urethane
No other
significant
abnormalities
the
zinc concenin the leuko-
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
BERT
Figure
to
iD depicts
our
normal
is significant
were
red
or due
zinc
to chance
unit
in the whole
any significant
red
cell
zinc
spectively,
returned
to
therapy.
In Case
stitution
of therapy.
366th
3oth
and
following
normal
days
369th
a definitely
Figures
while
normal
zinc
3,
4 and
under
Case 19
liver.
The
was
reached
normal
.
elevated,
normal
there
patients
(table
of erythrocytes
due
limits
million
to known
(fig. LA,
cells
(fig.
techB, C).
2.D)
and
by a prompt
response
concentration
Maintenance
had
369
the
showed
days
after
million
cells,
and absolute
number
Doses of liver therapy,
of reticgiven
at the
shown
per
top
of each
graph.
to
a test
dose
the
absolute
response
in
terms
of
rise in red blood
subsided.
of red
therapy
and
still
content.
concentration
in
is also
4oth
between
samples
366
zinc
in-
the
be obtained
taken
reticulocytosis
which
following
between
the earlier
by arrows
concentration
maintenance
69 days
could
samples
zinc
zinc
under
obtainable
While
erythrocyte
accompanied
levels.
2.1
erythrocyte
a prompt
the reticulocyte
in the zinc
cases,
zinc nor white
blood
distribution
picture.
within
per cent reticulocytes
as a function
of time.
response
anemia
content
erythrocyte
thereafter
were
unit
are indicated
fall
progressive
in
care,
when
the
normal
obtained
concentration,
the
of these
plasma
normal
per
no samples
shows
count
continued
was
within
57-2.
samples
in Case
figure
reticulocyte
reticulocyte
were
no
hospital
in
exception
anemia)
66 and 107 have
distribution
curve.
whether
or not this
‘
normal
show
133,
in relation
cell
group.
(calculated
19,
blood
cell count,
the
in one ml. of blood
of anemia
patients
are elevated
significantly
above
the
of therapy
and after an initial
rise, the unit
a prolonged
period.
In Cases
and 12.8, samOn the 55th and 66th days of sampling,
re-
Similarly,
were
the
461
98 (sickle
in pernicious
in unit zinc
of therapy,
remained
post-therapy
begun
cases
Cases
io6,
of the normal
to determine
of this
and
were
2.1-I
values
II
and
blood
zinc. Neither
deviation
from
the
levels
of therapy.
days
was
the red
ulocytes,
series
concentrations
In Case
increased
treatment
in these
observed
increase
institution
levels,
and
132.,
GIBSON,
anemia)
With
cell
per cc. of packed
cells)
of untreated
normal
range.
Following
institution
zinc content
falls successively
over
ples were obtained
at close intervals.
and
G.
pattern
scattering.
red
of leukocytes
in samples
Other
leukocyte
zinc
error.
The
cell
JOHN
95 (refractory
in zinc concentration
due to a marked
apparently
nical
blood
in the
which
are reflected
cell zinc presents
The
AND
elevations
above
the normal.
just above
the upper
limit
a larger
number
of observations
changes
are
VALLEE
Cases
no abnormalities
The
2.)
the
series.
show
significant
zinc concentrations
It would require
L.
During
blood
this
cells
cell count
period
which
no visible
effect
similar
to those
of
which
there was
eventually
on the
zinc
a
con-
centration.
The
features
of Case
for figure
3 Therapy
in zinc concentration
tirely
normal
within
levels
Case
these
to
i
12.7
two
evaluate
ml.
on
57 (fig.
the limits
within
(fig.
)
the
of
days
differs
technical
following
materially
Coincidental
instances.
1/14/48,
4) were
essentially
was spaced
very nearly
identically.
at the height
of reticulocytosis.
.
potency
with
the liver
a subsequent
of
error.
The
institution
in both
with
extract
used
submaximal
just
described
was a slight
rise
this rise is en-
unit
zinc concentration
of liver therapy.
character
therapy,
There
However,
and
degree
observations
were made.
reticulocyte
fell
of response
on
this
The patient
response.
to
from
patient
received
The first
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
462,
ZINC
zinc
sample
daily
was
therapy
which
response
obtained
with
CONTENT
near
the extract
became
OF
the
was
maximal
height
instituted.
on
the
WHOLE
BLOOD
ioth
WHOLE
BLOOD
of
this
reaction.
Thereafter,
This
resulted
in a good
day
following
PLASMA
GAMMA
PER
ML.
GAMML
PER
ML.
the
LEUCOCYTES
liver
injection.
ERYTHROCYTES
GISMMA
PER
MILLION
CELLS
x
first
intensive
reticulocyte
GAMMA
PER
MILLION
CELLS
o_2
f
I92
x
IO
f
I5O
II...
e
25’
II
7
It
6
C$#{149}
I
FIG.
of zinc
i-Distribution
pernicious
The
anemia.
mean
and
in whole
2.
standard
blood,
plasma,
deviations
A prompt
rise in total
red blood
cell count
zinc concentration
per million
cells during
reached
a peak at the height
of reticulocytosis
Thereafter,
the
zinc
concentrations
fell
leukocytes
of the
and
comparable
accompanied
this
period
and fell
to normal
levels
erythrocytes,
normal
in patients
values
are
with
indicated.
this phenomenon.
The
rose
progressively
and
concomitantly
with
it.
in a fashion
similar
to the
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
BERT
LIVER
L.
VALLEE
EXTRACT
AND
Mu
U
1515
15
JOHN
G.
GIBSON,
463
II
Z
$9
4
-o
RET1
20
.,.“.
10
0
10
FIG.
3.-Casc
19.
absolute
number
of time,
under
liver
therapy.
Solid
circles
=
Erythrocyte
Open
circles
Solid
triangles
Open
15
Erythrocyte
zinc
of reticulocytes,
Red
=
Per
=
triangles
=
as well
Blood
red
as absolute
Zinc
concentration
Cell
count.
cent
reticulocyte
Absolute
number
30
25
20
concentration,
blood
number
40
cell
count,
per
of unreticulated
per
million
45
cent
reticulocytes
erythrocytes,
and
as a function
cells,
count.
of
reticulocytes.
Z-57
5
0.
..0
/
/
0’
/
RElICS.
/
,
30
20
U
0
5
FIG.
4.-Case
absolute number
of
time,
under
7.
Erythrocyte
concentration,
of reticulocytes, as well
liver
therapy.
Symbols
20
5
zinc
as absolute
as in figure
25
red
3.
number
30
blood
cell
35
count,
of unreticulated
per
47
cent
erythrocytes,
61
54
reticulocytes
93
and
as a function
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
ICC
EACN
U
7
Z I28
6
5
4
3C
20
IC
C
IS
FIG.
.-Casc
absolute
number
of time,
under
12.;.
Erythrocytc
25
20
DAYS
OF
30
zinc concentration,
red blood
of rcticulocy’tes, as well as absolute number
liver
therapy.
Symbols
35
OBSERVATION
as in figure
cell count,
per cent reticulocytcs land
of unreticulated erythrocyEcs,
as a function
3.
CASE
CASE
CASE
C*SE
9
2’
-9
57
26
6
4
6
0
0
2
RED
Fio.
jn
6.-Zinc,
4 patients
in gamma
with
pernicious
X
,o
anemia,
per million
under
3
BLOOD
CELLS
red
cells,
therapy.
464
4
iwo,e
in relation
to the
red cell
count,
showing
a fall
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
BERT
ones
shown
in Cases
L.
and
19
VALLEE
7.
AND
The
JOHN
normal
G.
level
GIBSON,
was
465
II
attained
within
Case 13 I , where
only
three
samples
were
obtained,
a normal
on the 69th
day post-therapy.
Whether
or not this response
of the zinc concentration
was
ticular
liver
extract
used,
the
dosage
given,
or whether
66 days.
value
was
related
to the
is a property
it
In
found
par-
of young
cells released
from
the bone marrow
in pernicious
anemia
under
the stimulus
liver therapy,
we are unable
to conclude
on the basis of our present
observations.
In the 3 cases we were able to follow,
the erythrocyte
zinc concentration
turned
to normal
levels
approximates
the mean
mined
with
that
the
N’5 labelled
change
pernicious
glycine
in zinc
anemia
million
cells,
reaches
normal,
the normal
coinciding
red
the
size
tribute
to the
increase
over
nomenon
a slope
anemia,
the fall
was
zinc
8
of the
influence
count.
than
of the
of zinc and
indicating
systems
are structurally
In sickle
cell anemia,
vated
in one out of three
two standard
deviations
unit
cells
per
was
of red
concentration
is
one of increased
anemia,
drop
carbonic
that
cc.
zinc
extract,
zinc
in
per
concentration
normal
packed
in spite
cells.
as a factor
per
million
carbonic
in hemoglobin.
anhydrase
are
the hemoglobin
the
could
cells.
con-
A definite
The
anhydrase
In contrast,
of low
Thereby
which
nevertheless
noticed.
cellular
mass.
and
of
and
cell count
has returned
to
normal
size. In the second-
of
cells
believe
cell.
in micrograms
unit
remains
eliminated
concentration
pernicious
red blood
toward
We
replacement
of liver
The
re-
This time closely
anemia
as deter-
and
a function
the
cell
calculated
cell
zinc
simply
to that
the increase
in hemoglobin
blood
per
also
individual
the normal
is therefore
not
other
red
concentration
zinc
parallel
under
at the time when
the
a return
of the M.C.V.
increased
In anemias
on
to the
level
with
of the
Shemin
is probably
formed
respectively.
in pernicious
of the death
rate of the pernicious
anemia
unit zinc concentration
in red blood
cells
zinc
blood
counts.
Red blood
cell
increased
by cells
in relation
anemias,
by London,
concentration
cells
effect is an expression
Figure
6 shows
the
ary
within
55, 66 and 69 days
life span
of erythrocytes
of
phe-
decrease
in pernicious
inversely
proportional
and carbonic
anhydrase
to
discrete
though
functionally
related.
the zinc concentration
of erythrocytes
was markedly
dcsamples
on 2. patients.
The other
two samples
were above
from the normal
mean
but so close that
they could
not
be thought
to be statistically
significant.
More
observations
required
before a definitive
statement
about
zinc distribution
Zinc is known
to be an integral
component
of the enzyme
in this condition
can be made.
carbonic
anhydrase
are
.
‘ #{176}
The
functional
significance
of this enzyme
in the anemias
has recently
been scrutinized,”
and the quantitative
relationship
of zinc and enzyme
activity
has been
determined
independently
on samples
of venous
blood,
and is being reported
in two
other
communications)e,
13
CoNcLusIoNs
i.
The
zinc
content
determined
in
pernicious
anemia.
2.0
of whole
patients
with
blood,
plasma,
miscellaneous
leukocytes
anemias
and
and
erythrocytes
in
9 patients
was
with
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
466
ZINC
Unit
2..
packed
‘
CONTENT
values
for erythrocytes
cells)
were within
the
nicious
anemia.
3 In pernicious
vated
above
normal.
in unit value
which
anemia,
Under
reached
limits
OF
WHOLE
BLOOD
(zinc
in gamma
of normality
in the
per
million
cells or per cc. of
anemias,
other
than per-
unit
values
for erythrocytes
were
significantly
dcsuccessful
liver therapy
there
was a progressive
fall
normal
when
the red blood
cell count
had risen
to
normal.
4. The
anemia
rate
ofdecrease
is comparable
institution
of
in unit zinc
the probable
to
value of the circulating
red cells
death
rate of cells in circulation
in pernicious
prior to the
therapy.
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B. L.,
I VALLEE,
kocytes
2
SurroN,
Studies
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2.ND,
S
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A method
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Issue,
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E.
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MANN,
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LONDON,
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L.,
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176.’
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__, ,
B. L.,
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Acad.
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LARSON,
AND
The
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Biol. Chem.
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AND
--,
4 SMITH,
G.,
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and erythrocytes.J.
W. R. , AND NELSON,
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3
AND
GIBSON,
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2.ND:
in
The
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in
and
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p. 467.
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red
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in normals
and
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J.
Clin.
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
1949 4: 455-466
THE ZINC CONTENT OF WHOLE BLOOD, PLASMA, LEUKOCYTES AND
ERYTHROCYTES IN THE ANEMIAS
BERT L. VALLEE and JOHN G. GIBSON II
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