561 these cultures were similar to those in the autolomixed leucocyte culture (see table). On the other hand, gous vigorous stimulation was observed in allogeneic cultures containing non-spermatozoal seminal cells. We conclude that spermatozoa per se are not responsible for the stimulation observed in mixed sperm/leucocyte cultures. All semen samples contain non-spermatozoal cells, but the numbers vary considerably between donors and at different times in the one donor. It is not surprising that variable levels of stimulation are a common feature of mixed sperm/leucocyte cultures, since the degree of stimulation is likely to be modulated not only by the numbers of non-spermatozoal cells but also by the types of cells present in the semen. Further studies are being undertaken to determine the types of cell present in semen, and their capacity to induce immunological responses, and to investigate the stimulatory ability of spermatozoa in secondary mixed sperm/leucocyte cultures. I. S. MISKO B. BOETTCHER Department of Biological Sciences, T. K. ROBERTS University of Newcastle,
poration in
New South Wales
2308, Australia
D. J. KAY
PROSTAGLANDINS AND ACTINIC CANCER
SiR,--Greaves and others have shown that prostaglandins (P.G.) are increased in human skin after exposure to ultraviolet light in the "sunburn" spectrum (290-320 nm).l,2 Since there is evidence that p.G.E reduces proliferative activity in the epidermis, Professor Greaves (Jan. 28, p. 189) proposes that this substance may reduce the vulnerability of epidermal cells to the mutagenic effects of ultraviolet light. We have also been interested in the relation between p.G.E formation and skin malignancies, but would suggest that the inhibitory effect of p.G.E on epidermal proliferation may be more than countered by other effects of this substance. Immunological surveillance seems to play an important role in limiting premalignant and malignant lesions of the skin. This is suggested by the increased incidence of skin cancers in immunosuppressed patients and by the increased incidence of light-induced cancers in immunosuppressed laboratory animals.3,4 Acute exposure to ultraviolet light greatly reduces the ability of mice to reject transplanted skin tumours.’·6 Prostaglandins, particularly p.G.E2, suppress immune function and may be the mediator by which suppressor cells exert their effects on immune responses. 1,8 We suggest that the p.G.E2 released in the skin after irradiation with ultraviolet light may suppress immune responses in the skin and interfere with normal immunological surveillance. This effect probably completely offsets any protective effects of prostaglandin formation. Suppression of immune responses by ultraviolet-evoked prostaglandin formation would explain the increased incidence of human skin cancers in the months of more intense and more prolonged light exposure." It could also explain the more severe manifestations of viral exanthems in light-exposed skin. 111 We agree with Greaves that further study of the relation between prostaglandin formation and actinic cancer is indicated, but the role of immune responses to skin tumours and 1. Greaves, M. W., Sonderguard, J. S. J. invest. Derm. 1970, 54, 365. 2. Snyder, D. S., Eaglestein, W. ibid. 1973, 60, 110 3. Maize, J. C. J. Am. med.Ass. 1977, 237, 1857. 4. Koranda, F. C., Loeffler, R. T., Koranda, D. M., Penn, I. J. invest. Derm. 1976, 66, 269. 5. Kripke, M. L. J. natn. Cancer Inst. 1974, 53, 1333. 6. Spellman, C. W., Woodward, J. G., Daynes, R. A. Transplantation, 1977, 24, 112. 7. Goldyne, M. E. Int. J. Derm. 1977, 16, 701. 8. Goodwin, J. S., Bankhurst, A. D., Messner, R. P. J. exp. Med. 1977, 146, 1719.
the
these responses
should
by prostaglandins
Department of Medicine, School of Medicine, University of New Mexico, Albuquerque, New Mexico 87131, U.S.A.
EDGAR B. SMITH WILLIAM V. MASON JAMES S. GOODWIN
AFLATOXIN B1 AND REYE’S SYNDROME
SiR,—The aetiology of Reye’s syndrome,’ a distinct clinical entity characterised by acute encephalopathy and fatty degeneration of the viscera, remains obscure. Numerous aetiological agents including viruses, fungi, toxins, and drugs have all been incriminated but no direct cause-and-effect relationship has been established. The hepatotoxic effect of anatoxin B, and the isolation of aflatoxin Bl at necropsy from the tissue of 22 of 23 cases of Reye’s syndrome in Northern Thailand have stimulated interest in the possible role of aflatoxin B, in the aetiology of the syndrome. Aflatoxins have been associated at necropsy with Reye’s syndrome in New Zealand (2 cases),3 Czechoslovakia (2 cases),4 and in the United States (1 case).! We know of no previously reported cases in which aflatoxin B,was found in the blood of patients with Reye’s syndrome during the acute phase of the disease. We have seen two such cases. cases were preceded by viral illness and the patients vomiting, hyperventilation, hepatomegaly, decerebrate posturing, seizures, and coma. Serum glutamic-oxaloacetic transaminase was 396-888 and 585-616 units/ml respectively; lactic dehydrogenase was 897-1224 and 1653-5820 units/ml respectively; bloodammonia was 200-720 and 175-229 fLgldl respectively; bloodglucose was 39 and 141 mg/ml respectively; and aflatoxin B6 was 11.93 and 31.3 ng/ml respectively. Both children died shortly after admission. Reye’s syndrome was confirmed at necropsy in case 1. Necropsy was denied in
Both showed
2. We now have studies under way cance of these findings. Departments of Pediatrics and Pharmacology, University of Mississippi case
School of Medicine, Jackson, Mississippi 39216, U.S.A.
to
determine the
signifi-
GWENDOLYN R. HOGAN NELL J. RYAN A. WALLACE HAYES
ORIGIN OF MONOCLONAL ANTIBODIES
SiR,-In your editorial of Feb. 4 (p. 252)
you cite us as havfound a monoclonal antistreptolysin 0 antibody in a patient only a few months after the onset of symptoms, stating that such a time interval would not be incompatible with a monoclonal immune response. In fact this interval was no more than three weeks in one of our two cases; in the other one the abnormal component was discovered much later. Could an observable monoclonal immune response be mounted in such a short period? Hardly any data are available on this point. Radi et al. detected monoclonal antibodies against human serum in two bone-marrow depleted and reconstituted monkeys about ten days after challenge. However, in
ing
-
1. 2.
Reye, R. D. K., Morgan, G., Baral, J. Lancet, 1963, ii, 749. Shank, R. C., Johnsen, D. O., Tanticharoenyos, P., Wooding, W. W., Bourgeois, C. H. Toxicol. appl. Pharmacol. 1971, 20, 227. 3. Becroft, D. M. O., Webster, D. R. Brit. med. J. 1972, iv, 117. 4. Dvorackova, I., Brodsky, P., Cerman, J. Nutr. Reports Int. 1974, 10, 89. 5. Chaves-Carballo, E., Ellefson, R. D., Gomez, M. R. Mayo Clin. Proc. 1976, 6.
51, 48. Unger, P. D., Mehendale, 1977, 41, 523.
7. 8.
Lustermans, F. A. T., Klein, F. J. clin. Path. 1977, 30, 851. Rádl, J., van den Berg, P., Voormolen, M., Hendriks, W.
9. Goodwin,
J. S., Selinger, D., Messner, R. P., Reed, W. Infect Immun. 1978, (in the press). 10. Freeman, R. G., Knox, J. M. Archs Derm. 1970, 101, 403. 11. Gilchrest, B., Baden, H. P. Pediatrics, 1974, 54, 136.
suppression of neglected.
not be
U. W. Clin.
H.
M., Hayes, A. W. Toxicol. Appl. Pharmacol.
exp. Immun. 1974, 16, 259.
D. H.,
Schaefer,
poration in
New South Wales
2308, Australia
D. J. KAY
PROSTAGLANDINS AND ACTINIC CANCER
SiR,--Greaves and others have shown that prostaglandins (P.G.) are increased in human skin after exposure to ultraviolet light in the "sunburn" spectrum (290-320 nm).l,2 Since there is evidence that p.G.E reduces proliferative activity in the epidermis, Professor Greaves (Jan. 28, p. 189) proposes that this substance may reduce the vulnerability of epidermal cells to the mutagenic effects of ultraviolet light. We have also been interested in the relation between p.G.E formation and skin malignancies, but would suggest that the inhibitory effect of p.G.E on epidermal proliferation may be more than countered by other effects of this substance. Immunological surveillance seems to play an important role in limiting premalignant and malignant lesions of the skin. This is suggested by the increased incidence of skin cancers in immunosuppressed patients and by the increased incidence of light-induced cancers in immunosuppressed laboratory animals.3,4 Acute exposure to ultraviolet light greatly reduces the ability of mice to reject transplanted skin tumours.’·6 Prostaglandins, particularly p.G.E2, suppress immune function and may be the mediator by which suppressor cells exert their effects on immune responses. 1,8 We suggest that the p.G.E2 released in the skin after irradiation with ultraviolet light may suppress immune responses in the skin and interfere with normal immunological surveillance. This effect probably completely offsets any protective effects of prostaglandin formation. Suppression of immune responses by ultraviolet-evoked prostaglandin formation would explain the increased incidence of human skin cancers in the months of more intense and more prolonged light exposure." It could also explain the more severe manifestations of viral exanthems in light-exposed skin. 111 We agree with Greaves that further study of the relation between prostaglandin formation and actinic cancer is indicated, but the role of immune responses to skin tumours and 1. Greaves, M. W., Sonderguard, J. S. J. invest. Derm. 1970, 54, 365. 2. Snyder, D. S., Eaglestein, W. ibid. 1973, 60, 110 3. Maize, J. C. J. Am. med.Ass. 1977, 237, 1857. 4. Koranda, F. C., Loeffler, R. T., Koranda, D. M., Penn, I. J. invest. Derm. 1976, 66, 269. 5. Kripke, M. L. J. natn. Cancer Inst. 1974, 53, 1333. 6. Spellman, C. W., Woodward, J. G., Daynes, R. A. Transplantation, 1977, 24, 112. 7. Goldyne, M. E. Int. J. Derm. 1977, 16, 701. 8. Goodwin, J. S., Bankhurst, A. D., Messner, R. P. J. exp. Med. 1977, 146, 1719.
the
these responses
should
by prostaglandins
Department of Medicine, School of Medicine, University of New Mexico, Albuquerque, New Mexico 87131, U.S.A.
EDGAR B. SMITH WILLIAM V. MASON JAMES S. GOODWIN
AFLATOXIN B1 AND REYE’S SYNDROME
SiR,—The aetiology of Reye’s syndrome,’ a distinct clinical entity characterised by acute encephalopathy and fatty degeneration of the viscera, remains obscure. Numerous aetiological agents including viruses, fungi, toxins, and drugs have all been incriminated but no direct cause-and-effect relationship has been established. The hepatotoxic effect of anatoxin B, and the isolation of aflatoxin Bl at necropsy from the tissue of 22 of 23 cases of Reye’s syndrome in Northern Thailand have stimulated interest in the possible role of aflatoxin B, in the aetiology of the syndrome. Aflatoxins have been associated at necropsy with Reye’s syndrome in New Zealand (2 cases),3 Czechoslovakia (2 cases),4 and in the United States (1 case).! We know of no previously reported cases in which aflatoxin B,was found in the blood of patients with Reye’s syndrome during the acute phase of the disease. We have seen two such cases. cases were preceded by viral illness and the patients vomiting, hyperventilation, hepatomegaly, decerebrate posturing, seizures, and coma. Serum glutamic-oxaloacetic transaminase was 396-888 and 585-616 units/ml respectively; lactic dehydrogenase was 897-1224 and 1653-5820 units/ml respectively; bloodammonia was 200-720 and 175-229 fLgldl respectively; bloodglucose was 39 and 141 mg/ml respectively; and aflatoxin B6 was 11.93 and 31.3 ng/ml respectively. Both children died shortly after admission. Reye’s syndrome was confirmed at necropsy in case 1. Necropsy was denied in
Both showed
2. We now have studies under way cance of these findings. Departments of Pediatrics and Pharmacology, University of Mississippi case
School of Medicine, Jackson, Mississippi 39216, U.S.A.
to
determine the
signifi-
GWENDOLYN R. HOGAN NELL J. RYAN A. WALLACE HAYES
ORIGIN OF MONOCLONAL ANTIBODIES
SiR,-In your editorial of Feb. 4 (p. 252)
you cite us as havfound a monoclonal antistreptolysin 0 antibody in a patient only a few months after the onset of symptoms, stating that such a time interval would not be incompatible with a monoclonal immune response. In fact this interval was no more than three weeks in one of our two cases; in the other one the abnormal component was discovered much later. Could an observable monoclonal immune response be mounted in such a short period? Hardly any data are available on this point. Radi et al. detected monoclonal antibodies against human serum in two bone-marrow depleted and reconstituted monkeys about ten days after challenge. However, in
ing
-
1. 2.
Reye, R. D. K., Morgan, G., Baral, J. Lancet, 1963, ii, 749. Shank, R. C., Johnsen, D. O., Tanticharoenyos, P., Wooding, W. W., Bourgeois, C. H. Toxicol. appl. Pharmacol. 1971, 20, 227. 3. Becroft, D. M. O., Webster, D. R. Brit. med. J. 1972, iv, 117. 4. Dvorackova, I., Brodsky, P., Cerman, J. Nutr. Reports Int. 1974, 10, 89. 5. Chaves-Carballo, E., Ellefson, R. D., Gomez, M. R. Mayo Clin. Proc. 1976, 6.
51, 48. Unger, P. D., Mehendale, 1977, 41, 523.
7. 8.
Lustermans, F. A. T., Klein, F. J. clin. Path. 1977, 30, 851. Rádl, J., van den Berg, P., Voormolen, M., Hendriks, W.
9. Goodwin,
J. S., Selinger, D., Messner, R. P., Reed, W. Infect Immun. 1978, (in the press). 10. Freeman, R. G., Knox, J. M. Archs Derm. 1970, 101, 403. 11. Gilchrest, B., Baden, H. P. Pediatrics, 1974, 54, 136.
suppression of neglected.
not be
U. W. Clin.
H.
M., Hayes, A. W. Toxicol. Appl. Pharmacol.
exp. Immun. 1974, 16, 259.
D. H.,
Schaefer,
