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Skin Copper Levels in Psoriasis
SKIN COPPER LEVELS IN PSORIASIS* GEORGE LIPKIN, M.D., JEAN GOWDEY, M.S. AND VICTOR R. WHEATLEY, PH.D. In a previous communication we reviewed the evidence that copper plays an essential role in the normal keratinization process of animal skin, and
reported the finding of significantly elevated serum copper levels in a group of psoriatics (1). Elevation of serum copper levels may also occur in a wide variety of endocrine, neoplastic, infectious, nutritional, metabolic, and inflammatory disturbances. The question, therefore, arose as to whether the serum copper findings in psoriasis merely represent a non-specific response to an inflammatory process, or whether they might be
associated with quantitative or qualitative abnormalities in tissue copper. In an initial attempt
to clarify this problem, a quantitative study of tissue copper in psoriatic skin was undertaken.
solution (pH 7.5 to 7.9). Next 0.1 ml of biscyclohexanoneoxalyldihydrazone (saturated solution
in 50% ethyl alcohol) was added, and the total
volume adjusted to 1.75 cc with redistilled water. Color development was allowed to proceed for at least five minutes, and spectrophotometric readings taken at a w- re length of 600 mu within one hour. Suitable controls of copper sulphate pentahydrate in concentrations of 1 to 4 mcg/ml were run simultaneously. All readings were made with a Beckmann DB spectrophotometer. All glassware was thoroughly cleaned and washed in redistilled water.
Aliquots of local anesthetics used in taking biopsy specimens were checked to rule out any significant copper content. Subjects. Tissue copper levels were determined in normal appearing skin of 19 cadavers, in uninvolved skin of 19 psoriatics, and in involved skin of 30 psoriatics.
METHOD
RESULTS
Procedure. Tissue copper was determined by a
The results of the assays are shown in Table I. modification of tbe serum copper procedure of The copper values for the cadaver controls Peterson and Bollier (2), utilizing the ash residue of incinerated whole skin. Tissue biopsy speci- ranged from 0.3 to 29.3 with a mean value of 6.1 mens were obtained by means of 4 to 6 mm stain- (average deviation = 4.7). Values for involved less steel punches from both involved and un- psoriatic skin ranged from 0.2 to 26.4 with the involved skin of psoriatic patients and from apparently normal skin of cadavers 12 hours or mean value at 4.1 (average deviation = 3.8). For less post-mortem. Subcutaneous fat was trimmed uninvolved psoriatic skin, values ranged from 0.1 off and the remaining whole skin dried, first for 24 to 35.4, with a mean value of 6.0 (average deviahours in an incubator at 37° C. and then for 48 tion = 6.7). to 96 hours in a desiccator over CaC12 to constant Statistical evaluation failed to reveal any sigweight. The weighed tissues were then gradually incinerated in Coors crucibles in a muffle oven to nificant differences between the values found for 500° C. over a 4 to 6 hour period to obtain the ash the three groups. In order to rule out possible residues. regional influences, the values for cadaver skin The copper content of each of the ash residues from 13 abdominal specimens were compared with was then determined as follows: The ash was carefully transferred to a Pyrex centrifuge tube, dis- those for psoriatic skin from 12 abdominal samsolved in 0.5 ml of 2N HCl and brought to a volume ples. No significant difference was found, the of 1 ml with redistilled water. To this solution mean values for the two groups being 5.6 and 5.8, was added one drop of a 0.1% alcoholic solution of Among the psoriatic patients, no phenolphthalein indicator. Saturated tribasic respectively. potassium phosphate was added dropwise with correlation was found between severity of the stirring until the solution just turned pink (pH 80. to 8.2). Then 2N RC1 was added dropwise (one to
three drops) until one drop just decolorized the Received for publication January 29, 1963. * From the Department of Dermatology, New
York University Schools of Medicine, and the Skin
and Cancer Unit of University Rospital, New York, N. Y. This investigation was supported by the United States Public Health Service Grant Number RG7534 (Cl).
psoriasis clinically and the tissue copper levels. DISCUSSION
According to Goldblum and co-workers (3), skin copper levels may vary considerably, the normal range lying between 0.74 and 8.8 mcg/100
mg dry weight of tissue, a twelve-fold variation
between minimum and maximum. This wide variation was the most striking feature noted in
205
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
206
TABLE I Subject
Age
Sex
Race
Biopsy Site
TABLE I—Continued Tissue Copper
[Gamma! 100 mg
Subject
Age
Sex
Race
5 6
56 51 61
F
Elbow
60 65
M
53
M
53
F
53
M M M M M M M M
W W W W W W W W W W W W W W
N
Elbow Leg
F F
W W W N W W W W W W
M
Y
Leg
Biopsy Site
dry weight]
A. Normal Controls (Cadaver Skin)* 1 2 3 4 5 6 7 8 9 10 11 12 13
14 15 16 17 18 19
32 71 43 31 13/i 29 36 24 50 32 51 73 46 64 23 51 52 55 62
M M M M M M M
F F M M
F F M M M
F M M
w w w w w w w N
w w N
w w w N N
w w w
Abdomen Abdomen Abdomen Chest Abdomen Abdomen Abdomen Abdomen Abdomen Abdomen Abdomen
Back Chest Chest Abdomen Abdomen Abdomen Elbow Elbow
10.6
4.0 2.0 3.7 3.0 5.4 7.3 6.9 0.3 19.6
7.7 0.6 4.7 0.3 1.4 1.3 3.2 29.3
4.3
B. Psoriatics—-ljninvolved Skinf 1
2 3 4 5 6 7 8 9
52 58 17 38 49 53
M
55
M M M M M M
55
44
10
61
11
74
12 13 14 15 16 17 18 19
77 51
60 45 58 26
F F F F F
F F M
59
F F F
40
F
w w w w w w w w w w w w w w w w w
w w
Elbow Elbow Elbow Elbow Elbow Abdomen Abdomen Elbow Elbow Elbow Elbow Elbow Back Elbow Elbow Elbow Elbow Elbow Elbow
35.4
8.1 20.2 11.5
0.1 18.5
0.1 0.2 0.8 6.5 2.0
3.2 1.4
0.5 2.0 2.0 0.4 1.8 0.2
C. Psoriatics—Involved Skint 1 2 3 4
40 68 30 70
M M M M
w Y
w w
Abdomen Abdomen Elbow Elbow
26.4
5.7 1.3 13.7
7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
45 15
58 78 46 33
70 51
60 38 29
69 54 20 40 26 48 67
= = Mean =
* Mean f Mean
M
F F
F F M M M M
F F
Abdomen Abdomen Leg Abdomen Abdomen Leg
Elbow
Abdomen
Elbow Elbow Abdomen Abdomen Abdomen
Elbow Back Elbow Leg Abdomen Abdomen Elbow Elbow
Tissue Copper
[Gamma! 100 mg. dry weight]
4.8 1.1
6.0 0.6 15.6
1.6
2.9 5.3 3.0 0.8 0.6 4.1
2.2 0.4 12.1
0.6 0.2 2.5
0.2
Leg
1.1 2.1 1.8 0.8 1.4 2.1 1.8
Average deviation = 4.7. Average deviation = 6.7. 4.1; Average deviation = 3.8. 6.1, 6.0,
our own material in each of the three groups studied. In terms of the normal range quoted above, 13 of 19 normal control specimens, 20 of 30 involved
psoriatic specimens, and 9 of 19 uninvolved psoriatic samples fell within this range, with the remainder of specimens about equally divided between higher and lower values. This study fails to reveal any significant difference between tissue copper levels of normal skin and both clinically involved and uninvolved skin of psoriatics. These results are in contrast to those of MacCardle and coworkers (4) some 20
years ago, who reported an elevation of tissue copper in 13 psoriatic specimens on spectrographic analysis. We cannot explain these differences in results, but it appears possible that they arise from factors inherent in the different meth-
SKIN COPPER IN PSORL&SIS
207
ods used. In the earlier study, samples of approxi- from 19 psoriatics and in involved skin from 30 mately equal volume were wet ashed for purposes psoriatics. No significant differences were found. of are spectrography, whereas in the current (2) The range of tissue copper levels was found study, dry ashed samples were used in a spectro- to be quite wide in both normal and psoriatic skin. photometric procedure, and all data calculated (3) The elevated serum copper levels found in on a dry weight basis. psoriasis appear to be unaccompanied by quantiAs mentioned above, the wide range of normal tative tissue copper alterations.
tissue copper values found in the present series confirms the findings of Goldblum et at. (3), and suggests the importance of sufficiently large num-
REFERENCES 1. LIvKIN, C., HRRRMANN, F. J. AND MANDOL, L.: Studies on serum copper: I. Serum copper
bers of samples in any such analysis. Although levels in patients with psoriasis. 4. Invest. one cannot completely exclude the possibility of 1)erm., 39: 543, 1962. subtle alterations in activity of copper-containing 2. PETERSON, R. E. AND BOLLIER, M. E.: Specenzymes in psoriatic skin without further study, trophotometric determination of serum copper with biscyclohexanoneoxalyldihydrathe present work suggests that the previously zone. Anal. Chemistry, 27: 1195, 1955. noted elevation of serum copper may represent a 3. COLDBLUM, R. W., DERBY, S .AND LERNER, A. B.: The metal content of skin, nails and systemic response to an inflammatory condition, hair. J. Invest. Derm., 20: 13, 1953. unrelated to any gross tissue copper alteration. SUMMARY
(1) Tissue copper levels were determined in normal skin from 19 cadavers, in uninvolved skin
4. MAcCARDLE, R. C., ENGMAN, M. F., Ja. AND ENGMAN, M. F.: The spectrographic analysis
of neurodermatitic lesions: a human magnesium deficiency. Arch. Derm. (Chicago),
44: 429, 1941.
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.
reported the finding of significantly elevated serum copper levels in a group of psoriatics (1). Elevation of serum copper levels may also occur in a wide variety of endocrine, neoplastic, infectious, nutritional, metabolic, and inflammatory disturbances. The question, therefore, arose as to whether the serum copper findings in psoriasis merely represent a non-specific response to an inflammatory process, or whether they might be
associated with quantitative or qualitative abnormalities in tissue copper. In an initial attempt
to clarify this problem, a quantitative study of tissue copper in psoriatic skin was undertaken.
solution (pH 7.5 to 7.9). Next 0.1 ml of biscyclohexanoneoxalyldihydrazone (saturated solution
in 50% ethyl alcohol) was added, and the total
volume adjusted to 1.75 cc with redistilled water. Color development was allowed to proceed for at least five minutes, and spectrophotometric readings taken at a w- re length of 600 mu within one hour. Suitable controls of copper sulphate pentahydrate in concentrations of 1 to 4 mcg/ml were run simultaneously. All readings were made with a Beckmann DB spectrophotometer. All glassware was thoroughly cleaned and washed in redistilled water.
Aliquots of local anesthetics used in taking biopsy specimens were checked to rule out any significant copper content. Subjects. Tissue copper levels were determined in normal appearing skin of 19 cadavers, in uninvolved skin of 19 psoriatics, and in involved skin of 30 psoriatics.
METHOD
RESULTS
Procedure. Tissue copper was determined by a
The results of the assays are shown in Table I. modification of tbe serum copper procedure of The copper values for the cadaver controls Peterson and Bollier (2), utilizing the ash residue of incinerated whole skin. Tissue biopsy speci- ranged from 0.3 to 29.3 with a mean value of 6.1 mens were obtained by means of 4 to 6 mm stain- (average deviation = 4.7). Values for involved less steel punches from both involved and un- psoriatic skin ranged from 0.2 to 26.4 with the involved skin of psoriatic patients and from apparently normal skin of cadavers 12 hours or mean value at 4.1 (average deviation = 3.8). For less post-mortem. Subcutaneous fat was trimmed uninvolved psoriatic skin, values ranged from 0.1 off and the remaining whole skin dried, first for 24 to 35.4, with a mean value of 6.0 (average deviahours in an incubator at 37° C. and then for 48 tion = 6.7). to 96 hours in a desiccator over CaC12 to constant Statistical evaluation failed to reveal any sigweight. The weighed tissues were then gradually incinerated in Coors crucibles in a muffle oven to nificant differences between the values found for 500° C. over a 4 to 6 hour period to obtain the ash the three groups. In order to rule out possible residues. regional influences, the values for cadaver skin The copper content of each of the ash residues from 13 abdominal specimens were compared with was then determined as follows: The ash was carefully transferred to a Pyrex centrifuge tube, dis- those for psoriatic skin from 12 abdominal samsolved in 0.5 ml of 2N HCl and brought to a volume ples. No significant difference was found, the of 1 ml with redistilled water. To this solution mean values for the two groups being 5.6 and 5.8, was added one drop of a 0.1% alcoholic solution of Among the psoriatic patients, no phenolphthalein indicator. Saturated tribasic respectively. potassium phosphate was added dropwise with correlation was found between severity of the stirring until the solution just turned pink (pH 80. to 8.2). Then 2N RC1 was added dropwise (one to
three drops) until one drop just decolorized the Received for publication January 29, 1963. * From the Department of Dermatology, New
York University Schools of Medicine, and the Skin
and Cancer Unit of University Rospital, New York, N. Y. This investigation was supported by the United States Public Health Service Grant Number RG7534 (Cl).
psoriasis clinically and the tissue copper levels. DISCUSSION
According to Goldblum and co-workers (3), skin copper levels may vary considerably, the normal range lying between 0.74 and 8.8 mcg/100
mg dry weight of tissue, a twelve-fold variation
between minimum and maximum. This wide variation was the most striking feature noted in
205
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
206
TABLE I Subject
Age
Sex
Race
Biopsy Site
TABLE I—Continued Tissue Copper
[Gamma! 100 mg
Subject
Age
Sex
Race
5 6
56 51 61
F
Elbow
60 65
M
53
M
53
F
53
M M M M M M M M
W W W W W W W W W W W W W W
N
Elbow Leg
F F
W W W N W W W W W W
M
Y
Leg
Biopsy Site
dry weight]
A. Normal Controls (Cadaver Skin)* 1 2 3 4 5 6 7 8 9 10 11 12 13
14 15 16 17 18 19
32 71 43 31 13/i 29 36 24 50 32 51 73 46 64 23 51 52 55 62
M M M M M M M
F F M M
F F M M M
F M M
w w w w w w w N
w w N
w w w N N
w w w
Abdomen Abdomen Abdomen Chest Abdomen Abdomen Abdomen Abdomen Abdomen Abdomen Abdomen
Back Chest Chest Abdomen Abdomen Abdomen Elbow Elbow
10.6
4.0 2.0 3.7 3.0 5.4 7.3 6.9 0.3 19.6
7.7 0.6 4.7 0.3 1.4 1.3 3.2 29.3
4.3
B. Psoriatics—-ljninvolved Skinf 1
2 3 4 5 6 7 8 9
52 58 17 38 49 53
M
55
M M M M M M
55
44
10
61
11
74
12 13 14 15 16 17 18 19
77 51
60 45 58 26
F F F F F
F F M
59
F F F
40
F
w w w w w w w w w w w w w w w w w
w w
Elbow Elbow Elbow Elbow Elbow Abdomen Abdomen Elbow Elbow Elbow Elbow Elbow Back Elbow Elbow Elbow Elbow Elbow Elbow
35.4
8.1 20.2 11.5
0.1 18.5
0.1 0.2 0.8 6.5 2.0
3.2 1.4
0.5 2.0 2.0 0.4 1.8 0.2
C. Psoriatics—Involved Skint 1 2 3 4
40 68 30 70
M M M M
w Y
w w
Abdomen Abdomen Elbow Elbow
26.4
5.7 1.3 13.7
7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
45 15
58 78 46 33
70 51
60 38 29
69 54 20 40 26 48 67
= = Mean =
* Mean f Mean
M
F F
F F M M M M
F F
Abdomen Abdomen Leg Abdomen Abdomen Leg
Elbow
Abdomen
Elbow Elbow Abdomen Abdomen Abdomen
Elbow Back Elbow Leg Abdomen Abdomen Elbow Elbow
Tissue Copper
[Gamma! 100 mg. dry weight]
4.8 1.1
6.0 0.6 15.6
1.6
2.9 5.3 3.0 0.8 0.6 4.1
2.2 0.4 12.1
0.6 0.2 2.5
0.2
Leg
1.1 2.1 1.8 0.8 1.4 2.1 1.8
Average deviation = 4.7. Average deviation = 6.7. 4.1; Average deviation = 3.8. 6.1, 6.0,
our own material in each of the three groups studied. In terms of the normal range quoted above, 13 of 19 normal control specimens, 20 of 30 involved
psoriatic specimens, and 9 of 19 uninvolved psoriatic samples fell within this range, with the remainder of specimens about equally divided between higher and lower values. This study fails to reveal any significant difference between tissue copper levels of normal skin and both clinically involved and uninvolved skin of psoriatics. These results are in contrast to those of MacCardle and coworkers (4) some 20
years ago, who reported an elevation of tissue copper in 13 psoriatic specimens on spectrographic analysis. We cannot explain these differences in results, but it appears possible that they arise from factors inherent in the different meth-
SKIN COPPER IN PSORL&SIS
207
ods used. In the earlier study, samples of approxi- from 19 psoriatics and in involved skin from 30 mately equal volume were wet ashed for purposes psoriatics. No significant differences were found. of are spectrography, whereas in the current (2) The range of tissue copper levels was found study, dry ashed samples were used in a spectro- to be quite wide in both normal and psoriatic skin. photometric procedure, and all data calculated (3) The elevated serum copper levels found in on a dry weight basis. psoriasis appear to be unaccompanied by quantiAs mentioned above, the wide range of normal tative tissue copper alterations.
tissue copper values found in the present series confirms the findings of Goldblum et at. (3), and suggests the importance of sufficiently large num-
REFERENCES 1. LIvKIN, C., HRRRMANN, F. J. AND MANDOL, L.: Studies on serum copper: I. Serum copper
bers of samples in any such analysis. Although levels in patients with psoriasis. 4. Invest. one cannot completely exclude the possibility of 1)erm., 39: 543, 1962. subtle alterations in activity of copper-containing 2. PETERSON, R. E. AND BOLLIER, M. E.: Specenzymes in psoriatic skin without further study, trophotometric determination of serum copper with biscyclohexanoneoxalyldihydrathe present work suggests that the previously zone. Anal. Chemistry, 27: 1195, 1955. noted elevation of serum copper may represent a 3. COLDBLUM, R. W., DERBY, S .AND LERNER, A. B.: The metal content of skin, nails and systemic response to an inflammatory condition, hair. J. Invest. Derm., 20: 13, 1953. unrelated to any gross tissue copper alteration. SUMMARY
(1) Tissue copper levels were determined in normal skin from 19 cadavers, in uninvolved skin
4. MAcCARDLE, R. C., ENGMAN, M. F., Ja. AND ENGMAN, M. F.: The spectrographic analysis
of neurodermatitic lesions: a human magnesium deficiency. Arch. Derm. (Chicago),
44: 429, 1941.
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.