156 PROTECTIVE ACTIVITY OF WHOOPING-COUGH CONVALESCENT SERUM AND SERUM-IgA LEVEL IN MICE INFECTED WITH BORDETELLA PERTUSSIS
SIR,—The mechanism of active and passive immunity against whooping-cough remains an enigma. A new approach is suggested by a comparison of data reported by Winter’ and Geller and Pittman.2 The comparison shows a similarity in the time sequence of a striking increase in the protective activity of whooping-cough convalescent serum and in the serum-IgA level of mice infected by nasal instillation of Bordetella pertussis. In 1953 Winter compared the agglutinin, hacmagglutinin, and protective titres of convalescent sera of whooping-cough patients. Her purpose was to ascertain which antibody best reflected the immunity acquired during the disease. The percentages of the patients who showed increases in titre were for agglutinins 62% (31/50), for hxmagglutinins 14% (7/50), and for protective activity 100% (20/20). The children were bled on admission to hospital and at intervals of two or three weeks during the course of the disease. The sera from each individual were stored in dry ice until collection was complete, and then tested concurrently. Protective activity (P.D.so) was titrated against a lethal B. pertussis respiratory infection in mice. The results, reported for the individual sera of each patient, showed a fourfold to tenfold increase in protective activity. To obtain an overall picture of the increase relative to the duration of the disease, I calculated the geometric mean P.D.so of the sera of all patients collected at the corresponding week of the disease. If less than 0-2 ml, the 1-.D.,, was assigned a value of 0.4 ml. The accompanying figure shows that up to four weeks there was only a slight rise in titre from 1/3.1 to 1/7.6. By five weeks the titre had jumped to 1/34, and at six weeks the titre reached a peak of 1/42. The figure also shows the same time sequence in a considerable rise in serum-IgA level of mice infected by nasal instillation of B. pertussis .2 In the two mouse experiments the peak came at six or seven weeks. At this time the IgA constituted more than 30% of the total serum-immunoglobulin. Unfortunately, the B. pertussis specificity of the immune globulins was not determined. The sublethal B. pertussis infection of the mouse resembles the human infection in its pathological changes in the persistence of the bacteria in the respiratory system. Recovery-rate of bacteria is usually high for 20 days: then it declines to nil or a low rate by 30 days.2 3 Another similarity is the time of appearance of passive protective antibodies in the serum of the infected mouse and of man. North’*observed that mouse serum 14 days after infection did not protect against the lethal mouse infection, whereas the serum 30 to 50 days after infection was protective. As early as 1923 Debré reported that human serum collected after 4 weeks of the disease protected intimately exposed children when it was given during the incubation 5
stage. Serum-IgA
is immunochemically and physiochemically different from the externally secreted IgA which acts locally in inhibiting adhesion of bacteria to tissue (cf. Hanson and Brandtzaeg6)—that is, the first line of defence. The function of serum-IgA has not been clearly defined. Nevertheless, the increase in serum-IgA in the B. pertussis respiratory infected mouse seems at least to indicate a protective immunological response. The time sequence of the two responses offers a new approach to the study of the class(es) of immune globulins that may be involved in protective immunity against whoopingJ. L. Proc. Soc. exp. Biol. Med. 1953, 83, 866. Geller, B. D., Pittman, M. Infect. Immun. 1973, 8, 83. 3. Pittman, M. Proc. Soc. exp. Biôl. Med. 1951, 77, 70. 4. North, E. A. Aust. J. exp. Biol. med. Sci. 1946, 24, 253. 5. Debré, R. Bull. Acad. Nat. Méd., Paris. 1923, 89, 348. 6. Hanson, L. A., Brandtzaeg, P. in Immunologic Disorders in Infants and Children (edited by E. R. Stiehm and V. A. Fulginiti); p. 107. Philadelphia, 1973. 1. Winter,
2.
Week after onset of whoop
in
children and after nasal instigation of 8 pertussis in mice
of whooping-cough convalethal Bordetella pertussis respiratory infection,’ with increase of serum-IgA level in mice after sublethal infection.a
Comparison lescent
of increase in
serum
against
P.D.50 of human
serum
expressed as dilution.
protective activity
mouse
(g.m.t. of the number of
sera
in
parentheses
•—•.
IgA level of a serum pool from 4 and 0, A--experiment 2, respectively. 0 ---
5 mice in A.
experiment
1 and
cough and in the duration of immunity. The product, pertussis immune globulin (human), which is largely IgG and contains less IgA than its source plasma has been reported to be ineffective.7-9 However, antibody and its schedule may have been deficient relative to more effective antipertussis serum. 10 In addition to its application in immunological studies the mouse model may be useful in the study of the pathogenesis of whooping-cough and the altered pharmacological reactions induced by B. pertussis. Bureau of Biologics, Food and Drug Administration, Bethesda, Maryland 20014, U.S.A.
MARGARET PITTMAN
COMBINED SLEEP DEPRIVATION AND CLOMIPRAMINE IN PRIMARY DEPRESSION
SIR,—In primary depression a quick but short remission (about 24 hours) can be achieved by depriving the patient of a night’s sleep.11-14 The antidepressive drugs (tricyclics) act in the reverse way: after a delay, a long-lasting remission may follow.15 -17 This delayed onset of all known antidepressive drugs is a grave disadvantage. We therefore examined the effects of combined sleep deprivation and clomipramine. We treated 16 patients with primary depression, 18 aged 7. Morris, D., McDonald, J. C. Archs Dis. Childh. 1957, 32, 236. 8. Bass, J. W., Klenk, L., Kotheimer, J. B., Linnemann, C. C., Smith, M. H. D. J. Pediat. 1969, 75, 768. 9. Balagatas, R. C., Nelson, K. E., Levin, S., Gotoff, S. P. ibid, 1971, 79, 203 10. McGuinness, A. C., Armstrong, J. G., Felton, H. M. ibid. 1944, 24, 249.
Matussek, N., Ackenheil, M., Athen, D., Beckmann, H., Benkert, O, Dittmer, T., Hippius, H., Loosen, P. T., Ruether, E., Scheller, M. Pharmakopsychiatrie, 1974, 7, 108. 12 Loosen, P. T., Ackenheil, M., Athen, D., Beckmann, H., Benkert, O, Dittmer, T., Hippius, H., Matussek, N., Ruether, E., Scheller, M. Arzneimittelforschung (Drug Res.), 1974, 24, 1075. 13. Pflug, B., Toelle, R. Nervenarzt. 1971, 42, 117. 14. Pflug, B. ibid. 1972, 43, 614. 15. Escobar, J., Flemenbaum, J. A., Schiele, B. D Psychopharmacology, 1973, 33, 111. 16. Jovanovic, U. J., Sattes, H. Schweiz med. Wschr 1966, 97, 1617 17. Schmidt, M., Gerke, H. Med Welt, 1972, 23, 466. 18. Feighner, J. P., Robins, E., Guze, S. G., Woodruff, R A., Winokur, G., Munoz, R. Archs gen. Psychiat. 1972, 26, 57. 11.
157
LECTURER/SENIOR MEDICAL OFFICER IN CHILD HEALTH AT LEEDS Prof. R. W. SMITHELLS (Department of Paediatrics and Child Health, University of Leeds, 27 Blundell Street, Leeds LS 3ET) writes: "May I call attention to a revised advertisement for a post appearing on p. 18 of this issue? The newly created post of lecturer/senior medical officer in child health at Leeds was first advertised in your issue of July 3, but an unfortunate printing error gave the salary range as £3742—£4740. The salary will be on the scale £3742—£7440. I hope any readers who lost interest on sight of the salary will be reassured."
Commentary from
Depression scores in both groups: Hamilton rating scale for depression (HRS) and von Zerssen’s self-rating scale for depression (ZS). Time observed: 22 days. Dotted line: clomipramine. Solid line: sleep
Charges
deprivation plus clomipramine. Pa
SIR,—The mechanism of active and passive immunity against whooping-cough remains an enigma. A new approach is suggested by a comparison of data reported by Winter’ and Geller and Pittman.2 The comparison shows a similarity in the time sequence of a striking increase in the protective activity of whooping-cough convalescent serum and in the serum-IgA level of mice infected by nasal instillation of Bordetella pertussis. In 1953 Winter compared the agglutinin, hacmagglutinin, and protective titres of convalescent sera of whooping-cough patients. Her purpose was to ascertain which antibody best reflected the immunity acquired during the disease. The percentages of the patients who showed increases in titre were for agglutinins 62% (31/50), for hxmagglutinins 14% (7/50), and for protective activity 100% (20/20). The children were bled on admission to hospital and at intervals of two or three weeks during the course of the disease. The sera from each individual were stored in dry ice until collection was complete, and then tested concurrently. Protective activity (P.D.so) was titrated against a lethal B. pertussis respiratory infection in mice. The results, reported for the individual sera of each patient, showed a fourfold to tenfold increase in protective activity. To obtain an overall picture of the increase relative to the duration of the disease, I calculated the geometric mean P.D.so of the sera of all patients collected at the corresponding week of the disease. If less than 0-2 ml, the 1-.D.,, was assigned a value of 0.4 ml. The accompanying figure shows that up to four weeks there was only a slight rise in titre from 1/3.1 to 1/7.6. By five weeks the titre had jumped to 1/34, and at six weeks the titre reached a peak of 1/42. The figure also shows the same time sequence in a considerable rise in serum-IgA level of mice infected by nasal instillation of B. pertussis .2 In the two mouse experiments the peak came at six or seven weeks. At this time the IgA constituted more than 30% of the total serum-immunoglobulin. Unfortunately, the B. pertussis specificity of the immune globulins was not determined. The sublethal B. pertussis infection of the mouse resembles the human infection in its pathological changes in the persistence of the bacteria in the respiratory system. Recovery-rate of bacteria is usually high for 20 days: then it declines to nil or a low rate by 30 days.2 3 Another similarity is the time of appearance of passive protective antibodies in the serum of the infected mouse and of man. North’*observed that mouse serum 14 days after infection did not protect against the lethal mouse infection, whereas the serum 30 to 50 days after infection was protective. As early as 1923 Debré reported that human serum collected after 4 weeks of the disease protected intimately exposed children when it was given during the incubation 5
stage. Serum-IgA
is immunochemically and physiochemically different from the externally secreted IgA which acts locally in inhibiting adhesion of bacteria to tissue (cf. Hanson and Brandtzaeg6)—that is, the first line of defence. The function of serum-IgA has not been clearly defined. Nevertheless, the increase in serum-IgA in the B. pertussis respiratory infected mouse seems at least to indicate a protective immunological response. The time sequence of the two responses offers a new approach to the study of the class(es) of immune globulins that may be involved in protective immunity against whoopingJ. L. Proc. Soc. exp. Biol. Med. 1953, 83, 866. Geller, B. D., Pittman, M. Infect. Immun. 1973, 8, 83. 3. Pittman, M. Proc. Soc. exp. Biôl. Med. 1951, 77, 70. 4. North, E. A. Aust. J. exp. Biol. med. Sci. 1946, 24, 253. 5. Debré, R. Bull. Acad. Nat. Méd., Paris. 1923, 89, 348. 6. Hanson, L. A., Brandtzaeg, P. in Immunologic Disorders in Infants and Children (edited by E. R. Stiehm and V. A. Fulginiti); p. 107. Philadelphia, 1973. 1. Winter,
2.
Week after onset of whoop
in
children and after nasal instigation of 8 pertussis in mice
of whooping-cough convalethal Bordetella pertussis respiratory infection,’ with increase of serum-IgA level in mice after sublethal infection.a
Comparison lescent
of increase in
serum
against
P.D.50 of human
serum
expressed as dilution.
protective activity
mouse
(g.m.t. of the number of
sera
in
parentheses
•—•.
IgA level of a serum pool from 4 and 0, A--experiment 2, respectively. 0 ---
5 mice in A.
experiment
1 and
cough and in the duration of immunity. The product, pertussis immune globulin (human), which is largely IgG and contains less IgA than its source plasma has been reported to be ineffective.7-9 However, antibody and its schedule may have been deficient relative to more effective antipertussis serum. 10 In addition to its application in immunological studies the mouse model may be useful in the study of the pathogenesis of whooping-cough and the altered pharmacological reactions induced by B. pertussis. Bureau of Biologics, Food and Drug Administration, Bethesda, Maryland 20014, U.S.A.
MARGARET PITTMAN
COMBINED SLEEP DEPRIVATION AND CLOMIPRAMINE IN PRIMARY DEPRESSION
SIR,—In primary depression a quick but short remission (about 24 hours) can be achieved by depriving the patient of a night’s sleep.11-14 The antidepressive drugs (tricyclics) act in the reverse way: after a delay, a long-lasting remission may follow.15 -17 This delayed onset of all known antidepressive drugs is a grave disadvantage. We therefore examined the effects of combined sleep deprivation and clomipramine. We treated 16 patients with primary depression, 18 aged 7. Morris, D., McDonald, J. C. Archs Dis. Childh. 1957, 32, 236. 8. Bass, J. W., Klenk, L., Kotheimer, J. B., Linnemann, C. C., Smith, M. H. D. J. Pediat. 1969, 75, 768. 9. Balagatas, R. C., Nelson, K. E., Levin, S., Gotoff, S. P. ibid, 1971, 79, 203 10. McGuinness, A. C., Armstrong, J. G., Felton, H. M. ibid. 1944, 24, 249.
Matussek, N., Ackenheil, M., Athen, D., Beckmann, H., Benkert, O, Dittmer, T., Hippius, H., Loosen, P. T., Ruether, E., Scheller, M. Pharmakopsychiatrie, 1974, 7, 108. 12 Loosen, P. T., Ackenheil, M., Athen, D., Beckmann, H., Benkert, O, Dittmer, T., Hippius, H., Matussek, N., Ruether, E., Scheller, M. Arzneimittelforschung (Drug Res.), 1974, 24, 1075. 13. Pflug, B., Toelle, R. Nervenarzt. 1971, 42, 117. 14. Pflug, B. ibid. 1972, 43, 614. 15. Escobar, J., Flemenbaum, J. A., Schiele, B. D Psychopharmacology, 1973, 33, 111. 16. Jovanovic, U. J., Sattes, H. Schweiz med. Wschr 1966, 97, 1617 17. Schmidt, M., Gerke, H. Med Welt, 1972, 23, 466. 18. Feighner, J. P., Robins, E., Guze, S. G., Woodruff, R A., Winokur, G., Munoz, R. Archs gen. Psychiat. 1972, 26, 57. 11.
157
LECTURER/SENIOR MEDICAL OFFICER IN CHILD HEALTH AT LEEDS Prof. R. W. SMITHELLS (Department of Paediatrics and Child Health, University of Leeds, 27 Blundell Street, Leeds LS 3ET) writes: "May I call attention to a revised advertisement for a post appearing on p. 18 of this issue? The newly created post of lecturer/senior medical officer in child health at Leeds was first advertised in your issue of July 3, but an unfortunate printing error gave the salary range as £3742—£4740. The salary will be on the scale £3742—£7440. I hope any readers who lost interest on sight of the salary will be reassured."
Commentary from
Depression scores in both groups: Hamilton rating scale for depression (HRS) and von Zerssen’s self-rating scale for depression (ZS). Time observed: 22 days. Dotted line: clomipramine. Solid line: sleep
Charges
deprivation plus clomipramine. Pa
