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THE
iNTESTINAL
CONTENT
THE
By
H
RONALD
ECENT
in the
antianemic
preparation
shown
have
that
United
States
and
extrinsic
factor
B1, and
which
that
vitamin
simultaneously
Many
was
effect
various
decreasingly
colon,
Bethell
question
OF
FACTORS
by
devoid
of
active
principle
stomach.
body
Berk
his
response
when
normal
human
cc.
the
hours.
in
of hogs’
in
intestines.
the
order
fundus.
The interpretation
and his associates5
have
He
and
that
given
gastric
by mouth
to
juice is given
et al.i4
showed
pooled
human
anemia
patients.
of desiccated
ex-
Uotila3#{176}obtained
an
from
the whole
these
duodenum,
of these results
is, however,
shown
that when
vitamin
Hall
to be effective
effect
suggested
to
of intrinsic
associates2
pernicious
ileum,
more
known
filtered
hemopoietic
pylorus,
the
chemically
action
Hall
of Berkefeld
activity
on
and
of a few
of io
in
related
by the
B12, in doses
vitamin
been
of pernicious
have modified the classic
principle.
They
suggest
or closely
the
potent
crystalline
B,, have
main
levels of the intestinal
tract.
Thus,
he made
dried
powdered
preparations
levels
effective
vitamin
B1, is the
a period
reported
their
treatment
hemopoietic
have
of very
named
and
of
by Rickes
isolation
in the
that
administration
various
when
of the
fault
synthesis
announcements
acid
with
at
the
used
to
(L0ND.)
mechanism
when
the
shown
the
.C.P.
announced
workers
FOR
AND
M.R
of
in Britain
available
or within
it,
oral
from
antianemic
at
the
to produce
a hemopoietic
patients
in relapse
unless
investigators
made
tissue
F.R.C.P.ED.,
be identical
largely
with
daily
juice
tracts
may
have
fails
anemia
gastric
B.,
Berk and his co-workers’
formation
of the hemopoietic
is made
it
is secreted
parenterally
pernicious
the
Smith’s
response
that
and his co-workers’5
that
reopened
a hemopoietic
and it appears
the
factor
CH
substances from
liver.
The
American
vitamin
B,2. Both
pteroylglutamic
concentrated
liver extracts.
theory
of Castle7’#{176} on the
vitamin
ANEMIA
anemia.
In 3945,
Angier
et al.’
acid, and in 1948 came the simultaneous
to produce
anemia,
PERNICIOUS
M.B.,
GIRDWOOD,
.
developments
in pernicious
pteroylglutamic
et al.2’
IN
GROWTH
OF STREPTOCOCCUS
FAECAL1S
LACTOBAC1LLUS
LEICHMANNII
powders
were
jejunum,
cardia,
extremely
difficult.
B1, is given
orally
in
combination
with
an extract
made from hogs’
duodenal
mucosa,
it is effective
in
doses
not much
greater
than
those
required
parenterally.
Bethell
et al.4 have
shown
relatively
large daily fecal excretions
of vitamin
B,, in 4 untreated
pernicious
anemia
patients,
with
pernicious
nicious
anemia
acid”
in the
daily;
grams
It would
have
feces of
whereas,
appear,
hemopoietic
From
(Rockefeller
the
and
Bethell6
anemia,
patients.
Thomas
Travelling
has
using
Denko
young
men
the dietary
therefore,
Henry
Research
that
Simpson
hemopoietic
from
the feces
have
estimated
on a “normal”
intake
was
that
activity,
obtained
an extract
et al.’3
the
the
Memorial
contents
feces
do
Institute
Fellow).
1009
diet.
only
The
for
average
was
304
micro-
62. micrograms.
of the
have
responses
in 2. patients
of other
untreated
perthe excretion
of “folic
stomach
such
Medical
do not
activity,
Research,
in themselves
and
Ann
that
Arbor,
extracts
Mich.
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1010
INTESTINAL
made
from
the
wall
would
be of some
small
contain
intestine
folic
whether
of the
interest
in
acid
there
small
GROWTH
small
with
were
pteroylglutamic
from
the
stomach,
tube
period
of the
sterile
syringe.
tube
out
arthritis,
acid
of the
and
the
if possible
investigations,
which
A specimen
to reach
the
lasted
was
terminal
ileum,
fluoroscopy
A sterile
patients
assay,
and
substances
Canton
No
tube
food
hours.
in the
means.
was
Specimens
were
that
during
withdrawn
the
with
a
In all cases,
the
and
of
levels
and the position
given
experiment.
i
controls,
amounts
at various
passed,
in Cases
two
the
patients
was
indicated
reached
and
to measure
or drink
of the
counts
been
anemia,
was
of these
termination
bacterial
it had
It
of the
by other
pernicious
secretion
at the
but
that
of such
intention
thirty-six
obtained
suggested
The
of fluoroscopy.
for some
of stool
and in nonanemic
microbiologic
by
from
obesity.
cecum.
degrees.
secretions
PATIENTS
gastro-intestinal
means
the
or destruction
suffering
with
to the
by
in varying
extent
or destruction
patients
other
at intervals
activity
production
ON
B1, in the
down,
checked
although
on three
and
vitamin
going
was
appeared
entered,
synthesis
or of their
carried
rheumatoid
ANEMIA
to what
OBSERVATIONS
Investigations
One
have
pernicious
anemia
B,, demonstrable
of the
.
PERNICIOUS
therefore,
patients
with
and vitamin
by bacteria,
IN
intestine
to know,
is evidence
intestine
FACTORS
cecum
itself
the
was
not
i.
METHODS
acid
Pteroylglutamic
the
growth
of free
possible
pteroylglutamic
conjugates
et al.2’ that
Vitamins
vitamin
B,,
Moreover,
B,,
acid
may
added
to the
minutes,
and
The
fasting
from
gastric
some
contents
Bacterial
on
Brain
Since
counts
Heart
all
the
tests
in a refrigerator
the
were
predominant
temperature.
the
control
this
when
for
when
time
of the
material
and
that
acid
Lactobacillus
acid
the
23
vitamin
B,,
of thioglycollic
always
added
exactly
not
it was
was
as
organism.’7’
was
experiment
of
to be assayed
amounts
of autoclaving
thioglycollic
assay
hydrolysis
and Swendseid
using
the
small
of this
measuring
pteroylglutamic
growth
procedure,
conditions
to the
present
patient
had
out
on many
Agan,
and
counts
bacterial
counts,
suffering
not
stain
eating
of the
were
possible
to the medium,
other
poorly
samples,
made
at
various
the
specimens
were
the
way
typical
had
had
used,
been
of the
the
specimens
eating
patients
cases
a low
calorie
a normal
diet,
of appetite.
of a three-day
Each
taking
been
of lack
immediately,
fecal
in every
dilutions
end
to freezing.
The
acid;
patient
out
used.
hydrochloric
were
because
be carried
prior
free
and
obesity
done
being
undnied
from
The
been
being
could
counts
Gram’s
contained
achlonhydnia,
investigation.
carried
specimen
fast
control
anemia
bacterial
patients
histamine
The
bacteria,
For
had
anemia.
on each
but
in the
increased
the
the
et al.”
that
of autoclaving
out
B,, content
of both
pernicious
Infusion
of time
investigation,
Under
vitamin
anemia
prior
with
length
to be much
In this
body.
of Skeggs
other
and
a satisfactory
produce
enzymatic
by Bethell
et al.3
than
each
Elvehjem’8,
organism,
discontinued.
pernicious
patients
replace
and
this
to the
method
satisfactory
in carrying
appears
pounds.
i
of the
is less
the
importance
tested
of Tepley
With
effort
was made to
has been suggested
it
can
that
medium.
was
time
for
but
that
shown
pressure
increase
diet
medium
the
estimation.
test
factors
have
culture
the
pernicious
the
several
or fluid
of Addisonian
but
of
modification
suffering
using
No
This
be of great
a consistent
this
be obtained.
acid,
organism.
et al.26
substance
to show
and
one
of any
out
when present
in food,
are available
were done by a modification
of the
test
activity
are
seven
is only
Stokstad
content
carried
R. by turbidity
acid can
of pteroylglutamic
as the
3i3
were
faecalis
such forms,
B,, assays
leichmannii
for
assays
of Streptococcus
sample
period
samples
sample
was
were
dried
and
a correction
then
of the
investigation
the
blood
cells
being
plated
of incubation.
were
also
kept
slowly
made
frozen
examined
for
at a low
for the
dried
weight.
The
control
patients
were:
hemoglobin
per
ioo
patients
Case
ia.i
ml.,
red
had
z,
Gm.
blood
normal
hemoglobin
per
cells
JOG
blood
6.7
ml.,
1,700,000
red
counts.
Gm.
per
blood
per
cu.
At the
time
ml.,
ned
100
cells
mm.
3,700,000
pen
Cu.
mm.;
,,6oo,ooo
Case
per
counts
Cu.
3, hemoglobin
of the
other
Case
mm.;
4.2.
Gm.
2,
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
RONALD
H.
G1RDWOOD
RESULTS
The results
of the investigation
that
the marking
that
has been
indication
of the
all
fluoroscopy
cases,
from
In
the
terminal
one
patient
made
could
tested
distance
that
region
OBTAINED
are given
in table
i.
It should
reached
on the intestinal
tube
the
indicated
tube
has
that
of the
with
severe
1011
the
passed
along
last
specimen
colitis,
in
the
be remembered
may give little
intestinal
was
tract.
withdrawn
In
at
least
ileum.
ulcerative
whom
an
attempt
had
been
to pass a long intestinal
tube to the cecum
in order
that
the cecal contents
be aspirated
continuously,
a specimen
of the fluid
thus
withdrawn
was
for L. leichmannii
and S. faecalis
factors.
The results
of these
tests
were
.0305
micrograms
tamic
per
acid.
colonies
per
that
the
was
ml.
of “vitamin
Using
cc.
the
Although
tube
had
obtained
micrograms
the
receiving
counts
was
cecum.
only
fecal,
At
fluids
ml. of pteroylglurevealed
i,ioo,ooo
per
colony
withdrawn
reached
was
12..I
to above,
material
quite
patient
and
referred
the
not
the
B12”
medium
the
fluoroscopy
time
by
that
revealed
this
specimen
mouth.
Bacteriology
No
effort
was
secretions
and
intestinal
were
cc.
of gastric
anaerobic
workers
abnormally
the
high
present
mainly
in the
the
lower
part
of the
Gram
be noted
had
the
the
content
but
that
lower
part
of
end
this
in the
contents
aspirated
of
ileum.
were
had
of the
who
factors
were
high
values
terminal
attempts
Moench
the
were
duodenal
chief
pernicious
the
made
et al.’9
and
B. welchii
at
patients.
In
anemia
The
frozen
in
organisms
including
and
bacilli.
a large
of both
The
ileum
Pseudomonas
No
but
gastric
of both
had
amount
of these
the
viable
pernicious
gastric
only
counts
anemia.
flora,
intestinal
the
contents
were
organisms
anemia
present
patients
and
bacilli.
Case
the
in
negative
such
samples,
in
the
on
since
incorporate
intestinal
tracts
intestine
negative
that
patient’s
colitis
ulcerative
small
smallest
of
Gram
included
on
out
to ioo,ooo,ooo
of the
seen
and
been
to
pernicious
intestinal
organisms
carried
ioo,ooo
most
studies
counts
not
decided
increase
the
cocci
were
intestine
the
the
of
from
of
have
found
cases
an
levels
positive
controls
it will
in io
2.
was
however,
shown
series,
Gram
it
organisms
bacteriologic
bacterial
and
i
when
juice
have
detailed
and
of Cases
Davidson,”
to grow
out
patients,
available
investigation.
other
to carry
of these
secretions
specimens
per
made
of most
number
the
was
similar
in the
predominant
ileum.
stomach
present
as Aerobacter
S. faecalis
The
pyocyaneus,
and
organisms
identified
for
of organisms
L. leichmannii
and
cloacac.
L.
it was
in
terminal
The
the
patient
growth
in the
organisms
viridans
small
factors,
to what
leichmannii
predominant
Streptococcus
in the
S. faecal:s
(mitis)
and
in
with
factors
material
aostridium
:nnominatum.
DiscussIoN
The
number
ulcerative
neither
colitis,
in
the
of cases
in
control
here
whom
patients
reported
is very
conditions
nor
were
in
the
ones
small,
very
with
but
if we
abnormal,
it
pernicious
omit
may
anemia
the
be
case
said
was
of
that
there
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1012.
INTESTINAL
TABLE
GROWTH
,.-Conent
Growth
of
FACTORS
Factors
of
the
IN
L. leichmannii
for
Pernicious
I
Anemia
Specimen
Gastric
juice
ANEMIA
S. faecalis
and
B,1
.076
Jejunal
.0057
.038
4 feet
.0053
.077
.oo68
.183
feet
.0054
.46
feet
.0040
feet
acte,nia Count
onies per m.
0
ml.)
-
.336
.0048
Feces
per
(Micrograms
.042.
6
B
Acid Content
pen ml.)
.oo6
feet
Levels
Various
Ptenoylglutamic
Content
(Micrograms
.oo5
Duodenal
at
Tract
Gastro-intestinal
Vitamin
Diagnosis
Case
PERNICIOUS
(per
.,,ii
gram,
io.o
dried)
(pen
gram,
52.0,000,000
dried)
(per
gram,
dried)
Pernicious
2.
Anemia
Gastric
juice
Duodenal
feet
6
feet
.013
.0076
.0013
.014
.00194
.2.4
.6
.002.58
Feces
(per
.1435
gram,
(per
14.0
dried)
gram,
380,000,000
dried)
(per
gram,
dried
3
Pernicious
Anemia
Gastric
juice
.0019
.115
480,000
Duodenal
.0014
4 feet
.ooi66
.047
Negligible
4
.oolI6
.113
Negligible
.0046
.
ioo
.0059
.2.2.5
Negligible
feet
feet
feet
Feces
Negligible
(per
.115
(per
11.1
dried)
gram,
gram,
410,000,000
dried)
(per
gram,
dried)
4
Rheumatoid
Arthritis
Gastric
.oo83
.039
Negligible
Duodenal
juice
.ooil
.083
Negligible
4 feet
.oo87
.010
110
.00103
.oIo
Negligible
.0015
.o8o
Negligible
.oolo
.o68
Negligible
feet
feet
feet
feet
.ooii
Feces
.052.
i8o
.083
9.4
(per
gram,
dried)
(per
gram,
15,100,000
dried)
(per
gram,
dried)
5
Obesity
Gastric
juice
.038
3,2.00
.ooo6
.02.0
2.40
Jejunal
.00115
.011
1,450,000
6
.ooo66
.013
52.000
7 feet
.0012.
.013
70,000
8 feet
.ooo8
.oi8
4,700,000
84 feet
.0004
.050
Feces
.116
Duodenal
feet
.0003
I
(per
gram,
14.8
dried)
1,960,000,000
(pen
gram,
4,900,000
dried)
(per
dried)
gram,
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
RONALD
evidence
of a consistent
along
the
increase
progressive
small
intestine
the free folic
of
H.
GIRDWOOD
increase
1013
of L. leichmannii
or decrease
during
fasting.
Cases
i and
acid of the secretions,
but the
did
2.
show
maximum
acid present
was only
.6 micrograms
per ml.
If conclusions
may be based
on variations
in such small
servations
may be considered
as evidence
that,
in pernicious
of growth
factors
subjects.
lower
the
levels
view
fails
for L. leichm4nnii
Moreover,
no
of the
that
intestine
the
to protect
in the
progressive
was
defective
from
(if,
grams
by
the
of
secretion
had
in
this
dosage.
West
and
given by mouth.
The source of both
in
the
stomachs
seem
that
products
of
viously
ingested
factors
tion
this
on
terial
sprue
absorb
anemia
such
is said
the cecum
were
to
the
large
matter,
and
or
be
who
of
to
the
a part
in
some
of
hence
a
it
is not
the
valuable
speculain
the
severe
able
of
pteroylglu-
from
pernicious
combined
factor
was
secre-
taking
anemia
to
Changes
subacute
that
bacpatients
be
of intrinsic
ml.
of
patients investigated
liquid
to
would
matter
calculate
all
this
might
passes
from
normally
pass
of this
of
data
of
further
intestine.
of
acid
the
of pre-
amounts
bacteria
The
Investigation
collection
remains
suffering
of lack
would
from
place,
without
pre-
complications.
possible
acid
in a day.
but
400
day)3”
It
therefore
small
development
preventing
leichmannii
of possible
might
by
degree
micrograms
especially
the
of pteroylglutamic
play
the
small
in patients
the
micro-
claimed
micrograms
L.
importance
destruction
that
related
pteroylglutamic
intestine
and
part
or
io
6oo
and
obvious,
factor
of neurological
in man,
hours,
ileostomy
was
course
The
upper
synthesis
of synthesis
necessitating
twenty-four
The
cord
the
to
of variables,
however,
be of importance
even
might
that,
in the
B,,
the
well
development
fasting,
vitamin
in
of
have
obvious.
from
extremely
purpose.
is,
intrinsic
might
synthesis
the
little
be gaged
themselves,
or
number
micro-
may
to
is not
secretions
the
the
is .oo6
others
S. faecalis
intestine,
of
and
intestine
affecting
amount
view
serve
small
small
test)
administration
patients
intestinal
the
In
secreting
It
the
this
represents
response
of
anemia
tract.
response
growth
at
support
B,, in the upper intestinal
oral
a slight
these
factors
not
pernicious
although
a definite
of
be present,
equally
to the
venting
it
are
of the
and
since
the
sprue.
degeneration
tion
matter.
to
B1, synthesized
might
or
in
would
in
flora
acid
synthesis
question
who
bacterial
tamic
from
food
vitamin
intestines
come
found
synthesis
with
in
might
bacterial
growth
had
these
ohcontent
in control
the
do
with
this
to the
had
than
of
findings
by
anemia,
Hall’5
less
of folic
the
gastro-intestinal
that
response
Reisner3’
small
the
measured
pernicious
the factors for the
and
they
no
these
amount
quantities,
anemia,
is not
of vitamin
being
small
very
daily
with
and
content
amount
concentration
of patients
in
factor
et al.’4
B,2
orally,
only
The
I.
Hall
vitamin
response
given
is the
in Case
that
fact
small
this
ml.
per
grams
a
indeed,
the
Therefore,
destruction
It will be seen that the maximum
tract
intestine
in
noted.
gastric
B1,
vitamin
small
decrease
factors
a progressive
from
would
from
the
in the
ileum
present
table
i
the
small
normally
to
study
how
much
intestine
be a difficult
material
for
a period
be
obtained
from
a patient
of
the
average
adult
is 2.5
at
with
least
an
opening.
dried weight
of stool
passed
daily
by
tO
o
grams.
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1014
INTESTINAL
Thus,
from
may contain
acid daily.
given
table
about
Davidson
orally
GROWTH
FACTORS
IN
PERNICIOUS
ANEMIA
it will be seen that
the stools
of a case of pernicious
anemia
5 micrograms
of vitamin
B,, and 0.5 mg. of pteroylglutamic
and Girdwood”
showed
that
i mg.
of pteroylglutamic
acid
i,
daily
was
sufficient,
in some
patients
with
pernicious
anemia
in re-
lapse,
to give
a hemopoietic
response,
and numerous
workers
have
obtained
a
response
to i microgram
of vitamin
B1, given
parenterally
daily.
Thus,
it seems
likely
that
the
hemopoietic
pernicious
factors
anemic
control
enough
folic
anemia
in his
to
demonstrate
These
results
with
normal
diet.
of hogs’
the
for
those
of
stomach
in
absorption.
juice
or
It must
the
folic
the
that
et al.,”
Mitchell
to
activity
by
have
such
acid
and
apparently
at least
from
this
part
in
from
In
the food.
pernicious
It
anemia
these
anemia
small
these
substances,
unlikely
small intestine leading
to the destruction
acid
although
the
the
abnormal
of both
findings
on
intestinal
factors
may
the
be found
or
with
found
in the
the
levels
ulcerative
in that
ileum.
did
formation
Our
data
do
shown
pteroylglu-
not
of man,
not
suffering
seem
to
them
available
play
a
remissions
intestinal
in
flora
of
the
of significant
amounts
of maximum
absorption,
colitis
disease,
reported
intestine
making
of
in the
been
that
large
the
body
organism
spontaneous
in
interest.
organisms
has
part,
gastric
of
to the
the
view
the
in
a
available
be
One
from
and
at
due,
bowel
as in patients
changes
B,,
patient
the
on
normal
acid
bacteria
relapses
vitamin
conditions
patients
apart
with
was
availability
the
in
intestinal
that
associated
or
support
by bacteria
either
pteroylglutamic
data
patients
administration
would
by
aerogenes.
cases,
be
the
is Aerobacter
of
seems
can
about
B,,,
Thompson.’9
our
formation
by
by
rectal
administered
and
in pernicious
given
required
large
to synthesize folic
produced
is
absorb
anemia
a!.2’
is synthesized
Isbell,’8
that
B1, are
as well
disorder.
the
be said
vitamin
et
patient’s
vitamin
is known
the
Sharp
rectally
without
Thompson
it may
In conclusion,
tamic
by
B12 that
and
it
that
both
non-
can
when
times
to
B,2 in the
intestine; the ability of certain organisms
by Hutchings
of
from
patients
pernicious
shown
little
ten
response
using
or vitamin
amounts
in this
response
favorable
and
large
differ
although
least
selected
anemia
with
acid
not
of the stool are in fairly close agree-
who
experiments,
however,
free
that
is at
the vitamin
mucosa,
be said,
either
al.4
that
Further
duodenal
does
B,, content
et
making
producing
shown
route
vitamin
pernicious
to this preparation
for
this
&thell
It is possible
is
and
a hematopoietic
enema, the effective dose by
oral route.
ment
intestine,
Moore’#{176} has
patients.
acid
patient
large
indicate
relatively
not
entirely
that
large
of
under
amounts
rule
out
such
a mechanism.
SUMMARY
The
nicious
tained
of
gastric
juice
anemia
only
very
L. leichmannii,
increase
Both
or
and
and
decrease
pteroylglutamic
two
small
small
intestinal
control
amounts
which
acid
of three
obtained
during
of pteroylglutamic
include
of these
secretions
patients
vitamin
factors
and
B,,;
along
vitamin
there
the
cases
a period
of untreated
p:r-
of fasting
acid
or of factors
for
was
no
of a consistent
evidence
the
congrowth
intestine.
B,, appear
to be synthesized
in relatively
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
RONALD
large
amounts
output
in the
in the
large
intestine;
stools
may
be
pteroylglutamic
from
acid.
this
H
1015
in a patient
about
Similar
GIRDWOOD
.
with
micrograms
quantities
pernicious
anemia,
of vitamin
may
be
present
B,,
in
the
and
0.5
patients
daily
mg.
not
of
suffering
disorder.
ADDENDUM
Since
this
paper
administer
to
Royal
Infirmary,
micrograms
but
100
cc.
cent
for
anemia
Edinburgh,
ioo
normal
gastric
daily
and
a rise
a period
of
of red
cc.
for
of
normal
been
gastric
together
then
produced
per
possible
wards
juice
No
orally
2.,64o,000
found
Davidson’s
by enema.
days
from
has
Professor
days
given
four
it
in
four
juice
for
cells
twenty
publication
patient
B,, daily
by mouth
of
B,,
over
submitted
of vitamin
vitamin
per
was
a pernicious
together
to
2.5
resulted,
2.5
micrograms
of
a reticulocytosis
cu.mm.
the
with
improvement
with
to
of
of
per
3,170,000
8.4
cu.mm.
days.
ACKNOWLEDGMENTS
The
author
carrying
Dr.
C. C. Sturgis
this investigation,
of
for invaluable
University
to thank
wishes
out
advice
and
on the microbiologic
of Michigan,
for granting
and
Dr.
F. H.
and
their interest
for
assay
facilities
work,
Bethell
for
advice,
and
and
the
facilities
to thank
H. R. Morgan,
Dr.
for bacteriologic
granted
Dr.
M.
School
for
the
E. Swendseid
of Public
Health,
studies.
REFERENCES
R.
ANGIER,
B.,
identical
2
on
H.,
with
L.,
BERK,
WALLER,
E.
NORTHEY,
etiologic
as food
F. H.,
Metabolic
macnocytic
the
on
CASTLE,
W.
The
effect
human
CASTLE,
M.
of the
M.
MEYERS,
C.,
B,,
communication,
on the
administration
to pernicious
anemia
chromic
anemia
W.
pernicious
no
substances
B.,
AND
beef muscle after
IV.
II.
incubation
B,,
0.
BIRD,
D.,
AND
R. A.:
BROWN,
I. Hematologic
& Clin.
Med.
32.’
anemia
pernicious
3,
and
1947.
and
puerpenal
H. G.:
Observa-
1948.
R. B.,
duodenum,
in combination
with
relationship
with
A biologic
AND
and
RICHARDS,
the
extracts
of achylia
pernicious
free
hydrochloric
anemia.
W. C.:
The
with
assay
acid
in pernicious
TOWNSEND,
anemia.
E.,
B,, in
2.7,
and
patients
free hydrochloric
having
hematopoietic
Observations
of vitamin
treatment
of duodenal
of pernicious
mucosa.
Univ.
1948.
etiologic
to
anemia.
having
M.:
EPSTEIN,
X. Activity
J. Lab.
NELIGH,
stomach
AND
conjugate.
anemia.
R. B.: Vitamin
in hog
E.,
of a compound
1948.
M.
25.’
SUB-
KUH,
1945.
2.2.7,
hexaglutamyl
Research
F.,
49, ‘949.
is.
Personal
its
macnocytic
Clin.
vitamin
911,
M.
Synthesis
JR.:
R.,
E. L. R.,
STOKSTAD,
HULTQUIST,
anemia.
SWEND5EID,
and
NELIGH,
E.,
administered
Observations
239:
with
factors
Arbor)
J. Med.
G. A.,
Soc.
102.’
ANKER,
to pernicious
acid
AND
Science
R. W.,
effect
that
acid
and
Am.
Observations
of
normal
the
J.
of patients
of the
M.
on the
administration
gastric
juice.
Sc.
role
182:
etiologic
to
Am.
to pernicious
of the contents
Am. J. M. Sc.
on the etiologic
of the gastric
and
gastnica
anemia
stomach recovered after the ingestion of beef muscle.
W. B., HEATH,
C. W., AND STRAUSS,
M. B.: Observations
nicious
to
C.,
liver.
J.,
J. M.,
SMiTh,
gastnica
ANDREWS,
Central
SWENDSEID,
(Ann
B.:
gastrica
CASTLE,
M.
Proc.
hemopoietic
F. H.:
6 BETHELL,
England
on patients
MEYERS,
by orally
Bull.
Hosp.
New
of pteroylglutamic
anemia.
F. H.,
“BETHELL,
from
AND
J.,
SEMB,
M.
FAHREr-IBACH,
HEINLE,
of achylia
studies
F. H.,
BETHELL,
isolated
A. D.,
J. H.,
MOWAT,
B.,
J. P.,
SICKELS,
factor
M. C.,
MEYERS,
excretion
R.,
WELCH,
factor.
function
urinary
anemia
B.,
D.
COSULICH,
relationship
(extrinsic)
BET1SELL,
tions
L. casei
W.
B. L.,
HUTCHINGS,
D.
SEEGER,
the
CASTLE,
the
J. H.,
C. W.,
BOOTHE,
Y.,
BAROW,
secretions
without
anemia
I.
1919.
of patients
of
achylia
with
or with
perhypo-
impermeability
to
1931.
relationship
178:
748,
relationship
of intestinal
741,
patients
J. M. Sc.
178.’
anemia.
of the normal
with
764,
of achylia
pernicious
1919.
gastnica
anemia
of
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1016
iO
INTESTINAL
W.
CAStLE,
achylia
B.
and
effect
of liver
B.:
‘0.’
i3a
C. W.,
DENKO,
leading
feeding.
Am.
33,
of
P. F.,
edition,
Proc.
B. E.:
i8o.’
305,
properties
KITAY,
E.,
lactic
Univ.
Meet.,
reaction
and
increased
etiologic
between
blood
J. Path.
normal
human
formation
similar
MOENCH,
anemia
gastric
to the
urine
and
feces
T. E.,
FR1EDMANN,
of seven
normal
AND
adults.
YOUMANS,
Arch.
Biochem.
A Textbook
20 MOORE,
Clinic
99,
24.’
AND
21
22
B11. Science
SHARP,
E. A.,
administration
pooled
L.,
Biol.
Chem.
E. R,:
I5BELL,
reference
by Si’iEs,
N. G.,
BRINK,
396,
107.’
gastric
in pernicious
Preliminary
W. H.:
Growth
factors
for bacteria;
by certain
lactic
acid bacteria.
J. Biol.
E. E.: The non-specificity
of thymidine
993,
177.’
and
Purification
Chem.
141.’
as a growth
511,
1941.
factor
for
for the
rat.
1949.
Intestinal
bacterial
J. C.:
synthesis
of B vitamins
of the fecal flora in 33 cases
Analysis
to B. welchii.J.
T. D.: Experiences
as a source
Infect.
with
Dis. 37: ,6i,
Folic Acid.
of pernicious
1915.
Chicago,
The
Year
Book
Pub-
R. M.,
AND
VONDER
and duodenum
to the Editor.
J.
HUFF,
F. R.,
KONIUSZY,
T.
WooD,
R.,
AND
FOLKER5,
K.:
anemia:
The
W.,
used
Lancet
WRIGHT,
E. C.:
HE1DE,
to induce
i.
2.39,
L. D.,
Pernicious
remissions.
Ann.
mt.
Med.
4.’
BOSSHARDT,
D. K.:
The
use
T.
H.:
DORNBUSH,
Microbiological
behavior
1181,
of various
1931.
of Lactobacillus
the microbiologic
assay of the animal
protein
factor.
J. Biol. Chem.
E. L.: Purification
of antianaemic
factors
from liver.
Nature,
London
i6i.’
E. L. R.,
vitamin
1949.
AND
in
26 STOKSTAD,
Crystalline
1948.
MCKEAN,
H. R.,
J UKES,
B,,
juice:
of vitamin
human
1947.)
of stomach
G. E.: Letter
24 SKEGGS,
6th
1949,
1949.
PETERSON,
factor
required
S., AND SNELL,
J.
J. F., editor),
(Fulton,
et al.5
N.,
W.
bacteria.
H. K., AND
lishers,
RICICEs,
E.
of Physiology
Co.
by Bethell
with
particular
C. V.: (quoted
25 SMITH,
of
& Bact.
3i: 557, 1918.
Bnit. M. J. i. 587, 1947.
agent.
G. H.,
BERRYMAN,
the
Texas
Pub. No. 42.37: 115,
1941.
L. M., KAHN,
M. C., AND TORREY,
mannii
relationship
1930.
W.,
in
G. R.:
Mayo
BoHoNos,
MCNLrrr,
MITCHELL,
23 SHAW,
of the
E. H., AND CAMPBELL,
D. C.: Oral
of intrinsic
factor
in Berkefeld-filtened
of an eluate
acid
extracts
on the
flora in pernicious
anemia.
R. H.: Folic acid as a therapeutic
PORTER,J.
B. Saunders
Staff
Quoted
B. L.,
16 HUTCHINGS,
19
nature
The
ANEMIA
W. : Observations
improvement
vitamins
COWGILL,
W.
B. E., MORGAN,
I. Presence
report.
18
Sc.
GIRDWOOD,
W. E.,
AND
p. 997,
HALL,
M.
B-complex
anemia.
‘
III.
PERNICIOUS
1946.
FENTON,
HALL,
C.
to clinical
J.
IN
HEATH,
AND
,
gastro-intestinal
GRUNDY,
Excretion
FACTORS
anemia.
muscle
L. S. P.: The
L. S. P., AND
12 DAVIDSON,
J.
to pernicious
beef
#{176}DAVIDSON,
13
W. C.
TOWNSEND,
,
gastnica
juice
GROWTH
A. C.,
FRANKLIN,
A. L.,
HOFFMANN,
assay
of vitamin
B,,
Lactobacillus
by
C. E.,
176.’
638,
1948.
B. L.,
HUTCH1NGS,
leichmanii.
leich1948.
1459,
Federation
AND
Proc.
8.’ 2.57, 1949.
M. E., BIRD,
acid and its
27 SWENDSE1D,
glutamic
Effect
28
TEPLY,
and
of a conjugase
J.,
L.
“folic
acid.”
R. C.:
29 THOMPSON,
87, 1941.
30 UOTILA,
U.:
31 WEST,
AND
R.,
On
the
inhibitor.
ELVEHJEM,
J.
Biol.
antianemic
Physicians,
i;7.’
703,
of B vitamins
function
E. H.:
AND
II.
BETHELL,
Urinary
F. H.: Metabolic
excretion
studies
J. Lab. & Clin. Med. 32.’ 2.3, 1947.
C. A.: The titrimetnic
determination
Chem.
Synthesis
AND REISNER,
of American
0. D., BROWN,
R. A.,
hexaglutamyl
conjugate.
Communication
1949.
function
of pteroylon normal
persons.
of “Lactobacillus
casei
factor”
1945.
by
of the
bacteria
in
small
intestine.
to
pure
the Sixty-Sconid
culture.
Acta
Univ.
med.
Annual
Texas
Scandinav.
Meeting
Pub.,
95:
of the
No.
415,
42.37:
1938.
Association
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1950 5: 1009-1016
THE INTESTINAL CONTENT IN PERNICIOUS ANEMIA OF FACTORS FOR
THE GROWTH OF STREPTOCOCCUS FAECALIS AND LACTOBACILLUS
LEICHMANNII
RONALD H. GIRDWOOD
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