- Email: [email protected]
Yy CHROMOSOMAL CHIMÆRISM
590
connection, I wish
to
clarify
two
points
in relation to the
reovirus-3 system.
Yy
CHROMOSOMAL CHIMÆRISM
SiR,-Dr. Nuzzo and his colleagues (July 30) used the
1. It emphasises the importance of a ubiquitous virus (human, animal, plant, and insect) being the prime initiating agent for whatever changes may later occur in the host to result in autoimmune disease and/or neoplasia. 2. It offers an excellent opportunity to examine more closely the interesting issues raised by Professor Dameshek, Mr. Keast, and Dr. Papadimitriou, and myself. 1213 With regard to this second point, it now appears likely that two cell types rather than one may be involved in the reovirus-3 induction of murine lymphoma 2731/L and/or runting. Karyotype studies on 2731/L cells by Keast 14 indicate that
variation in length of the Y chromosome for exclusion of paternity. We have observed " Yy " chromosomal chimaensm in an infant with apparent graft-versus-host reaction following intrauterine transfusion for erythroblastosis foetalis. A male infant was born at 33 weeks’ gestation after receiving 3 intrauterine transfusions between 27 and 31 weeks’ gestation. Although he required 6 exchange transfusions at birth and several small booster transfusions over the next few weeks, he recovered and was discharged well at 7 weeks of age. A week later he was admitted to this hospital because of vomiting, two populations of cells predominate. And I 15 have shown diarrhoea, and jaundice. He was ill, with enlarged liver, and a that the 2731/L tumour carries a complement-fixing necrotic ulcer over the sacrum. Peripheral blood showed antigen reacting specifically with reovirus-3. On the pancytopenia with absent reticulocytes and granulocytes. other hand, a similar type of lymphoma (553) induced in the Bone-marrow smear showed no granulocytic precursors, but same strain of mice by the Schwartz-Beldotti method does not instead there were predominantly immature monocytes, and produce runting nor does it contain the reovirus-3 complement- many histiocytes which had phagocytosed intact lymphocytes. fixing antigen.16 Finally Keast and I 17 have reported on an Supportive therapy was accompanied by gradual clinical and interesting light mitochondrial fraction of the 2731/L murine haematological improvement. A month after admission, howlymphoma cell. This fraction may cause death, runting, and/or ever, he got Pseudomonas aeruginosa bronchopneumonia and lymphomas. Ribonuclease treatment may remove both lethal died shortly thereafter. and runting capacities, while leaving the tumorigenic activity Culture of peripheral-blood lymphocytes obtained at 10 intact. Desoxyribonuclease treatment does not remove the weeks of age, and of thymic tissue obtained at necropsy showed lethal factors, although a few survivors appear as runts without two cell populations, distinguished by variations in length of lymphomas. the Y chromosome-" Yy " chimserism. The Y chromosomes These observations, at least, show that the Stanley-Walters of the father were very long, whereas those of the donor of the and Schwartz-Beldotti observations are by no means incomfirst intrauterine transfusion were short. It is apparent that the patible, and may eventually be better understood in terms of donor leucocytes established a graft in the foetus at an age cellular and macromolecular biology. when it had not achieved full immunological competence. Department of Microbiology, To avert this complication of fatal transfusion we urge that School of Medicine, efforts be made to render such blood free of leucocytes before University of Western Australia, Victoria Square, Perth, administration. N. F. STANLEY. Western Australia. A complete report of this case is in preparation. This work was supported in part by U.S. Public Health Service grants HD-1313 and AM-9112 from the National Institutes of Health.
GASTRIC CARCINOMA AND EARLY PERNICIOUS ANÆMIA SIR,-Dr. Shearman and his colleagues (Aug. 20) provide evidence that patients with gastric carcinoma have a high incidence of achlorhydria and hypochlorhydria, and thus, by inference, of atrophic gastritis."In 7 of their 35 patients failure of secretion from atrophic gastric mucosa led to frank or latent pernicious anaemia, and in another 5 patients low serumvitamin-Bn levels were found which were not, however, in the
pernicious-anaemia range. Accepting that their findings indicate an association between atrophic gastritis and carcinoma of the stomach, what is it about atrophic gastric mucosa that predisposes to cancer ? To the histologist atrophic mucosa looks thin because of atrophy of both glandular and epithelial parts of the mucosa. The static microscopic appearance does not, however, reveal the dynamic state of surface epithelial cells in this tissue. My co-workers and I have published evidence 19 that the production and loss (turnover) of gastric epithelial cells in atrophic gastritis, whether or not associated with pernicious anxmia, is more rapid than normal. It is perhaps this hyperdynamic turnover of surface epithelial cells in atrophic gastritis that is premalignant and is a factor predisposing patients with pernicious anaemia to carcinoma of the stomach. Carcinoma is after all " A malignant new growth made up of epithelial cells..." 20; a more intimate knowledge of these cells may reveal clues to the pathogenesis of gastric cancer. St. Thomas’s Hospital, D. N. CROFT. London S.E.1. 12. Stanley, N. F. ibid. p. 961. 13. Stanley, N. F., Walters, M. N.-I. ibid. p. 962. 14. Keast, D. Expl Cell Res. (in the press). 15. Stanley, N. F. Proceedings of the Kampala Conference on the Chemotherapy of Burkitt’s Lymphona, January, 1966. 16. Keast, D., Stanley, N. F. Unpublished. 17. Stanley, N. F., Keast, D. Perspectives in Virology V (in the press). 18. Bock, O. A. A., Richards, W. C. D., Witts, L. J. Gut, 1963, 4, 112. 19. Croft, D. N., Pollock, D. J., Coghill, N. F. ibid. 1966, 7, 333. 20. Dorland’s Illustrated Medical Dictionary. London, 1965.
St.
Christopher’s Hospital for Children and the Department of Pediatrics, Temple University School of Medicine, Philadelphia, Pennsylvania 19133.
J. LAWRENCE NAIMAN HOPE H. PUNNETT MARIE L. DESTINE HAROLD W. LISCHNER.
DOUBLE Ph1 CHROMOSOMES IN LEUKÆMIA SIR,- The two patients with atypical chronic granulocytic leukxmia reported by Dr. Erkman and her colleagues’I exhibited, on direct bone-marrow preparations, double Ph’ chromosomes in hyperdiploid cells only, whereas one Ph’ chromosome was demonstrated in cells with normal diploid number. Chromosomal analysis performed by the direct method2 in the two patients we have reported 3--one with " blast crisis" of chronic granulocytic leukaemia and the other with acute granulocytic leukxmia-revealed two Phl chromosomes in 100% of the bone-marrow cells. This finding was present not only in hyperdiploid cells-similar results have been presented from other laboratories 4-s-but also in diploid and even hypodiploid cells, a finding which has never been described before.3 The patient with chronic granulocytic leukaemia reported by and Woodliff and Douganeventually Dougan and Woodliff succumbed in " blast crisis " after a lapse of 17 months. Hyperdiploid cells contained two PhI chromosomes, whereas only one PhI chromosome was found in cells containing the 1. Erkman, B., Crookston, J., Conen, P. E. Lancet, 1966, i, 368. 2. Kiossoglou, K. A., Mitus, W. J., Dameshek, W. Am. J. clin. Path. 1964. 41, 183. 3. Kiossoglou, K. A., Mitus, W. J., Dameshek, W. Lancet, 1965, ii, 665 4. Kemp, N. H., Stafford, J. L., Tanner, R. Br. med. J. 1964, i, 1010. 5. Hammouda, F., Quaglino, D., Hayhoe, F. G. J. ibid. p. 1275. 6. de Grouchy, J., de Nava, C., Bilski-Pasquier, G. Now. Revue fr. H 1965, 5, 69. 7. Dougan, L., Woodliff, H. J. Nature, Lond. 1965, 205, 405. 8. Woodliff, H. J., Dougan, L. Lancet, 1966, i, 771.
connection, I wish
to
clarify
two
points
in relation to the
reovirus-3 system.
Yy
CHROMOSOMAL CHIMÆRISM
SiR,-Dr. Nuzzo and his colleagues (July 30) used the
1. It emphasises the importance of a ubiquitous virus (human, animal, plant, and insect) being the prime initiating agent for whatever changes may later occur in the host to result in autoimmune disease and/or neoplasia. 2. It offers an excellent opportunity to examine more closely the interesting issues raised by Professor Dameshek, Mr. Keast, and Dr. Papadimitriou, and myself. 1213 With regard to this second point, it now appears likely that two cell types rather than one may be involved in the reovirus-3 induction of murine lymphoma 2731/L and/or runting. Karyotype studies on 2731/L cells by Keast 14 indicate that
variation in length of the Y chromosome for exclusion of paternity. We have observed " Yy " chromosomal chimaensm in an infant with apparent graft-versus-host reaction following intrauterine transfusion for erythroblastosis foetalis. A male infant was born at 33 weeks’ gestation after receiving 3 intrauterine transfusions between 27 and 31 weeks’ gestation. Although he required 6 exchange transfusions at birth and several small booster transfusions over the next few weeks, he recovered and was discharged well at 7 weeks of age. A week later he was admitted to this hospital because of vomiting, two populations of cells predominate. And I 15 have shown diarrhoea, and jaundice. He was ill, with enlarged liver, and a that the 2731/L tumour carries a complement-fixing necrotic ulcer over the sacrum. Peripheral blood showed antigen reacting specifically with reovirus-3. On the pancytopenia with absent reticulocytes and granulocytes. other hand, a similar type of lymphoma (553) induced in the Bone-marrow smear showed no granulocytic precursors, but same strain of mice by the Schwartz-Beldotti method does not instead there were predominantly immature monocytes, and produce runting nor does it contain the reovirus-3 complement- many histiocytes which had phagocytosed intact lymphocytes. fixing antigen.16 Finally Keast and I 17 have reported on an Supportive therapy was accompanied by gradual clinical and interesting light mitochondrial fraction of the 2731/L murine haematological improvement. A month after admission, howlymphoma cell. This fraction may cause death, runting, and/or ever, he got Pseudomonas aeruginosa bronchopneumonia and lymphomas. Ribonuclease treatment may remove both lethal died shortly thereafter. and runting capacities, while leaving the tumorigenic activity Culture of peripheral-blood lymphocytes obtained at 10 intact. Desoxyribonuclease treatment does not remove the weeks of age, and of thymic tissue obtained at necropsy showed lethal factors, although a few survivors appear as runts without two cell populations, distinguished by variations in length of lymphomas. the Y chromosome-" Yy " chimserism. The Y chromosomes These observations, at least, show that the Stanley-Walters of the father were very long, whereas those of the donor of the and Schwartz-Beldotti observations are by no means incomfirst intrauterine transfusion were short. It is apparent that the patible, and may eventually be better understood in terms of donor leucocytes established a graft in the foetus at an age cellular and macromolecular biology. when it had not achieved full immunological competence. Department of Microbiology, To avert this complication of fatal transfusion we urge that School of Medicine, efforts be made to render such blood free of leucocytes before University of Western Australia, Victoria Square, Perth, administration. N. F. STANLEY. Western Australia. A complete report of this case is in preparation. This work was supported in part by U.S. Public Health Service grants HD-1313 and AM-9112 from the National Institutes of Health.
GASTRIC CARCINOMA AND EARLY PERNICIOUS ANÆMIA SIR,-Dr. Shearman and his colleagues (Aug. 20) provide evidence that patients with gastric carcinoma have a high incidence of achlorhydria and hypochlorhydria, and thus, by inference, of atrophic gastritis."In 7 of their 35 patients failure of secretion from atrophic gastric mucosa led to frank or latent pernicious anaemia, and in another 5 patients low serumvitamin-Bn levels were found which were not, however, in the
pernicious-anaemia range. Accepting that their findings indicate an association between atrophic gastritis and carcinoma of the stomach, what is it about atrophic gastric mucosa that predisposes to cancer ? To the histologist atrophic mucosa looks thin because of atrophy of both glandular and epithelial parts of the mucosa. The static microscopic appearance does not, however, reveal the dynamic state of surface epithelial cells in this tissue. My co-workers and I have published evidence 19 that the production and loss (turnover) of gastric epithelial cells in atrophic gastritis, whether or not associated with pernicious anxmia, is more rapid than normal. It is perhaps this hyperdynamic turnover of surface epithelial cells in atrophic gastritis that is premalignant and is a factor predisposing patients with pernicious anaemia to carcinoma of the stomach. Carcinoma is after all " A malignant new growth made up of epithelial cells..." 20; a more intimate knowledge of these cells may reveal clues to the pathogenesis of gastric cancer. St. Thomas’s Hospital, D. N. CROFT. London S.E.1. 12. Stanley, N. F. ibid. p. 961. 13. Stanley, N. F., Walters, M. N.-I. ibid. p. 962. 14. Keast, D. Expl Cell Res. (in the press). 15. Stanley, N. F. Proceedings of the Kampala Conference on the Chemotherapy of Burkitt’s Lymphona, January, 1966. 16. Keast, D., Stanley, N. F. Unpublished. 17. Stanley, N. F., Keast, D. Perspectives in Virology V (in the press). 18. Bock, O. A. A., Richards, W. C. D., Witts, L. J. Gut, 1963, 4, 112. 19. Croft, D. N., Pollock, D. J., Coghill, N. F. ibid. 1966, 7, 333. 20. Dorland’s Illustrated Medical Dictionary. London, 1965.
St.
Christopher’s Hospital for Children and the Department of Pediatrics, Temple University School of Medicine, Philadelphia, Pennsylvania 19133.
J. LAWRENCE NAIMAN HOPE H. PUNNETT MARIE L. DESTINE HAROLD W. LISCHNER.
DOUBLE Ph1 CHROMOSOMES IN LEUKÆMIA SIR,- The two patients with atypical chronic granulocytic leukxmia reported by Dr. Erkman and her colleagues’I exhibited, on direct bone-marrow preparations, double Ph’ chromosomes in hyperdiploid cells only, whereas one Ph’ chromosome was demonstrated in cells with normal diploid number. Chromosomal analysis performed by the direct method2 in the two patients we have reported 3--one with " blast crisis" of chronic granulocytic leukaemia and the other with acute granulocytic leukxmia-revealed two Phl chromosomes in 100% of the bone-marrow cells. This finding was present not only in hyperdiploid cells-similar results have been presented from other laboratories 4-s-but also in diploid and even hypodiploid cells, a finding which has never been described before.3 The patient with chronic granulocytic leukaemia reported by and Woodliff and Douganeventually Dougan and Woodliff succumbed in " blast crisis " after a lapse of 17 months. Hyperdiploid cells contained two PhI chromosomes, whereas only one PhI chromosome was found in cells containing the 1. Erkman, B., Crookston, J., Conen, P. E. Lancet, 1966, i, 368. 2. Kiossoglou, K. A., Mitus, W. J., Dameshek, W. Am. J. clin. Path. 1964. 41, 183. 3. Kiossoglou, K. A., Mitus, W. J., Dameshek, W. Lancet, 1965, ii, 665 4. Kemp, N. H., Stafford, J. L., Tanner, R. Br. med. J. 1964, i, 1010. 5. Hammouda, F., Quaglino, D., Hayhoe, F. G. J. ibid. p. 1275. 6. de Grouchy, J., de Nava, C., Bilski-Pasquier, G. Now. Revue fr. H 1965, 5, 69. 7. Dougan, L., Woodliff, H. J. Nature, Lond. 1965, 205, 405. 8. Woodliff, H. J., Dougan, L. Lancet, 1966, i, 771.