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Chloramphenicol (Chloromycetin) in the Treatment of Chronic Discoid Lupus Erythematosus
PRELIMINARY AND SHORT REPORTS CHLORAMPHENICOL (CHLOROMYCETIN) IN THE TREATMENT OF CHRONIC DISCOID LUPUS ERYTHEMATOSUS* A PRELIMINARY REPORT
HARRY M. ROBINSON, M.D.
The treatment of chronic discoid lupus erythematosus has shown a percentage of cures ranging from 37% to 66% (1, 2, 3, 4), with the gold and bismuth compounds. In 128 consecutive cases, the percentage of cures was 14% in our experience, and these occurred principally
in "young' lesions of less than three years duration. It is apparent that there is a need for new drugs which might cure patients in whom neither gold nor bismuth was effective. While using chioramphenicolt in early syphilis and gonorrhea Neisseria (5) it seemed desirable to try it in chronic discoid lupus erythematosus. A preliminary report is offered. Thirteen cases are reported. Five have shown complete regression of lesions, one was transformed into the acute disseminated type, six became improved and one showed no improvement. REPORT OF CASES
M.
T. A
26 year old Negress, first seen June 21, 1949. There were five lesions of two years'
Placed on chioramphenicol capsules, one (250 mg.) four times a day. Treatment discontinued October 15, 1949, all lesions having involuted; she had taken 504 capsules. duration.
M. S. A 42 year old, white female, first seen in 1940. There were two lesions, one on the left buccal surface 3 cm. in diameter, and one on the nose. She had received in 1946, one injection of bismuth subsalicylate and twelve injections of gold sodium thiosulfate, without improvement. Thereafter, carbon dioxide snow was used. As the condition persisted, the patient discontinued treatment. Placed on cliloramphenicol June 30, 1949. She took one capsule every two hours (12 daily) for three weeks and one every four hours (5 daily) for fourteen weeks. The buccal lesion healed after 24 capsules. Treatment stopped October 17, both lesions having healed. Number of capsules: 742. A. C. A 61 year old Negress, first seen April 25, 1947 with numerous lesions present since
1936. She had received twelve treatments of bismuth subsalicylate without benefit. She was placed on chloramphenicol July 6, 1949, routine schedule (one capsule four times daily). There was no improvement, and treatment was stopped October 17, 1949 after taking 238
capsules.
M. R. A 42 year old Negress, was first seen August 4, 1949, having two les
and in the right ear which were present for three years. No previous treatment. Started on chioramphenicol; on August 2,5, she had taken 84 capsules Ljoi had cleared up. D. M. A 41 year old Negress first seen August 4, 1949 presenting 28 lesions, of 15 months' duration. She was placed on cliloramphenicol August 4, 1949. Six of the 28 lesions are im-
proved. The rest have completely cleared, leaving a smooth hyperpigmentation. Treatment was temporarily stopped on October 17, 1949. She had taken 280 capsules. * From
the Department of Dermatology, School of Medicine, University of Maryland. t This work was made possible through the courtesy of Parke, Davis & Company who supplied the chloramphenicol. Received for publication December 12, 1949. 309
310
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
F. J. A 41 year old Negro, first seen July 16, 1949. He had received three injections of bismuth without result. Began chloramphenicol August 9, and on October 15 had received
184 capsules. Of the nine lesions present, four have cleared up. The remaining five are improved.
K. B. A 34 year old, white female, first seen in 1933. She had received 77 intravenous injections of gold, 11 intramuscular injections of bismarsen, and 14 of bismuth subsalicylate.
Only cryotherapy and applications of liquefied phenol helped. On August 9, 1949 she returned with 2 active lesions on the buccal surface of the upper lip and on the vermillion border of the lower lip. Discharged October 18, 1949, having taken 250 capsules; both lesions had undergone involution. E. A. A 2,5 year old, white female, first seen September 7, 1945. She had received 12 injections of gold and 5 injections of bismuth. Bistrimate tablets were prescribed, which she took for eight months without benefit. Began chioramphenicol August 12, and was discharged October 14 as cured, having taken 252 capsules. M. L. A 28 year old, Negress, first seen August 23, 1949. There were seven lesions on her face and ears, present for five years. Urinalysis showed a trace of albumin. Placed on chlor-
amphenicol. On September 24, while on chloramphenicol, numerous well-defined, erythematous lesions had appeared over the entire body. She felt sick and weak, and the legs, ankles, feet and face were edematous. Temperature was 100°F. Blood pressure—132/78. Urinalysis—Albumin, four plus; Sugar, one plus. She had taken 140 capsules. She was hospitalized and a diagnosis of acute disseminated lupus erythematosus was made. Biopsy report has verified the diagnosis. Blood examination showed on September 26, Albumin— 3.93; Globulin—2.23; Urea nitrogen—lO; Hemoglobin—83%, 12.1 grams; Hematocrit—38;
Corrected sedimentation rate—2. Further chloramphenicol was given which the patient vomited. There now appeared numerous irregular shaped bullae conforming to the underlying lesions. Temperature rose to 102.4°F. On October 11, 1949 all joints were tender, and swollen. October 20, 1949 there was a four plus albuminuria with granular casts and white
and red cells; sugar, negative. Four days later there had developed an infarct in the base of the right lung. One week later there was an infarct in the base of the left lung. Blood examination on November 4 showed, Albumin—2.51; Globulin—3.19; Urea nitrogen—12; Hemoglobin—56%, 8.2 grams; Hematocrit—29; Corrected sedimentation rate—27. All blood cultures have been negative. All skin lesions have completely regressed.
P. B. A 45 year old Negress, had the condition since January, 1949. This patient had received para-aminobenzoic acid from April 23 to May 2, during which she received 182 grams. She had a rise in temperature ranging from 100 to 105°F. After two and one-half days of fever under para-aminobenzoic acid, the drug was discontinued. Temperature immediately fell to normal. She was given one injection of bismuth subsalicylate, but failed to return until August 23 when she was given chloramphenicol. On October 18, she had taken 182 capsules; all lesions had improved. G. B. A 35 year old, white female, first seen September 6, with several lesions on the vermillion border of the upper lip, the largest 3 x 6 mm. in diameter. Began chloramphenicol
therapy on this date. On October 17, she had taken 196 capsules. All but one lesion had involuted. C. B. A 35 year old, white female, first seen July 24, 1948, presenting lesions of seventeen
months' duration. She had had ultraviolet ray treatments and penicillin injections. She received eleven injections of bismuth subsalicylate and two injections of bismarsen, without
benefit. Cryotherapy gave a fair cosmetic result. She returned September 17, 1949, pre-
CHLORAMPHENICOL IN DISCOID LIJPIJS ERYTHEMATOSUS
311
senting five lesions on the right cheek. Placed on chloramphenieol and on October 17, 1949
had taken 104 capsules. All lesions are improved.
A. P. A 27 year old, white female, had the eruption five years. She had received five injections of bismuth and a similar number of injections of gold without benefit. Took bistrimate tablets for one month without improvement. Cryotherapy was then used with good results. She returned September 20, 1949 with two new lesions and was given chioramphenicol capsules. Up to October 14, 1949 she had taken 140 capsules and both lesions were improved. SUMMARY AND CONCLUSION
Thirteen patients having chronic discoid lupus erythematosus have been treated with ehioramphenicol, 250 milligrams per capsule, four times daily. One patient took one capsule
every two hours, day and night for three weeks and five daily thereafter. In five patients all lesions have completely regressed. In six, the lesions showed moderate to marked improvement. One patient developed the acute disseminated type of eruption. In one patient there was no improvement.
REFERENCES 1. FRANKLIN, JOHN L.: Treatment of lupus erythematosus with sanocrysin; Brit. J. Dermat., 46: 66, February 1934.
2. SMITH, A. G.: Gold and bismuth treatment of lupus erythematosus; Brit. J. Dermat., 46: 399, October 1934. 3. WRIGHT, CARROLL: Ten years experience in the treatment of lupus erythematosus with gold compounds; Arch. Dermat. Syph., 33: 413, March 1936. 4. Weiss, RICHARD S., CONRAD, ADOLPH H., CONRAD, ADOLPH H., JR. AND PFAFF, RICHARD
.
0.: Treatment of lupus erythematosus with bismarsen; Arch. Dermat. Syph., 44: 1009, December 1941.
H. M. AND ROBINSON, H. M., JR.: Chloramphenicol in the Treatment of Syphilis and Gonorrhea; South. M. J., November 1949.
RoBINsON,
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.
HARRY M. ROBINSON, M.D.
The treatment of chronic discoid lupus erythematosus has shown a percentage of cures ranging from 37% to 66% (1, 2, 3, 4), with the gold and bismuth compounds. In 128 consecutive cases, the percentage of cures was 14% in our experience, and these occurred principally
in "young' lesions of less than three years duration. It is apparent that there is a need for new drugs which might cure patients in whom neither gold nor bismuth was effective. While using chioramphenicolt in early syphilis and gonorrhea Neisseria (5) it seemed desirable to try it in chronic discoid lupus erythematosus. A preliminary report is offered. Thirteen cases are reported. Five have shown complete regression of lesions, one was transformed into the acute disseminated type, six became improved and one showed no improvement. REPORT OF CASES
M.
T. A
26 year old Negress, first seen June 21, 1949. There were five lesions of two years'
Placed on chioramphenicol capsules, one (250 mg.) four times a day. Treatment discontinued October 15, 1949, all lesions having involuted; she had taken 504 capsules. duration.
M. S. A 42 year old, white female, first seen in 1940. There were two lesions, one on the left buccal surface 3 cm. in diameter, and one on the nose. She had received in 1946, one injection of bismuth subsalicylate and twelve injections of gold sodium thiosulfate, without improvement. Thereafter, carbon dioxide snow was used. As the condition persisted, the patient discontinued treatment. Placed on cliloramphenicol June 30, 1949. She took one capsule every two hours (12 daily) for three weeks and one every four hours (5 daily) for fourteen weeks. The buccal lesion healed after 24 capsules. Treatment stopped October 17, both lesions having healed. Number of capsules: 742. A. C. A 61 year old Negress, first seen April 25, 1947 with numerous lesions present since
1936. She had received twelve treatments of bismuth subsalicylate without benefit. She was placed on chloramphenicol July 6, 1949, routine schedule (one capsule four times daily). There was no improvement, and treatment was stopped October 17, 1949 after taking 238
capsules.
M. R. A 42 year old Negress, was first seen August 4, 1949, having two les
and in the right ear which were present for three years. No previous treatment. Started on chioramphenicol; on August 2,5, she had taken 84 capsules Ljoi had cleared up. D. M. A 41 year old Negress first seen August 4, 1949 presenting 28 lesions, of 15 months' duration. She was placed on cliloramphenicol August 4, 1949. Six of the 28 lesions are im-
proved. The rest have completely cleared, leaving a smooth hyperpigmentation. Treatment was temporarily stopped on October 17, 1949. She had taken 280 capsules. * From
the Department of Dermatology, School of Medicine, University of Maryland. t This work was made possible through the courtesy of Parke, Davis & Company who supplied the chloramphenicol. Received for publication December 12, 1949. 309
310
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
F. J. A 41 year old Negro, first seen July 16, 1949. He had received three injections of bismuth without result. Began chloramphenicol August 9, and on October 15 had received
184 capsules. Of the nine lesions present, four have cleared up. The remaining five are improved.
K. B. A 34 year old, white female, first seen in 1933. She had received 77 intravenous injections of gold, 11 intramuscular injections of bismarsen, and 14 of bismuth subsalicylate.
Only cryotherapy and applications of liquefied phenol helped. On August 9, 1949 she returned with 2 active lesions on the buccal surface of the upper lip and on the vermillion border of the lower lip. Discharged October 18, 1949, having taken 250 capsules; both lesions had undergone involution. E. A. A 2,5 year old, white female, first seen September 7, 1945. She had received 12 injections of gold and 5 injections of bismuth. Bistrimate tablets were prescribed, which she took for eight months without benefit. Began chioramphenicol August 12, and was discharged October 14 as cured, having taken 252 capsules. M. L. A 28 year old, Negress, first seen August 23, 1949. There were seven lesions on her face and ears, present for five years. Urinalysis showed a trace of albumin. Placed on chlor-
amphenicol. On September 24, while on chloramphenicol, numerous well-defined, erythematous lesions had appeared over the entire body. She felt sick and weak, and the legs, ankles, feet and face were edematous. Temperature was 100°F. Blood pressure—132/78. Urinalysis—Albumin, four plus; Sugar, one plus. She had taken 140 capsules. She was hospitalized and a diagnosis of acute disseminated lupus erythematosus was made. Biopsy report has verified the diagnosis. Blood examination showed on September 26, Albumin— 3.93; Globulin—2.23; Urea nitrogen—lO; Hemoglobin—83%, 12.1 grams; Hematocrit—38;
Corrected sedimentation rate—2. Further chloramphenicol was given which the patient vomited. There now appeared numerous irregular shaped bullae conforming to the underlying lesions. Temperature rose to 102.4°F. On October 11, 1949 all joints were tender, and swollen. October 20, 1949 there was a four plus albuminuria with granular casts and white
and red cells; sugar, negative. Four days later there had developed an infarct in the base of the right lung. One week later there was an infarct in the base of the left lung. Blood examination on November 4 showed, Albumin—2.51; Globulin—3.19; Urea nitrogen—12; Hemoglobin—56%, 8.2 grams; Hematocrit—29; Corrected sedimentation rate—27. All blood cultures have been negative. All skin lesions have completely regressed.
P. B. A 45 year old Negress, had the condition since January, 1949. This patient had received para-aminobenzoic acid from April 23 to May 2, during which she received 182 grams. She had a rise in temperature ranging from 100 to 105°F. After two and one-half days of fever under para-aminobenzoic acid, the drug was discontinued. Temperature immediately fell to normal. She was given one injection of bismuth subsalicylate, but failed to return until August 23 when she was given chloramphenicol. On October 18, she had taken 182 capsules; all lesions had improved. G. B. A 35 year old, white female, first seen September 6, with several lesions on the vermillion border of the upper lip, the largest 3 x 6 mm. in diameter. Began chloramphenicol
therapy on this date. On October 17, she had taken 196 capsules. All but one lesion had involuted. C. B. A 35 year old, white female, first seen July 24, 1948, presenting lesions of seventeen
months' duration. She had had ultraviolet ray treatments and penicillin injections. She received eleven injections of bismuth subsalicylate and two injections of bismarsen, without
benefit. Cryotherapy gave a fair cosmetic result. She returned September 17, 1949, pre-
CHLORAMPHENICOL IN DISCOID LIJPIJS ERYTHEMATOSUS
311
senting five lesions on the right cheek. Placed on chloramphenieol and on October 17, 1949
had taken 104 capsules. All lesions are improved.
A. P. A 27 year old, white female, had the eruption five years. She had received five injections of bismuth and a similar number of injections of gold without benefit. Took bistrimate tablets for one month without improvement. Cryotherapy was then used with good results. She returned September 20, 1949 with two new lesions and was given chioramphenicol capsules. Up to October 14, 1949 she had taken 140 capsules and both lesions were improved. SUMMARY AND CONCLUSION
Thirteen patients having chronic discoid lupus erythematosus have been treated with ehioramphenicol, 250 milligrams per capsule, four times daily. One patient took one capsule
every two hours, day and night for three weeks and five daily thereafter. In five patients all lesions have completely regressed. In six, the lesions showed moderate to marked improvement. One patient developed the acute disseminated type of eruption. In one patient there was no improvement.
REFERENCES 1. FRANKLIN, JOHN L.: Treatment of lupus erythematosus with sanocrysin; Brit. J. Dermat., 46: 66, February 1934.
2. SMITH, A. G.: Gold and bismuth treatment of lupus erythematosus; Brit. J. Dermat., 46: 399, October 1934. 3. WRIGHT, CARROLL: Ten years experience in the treatment of lupus erythematosus with gold compounds; Arch. Dermat. Syph., 33: 413, March 1936. 4. Weiss, RICHARD S., CONRAD, ADOLPH H., CONRAD, ADOLPH H., JR. AND PFAFF, RICHARD
.
0.: Treatment of lupus erythematosus with bismarsen; Arch. Dermat. Syph., 44: 1009, December 1941.
H. M. AND ROBINSON, H. M., JR.: Chloramphenicol in the Treatment of Syphilis and Gonorrhea; South. M. J., November 1949.
RoBINsON,
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.