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IMMUNOLOGY OF THYROID DISEASE
1148
ordinary steel screwdrivers and drills
or taken special We have had a number of cases of minor trouble and these, but only these, might be attributed to metallic transfer. J. H. HICKS.
care
to avoid attrition.
IMMUNOLOGY OF THYROID DISEASE SiR,-It is to be regretted that your admirable leader last week on the new concept of thyroid disease makes no mention of the pioneer work of Loeb on tissue transpla,ntation and organ specificity, a comprehensive account of which is given in his book The Biological Basis of
Individuality. Loeb probably did more experimental work on this subject than any other investigator before or since-work involving transplantation of every variety of tissue and organ under almost any conceivable given set of circumstances. Those of us interested in tissue transplantation are becoming more and more aware that Loeb has already anticipated most of the " original " work and new " theories " of today, many of which are, in fact, his ideas wrapped up in a more modern terminology. Just as today the neurohistologist finds himself confirming Cajal’s work of fifty years ago, much of modern grafting experiment is a repetition of the work of Loeb. Had his book been published today, instead of 1945, it would in many ways have been regarded as the most up-to-date and authoritative work on the subject. Department of Anatomy, University of Glasgow.
G. M. WYBURN.
CANCER AND ATHEROSCLEROSIS SiR,-I was much interested by your annotation of Feb. 16. I think it would be useful to mention the work of S. G. Zondek on malignant growths original and essential hypertension1 and on the inhibiting influence of essential hypertension on malignant growths
and rheumatoid arthritis.2 Hadassah Municipal Hospital, Tel Aviv, Israel.
I. LURJE.
IDENTIFICATION OF THE "FOURTH TYPE" OF POLIOMYELITIS VIRUS
January, 1956, the Russian virologists reported that they had isolated a new immunological type of poliomyelitis virus from the faeces of three children with bulbospinal poliomyelitis. This they designated type IV poliomyelitis virus. SiR,,-In
Chumakov et al.3
The three strains were named AB IV, MK iv, an GZ iv. The first two were isolated in monkeys (Rhesus macacus) in which they gave rise to paralyses and pathological anatomical changes which resembled those of poliomyelitis. Brain and spinal-cord passage material from monkeys caused paralyses when injected into suckling mice, suckling hamsters, and suckling cottonrats as well as in adult cotton-rats. Relatively high virus titres were found in most of the viscera of the suckling cotton-rats. On histopathological examination of the central nervous system, poliomyelitis-like changes were found in the monkeys as well as in the cottonThe strain Gz IV was isolated in adult cottonrats. rats and in newborn mice, and had the same animal pathogenicity as the other two. None of the strains were pathogenic for adult mice. The pathogenicity of the virus for monkeys and cotton-rats was regarded by Chumakov et al. as indicating that the virus belonged to the poliovirus group. By extensive cross-immunisation experiments on monkeys and cotton-rats they were able to show that the strains were identical immunologically but that they were not identical with the poliomyelitis types I, 11, and III. 1. Zondek, S. G., Tchetchik, M. Brit. J. Cancer, 1953, 7, 418. 2. Zondek, S. G. Acta med. scand. 1955, 152. 3. Chumakov, M. P., Voroshilova, M. K., Zhevandrova, V. I., Mirova, L. L., Itselis, F. G., Robinzon, T. A. Vopr. Virus, 1956, 1, 16.
One of the strains, AB iv (brain material from cottonwas kindly sent by Dr. Chumakov to the Department of Virus Research here for further study.
rat),
The passage material was inoculated into tissue-cultures of human embryonic lung. No degenerative changes could be detected. In spite of the pathogenicity of the virus for monkeys, it was suspected to belong to the Coxsackie group. In suckling mice the typical flaccid paralyses were found. After a few passages the material reached a titre of about 10-6, and, by neutralisation tests with hyperimmune sera against Dalldorf type-strains A1-A1O0 and B,-B,, it was found that the strains under investigation were immunologically identical with Coxsackie virus type A7. NEUTRALISATION TESTS IN SUCKLING MICE WITH RUSSIAN STRAIN AB IV AND COXSACKIE VIRUS TYPE A7
CROSSWISE THE
* serum titre expressed in reg. log.
This
was confirmed by crosswise neutralisation tests (see accompanying table). Histopathological examination of one of the mice with typical flaccid paralyses showed diffuse and very pronounced changes in the skeletal muscles. The lesions were mainly
necrotic and necrobiotic in nature. No lesions were observed in the brain, cord, or other organs. The histological picture of the muscles resembled in principle that associated with Coxsackie-virus (subgroup A) infections in mice. The original Russian material was inoculated intracerebrally into cotton-rats aged 8-9 weeks and 1 year. Both groups of animals came down with flaccid paralyses after an incubation period of 5-7 days. Microscopic examination of a large number of muscle groups as well as viscera of cotton-rats gave negative results, and no lesions could be found in the brain. In the cord, however, limited and slight changes were seen in all four animals examined. These changes were localised to the grey matter, in particular to the anterior horns, but in a few instances lesions were also found in the posterior horns. In the affected areas, necrotic and necrobiotBc ganglion-cells were observed with destruction of the tigroid substance. Apart from these changes, there were small accumulations of inflammatory cells, principally polymorphonuclear
leucocytes. It therefore appears, from the Russian results and own, that a virus strain immunologically identical with Coxsacke virus type A7 can produce a poliomyelitislike syndrome in monkeys. A new observation is also the pathogenicity for adult cotton-rats. our
Abel,4who studied the Russian type-iv poliomyelitis virus could confirm that the agent was immunologically identical with Coxsackie virus type A7. He performed a
thoroughly,
series of blind passages in tissue-culture and found a weak cytopathogenicity appearing after 11 passages. After 30 passages the changes were pronounced. In this connection it may be mentioned that Svedmyr et a1.,5 in cooperation with Johnsson,6have studied two Coxsackie type A7 strains which were isolated from fascal specimens in tissue-culture, One of them was also isolated directly in suckling mice. The cytopathogenicity to tissue-cultures was still weak and irregular after fifteen passages. Horstmann and Manuelidisobserved ataxia, tremor, and weakness after inoculation of one of the Russian strains in monkeys. They found lesions similar to those ofpoliomyeutis. but somewhat differently localised.
The question of the connection between the Russian strains and the clinical manifestations in the three children must be left open at the moment. Attention 4. Habel, K. Personal communication. 5. Svedmyr, A., Melén, B., Kjellén, L. Acta med. Scand. 1956 suppl. 316, 20. 6. Johnsson, T. Ibid, p. 33. 7. Horstmann, D. M., Manuelidis, E. Fed. Proc. 1957, 16, 418..
ordinary steel screwdrivers and drills
or taken special We have had a number of cases of minor trouble and these, but only these, might be attributed to metallic transfer. J. H. HICKS.
care
to avoid attrition.
IMMUNOLOGY OF THYROID DISEASE SiR,-It is to be regretted that your admirable leader last week on the new concept of thyroid disease makes no mention of the pioneer work of Loeb on tissue transpla,ntation and organ specificity, a comprehensive account of which is given in his book The Biological Basis of
Individuality. Loeb probably did more experimental work on this subject than any other investigator before or since-work involving transplantation of every variety of tissue and organ under almost any conceivable given set of circumstances. Those of us interested in tissue transplantation are becoming more and more aware that Loeb has already anticipated most of the " original " work and new " theories " of today, many of which are, in fact, his ideas wrapped up in a more modern terminology. Just as today the neurohistologist finds himself confirming Cajal’s work of fifty years ago, much of modern grafting experiment is a repetition of the work of Loeb. Had his book been published today, instead of 1945, it would in many ways have been regarded as the most up-to-date and authoritative work on the subject. Department of Anatomy, University of Glasgow.
G. M. WYBURN.
CANCER AND ATHEROSCLEROSIS SiR,-I was much interested by your annotation of Feb. 16. I think it would be useful to mention the work of S. G. Zondek on malignant growths original and essential hypertension1 and on the inhibiting influence of essential hypertension on malignant growths
and rheumatoid arthritis.2 Hadassah Municipal Hospital, Tel Aviv, Israel.
I. LURJE.
IDENTIFICATION OF THE "FOURTH TYPE" OF POLIOMYELITIS VIRUS
January, 1956, the Russian virologists reported that they had isolated a new immunological type of poliomyelitis virus from the faeces of three children with bulbospinal poliomyelitis. This they designated type IV poliomyelitis virus. SiR,,-In
Chumakov et al.3
The three strains were named AB IV, MK iv, an GZ iv. The first two were isolated in monkeys (Rhesus macacus) in which they gave rise to paralyses and pathological anatomical changes which resembled those of poliomyelitis. Brain and spinal-cord passage material from monkeys caused paralyses when injected into suckling mice, suckling hamsters, and suckling cottonrats as well as in adult cotton-rats. Relatively high virus titres were found in most of the viscera of the suckling cotton-rats. On histopathological examination of the central nervous system, poliomyelitis-like changes were found in the monkeys as well as in the cottonThe strain Gz IV was isolated in adult cottonrats. rats and in newborn mice, and had the same animal pathogenicity as the other two. None of the strains were pathogenic for adult mice. The pathogenicity of the virus for monkeys and cotton-rats was regarded by Chumakov et al. as indicating that the virus belonged to the poliovirus group. By extensive cross-immunisation experiments on monkeys and cotton-rats they were able to show that the strains were identical immunologically but that they were not identical with the poliomyelitis types I, 11, and III. 1. Zondek, S. G., Tchetchik, M. Brit. J. Cancer, 1953, 7, 418. 2. Zondek, S. G. Acta med. scand. 1955, 152. 3. Chumakov, M. P., Voroshilova, M. K., Zhevandrova, V. I., Mirova, L. L., Itselis, F. G., Robinzon, T. A. Vopr. Virus, 1956, 1, 16.
One of the strains, AB iv (brain material from cottonwas kindly sent by Dr. Chumakov to the Department of Virus Research here for further study.
rat),
The passage material was inoculated into tissue-cultures of human embryonic lung. No degenerative changes could be detected. In spite of the pathogenicity of the virus for monkeys, it was suspected to belong to the Coxsackie group. In suckling mice the typical flaccid paralyses were found. After a few passages the material reached a titre of about 10-6, and, by neutralisation tests with hyperimmune sera against Dalldorf type-strains A1-A1O0 and B,-B,, it was found that the strains under investigation were immunologically identical with Coxsackie virus type A7. NEUTRALISATION TESTS IN SUCKLING MICE WITH RUSSIAN STRAIN AB IV AND COXSACKIE VIRUS TYPE A7
CROSSWISE THE
* serum titre expressed in reg. log.
This
was confirmed by crosswise neutralisation tests (see accompanying table). Histopathological examination of one of the mice with typical flaccid paralyses showed diffuse and very pronounced changes in the skeletal muscles. The lesions were mainly
necrotic and necrobiotic in nature. No lesions were observed in the brain, cord, or other organs. The histological picture of the muscles resembled in principle that associated with Coxsackie-virus (subgroup A) infections in mice. The original Russian material was inoculated intracerebrally into cotton-rats aged 8-9 weeks and 1 year. Both groups of animals came down with flaccid paralyses after an incubation period of 5-7 days. Microscopic examination of a large number of muscle groups as well as viscera of cotton-rats gave negative results, and no lesions could be found in the brain. In the cord, however, limited and slight changes were seen in all four animals examined. These changes were localised to the grey matter, in particular to the anterior horns, but in a few instances lesions were also found in the posterior horns. In the affected areas, necrotic and necrobiotBc ganglion-cells were observed with destruction of the tigroid substance. Apart from these changes, there were small accumulations of inflammatory cells, principally polymorphonuclear
leucocytes. It therefore appears, from the Russian results and own, that a virus strain immunologically identical with Coxsacke virus type A7 can produce a poliomyelitislike syndrome in monkeys. A new observation is also the pathogenicity for adult cotton-rats. our
Abel,4who studied the Russian type-iv poliomyelitis virus could confirm that the agent was immunologically identical with Coxsackie virus type A7. He performed a
thoroughly,
series of blind passages in tissue-culture and found a weak cytopathogenicity appearing after 11 passages. After 30 passages the changes were pronounced. In this connection it may be mentioned that Svedmyr et a1.,5 in cooperation with Johnsson,6have studied two Coxsackie type A7 strains which were isolated from fascal specimens in tissue-culture, One of them was also isolated directly in suckling mice. The cytopathogenicity to tissue-cultures was still weak and irregular after fifteen passages. Horstmann and Manuelidisobserved ataxia, tremor, and weakness after inoculation of one of the Russian strains in monkeys. They found lesions similar to those ofpoliomyeutis. but somewhat differently localised.
The question of the connection between the Russian strains and the clinical manifestations in the three children must be left open at the moment. Attention 4. Habel, K. Personal communication. 5. Svedmyr, A., Melén, B., Kjellén, L. Acta med. Scand. 1956 suppl. 316, 20. 6. Johnsson, T. Ibid, p. 33. 7. Horstmann, D. M., Manuelidis, E. Fed. Proc. 1957, 16, 418..