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CLONIDINE IN SEVERE HYPERTENSION
317 CELLULAR IMMUNITY IN MULTIPLE SCLEROSIS
SIR,—Studies of cell-mediated 2 immunity in subacute sclerosing panencephalitis (S.S.P.E .)1 and in multiple sclerosis (M.S.)3-6 are in disagreement. We have repeated the leucocyte-migration studies3-6 in M.s. using a purified measles antigen prepared at the Center for Disease Control (C.D.C.), Atlanta, by one of us (J.A.Z.): Measles virus, Philadelphia/26 Edmonston strain, was obtained from
the C.D.C. Passage history Wish/25, FU3, Veio/5. Vero cells were infected with seed virus. After maximum cytopathic effect cells were scraped, frozen, thawed, and disrupted by homogenisation. The lysate was centrifuged and the supernate was spun off over a 30%w/v sucrose cushion. The pellet was suspended in water and extracted with ’Tween 80’ and ether. Ether was removed by centrifugation, collection of the aqueous phase, and bubbling with nitrogen. This removes viral membrane, leaving nucleocapsid material. This was dialysed against phosphate-buffered saline, lyophylised and frozen at —70°C. The titre of 50 µl of the material was 32 hmmagglutination units. This antigen is non-infectious and non-toxic in human lymphocyte cultures stimulated with phyto-hsemagglutinin.
measles antigen (FLOW) kindly supplied by Dr J. B. Zabriskie was also used. 8 children who had had natural measles or measles vaccination were used to assay the antigenicity of the C.D.C. preparation, and we found an adequate diIn
some cases
rect
leucocyte-migration-inhibition
response to
1/10
or
1/20
dilution of C.D.C. measles-virus antigen. Parainfluenza virus (FLOW) was also used in leucocyte studies. The sera of the patients were assayed for measles antibody haemagglutination inhibition (H.A.I.) titres. 28 patients with M.s and 1 patient with S.S.P.E. were studied. There were 26 controls with various neurological and non-neurological diseases other than M.S. Controls and patients were matched for sex and age. Using the C.D.C. purified measles antigen at 1/20 dilution we found the mean inhibition of migration for M.s. patients was 393% (table). There was no significant difference in the MEAN
(AND S.E.) LEUCOCYTE-MIGRATION INHIBITION AND H.A.I. TITRES
using drugs and procedures (azathioprine, corticosteroids, anti-lymphocyte serum,9 thoracic-duct drainage’") that depress cellular immunity to treat M.S. Investigators must conclusively demonstrate whether cellumeasles virus in M.S. exists or not. For the direct leucocyte-migration test, a purified, defined, and standardised measles-virus antigen used concurrently by various laboratories is necessary. Different structural components of measles are variably immunogenic after natural infection, active immunisation, or during S.S.P.E.11 In M.S. there may be raised antibody concentrations to the viral envelope rather than to the nucleocapsid.12 It would seem essential to make use of both the viral envelope and nucleocapsid material in any study of cell-mediated immunity of M.S. patients to measles.
lar anergy
to
Immunology-Connective Tissue Division, Department of Medicine, St Vincent’s Hospital and Medical Center, New York, N.Y. 10011, U.S.A.
H. BARTFELD
Division of Infectious Diseases, Children’s Hospital Medical Center, Boston, Massachusetts.
J. A. ZAIA
Neurology Department, St Vincent’s Hospital and Medical Center, New York.
H. DONNENFELD
CLONIDINE IN SEVERE HYPERTENSION
SIR,—Our findings13 contrast with Gennery’s experience14 with intravenous clonidine in severe hypertension. When clonidine was given to seven patients with accelerated-phase hypertension arterial pressure rose in all seven by 14% on average and by more than 30% in two. Georgetown University Medical Division, District of Columbia Hospital, Washington D.C. 20003, U.S.A.
FRANK A.
FINNERTY, JR.
FOR M.S. PATIENTS AND CONTROLS
CHOLERA SYNDROME IN WEST BENGAL .
,
response of active and inactive cases. There was no significant difference in the cell-mediated response of M.S. and control patients. We found a significant difference in the antigenic potency of FLOW and C.D.C. measles antigens for both mt.s. and control cases; 6 cases had mean migration inhibitions of 47.8% (S.E. 3-6%) with C.D.C. measles virus and 135% (s.E. 2.7%) with FLOW measles-virus antigen (p<0.001). There was no difference in the response of M.S. and control patients’ leucocytes to parainfluenza virus (see table). The difference in H.A.I. titres for measles antibody between 20 M.S. cases and 14 adult controls was not statistically significant
(P>O. 1).
seem:, that m-vitro cellmar anergy to a purified measlesvirus antigen and parainfluenza-virus antigen, as measured by the leucocyte-migration-inhibition test, was not present in this group of 28 M.S. patients. Studies are in progress using transfer factor made from donors with cellular reactivity to measles antigen as measured by the direct leucocyte-migration test to treat M.s. by stimulating cellular immunity to measles.7 11 Other investigators are
It
SIR--The interplay of Vibrio eltor in cases of cholera in West Bengal, India, was first recorded in 1964.’’’ In six years this strain had almost replaced V.cholerœ here.16 The preponderance of Vcholerce over V.eltor was again noticed in 1970. 17 In 1975, we evaluated 130 suspect cholera cases admitted to the Satya Bala Debi Infectious Diseases Hospital, Howrah. V.eltor, Vparahtemolyticus, non-agglutinable vibrios, Aeromonas hydrophila, and Plesiomonas shigelloides were respectively isolated from 110 (84.6%), 12 (9.2%), 18 (16.3%), 14 (12.7%), and 5 (4.5%) cases. Of the V.eltor strains, 105 (80.7%) were of Ogawa and 5 (3.9%) Inaba serotypes. During this study not a single strain of V.cholœ was recorded. The V.parahcemolyticus isolates belonged to the serotypes 01:K56, 02:K3, 04:K12, 04:K13, 04 :K55, 010:K19, 010 :K ?, of which one strain was completely untypable. Department of Bacteriology and Serology, School of Tropical Medicine, Calcutta-700012, and Satya Bala Debi Infectious Diseases Hospital, Howrah, West Bengal, India. 9.
Burnel, F. M. Lancet, 1968, ii, 610. Kreth, W. H., Kackell, M. Y. Ter Meulen, V. J. Immun. 1975, 114, 1042. 3 Utermohlen, V., Zabriskie, J. B. Lancet, 1973, ii, 1147. 4 Utermohlen, V., Zabnskie, J. B. exp. Med. 1973, 138, 1591. 5 Ciongoli, A. K., Platz, P., Dupont, B., Svejgaard, A., Fog, T., Jersild, C. 1 2
Lancet, 1973, ii, 1147.
Fuccillo, D. A., Abela, J. E., Traub, R. G., Gillespie, M. M., Beadle, E. L., Sever, J. L. ibid. 1975, i, 980. 7 Fog, T., Jersild, C., Dupont, B., Platz, P. J., Svejgaard, A., Thomsen, M., Midholm, S., Raun, N. E. Neurology, 1975, 25, 489. 8 Zabriskie, J. B., Utermohlen, V., Espinoza, L. R., Plank, C. R., Collins,
6
R. C. ibid
p. 490.
B. D. CHATTERJEE P. K. DE T. SEN I. B. MISRA
Lance, E. M., Abbosh, M., Kremer, J. V., Knight, S., Medawar,
P. ibid. p.
491.
10. Brendel, W., Ring, J., Seifert, J. ibid. p. 490. 11. Norrby, E., Enders-Ruckle, G., ter Meulen, V. J. infect. Dis. 1975, 132, 262. 12. Salmi, A. A., Norrby, E., Panelius, M. Infect. Immun. 1972, 6, 248. 13. Mroczek, W. J., Davidov, M., Finnerty, F. A., Jr. Clin. Pharmac. Ther. 1973, 14, 847. 14. Gennery, B. A. Lancet, 1975, ii, 1313. 15. Barua, D., Mukherjee, A. C., Sack, R. B. Bull. Calcutta Sch. trop. Med. 16. 17.
1964, 12, 55. K. N., Chatterjee, B. D., Mukherjee, M. K., Manji, 18, 9. Neogy, K. N., Chatterjee, B. D. Lancet, 1971, i, 347.
Neogy,
P. ibid.
1970,
SIR,—Studies of cell-mediated 2 immunity in subacute sclerosing panencephalitis (S.S.P.E .)1 and in multiple sclerosis (M.S.)3-6 are in disagreement. We have repeated the leucocyte-migration studies3-6 in M.s. using a purified measles antigen prepared at the Center for Disease Control (C.D.C.), Atlanta, by one of us (J.A.Z.): Measles virus, Philadelphia/26 Edmonston strain, was obtained from
the C.D.C. Passage history Wish/25, FU3, Veio/5. Vero cells were infected with seed virus. After maximum cytopathic effect cells were scraped, frozen, thawed, and disrupted by homogenisation. The lysate was centrifuged and the supernate was spun off over a 30%w/v sucrose cushion. The pellet was suspended in water and extracted with ’Tween 80’ and ether. Ether was removed by centrifugation, collection of the aqueous phase, and bubbling with nitrogen. This removes viral membrane, leaving nucleocapsid material. This was dialysed against phosphate-buffered saline, lyophylised and frozen at —70°C. The titre of 50 µl of the material was 32 hmmagglutination units. This antigen is non-infectious and non-toxic in human lymphocyte cultures stimulated with phyto-hsemagglutinin.
measles antigen (FLOW) kindly supplied by Dr J. B. Zabriskie was also used. 8 children who had had natural measles or measles vaccination were used to assay the antigenicity of the C.D.C. preparation, and we found an adequate diIn
some cases
rect
leucocyte-migration-inhibition
response to
1/10
or
1/20
dilution of C.D.C. measles-virus antigen. Parainfluenza virus (FLOW) was also used in leucocyte studies. The sera of the patients were assayed for measles antibody haemagglutination inhibition (H.A.I.) titres. 28 patients with M.s and 1 patient with S.S.P.E. were studied. There were 26 controls with various neurological and non-neurological diseases other than M.S. Controls and patients were matched for sex and age. Using the C.D.C. purified measles antigen at 1/20 dilution we found the mean inhibition of migration for M.s. patients was 393% (table). There was no significant difference in the MEAN
(AND S.E.) LEUCOCYTE-MIGRATION INHIBITION AND H.A.I. TITRES
using drugs and procedures (azathioprine, corticosteroids, anti-lymphocyte serum,9 thoracic-duct drainage’") that depress cellular immunity to treat M.S. Investigators must conclusively demonstrate whether cellumeasles virus in M.S. exists or not. For the direct leucocyte-migration test, a purified, defined, and standardised measles-virus antigen used concurrently by various laboratories is necessary. Different structural components of measles are variably immunogenic after natural infection, active immunisation, or during S.S.P.E.11 In M.S. there may be raised antibody concentrations to the viral envelope rather than to the nucleocapsid.12 It would seem essential to make use of both the viral envelope and nucleocapsid material in any study of cell-mediated immunity of M.S. patients to measles.
lar anergy
to
Immunology-Connective Tissue Division, Department of Medicine, St Vincent’s Hospital and Medical Center, New York, N.Y. 10011, U.S.A.
H. BARTFELD
Division of Infectious Diseases, Children’s Hospital Medical Center, Boston, Massachusetts.
J. A. ZAIA
Neurology Department, St Vincent’s Hospital and Medical Center, New York.
H. DONNENFELD
CLONIDINE IN SEVERE HYPERTENSION
SIR,—Our findings13 contrast with Gennery’s experience14 with intravenous clonidine in severe hypertension. When clonidine was given to seven patients with accelerated-phase hypertension arterial pressure rose in all seven by 14% on average and by more than 30% in two. Georgetown University Medical Division, District of Columbia Hospital, Washington D.C. 20003, U.S.A.
FRANK A.
FINNERTY, JR.
FOR M.S. PATIENTS AND CONTROLS
CHOLERA SYNDROME IN WEST BENGAL .
,
response of active and inactive cases. There was no significant difference in the cell-mediated response of M.S. and control patients. We found a significant difference in the antigenic potency of FLOW and C.D.C. measles antigens for both mt.s. and control cases; 6 cases had mean migration inhibitions of 47.8% (S.E. 3-6%) with C.D.C. measles virus and 135% (s.E. 2.7%) with FLOW measles-virus antigen (p<0.001). There was no difference in the response of M.S. and control patients’ leucocytes to parainfluenza virus (see table). The difference in H.A.I. titres for measles antibody between 20 M.S. cases and 14 adult controls was not statistically significant
(P>O. 1).
seem:, that m-vitro cellmar anergy to a purified measlesvirus antigen and parainfluenza-virus antigen, as measured by the leucocyte-migration-inhibition test, was not present in this group of 28 M.S. patients. Studies are in progress using transfer factor made from donors with cellular reactivity to measles antigen as measured by the direct leucocyte-migration test to treat M.s. by stimulating cellular immunity to measles.7 11 Other investigators are
It
SIR--The interplay of Vibrio eltor in cases of cholera in West Bengal, India, was first recorded in 1964.’’’ In six years this strain had almost replaced V.cholerœ here.16 The preponderance of Vcholerce over V.eltor was again noticed in 1970. 17 In 1975, we evaluated 130 suspect cholera cases admitted to the Satya Bala Debi Infectious Diseases Hospital, Howrah. V.eltor, Vparahtemolyticus, non-agglutinable vibrios, Aeromonas hydrophila, and Plesiomonas shigelloides were respectively isolated from 110 (84.6%), 12 (9.2%), 18 (16.3%), 14 (12.7%), and 5 (4.5%) cases. Of the V.eltor strains, 105 (80.7%) were of Ogawa and 5 (3.9%) Inaba serotypes. During this study not a single strain of V.cholœ was recorded. The V.parahcemolyticus isolates belonged to the serotypes 01:K56, 02:K3, 04:K12, 04:K13, 04 :K55, 010:K19, 010 :K ?, of which one strain was completely untypable. Department of Bacteriology and Serology, School of Tropical Medicine, Calcutta-700012, and Satya Bala Debi Infectious Diseases Hospital, Howrah, West Bengal, India. 9.
Burnel, F. M. Lancet, 1968, ii, 610. Kreth, W. H., Kackell, M. Y. Ter Meulen, V. J. Immun. 1975, 114, 1042. 3 Utermohlen, V., Zabriskie, J. B. Lancet, 1973, ii, 1147. 4 Utermohlen, V., Zabnskie, J. B. exp. Med. 1973, 138, 1591. 5 Ciongoli, A. K., Platz, P., Dupont, B., Svejgaard, A., Fog, T., Jersild, C. 1 2
Lancet, 1973, ii, 1147.
Fuccillo, D. A., Abela, J. E., Traub, R. G., Gillespie, M. M., Beadle, E. L., Sever, J. L. ibid. 1975, i, 980. 7 Fog, T., Jersild, C., Dupont, B., Platz, P. J., Svejgaard, A., Thomsen, M., Midholm, S., Raun, N. E. Neurology, 1975, 25, 489. 8 Zabriskie, J. B., Utermohlen, V., Espinoza, L. R., Plank, C. R., Collins,
6
R. C. ibid
p. 490.
B. D. CHATTERJEE P. K. DE T. SEN I. B. MISRA
Lance, E. M., Abbosh, M., Kremer, J. V., Knight, S., Medawar,
P. ibid. p.
491.
10. Brendel, W., Ring, J., Seifert, J. ibid. p. 490. 11. Norrby, E., Enders-Ruckle, G., ter Meulen, V. J. infect. Dis. 1975, 132, 262. 12. Salmi, A. A., Norrby, E., Panelius, M. Infect. Immun. 1972, 6, 248. 13. Mroczek, W. J., Davidov, M., Finnerty, F. A., Jr. Clin. Pharmac. Ther. 1973, 14, 847. 14. Gennery, B. A. Lancet, 1975, ii, 1313. 15. Barua, D., Mukherjee, A. C., Sack, R. B. Bull. Calcutta Sch. trop. Med. 16. 17.
1964, 12, 55. K. N., Chatterjee, B. D., Mukherjee, M. K., Manji, 18, 9. Neogy, K. N., Chatterjee, B. D. Lancet, 1971, i, 347.
Neogy,
P. ibid.
1970,