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CHROMOSOME BREAKAGE IN ATAXIA-TELANGIECTASIA
618 associated with, acute myeloid leuksemia have been reported recently,5-’ and the relationship between P.N.H. and acute leukaemia has been discussed with reference to the myeloproliferative disorders.Cytogenetic abnormalities similar those in our case have been observed in some cases of leukaemia 9,10 and its allied disorders," and in myeloOur proliferative disorders other than leukaemia.12,13 cytogenic findings suggest that P.N.H. may be one of the myeloproliferative disorders; and they further suggest the need for continued observation of patients with P.N.H. for the development of leuksemia. Low alkaline-phosphatase activity in the neutrophils of this patient may be related to the minute chromosome, as in cases of chronic myeloid leukaemia.14
to
This work was supported in part by Energy Agency (contract no. 557/RB). Department of Medicine, Research Institute for Nuclear Medicine and Biology, Hiroshima University. Red Cross Hospital,
Hiroshima, Japan.
Department Genetics, National Institute of Nutrition, Mexico. 5. 6. 7. 8. 9. 10. 11.
lymphoid) are taken to reject
skin responses to purified protein derivative (P.P.D.), dinitrochlorobenzene (D.N.C.B.), and dinitrofluorobenzene (D.N.F.B.).1-5 The response of peripheral lymphocytes to phytohasmagglutinin (P.H.A.)-which has been shown to reflect the integrity of the thymus-dependent system of
TAISO TSUCHIMOTO YUKIFUMI ISHII HARUTO UCHINO. SHOZO INOUE.
RUBÉN LISKER AZYADÉH COBO.
Holden, D., Lichtman, H. Blood, 1969, 33, 283. Jenkins, D. E., Jr., Hartmann, R. C. ibid. p. 274. Kaufmann, R. W., Schechter, G. P., McFarland, W. ibid. p. 287. Dameshek, W. ibid, p. 263. Nowell, P. C., Hungerford, A. L. Science, N.Y. 1960, 132, 1497. Sandberg, A. A., Ishihara, T., Kikuchi, Y., Crosswhite, L. H. Ann. N.Y. Acad. Sci. 1964, 113, 663. Rowley, J. D., Blaisdell, R. K., Jacobson, L. O. Blood, 1966, 27, 782.
Freireich, E. J., Whang, J., Tjio, J. H., Levin, R. H., Brittin, G. M., Frei, E. Clin. Res. 1964, 12, 284. 13. Jackson, J. G., Higgins, L. C. Archs intern. Med. 1967, 119, 403. 14. Alter, A. A., Lee, S. L., Pourfar, M., Dobkin, G. J. clin. Invest. 1962, 41, 1341. 15. Hecht, F., Koler, R., Rigas, D., Dahnke, G., Case, M., Tisdale, V., Miller, R. Lancet, 1966, ii, 1193. 16. Hecht, F., Case, M. Proceedings of a meeting of the American Society of Human Genetics, San Francisco, California, Oct. 1-4,
of leucocyte cultures from patients with tumours and from controls. Each dot represents the average uptake of three cultures. The ranges shown represent the mean 1 standard deviation (S.D.), and the mean ± twice the standard error (S.E.)
Tritiated-thymidine uptake (c.p.oi.)
lymphocytes 6-has been thoroughly studied in patients with lymphoid malignant disease, but is a controversial matter in patients with non-lymphoid tumours. 1-9 We have studied the P.H.A. response in 46 patients with a large variety of non-lymphoid tumours and in 28 age-matched controls. findings reflect a distinct deficiency of this form of lymphoid-cell response in patients with non-lymphoid neoplastic disease (see accompanying figure), and suggest that the degree of deficit may be related to the extent of the neoplasia. Our
Pediatric Research Laboratories and Department of Pediatrics, University of Minnesota,
Mineapolis, Minnesota 55455. 1. 2.
12.
1969.
manifested by prolongation of the time a graft, and poor delayed-hypersensitivity
the International Atomic
CHROMOSOME BREAKAGE IN ATAXIA-TELANGIECTASIA SIR,-In 1966, Hecht et al. described 3 patients with ataxia-telangiectasia in whose blood lymphocytes there was a high frequency (20 to 30%) of chromosome breakage.15 A recent follow-up study of one of these patients 16 revealed that structural chromosome abnormalities persisted in the lymphocytes but were absent in the bone-marrow and fibroblasts. We have recently seen an 8-year-old girl with a classic picture of ataxia-telangiectasia; and chromosome studies were done on the blood and bone-marrow. In a peripheralblood culture stimulated with phytohasmagglutinin (P.H.A.), 60 cells in metaphase were analysed under the microscope and chromosome breaks were observed in 22 (36-6%). They were present in one or two chromosomes of any given cell, did not appear to have any predilection for a particular chromosome group, were mostly of the single chromatid type, and no major rearrangements were seen. A direct bone-marrow chromosome analysis was performed: of 12 cells suitable for study, 4 had chromosome breaks of the single-chromatid type. The percentage of chromosome breaks in this patient’s blood and bone-marrow is much higher than that in our controls (which is around 2-8%), and can thus be regarded as definitely abnormal. The presence of chromosome abnormalities in the bone-marrow of patients with this syndrome have not been reported previously and are therefore of special interest. The patient has at present no signs of lymphoreticular malignant disease, and the blood-picture is normal. of
LYMPHOCYTE RESPONSE TO P.H.A. IN PATIENTS WITH NON-LYMPHOID TUMOURS SIR,-Deficiencies of cell-mediated immune responses in patients with malignant disease (lymphoid and non-
3. 4. 5. 6. 7. 8. 9.
DAVID B. GARRIOCH ROBERT A. GOOD RICHARD A. GATTI.
Logan, J. New Z. med. J. 1956, 55, 408. Schier, W. W., Roth, A., Ostroff, G., Schrift, M. H. Am. J. Med. 1956, 20, 94. Kelly, W. D., Good, R. A., Varco, R. L. Surgery Gynec. Obstet. 1958, 107, 565. Grace, J. T., Kondo, T. Ann. Surg. 1958, 148, 633. Southam, C. M. Cancer Res. 1960, 20, 271. Elves, M., Roath, S., Israels, M. C. G. Lancet, 1963, i, 806. Silk, M. Cancer, N. Y. 1967, 20, 2088. Nelson, H. S. J. Natn. Cancer Inst. 1969, 42, 765. Golob, E. K., Israsena, T., Quatrale, A. C., Becker, K. L. Cancer, N.Y. 1969, 23, 306.
to
This work was supported in part by Energy Agency (contract no. 557/RB). Department of Medicine, Research Institute for Nuclear Medicine and Biology, Hiroshima University. Red Cross Hospital,
Hiroshima, Japan.
Department Genetics, National Institute of Nutrition, Mexico. 5. 6. 7. 8. 9. 10. 11.
lymphoid) are taken to reject
skin responses to purified protein derivative (P.P.D.), dinitrochlorobenzene (D.N.C.B.), and dinitrofluorobenzene (D.N.F.B.).1-5 The response of peripheral lymphocytes to phytohasmagglutinin (P.H.A.)-which has been shown to reflect the integrity of the thymus-dependent system of
TAISO TSUCHIMOTO YUKIFUMI ISHII HARUTO UCHINO. SHOZO INOUE.
RUBÉN LISKER AZYADÉH COBO.
Holden, D., Lichtman, H. Blood, 1969, 33, 283. Jenkins, D. E., Jr., Hartmann, R. C. ibid. p. 274. Kaufmann, R. W., Schechter, G. P., McFarland, W. ibid. p. 287. Dameshek, W. ibid, p. 263. Nowell, P. C., Hungerford, A. L. Science, N.Y. 1960, 132, 1497. Sandberg, A. A., Ishihara, T., Kikuchi, Y., Crosswhite, L. H. Ann. N.Y. Acad. Sci. 1964, 113, 663. Rowley, J. D., Blaisdell, R. K., Jacobson, L. O. Blood, 1966, 27, 782.
Freireich, E. J., Whang, J., Tjio, J. H., Levin, R. H., Brittin, G. M., Frei, E. Clin. Res. 1964, 12, 284. 13. Jackson, J. G., Higgins, L. C. Archs intern. Med. 1967, 119, 403. 14. Alter, A. A., Lee, S. L., Pourfar, M., Dobkin, G. J. clin. Invest. 1962, 41, 1341. 15. Hecht, F., Koler, R., Rigas, D., Dahnke, G., Case, M., Tisdale, V., Miller, R. Lancet, 1966, ii, 1193. 16. Hecht, F., Case, M. Proceedings of a meeting of the American Society of Human Genetics, San Francisco, California, Oct. 1-4,
of leucocyte cultures from patients with tumours and from controls. Each dot represents the average uptake of three cultures. The ranges shown represent the mean 1 standard deviation (S.D.), and the mean ± twice the standard error (S.E.)
Tritiated-thymidine uptake (c.p.oi.)
lymphocytes 6-has been thoroughly studied in patients with lymphoid malignant disease, but is a controversial matter in patients with non-lymphoid tumours. 1-9 We have studied the P.H.A. response in 46 patients with a large variety of non-lymphoid tumours and in 28 age-matched controls. findings reflect a distinct deficiency of this form of lymphoid-cell response in patients with non-lymphoid neoplastic disease (see accompanying figure), and suggest that the degree of deficit may be related to the extent of the neoplasia. Our
Pediatric Research Laboratories and Department of Pediatrics, University of Minnesota,
Mineapolis, Minnesota 55455. 1. 2.
12.
1969.
manifested by prolongation of the time a graft, and poor delayed-hypersensitivity
the International Atomic
CHROMOSOME BREAKAGE IN ATAXIA-TELANGIECTASIA SIR,-In 1966, Hecht et al. described 3 patients with ataxia-telangiectasia in whose blood lymphocytes there was a high frequency (20 to 30%) of chromosome breakage.15 A recent follow-up study of one of these patients 16 revealed that structural chromosome abnormalities persisted in the lymphocytes but were absent in the bone-marrow and fibroblasts. We have recently seen an 8-year-old girl with a classic picture of ataxia-telangiectasia; and chromosome studies were done on the blood and bone-marrow. In a peripheralblood culture stimulated with phytohasmagglutinin (P.H.A.), 60 cells in metaphase were analysed under the microscope and chromosome breaks were observed in 22 (36-6%). They were present in one or two chromosomes of any given cell, did not appear to have any predilection for a particular chromosome group, were mostly of the single chromatid type, and no major rearrangements were seen. A direct bone-marrow chromosome analysis was performed: of 12 cells suitable for study, 4 had chromosome breaks of the single-chromatid type. The percentage of chromosome breaks in this patient’s blood and bone-marrow is much higher than that in our controls (which is around 2-8%), and can thus be regarded as definitely abnormal. The presence of chromosome abnormalities in the bone-marrow of patients with this syndrome have not been reported previously and are therefore of special interest. The patient has at present no signs of lymphoreticular malignant disease, and the blood-picture is normal. of
LYMPHOCYTE RESPONSE TO P.H.A. IN PATIENTS WITH NON-LYMPHOID TUMOURS SIR,-Deficiencies of cell-mediated immune responses in patients with malignant disease (lymphoid and non-
3. 4. 5. 6. 7. 8. 9.
DAVID B. GARRIOCH ROBERT A. GOOD RICHARD A. GATTI.
Logan, J. New Z. med. J. 1956, 55, 408. Schier, W. W., Roth, A., Ostroff, G., Schrift, M. H. Am. J. Med. 1956, 20, 94. Kelly, W. D., Good, R. A., Varco, R. L. Surgery Gynec. Obstet. 1958, 107, 565. Grace, J. T., Kondo, T. Ann. Surg. 1958, 148, 633. Southam, C. M. Cancer Res. 1960, 20, 271. Elves, M., Roath, S., Israels, M. C. G. Lancet, 1963, i, 806. Silk, M. Cancer, N. Y. 1967, 20, 2088. Nelson, H. S. J. Natn. Cancer Inst. 1969, 42, 765. Golob, E. K., Israsena, T., Quatrale, A. C., Becker, K. L. Cancer, N.Y. 1969, 23, 306.