825 survival of the graft from normal animals was 7-5 days, and that from animals with tumours, 14.3 days. 2. Studies of leucocyte histocompatibility antigens of cancer patients showed that only 2 out of 10 antigens examined were found more frequently among the cancer patients as compared with the controls.3 This fact indicates that the theory of compatibility between donors is most probably not the correct mean
one.
Lymphocytes from normal donors and from cancer patients were injected separately intradermally into the volar surface of each arm of 60 cancer-patient volunteers.4 It was found that in 52 cases normal lymphocytes caused greater skin erythematous reaction and induration than lymphocytes from cancer patients. This indicates that there is probably an antigen loss in the lymphocytes of cancer patients. 3.
Fig. 3-N.M.B.T. dose-response curves: in an infant (upper lines), and after a single 3 g. dose in an adult (lower line).
two
3. 4. a child with progressive vaccinia, and a series of healthy individuals. Serum levels of N.M.B.T. were determined by acidifying a 1 ml. sample ofnon-hsmolysed serum with 01ml. of2N hydrochloric acid, extracting with 1 ml. of toluene for 30 seconds, and centrifuging the extracts for 15 minutes at 3000 r.p.m. The absorptivity of the toluene layer was determined in a recording spectrophotometer between 450 and 350 m[J.. Peak heights were evaluated for serum extracts, and a standard and recovery curve was obtained (fig. 1). This shift towards the red end of the spectrum is most likely due to protein binding since it can be produced by adding toluenesolutions of N.M.B.T. to serum in vitro. Further study is under way to show that this procedure allows quantitation of the active principle.
Fig. 2 illustrates serum levels obtained by this method in an adult with eczema vaccinatum and appear to indicate that there is no cumulative effect of the drug with continued
therapy. In an infant treated for progressive vaccinia the serum drug levels were proportional to the amount of drug administered. Peak levels occurred 6 hours after drug administration, and after 41/2 hours in response to a single 3 g. dose in an 80 kg. man
(fig. 3).
_
Department of Pediatrics, University of Colorado Medical Center, Denver, Colorado, 80220.
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C. HENRY KEMPE DENIS RODGERSON OTTO F. SIEBER, JR.
SURVIVAL OF SKIN-GRAFTS FROM CANCER PATIENTS ON NORMAL RECIPIENTS
SIR,-We should like to bring further proof that diminished antigenicity of the skin in cancer patients is the most acceptable explanation for the findings of Dr. Amos and his colleagues (Feb. 20). We found1 that in patients with cancer subjected to two skin homotransplants-one from a normal donor and one from a cancer patient-the survival of the graft from the cancer patient was significantly prolonged in 20 out of 25 patients examined. The two possible mechanisms suggested were: (a) antigen loss in the skin of cancer patients; and (b) similarity in histocompatibility antigens among cancer patients. We therefore carried out the following
investigations: were subjected to two skin homonormal mouse and the other from a mouse with Ehrlich ascites tumour.2 The survival of grafts from the animals with the tumours was significantly prolonged: the
1. 25 normal albino mice
grafts-one from
1.
2.
a
Robinson, E., Ben-Hur, N., Shulman, J., Hochman, A., Neuman, Z. J. nat. Cancer Inst. 1965, 34, 185. Ben-Hur, N., Biran, S., Robinson, E. Unpublished.
ELIEZER ROBINSON.
Department of Oncology, Department of Plastic Surgery, Hadassah Hospital, Jerusalem.
N. BEN-HUR.
Robinson, E., Nelken, D. Cancer Res. (m the press). Robinson, E., Hochman, A. Unpublished.
Obituary PHILIP S. HENCH M.D.
Pittsburgh
Dr. Philip Hench, who shared with Dr. E. C. Kendall and Prof. T. Reichstein the 1950 Nobel prize for medicine, died at Rochester, Minnesota, on March 31. He was born in 1896 in Pittsburgh, where in 1920 he graduated M.D. His long association with the Mayo Clinic began in the
following year. As early as 1929, Hench’s ,
studies of rheumatic fever revealed the profound effect of certain physical states on the course of the disease; in his Heberden oration in 1948 he said that the remissions associated with them were more satisfactory and commoner than those achieved by He any known treatment. based twenty years’ research on these observations, and when his friend Kendall isolated compound E, later to be named cortisone, Hench was ready. to apply the discovery to clinical medicine. As Pickering observed 1: Hench’s of not a in the it cortisone was flash discovery pan; was the fruit of a lifetime’s use of the experimental method in the treatment of rheumatoid arthritis ". Many people were disappointed when, after a year or two, cortisone was found not to be quite the panacea they had thQught it. Hench was not one of them; in the excitement that attended his success, his was almost a lone voice preaching restraint. At the International Congress on Rheumatic Diseases in New York in 19492 presenting the results of his work, he insisted that he was not even describing a new treatment, but a study of the effects of a hormone on the mechanism of rheumatoid arthritis. His example of patient determination in research and calm judgment in the moment of discovery may, in the long run, be even more precious than the discovery itself. "
1. Pickering, G. W. 2. ibid. 1949, ii, 24.
Lancet, 1950, ii,
81.