- Email: [email protected]
Some Observations on Peripheral Blood Flow During Administration of Ethylene Diamine Tetraacetic Acid (EDTA)1
SOME OBSERVATIONS ON PERIPHERAL BLOOD FLOW DURING ADMINISTRATION OF ETHYLENE DIAMINE TETRAACETIC ACID (EDTA) * SAM R. MASON, M.D., FRANCIS S. CALIVA, M.D. AND RICHARD H. LYONS, M.D.
maintained at 22° C 1° C for the 6 subjects. The patient with scieroderma was also studied in a room at 25° C 1° C. Skin temperatures
Ethylene diamine tetraacetic acid (EDTA) is
a chelating agent which has been used in the treatment of a number of seemingly unrelated conditions, all pertaining to the removal of a heavy metal from the body (1—6). Chelating
at multiple sites were recorded continuously using iron-constantan thermocouples. A record of the oral temperature was also obtained. Toe and finger flows were measured by the method of Simeone (9) with amplification of the oscillations in the recording machine (Grass). Hand blood flows, measured in our patient with scleroderma, were determined using a hand plethysmograph as previously described (10). Blood pressure measurements were made by auscultation intermittently throughout the procedure.
agents have the ability to combine with metallic ions rendering the metal no longer available for
its usual reactions. The chelate thus formed is excreted unchanged in the urine (6, 7). EDTA has no reported effect on the peripheral blood flow or skin. However, it was administered intravenously to three cases of scleroderma by Rukavina, et al (8) with considerable subjective
and objective improvement in the skin and
The subjects were allowed to adapt to the room osseous findings. During the course of therapy in two of these cases it was noted that the ex- for approximately 30 minutes. The protocol was tremities seemed warmer. However, peripheral thoroughly explained in an attempt to minimize vascular studies such as skin temperature meas- anxiety and control measurements were obtained. urements, histamine wheal and oscillometry, dem- Two and one-half grams of EDTA, * diluted in onstrated that no statistically significant changes 1000 cc. 5% D/W, was started intravenously.
occurred between the before and after com- The rate of administration varied, beginning slowly and then increasing to considerably faster speeds. Frequent blood flow determinations were
parisons. A patient with scieroderma involving primarily
the hands and forearms and with Raynaud's made. When very rapid rates of infusion were phenomenon was treated with EDTA by one of shown to produce no changes in the circulation us (RHL). It was observed that her extremities being studied the drip was slowed then stopped appeared warmer and more moist during infusions and follow-up determinations were made. The with 3.0 grams of EDTA. This patient's skin also total dose of drug administered ranged from 0.44 appeared more pliable after 2—3 weeks of this to 1.25 grams. Urinary Sulkowitch tests were therapy. Because of these observations a more done on 24 hour urine collections before, during intensive study of both this patient and of normal and after the experiment. individuals was undertaken to assess the periphRESULTS AND DISCUSSION
eral vascular effects of intravenously administered EDTA.
No significant clinical effects were noted during
the administration of EDTA to the 5 normal
METHODS
subjects. Two subjects complained of pain along the course of the vein receiving the infusion when
Five subjects, four men and one woman, with
no clinically detectable vascular disease were chosen. Their ages ranged from 24—50 years. The sixth subject, the patient with scleroderma, was 34 years of age. A constant temperature room was employed and the temperature was * From the Department of Medicine, Upstate Medical Center, State University of New York,
at a rapid rate of administration. This subsided promptly upon slowing the rate. No flushing, sweating or increased warmth was noted in any of these subjects.
Finger and toe cutaneous temperatures and finger and toe blood flows in the five normal * Supplied as Endrate Disodium by Abbott
Syracuse, New York. Received for publication September 18, 1958.
Laboratories, North Chicago, Ill. 1
2
THE JOTJRNAL OF INVESTIGATIVE DERMATOLOGY
TABLE 1
subjects demonstrated no significant changes during EDTA administration. Two of the five
Mean blood flow (cc./100 cc/mm.) Before EDTA
4 Hours During EDTA After EDTA
Finger
Toe
Finger
3.3 3.3
.83
2.0 1.2 9.8
J. C. K. B.
.55 10.4 1.10 6.6 .65 7.9 .33
H.Z. E. D.
J. 0.
10.2 13.1
Toe Finger
6.9 2.5
.35 .51 .56 .75 .54
Toe
.69 .41
The mean blood flow, to the finger and toe, in cc./100 cc. tissue/minute demonstrates no significant changes during EDTA administration. One
of the two subjects restudied 4 hours after the infusion showed a distinct rise in finger circulation. 90
w
subjects were restudied 4 hours after the infusion was stopped and in one of them a higher finger blood flow was demonstrated at this time. Table 1 is a chart of the mean blood flow to the finger
and toe of each subject before and during an infusion containing EDTA and includes the mean circulation to finger and toe of the two subjects restudied 4 hours later. Figure 1 is a graph of the finger and toe blood flows and skin temperatures during an EDTA infusion in one of our subjects.
The female patient with scleroderma and Raynaud's phenomenon, when studied as the above subjects, demonstrated significant increase
in the flows to the hand, finger, thumb and toe. This patient was studied on 4 occasions. The most pronounced augmentation of peripheral •_.___-_...S FINGER
K— — -K TOE
85 U)
80
o
U)
I70 65
—
5
•—• FINGER II— — K TOE
4 .8
_J -
3
LJ_ 0
no 00 0-. _J 0
2
1K'
C)
100
o 0
0 0
I
I I I 10 20 30 40 50 60i•••••• 70
8OMIN.
4 HRS. LATER
TIME —p
Fin. 1. Graphs showing the changes in the skin temperature and blood flow of a finger and toe of one
of the normal subjects before and during EDTA administration and four hours after the end of the infusion. No significant effects were noted.
3
STUDIES ON DLOOD FLOW WITH EDTA
TABLE 2
blood
flow occurred towards the end of the 5
hour infusion when she had received almost 3.0 grams of EDTA. Table 2 shows the mean blood At the End of During Before EDTA EDTA a 5 Hour flows before and towards the termination of the Infusion EDTA Infusion _________________________________ EDTA infusion. On each study a definite increase in circulation to the parts measured was noted. Hand Toe Hand Toe Thumb Toe
Mean blood flow (cc./100 cc/mire.) L. G.
4/21
0
.28
.38
Her pulse volumes were also observed to be decidedly raised and her skin more moist than before the treatment started. Skin temperature values of the fingers and toes also rose corre-
.41
Thumb
4/22 4/30
1.65 4.33
6.75 5.32
.51 .55
Finger
1.74
Finger
.77
5/1
0.9
2.7
.08
The mean blood flow in cc./100 cc. tissue/ minute to the distal extremities demonstrates a
spondingly with the increase in blood flow to the
parts. The measurement of blood flow to the thumb, finger and hand in this case was complicated by the thin tight skin over these areas, thereby diminishing the reservoir into which venous blood can expand. This fact makes the observed elevations in flow more striking. The explanation of the difference in response
decided increase towards the end of a 5 hour in- between this patient and the 5 normal subjects fusion containing 3.0 grams EDTA in a patient is unknown to us. It is possible that the normal subjects would have shown some augmentation with scieroderma. 2
.0
UdFIflV.r
——
2
______._0
ThUmb
—
uj2 I—
.5
w
2Ui
2
2
2
—-.0
0-
0
Room
——————
2
3
loll, Till.,
2. 2.
0 u. E
Oii
ool. 'n -
CONTROL MEASUREMENTS
5 HOURS LATER
2. Blood flow and skin temperature changes in patient with scieroderma. These rises were accompanied by a subjective and objective warmth as well as perspiration of the hands. FIG.
4
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
of peripheral blood flow if they had been studied over a more prolonged period of time. Also, the change observed does not necessarily indicate an increased circulation to the extremity but could
havc been due to the skin of the patient with scleroderma becoming more pliable in some manner. Or non-specific action may have occurred or a combination of factors may have accounted for the observed changes. Figure 2 is a graph demonstrating the skin temperature and blood flow changes noted during an EDTA infusion in our patient with scleroderma. No consistent changes in urinary calcium were noted in any of the subjects.
REFERENCES 1. GENREs, R. F. AND RAYMONO, S.: A new
clinical approach to the dissolution of urinary calculi. J. Urol., 65: 474, 1951. 2. Report of Conference at Massachusetts General Hospital on Use of Calcium Ethylenc-diamine tetra-acetate in Treating Heavy Metal Poisoning. Arch. md. Hygiene and Oecupat. Med., 7: 137, 1953. 3. WJsHINsKY, H., WEINBERG, T., PREv05T, E. M., BURGIN, B. AND MILLER, M. J.:
Ethylenediaminetetraacetic acid in the mobilization
and removal of iron in a case of hemochromatosis. J. Lab. & Clin. Med.,
42: 550,
corneal
1952. 5. PERRY,
SUMMARY
finger or toe skin temperatures or blood flows could be demonstrated. However, in a patient with moderately advanced scleroderma EDTA infusion was shown to produce a significant increase in measured blood flow to the finger, thumb, hand and toe. The reason for this difference is unknown but may relate to a number of different factors noteworthy of which is a possible non-specific loosening of the integument, thereby enabling truer measurements of peripheral blood flow. AcKNOWLEDGMENT
The authors with to acknowledge the technical assistance of Miss Madeline Tuori, RN.
M.: New treatment for calcific
opacities. Arch. Ophth., 48: 681,
H.M., JR. AND SCHROEDER, H.A.: Depression of cholesterol levels in human plasma
acetate
EDTA was administered by the intravenous route to 5 subjects to study the effect on the peripheral blood flow. No significant changes in
1953.
4. GRANT, W.
following ethylenediamine tetraand hydralazine. J. Chron. Dis.,
2: 520, 1955.
H.A.: A practical method for the reduction of plasma cholesterol in man. J. Chron. Dis., 4: 461, 1956. BEssMAN, S.P. AND D00EENB05, N.J.: Edi-
6. ScMROEDEE,
7.
torial—Chelation. Ann. Tnt. Med., 47: 1036, 1957.
S. RUKATINA, J.G., MENDEL5ON, C., PEICE, J.
M. BROWN, R.R. AND JoHNsoN, S.A.M.:
Scleroderma. I. Treatment of three cases of the non-calcific variety by chelation (EDTA). J.
9.
Invest. Dcrmat., 29: 273, 1957.
SIME0NE, F. A., CRANLEY, J. J., GRASS, A. M., LINTON, R. R. AND LYNN, R. B.: An
oscillographic plethysmograph using a new type transducer. Science, 116: 355, 1952.
F. S., GABEL, P. V., MUELLER, W. AND LyoNs, R. H.: Some transducers adaptable for water plethysmography. J.
10. CALITA,
Lab & Clin. Med., 48: 912, 1956.
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
94
linolenic acid extract. Arch. This pdf is a scanned copy UV of irradiated a printed document.
24. Wynn, C. H. and Iqbal, M.: Isolation of rat
skin lysosomes and a comparison with liver Path., 80: 91, 1965. and spleen lysosomes. Biochem. J., 98: lOP, 37. Nicolaides, N.: Lipids, membranes, and the 1966.
human epidermis, p. 511, The Epidermis
Eds., Montagna, W. and Lobitz, W. C. Acascopic localization of acid phosphatase in demic Press, New York. human epidermis. J. Invest. Derm., 46: 431, 38. Wills, E. D. and Wilkinson, A. E.: Release of 1966. enzymes from lysosomes by irradiation and 26. Rowden, C.: Ultrastructural studies of kerathe relation of lipid peroxide formation to tinized epithelia of the mouse. I. Combined enzyme release. Biochem. J., 99: 657, 1966. electron microscope and cytochemical study 39. Lane, N. I. and Novikoff, A. B.: Effects of of lysosomes in mouse epidermis and esoarginine deprivation, ultraviolet radiation and X-radiation on cultured KB cells. J. phageal epithelium. J. Invest. Derm., 49: 181, 25. Olson, R. L. and Nordquist, R. E.: Ultramicro-
No warranty is given about the accuracy of the copy.
Users should refer to the original published dermal cells. Nature, 216: 1031, 1967. version of1965. the material. vest. Derm., 45: 448, 28. Hall, J. H., Smith, J. G., Jr. and Burnett, S. 41. Daniels, F., Jr. and Johnson, B. E.: In prepa1967.
Cell Biol., 27: 603, 1965.
27. Prose, P. H., Sedlis, E. and Bigelow, M.: The 40. Fukuyama, K., Epstein, W. L. and Epstein, demonstration of lysosomes in the diseased J. H.: Effect of ultraviolet light on RNA skin of infants with infantile eczema. J. Inand protein synthesis in differentiated epi-
C.: The lysosome in contact dermatitis: A ration. histochemical study. J. Invest. Derm., 49: 42. Ito, M.: Histochemical investigations of Unna's oxygen and reduction areas by means of 590, 1967. 29. Pearse, A. C. E.: p. 882, Histochemistry Theoultraviolet irradiation, Studies on Melanin, retical and Applied, 2nd ed., Churchill, London, 1960.
30. Pearse, A. C. E.: p. 910, Histacheini.stry Thearetscal and Applied, 2nd ed., Churchill, London, 1960.
31. Daniels, F., Jr., Brophy, D. and Lobitz, W. C.: Histochemical responses of human skin fol-
lowing ultraviolet irradiation. J. Invest. Derm.,37: 351, 1961.
32. Bitensky, L.: The demonstration of lysosomes by the controlled temperature freezing section method. Quart. J. Micr. Sci., 103: 205, 1952.
33. Diengdoh, J. V.: The demonstration of lysosomes in mouse skin. Quart. J. Micr. Sci., 105: 73, 1964.
34. Jarret, A., Spearman, R. I. C. and Hardy, J. A.:
Tohoku, J. Exp. Med., 65: Supplement V, 10, 1957.
43. Bitcnsky, L.: Lysosomes in normal and pathological cells, pp. 362—375, Lysasames Eds., de Reuck, A. V. S. and Cameron, M. Churchill, London, 1953.
44. Janoff, A. and Zweifach, B. W.: Production of inflammatory changes in the microcirculation by cationic proteins extracted from lysosomes. J. Exp. Med., 120: 747, 1964.
45. Herion, J. C., Spitznagel, J. K., Walker, R. I. and Zeya, H. I.: Pyrogenicity of granulocyte lysosomes. Amer. J. Physiol., 211: 693, 1966.
46. Baden, H. P. and Pearlman, C.: The effect of ultraviolet light on protein and nucleic acid synthesis in the epidermis. J. Invest. Derm.,
Histochemistry of keratinization. Brit. J. 43: 71, 1964. Derm., 71: 277, 1959. 35. De Duve, C. and Wattiaux, R.: Functions of 47. Bullough, W. S. and Laurence, E. B.: Mitotic control by internal secretion: the role of lysosomes. Ann. Rev. Physiol., 28: 435, 1966. the chalone-adrenalin complex. Exp. Cell. 36. Waravdekar, V. S., Saclaw, L. D., Jones, W. A. and Kuhns, J. C.: Skin changes induced by
Res., 33: 176, 1964.
maintained at 22° C 1° C for the 6 subjects. The patient with scieroderma was also studied in a room at 25° C 1° C. Skin temperatures
Ethylene diamine tetraacetic acid (EDTA) is
a chelating agent which has been used in the treatment of a number of seemingly unrelated conditions, all pertaining to the removal of a heavy metal from the body (1—6). Chelating
at multiple sites were recorded continuously using iron-constantan thermocouples. A record of the oral temperature was also obtained. Toe and finger flows were measured by the method of Simeone (9) with amplification of the oscillations in the recording machine (Grass). Hand blood flows, measured in our patient with scleroderma, were determined using a hand plethysmograph as previously described (10). Blood pressure measurements were made by auscultation intermittently throughout the procedure.
agents have the ability to combine with metallic ions rendering the metal no longer available for
its usual reactions. The chelate thus formed is excreted unchanged in the urine (6, 7). EDTA has no reported effect on the peripheral blood flow or skin. However, it was administered intravenously to three cases of scleroderma by Rukavina, et al (8) with considerable subjective
and objective improvement in the skin and
The subjects were allowed to adapt to the room osseous findings. During the course of therapy in two of these cases it was noted that the ex- for approximately 30 minutes. The protocol was tremities seemed warmer. However, peripheral thoroughly explained in an attempt to minimize vascular studies such as skin temperature meas- anxiety and control measurements were obtained. urements, histamine wheal and oscillometry, dem- Two and one-half grams of EDTA, * diluted in onstrated that no statistically significant changes 1000 cc. 5% D/W, was started intravenously.
occurred between the before and after com- The rate of administration varied, beginning slowly and then increasing to considerably faster speeds. Frequent blood flow determinations were
parisons. A patient with scieroderma involving primarily
the hands and forearms and with Raynaud's made. When very rapid rates of infusion were phenomenon was treated with EDTA by one of shown to produce no changes in the circulation us (RHL). It was observed that her extremities being studied the drip was slowed then stopped appeared warmer and more moist during infusions and follow-up determinations were made. The with 3.0 grams of EDTA. This patient's skin also total dose of drug administered ranged from 0.44 appeared more pliable after 2—3 weeks of this to 1.25 grams. Urinary Sulkowitch tests were therapy. Because of these observations a more done on 24 hour urine collections before, during intensive study of both this patient and of normal and after the experiment. individuals was undertaken to assess the periphRESULTS AND DISCUSSION
eral vascular effects of intravenously administered EDTA.
No significant clinical effects were noted during
the administration of EDTA to the 5 normal
METHODS
subjects. Two subjects complained of pain along the course of the vein receiving the infusion when
Five subjects, four men and one woman, with
no clinically detectable vascular disease were chosen. Their ages ranged from 24—50 years. The sixth subject, the patient with scleroderma, was 34 years of age. A constant temperature room was employed and the temperature was * From the Department of Medicine, Upstate Medical Center, State University of New York,
at a rapid rate of administration. This subsided promptly upon slowing the rate. No flushing, sweating or increased warmth was noted in any of these subjects.
Finger and toe cutaneous temperatures and finger and toe blood flows in the five normal * Supplied as Endrate Disodium by Abbott
Syracuse, New York. Received for publication September 18, 1958.
Laboratories, North Chicago, Ill. 1
2
THE JOTJRNAL OF INVESTIGATIVE DERMATOLOGY
TABLE 1
subjects demonstrated no significant changes during EDTA administration. Two of the five
Mean blood flow (cc./100 cc/mm.) Before EDTA
4 Hours During EDTA After EDTA
Finger
Toe
Finger
3.3 3.3
.83
2.0 1.2 9.8
J. C. K. B.
.55 10.4 1.10 6.6 .65 7.9 .33
H.Z. E. D.
J. 0.
10.2 13.1
Toe Finger
6.9 2.5
.35 .51 .56 .75 .54
Toe
.69 .41
The mean blood flow, to the finger and toe, in cc./100 cc. tissue/minute demonstrates no significant changes during EDTA administration. One
of the two subjects restudied 4 hours after the infusion showed a distinct rise in finger circulation. 90
w
subjects were restudied 4 hours after the infusion was stopped and in one of them a higher finger blood flow was demonstrated at this time. Table 1 is a chart of the mean blood flow to the finger
and toe of each subject before and during an infusion containing EDTA and includes the mean circulation to finger and toe of the two subjects restudied 4 hours later. Figure 1 is a graph of the finger and toe blood flows and skin temperatures during an EDTA infusion in one of our subjects.
The female patient with scleroderma and Raynaud's phenomenon, when studied as the above subjects, demonstrated significant increase
in the flows to the hand, finger, thumb and toe. This patient was studied on 4 occasions. The most pronounced augmentation of peripheral •_.___-_...S FINGER
K— — -K TOE
85 U)
80
o
U)
I70 65
—
5
•—• FINGER II— — K TOE
4 .8
_J -
3
LJ_ 0
no 00 0-. _J 0
2
1K'
C)
100
o 0
0 0
I
I I I 10 20 30 40 50 60i•••••• 70
8OMIN.
4 HRS. LATER
TIME —p
Fin. 1. Graphs showing the changes in the skin temperature and blood flow of a finger and toe of one
of the normal subjects before and during EDTA administration and four hours after the end of the infusion. No significant effects were noted.
3
STUDIES ON DLOOD FLOW WITH EDTA
TABLE 2
blood
flow occurred towards the end of the 5
hour infusion when she had received almost 3.0 grams of EDTA. Table 2 shows the mean blood At the End of During Before EDTA EDTA a 5 Hour flows before and towards the termination of the Infusion EDTA Infusion _________________________________ EDTA infusion. On each study a definite increase in circulation to the parts measured was noted. Hand Toe Hand Toe Thumb Toe
Mean blood flow (cc./100 cc/mire.) L. G.
4/21
0
.28
.38
Her pulse volumes were also observed to be decidedly raised and her skin more moist than before the treatment started. Skin temperature values of the fingers and toes also rose corre-
.41
Thumb
4/22 4/30
1.65 4.33
6.75 5.32
.51 .55
Finger
1.74
Finger
.77
5/1
0.9
2.7
.08
The mean blood flow in cc./100 cc. tissue/ minute to the distal extremities demonstrates a
spondingly with the increase in blood flow to the
parts. The measurement of blood flow to the thumb, finger and hand in this case was complicated by the thin tight skin over these areas, thereby diminishing the reservoir into which venous blood can expand. This fact makes the observed elevations in flow more striking. The explanation of the difference in response
decided increase towards the end of a 5 hour in- between this patient and the 5 normal subjects fusion containing 3.0 grams EDTA in a patient is unknown to us. It is possible that the normal subjects would have shown some augmentation with scieroderma. 2
.0
UdFIflV.r
——
2
______._0
ThUmb
—
uj2 I—
.5
w
2Ui
2
2
2
—-.0
0-
0
Room
——————
2
3
loll, Till.,
2. 2.
0 u. E
Oii
ool. 'n -
CONTROL MEASUREMENTS
5 HOURS LATER
2. Blood flow and skin temperature changes in patient with scieroderma. These rises were accompanied by a subjective and objective warmth as well as perspiration of the hands. FIG.
4
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
of peripheral blood flow if they had been studied over a more prolonged period of time. Also, the change observed does not necessarily indicate an increased circulation to the extremity but could
havc been due to the skin of the patient with scleroderma becoming more pliable in some manner. Or non-specific action may have occurred or a combination of factors may have accounted for the observed changes. Figure 2 is a graph demonstrating the skin temperature and blood flow changes noted during an EDTA infusion in our patient with scleroderma. No consistent changes in urinary calcium were noted in any of the subjects.
REFERENCES 1. GENREs, R. F. AND RAYMONO, S.: A new
clinical approach to the dissolution of urinary calculi. J. Urol., 65: 474, 1951. 2. Report of Conference at Massachusetts General Hospital on Use of Calcium Ethylenc-diamine tetra-acetate in Treating Heavy Metal Poisoning. Arch. md. Hygiene and Oecupat. Med., 7: 137, 1953. 3. WJsHINsKY, H., WEINBERG, T., PREv05T, E. M., BURGIN, B. AND MILLER, M. J.:
Ethylenediaminetetraacetic acid in the mobilization
and removal of iron in a case of hemochromatosis. J. Lab. & Clin. Med.,
42: 550,
corneal
1952. 5. PERRY,
SUMMARY
finger or toe skin temperatures or blood flows could be demonstrated. However, in a patient with moderately advanced scleroderma EDTA infusion was shown to produce a significant increase in measured blood flow to the finger, thumb, hand and toe. The reason for this difference is unknown but may relate to a number of different factors noteworthy of which is a possible non-specific loosening of the integument, thereby enabling truer measurements of peripheral blood flow. AcKNOWLEDGMENT
The authors with to acknowledge the technical assistance of Miss Madeline Tuori, RN.
M.: New treatment for calcific
opacities. Arch. Ophth., 48: 681,
H.M., JR. AND SCHROEDER, H.A.: Depression of cholesterol levels in human plasma
acetate
EDTA was administered by the intravenous route to 5 subjects to study the effect on the peripheral blood flow. No significant changes in
1953.
4. GRANT, W.
following ethylenediamine tetraand hydralazine. J. Chron. Dis.,
2: 520, 1955.
H.A.: A practical method for the reduction of plasma cholesterol in man. J. Chron. Dis., 4: 461, 1956. BEssMAN, S.P. AND D00EENB05, N.J.: Edi-
6. ScMROEDEE,
7.
torial—Chelation. Ann. Tnt. Med., 47: 1036, 1957.
S. RUKATINA, J.G., MENDEL5ON, C., PEICE, J.
M. BROWN, R.R. AND JoHNsoN, S.A.M.:
Scleroderma. I. Treatment of three cases of the non-calcific variety by chelation (EDTA). J.
9.
Invest. Dcrmat., 29: 273, 1957.
SIME0NE, F. A., CRANLEY, J. J., GRASS, A. M., LINTON, R. R. AND LYNN, R. B.: An
oscillographic plethysmograph using a new type transducer. Science, 116: 355, 1952.
F. S., GABEL, P. V., MUELLER, W. AND LyoNs, R. H.: Some transducers adaptable for water plethysmography. J.
10. CALITA,
Lab & Clin. Med., 48: 912, 1956.
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
94
linolenic acid extract. Arch. This pdf is a scanned copy UV of irradiated a printed document.
24. Wynn, C. H. and Iqbal, M.: Isolation of rat
skin lysosomes and a comparison with liver Path., 80: 91, 1965. and spleen lysosomes. Biochem. J., 98: lOP, 37. Nicolaides, N.: Lipids, membranes, and the 1966.
human epidermis, p. 511, The Epidermis
Eds., Montagna, W. and Lobitz, W. C. Acascopic localization of acid phosphatase in demic Press, New York. human epidermis. J. Invest. Derm., 46: 431, 38. Wills, E. D. and Wilkinson, A. E.: Release of 1966. enzymes from lysosomes by irradiation and 26. Rowden, C.: Ultrastructural studies of kerathe relation of lipid peroxide formation to tinized epithelia of the mouse. I. Combined enzyme release. Biochem. J., 99: 657, 1966. electron microscope and cytochemical study 39. Lane, N. I. and Novikoff, A. B.: Effects of of lysosomes in mouse epidermis and esoarginine deprivation, ultraviolet radiation and X-radiation on cultured KB cells. J. phageal epithelium. J. Invest. Derm., 49: 181, 25. Olson, R. L. and Nordquist, R. E.: Ultramicro-
No warranty is given about the accuracy of the copy.
Users should refer to the original published dermal cells. Nature, 216: 1031, 1967. version of1965. the material. vest. Derm., 45: 448, 28. Hall, J. H., Smith, J. G., Jr. and Burnett, S. 41. Daniels, F., Jr. and Johnson, B. E.: In prepa1967.
Cell Biol., 27: 603, 1965.
27. Prose, P. H., Sedlis, E. and Bigelow, M.: The 40. Fukuyama, K., Epstein, W. L. and Epstein, demonstration of lysosomes in the diseased J. H.: Effect of ultraviolet light on RNA skin of infants with infantile eczema. J. Inand protein synthesis in differentiated epi-
C.: The lysosome in contact dermatitis: A ration. histochemical study. J. Invest. Derm., 49: 42. Ito, M.: Histochemical investigations of Unna's oxygen and reduction areas by means of 590, 1967. 29. Pearse, A. C. E.: p. 882, Histochemistry Theoultraviolet irradiation, Studies on Melanin, retical and Applied, 2nd ed., Churchill, London, 1960.
30. Pearse, A. C. E.: p. 910, Histacheini.stry Thearetscal and Applied, 2nd ed., Churchill, London, 1960.
31. Daniels, F., Jr., Brophy, D. and Lobitz, W. C.: Histochemical responses of human skin fol-
lowing ultraviolet irradiation. J. Invest. Derm.,37: 351, 1961.
32. Bitensky, L.: The demonstration of lysosomes by the controlled temperature freezing section method. Quart. J. Micr. Sci., 103: 205, 1952.
33. Diengdoh, J. V.: The demonstration of lysosomes in mouse skin. Quart. J. Micr. Sci., 105: 73, 1964.
34. Jarret, A., Spearman, R. I. C. and Hardy, J. A.:
Tohoku, J. Exp. Med., 65: Supplement V, 10, 1957.
43. Bitcnsky, L.: Lysosomes in normal and pathological cells, pp. 362—375, Lysasames Eds., de Reuck, A. V. S. and Cameron, M. Churchill, London, 1953.
44. Janoff, A. and Zweifach, B. W.: Production of inflammatory changes in the microcirculation by cationic proteins extracted from lysosomes. J. Exp. Med., 120: 747, 1964.
45. Herion, J. C., Spitznagel, J. K., Walker, R. I. and Zeya, H. I.: Pyrogenicity of granulocyte lysosomes. Amer. J. Physiol., 211: 693, 1966.
46. Baden, H. P. and Pearlman, C.: The effect of ultraviolet light on protein and nucleic acid synthesis in the epidermis. J. Invest. Derm.,
Histochemistry of keratinization. Brit. J. 43: 71, 1964. Derm., 71: 277, 1959. 35. De Duve, C. and Wattiaux, R.: Functions of 47. Bullough, W. S. and Laurence, E. B.: Mitotic control by internal secretion: the role of lysosomes. Ann. Rev. Physiol., 28: 435, 1966. the chalone-adrenalin complex. Exp. Cell. 36. Waravdekar, V. S., Saclaw, L. D., Jones, W. A. and Kuhns, J. C.: Skin changes induced by
Res., 33: 176, 1964.