P.H.A. RESPONSE AND STEROID THERAPY
1
28 It thus appears that there is a sharp species difference in the size of the population of A.R.F. thymocytes, although pig (10°o) and Balb C mice e9(0) lie between the high and low levels of the other species tested. Micklem and Asfi 5 reported the detection of very occasional auto-rosette- forming cells in the lymphoid tissues of CBA and C57 Bl mice. Our preliminary results with CBA and NZB mice were 0’25°o and l’5°o, respectively, and there appears to be considerable strain variation in this species. We have also performed auto-rosette tests on peripheral blood lymphocytes of normal individuals and selected groups of hospital patients. The percentages of A.R.F. lymphocytes were much lower than for thymocytes, and were exceeded by the percentages of lymphocytes which bound 1 or 2 red cells. The average A.R.F. lymphocytes for 22 normal subjects (age range 18-55 years) was 3% (range 0 5°o—10°o). There was no obvious relationship with sex or age. Serial tests on subjects with a relatively high per- centage suggest that short-lived fluctuations may occur. Auto-rosette formation by granulocytes or monocytes was not observed. In 8 patients with myasthenia gravis, who had undergone thymectomy up to 8 years before testing, the mean was 2% (range 0-5%-3%), and in 9 patients with thyrotoxicosis, 3% (0-25°o-5%). We have observed un- usually high incidences among a group of 6 patients with melanoma, the mean being 9% and the range 1%-21%, and these preliminary findings suggest that a high inci- dence is related to advanced disease. The significance of this finding, which obviously requires confirmation with larger numbers of patients, is at present obscure. From these observations, which will be reported in greater detail elsewhere, we conclude that cortical thymo- cytes pass through a stage of differentiation during which they are capable of auto-rosette formation. The relationship between auto-rosette-forming thymocytes and peripheral blood lymphocytes is not known. As far as we are aware, the capacity of human lymphoid cells to form auto-rosettes has not been described previously. Indeed several groups of workers have not observed rosette formation in tests upon human thymocytes or lymphocytes with human red cells. 6-10 This discrepancy is almost certainly due to differences in technique. Baxley et al.1 have just reported binding of human red cells by human thymocytes, and binding of neuraminidase- treated human red cells by human peripheral-blood lymphocytes. University of Glasgow Department of Pathology, Western Infirmary, Glasgow G11 6NT. GAVIN SANDILANDS KATHLEEN GRAY ANNE COONEY J. D. BROWNING J. R. ANDERSON. P.H.A. RESPONSE AND STEROID THERAPY SiR,—The lymphocyte response with phytohxmag- glutinin (P.H.A.) has been assessed for a patient before, during, and after steroid therapy. It is suggested that this technique could be used as a measure of immuno- suppression and as a monitor of adrenal function. A 29-year-old woman had a P.H.A. response of 67’0°o before starting steroid therapy (the average control result in this labora- tory is 65’5O). After two months’ treatment and a reduction of 5. Micklem, H. S., Asfi, C. Archs Zool. exp. gén. 1971, 112, 105. 6. Coombs, R. R. A., Gurner, B. W., Wilson, A. B., Holm, G., Lindgren, B. Int. Archs Allergy, 1970, 39, 658. 7. Lay, W. H., Mendes, N. F., Bianco, C., Nussenzweig, V. Nature, 1971, 230, 531. 8. Chapel, H. M. Transplantation, 1973, 15, 320. 9. Gilbertsen, R. B., Metzgar, R. S. Fedn Proc. 1973, 32, 975. 10. Whittingham, S., Mackay, I. R. Cell. Immun. 1973, 6, 362. 11. Baxley, G., Bishop, G. B., Cooper, A. G., Wortis, H. H. Clin. exp Immunol. 1973, 15, 385. the dose from 80 mg. prednisone daily to 20 mg. per day the patient’s lymphocyte response.had fallen to 29-2%. It remained at this level, averaging 32-8%, for the following eighteen months with a maintenance dose of 15 mg. prednisone per day. Oral therapy was then discontinued. Six weeks after withdrawal of steroids the P.H.A. response was 18 1%. Corticotrophin was given over the following four weeks at 5-7-day intervals and doses varying from 20 units to 60 units. The patient’s lymphocyte response after four weeks’ corticotrophin was 70-9%. The method used for the above test requires 2 ml. of blood and results are obtained in three days. Velindre Hospital, Cardiff CF4 7XL. JUDITH BRAEMAN. Health Centre, Stanwell Road, Penarth, Glamorgan. M. J. C. POVEY. RATE OF WOUND HEALING SIR,-I do not agree with Dr Weber’s view (Aug. 4, p. 268) that the linear rate of healing in wounds is constant. A similar view stated that the rate of advance of the wound edge is a summation of the linear rate of growth of the epithelium and the connective-tissue components of the healing wound. Because the rates of advance of epithelial and connective-tissue fronts in tissue cultures would be linear, the healing-rates of wounds by this argument would be independent of the original size of the defect. However, this cannot be true, as is evident from the observations that although the rates of growth of epithelium and granulation tissue in cultures are con- sistent and reproducible, in-vivo measurements of the rate of advance of the wound edge in healing ulcers ranges from 0-208 mm. per day 1 to 1 mm. per day.2 One explana- tion of this inconsistency may be the disregard of the phenomenon of wound contraction. Both the extent and the rate of contraction are highly variable. The rate of contraction is not linear, but after a latent phase there is a rise which reaches a plateau long before healing is com- plete. Furthermore, the rate of contraction is known not to parallel the rate of epithelial or granulation-tissue proliferation. It is hard to see how a factor such as this can be compounded into a mathematical formula, par- ticularly because it may or may not exert a profound influence on the rate of wound healing and also because it is known to be affected by a large number of variables which in many instances cannot be objectively assessed and standardised or eliminated. Another point of importance which may explain the discordant results of the influence of zinc on the rate of healing of ulcers, and indeed many of the conflicting results on the subject of wound healing, may be the dis- regard of the phenomenon of epithelial-mesenchymal interaction. Studies on this subject were prompted by the experiments of Burrows 3 in 1924, and it has since been studied by many workers. 4-8 These studies demon- strate that each of these components in a healing wound influences the growth-rate and the behaviour of the other. The epithelium may initially invade and indeed stimulate granulation-tissue proliferation. With its maturation, the connective tissue in its turn inhibits epithelial proliferation and invasiveness. This would imply that the rate of epithelial growth is influenced by the age of the under- lying granulation which must, of course, vary from the 1. van den Brenk, H. A. S. Br. J. Surg. 1955, 43, 525. 2. Devito, R. V. Surg. Clins N. Am. 1965, 45, 441. 3. Burrows, M. T. J. med. Res. 1924, 44, 615. 4. Clarke, E. R., Clarke, E. L. Am. J. Anat. 1953, 93, 171. 5. Billingham, R. E., Reynolds, J. Br. J. plast. Surg. 1952, 5, 25. 6. Gillman, T., Penn, J. Med. Proc. suppl. 1956, 2, 121. 7. Bishop, G. H. Am. J. Anat. 1945, 76, 153. 8. Tarin, D., Croft, C. B. J. Anat. 1970, 106, 79.
Transcript of P.H.A. RESPONSE AND STEROID THERAPY
28
It thus appears that there is a sharp species difference inthe size of the population of A.R.F. thymocytes, althoughpig (10°o) and Balb C mice e9(0) lie between the high andlow levels of the other species tested. Micklem and Asfi 5
reported the detection of very occasional auto-rosette-
forming cells in the lymphoid tissues of CBA and C57 Blmice. Our preliminary results with CBA and NZB micewere 0’25°o and l’5°o, respectively, and there appears to beconsiderable strain variation in this species.We have also performed auto-rosette tests on peripheral
blood lymphocytes of normal individuals and selected
groups of hospital patients. The percentages of A.R.F.
lymphocytes were much lower than for thymocytes, andwere exceeded by the percentages of lymphocytes whichbound 1 or 2 red cells. The average A.R.F. lymphocytes for22 normal subjects (age range 18-55 years) was 3% (range0 5°o—10°o). There was no obvious relationship with sexor age. Serial tests on subjects with a relatively high per-centage suggest that short-lived fluctuations may occur.Auto-rosette formation by granulocytes or monocytes wasnot observed. In 8 patients with myasthenia gravis,who had undergone thymectomy up to 8 years before testing,the mean was 2% (range 0-5%-3%), and in 9 patients withthyrotoxicosis, 3% (0-25°o-5%). We have observed un-
usually high incidences among a group of 6 patients withmelanoma, the mean being 9% and the range 1%-21%,and these preliminary findings suggest that a high inci-dence is related to advanced disease. The significance ofthis finding, which obviously requires confirmation withlarger numbers of patients, is at present obscure.From these observations, which will be reported in
greater detail elsewhere, we conclude that cortical thymo-cytes pass through a stage of differentiation during whichthey are capable of auto-rosette formation. The relationshipbetween auto-rosette-forming thymocytes and peripheralblood lymphocytes is not known. As far as we are aware,the capacity of human lymphoid cells to form auto-rosetteshas not been described previously. Indeed several groupsof workers have not observed rosette formation in testsupon human thymocytes or lymphocytes with human redcells. 6-10 This discrepancy is almost certainly due to
differences in technique.Baxley et al.1 have just reported binding of human red
cells by human thymocytes, and binding of neuraminidase-treated human red cells by human peripheral-bloodlymphocytes.
University of GlasgowDepartment of Pathology,
Western Infirmary,Glasgow G11 6NT.
GAVIN SANDILANDSKATHLEEN GRAYANNE COONEY
J. D. BROWNINGJ. R. ANDERSON.
P.H.A. RESPONSE AND STEROID THERAPY
SiR,—The lymphocyte response with phytohxmag-glutinin (P.H.A.) has been assessed for a patient before,during, and after steroid therapy. It is suggested thatthis technique could be used as a measure of immuno-suppression and as a monitor of adrenal function.A 29-year-old woman had a P.H.A. response of 67’0°o before
starting steroid therapy (the average control result in this labora-tory is 65’5O). After two months’ treatment and a reduction of
5. Micklem, H. S., Asfi, C. Archs Zool. exp. gén. 1971, 112, 105.6. Coombs, R. R. A., Gurner, B. W., Wilson, A. B., Holm, G.,
Lindgren, B. Int. Archs Allergy, 1970, 39, 658.7. Lay, W. H., Mendes, N. F., Bianco, C., Nussenzweig, V. Nature,
1971, 230, 531.8. Chapel, H. M. Transplantation, 1973, 15, 320.9. Gilbertsen, R. B., Metzgar, R. S. Fedn Proc. 1973, 32, 975.
10. Whittingham, S., Mackay, I. R. Cell. Immun. 1973, 6, 362.11. Baxley, G., Bishop, G. B., Cooper, A. G., Wortis, H. H. Clin. exp
Immunol. 1973, 15, 385.
the dose from 80 mg. prednisone daily to 20 mg. per day thepatient’s lymphocyte response.had fallen to 29-2%. It remainedat this level, averaging 32-8%, for the following eighteen monthswith a maintenance dose of 15 mg. prednisone per day. Oraltherapy was then discontinued. Six weeks after withdrawal ofsteroids the P.H.A. response was 18 1%. Corticotrophin wasgiven over the following four weeks at 5-7-day intervals and dosesvarying from 20 units to 60 units. The patient’s lymphocyteresponse after four weeks’ corticotrophin was 70-9%.The method used for the above test requires 2 ml. of
blood and results are obtained in three days.Velindre Hospital,Cardiff CF4 7XL. JUDITH BRAEMAN.Health Centre,Stanwell Road,
Penarth,Glamorgan. M. J. C. POVEY.
RATE OF WOUND HEALING
SIR,-I do not agree with Dr Weber’s view (Aug. 4,p. 268) that the linear rate of healing in wounds is constant.A similar view stated that the rate of advance of thewound edge is a summation of the linear rate of growth ofthe epithelium and the connective-tissue components ofthe healing wound. Because the rates of advance of
epithelial and connective-tissue fronts in tissue cultureswould be linear, the healing-rates of wounds by thisargument would be independent of the original size of thedefect. However, this cannot be true, as is evident fromthe observations that although the rates of growth ofepithelium and granulation tissue in cultures are con-
sistent and reproducible, in-vivo measurements of the rateof advance of the wound edge in healing ulcers rangesfrom 0-208 mm. per day 1 to 1 mm. per day.2 One explana-tion of this inconsistency may be the disregard of thephenomenon of wound contraction. Both the extent andthe rate of contraction are highly variable. The rate ofcontraction is not linear, but after a latent phase there is arise which reaches a plateau long before healing is com-
plete. Furthermore, the rate of contraction is known notto parallel the rate of epithelial or granulation-tissueproliferation. It is hard to see how a factor such as thiscan be compounded into a mathematical formula, par-ticularly because it may or may not exert a profoundinfluence on the rate of wound healing and also because it isknown to be affected by a large number of variables whichin many instances cannot be objectively assessed andstandardised or eliminated.
Another point of importance which may explain thediscordant results of the influence of zinc on the rate of
healing of ulcers, and indeed many of the conflictingresults on the subject of wound healing, may be the dis-regard of the phenomenon of epithelial-mesenchymalinteraction. Studies on this subject were prompted bythe experiments of Burrows 3 in 1924, and it has sincebeen studied by many workers. 4-8 These studies demon-strate that each of these components in a healing woundinfluences the growth-rate and the behaviour of the other.The epithelium may initially invade and indeed stimulategranulation-tissue proliferation. With its maturation, theconnective tissue in its turn inhibits epithelial proliferationand invasiveness. This would imply that the rate of
epithelial growth is influenced by the age of the under-lying granulation which must, of course, vary from the
1. van den Brenk, H. A. S. Br. J. Surg. 1955, 43, 525.2. Devito, R. V. Surg. Clins N. Am. 1965, 45, 441.3. Burrows, M. T. J. med. Res. 1924, 44, 615.4. Clarke, E. R., Clarke, E. L. Am. J. Anat. 1953, 93, 171.5. Billingham, R. E., Reynolds, J. Br. J. plast. Surg. 1952, 5, 25.6. Gillman, T., Penn, J. Med. Proc. suppl. 1956, 2, 121.7. Bishop, G. H. Am. J. Anat. 1945, 76, 153.8. Tarin, D., Croft, C. B. J. Anat. 1970, 106, 79.
