- Email: [email protected]
OXYTOCIN
453 illustrate the behaviour with
megaloblasts began
to
megaloblasts.
"
Until the
divide, lymphocytes wandered at
random around the megaloblasts, showing no affinity for them. and wandering away again when they made contact. As soon as a megaloblast has entered into mitosis, and the stage has been reached where only a - mail bridge of cytoplasm unites the daughter cells, a lymphocyte is seen to dive upon them and to cross exactly midway. This behaviour is too often seen to be accidental; it produces a ludicrous appearance of the rutting of an umbilical cord. When it is appreciated that in many preparations there are comparatively few lymphocytes, that in all cases the preparations only thrive if the cells are well flattened out and separated, and that the zone of circulation of an individual lymphocyte is small, the frequency of this phenomenon indicates a purposive, concentrated and probably essential function." Lymphocytes thus show a remarkable affinity for cells and for cells in mitosis-that is, for activelygrowing and dividing cells. Humble and his colleagues suggest that the lymphocyte is a " mobile source of enzymes or metabolites which are particularly ill demand by actively growing and dividing cells." If this is so, malignant cells accumulate in lymph-nodes because, when they are brought there by lymphatic or Hood channels, they find a site particularly suitable for their growth and multiplication. So the lymphocyte functions in malignant disease as an agent hostile to the interests of the host since normally it furthers the growth and division of cells, regardless of their nature." Humble et al. note that in their serum-agar preparations 90% of the cells from inoculated primary tumours died within the first hour, whereas in preparations from secondary growths in bone-marrow or lymph-nodes 90% of the malignant cells survived. Another point they mention is that radiotherapy is known to cause a diminution in the number of lymphocytes in the blood and this may help, not hinder, the cessation of malignant
malignant
growth. The cultures in which these phenomena have been observed are, like all cultures, artificial affairs ; they differ mainly in that the cells are under some pressure from the superimposed coverslip. Changes in the lymphocytes like those described have not been observed in qbilli-clot cultures on slides or in roller tubes. But that does not mean that the observations are incorrect ;they are of much interest, and the ideas they stimulate about the function of the lymphocyte deserve further
exploration.
that the larger vessels do not undergo permanent changes. Most surgeons would treat the condition by decompression of the anterior tibial compartment, although few cases have been recognised early enough to assess the merits of this operation. Mavor 3 has lately identified what he takes to be a chronic form of this condition. His patient, a footballer, had pain in the front of the calf after exercise. There was no evidence of circulatory disorder, but two small muscle herniae were present over the upper part of the anterior tibial muscles on each side. After excision of the fascia over this muscle, the defect was repaired by a graft of fascia lata, and the patient’s symptoms subsided. Biopsy of the tibialis anterior showed no evidence of necrosis, and the diagnosis must remain uncertain. Nevertheless, there can be little doubt that attacks of pain in this region are common among athletes in training, who refer to them as shin splints." Whether they ever precede an acute attack is not clear, but muscle tenderness and swelling and redness of the overlying skin may all be present and subside with rest. The reluctance of athletes to seek medical advice when difficulties arise during training may account for the absence of recorded accounts of this chronic form. Thus, Woodward4 says " the only answer is to build up the tone of the muscle more gradually and the pain will die away." But were this unsuccessful, decompression of the anterior tibial compartment might be undertaken. "
OXYTOCIN
THE completion of chemical investigations of one of the polypeptide hormones of the posterior pituitary gland was recognised this year by the award of the Nobel prize for chemistry to Prof. Vincent du Vigneaud, of Cornell University Medical College, New York. du Vigneaud’s group have isolated, determined the structure of, and synthesised, oxytocin, the hormone responsible for uterine contraction and milk ejection. 5 6 The isolation of the factor was in itself a notable achievement, since the material is present in minute quantities in the gland and is unstable ; and each stage of purification had to be controlled by tedious and time-consuming bio-assays. Starting from some hundreds of thousands of hog and beef glands, the hormone was eventually isolated in an apparently homogeneous form by the techniques of counter-current distribution and electro-
phoresis. Total hydrolysis yielded a mixture of eight amino-acids and ammonia ; further degradative studies revealed that the components were arranged in peptide linkageas follows :
THE ANTERIOR TIBIAL SYNDROME 1B its acute form the anterior tibial
syndrome is now in the front of the leg Severe dearly recognised. pain afterexercise is associated with a firm swelling of the corsiflexors of the ankle and weakness or complete paralysis of these muscles. Barham Carter et al.1 described ’ patients with this syndrome in 1949. They regarded the condition as one of primary swelling of the muscles within the anterior fascial compartment of the leg, pro:.’ ing secondary ischæmia. The anterior tibial nerve often affected, and there was also paralysis of the mensor digitorum brevis and anaesthesia of the first ligital cleft. The necrosis of the muscles was rarely followed bs shortening-a feature distinguishing the consharply from Volkmann’s contracture. Hughes2 desneed3 cases of this type. After an investigation of the :-uppiy of the anterior compartment of the leg, he ’..l,1ed that spasm of the anterior tibial artery was the kely cause of the ischaemia. It is generally agreed .
.
ii, 928. B., Richards,
1. Carter, A. 2.
Hughes, J. R.
R. L., Zachary, R. B.
J. Bone Jt Surg. 1948, 30B, 581.
Lancet, 1949,
An important biological and chemical property is the reversible opening of the 20-membered ring by reduction of the -S-S- link of cystine to the -SH HS- form (i.e.,
cysteine residues). The synthesis was accomplished by condensing the protected tetrapeptide of cysteine-proline-leucine-glycinamide with the tripeptide isoleucine-glutamine-asparagine and then the product with the protected dipeptide Reductive removal of protective cysteine-tyrosine. the open chain ( -SH HS- ) form of the groupings gave hormone, and aeration in aqueous solution at neutrality gave natural oxytocin. The synthetic hormone had every chemical and biological property shown by the natural 3. Mavor, G. E. Ibid, 1956, 38B, 513. 4. Woodward, C. Sports Injuries. London, 1954. 5. du Vigneaud, V. Science, 1956, 123, 967. 6. du Vigneaud, V. Symposium on Peptide Chemistry, Chemical Society. London, 1955 ; p. 49.
454 and also showed very slight avian depressor, antidiadnuretic activity. These last three a are shown to properties high degree by another posterior pituitary hormone, vasopressin, which conversely has traces of oxytocin activity. As might have been expected, the hormones are chemically similar, the leucine and isoleucine residues of oxytocin being replaced by phenylalanine and arginine in vasopressin. The 20-membered ring is again present and can be reversibly opened by mild reduction. This 20-membered-ring type of structure is also present in insulin,7 and du Vigneaud feels that, although the insulin molecule is of a higher order of complexity than that of oxytocin, insulin, too, may be synthesised in the future. Furthermore, the antibiotic tyrocydin A also contains a large polypeptide ring,8 as does actinomycin D,9 in which the ring is attached to a heterocyclic ring
longer be martyrs to worms o faeces among the growing lettuces i obvious source of infection that the reformers hav Yet there is evidence that the mo no further. polluted water may be used for irrigating crop with impunity.12 Those races most plagued by infections and infestations have other more habits than the use of night-soil which may expla If they are to be of their misfortune. their excreta they must be given a r compost quantitative estimate of the benefits to be Equally it would be unwise to put too much tru freedom of composted excreta from all pa parasites. Such a claim may be made quite fair produce of a large mechanised plant, but th the scale of operations the less likely is the k complete. From the nature of the material i difficult to devise a process as efficient as a milk ising plant-which have been known to fail. typhoid bacillus in the wrong place can probabl
peptide,
would
pressor,
Undigested
system (phenazine). COMPOSTING
of human and animal excreta to increase the fertility of the land is a custom older than history. Mixed with vegetable matter they add humus to the soil, and, thanks to S. A. Waksman, we now know something of the scientific basis of this traditional practice. It would clearly be sound economy to turn to this purpose the THE
no
pers
an
epidemic.
use
nitrogenous wastes which are now discharged improvidently into the all-engulfing sea.10 The Borough of Southwark and the County of Dumfries have been pioneers of large-scale composting in this island and have little reason to regret their ventures. A recent monograph from the World Health Organisation suggests that there urban
few countries where similar or more ambitious proare not under trial or already established.11 It is an admirable book which, after a clear exposition of the principles of bacterial digestion, illustrates their application on a small as well as on a large scale. There is even a chapter on the production of methane for heating or lighting as a by-product of the communal village latrine. But the author (and others who have written on the same subject) would perhaps carry a little more conviction if he gave more attention to the objections to this process. Municipal authorities and farmers are those primarily interested. The former seldom neglect any source of income for the benefit of the ratepayers ; the latter welcome any source of profitable fertility. But there are in fact grave mechanical and financial impediments to the wide use of composted town wastes. These will be overcome in time, and when this economical practice has become the rule we shall have reason to be grateful to the quasi-religious fervour of its champions. (That is if we survive so long. Some of the more inflamed disciples of the compost-heap prophesy our speedy end from murrains and want, if we continue to poison So far the our fields with almost pure chemicals. figures of the Registrar-General do not support this
THE HUNTERS’ HOUSE
AN opportunity has come to acquire and pre house at Long Calderwood, East Kilbride, Lana where William Hunter was born in 1718 and hi John ten years later. It is, as our picture shows I Scots farm-house, typical of its period.
are
jects
thesis.) As doctors we are mainly concerned with the risks to health arising from using as a fertiliser faeces which may contain pathogenic bacteria or helminth ova. A major claim for composting is that the heat evolved is lethal to these ; and if the practice were adopted in those countries where night-soil is used on the growing crops-and that includes a large part of rural England-the inhabitants 7. Sanger, F., Thompson, E. O. P. Biochem. J. 1953, 53, 353. Sanger, F., Tuppy, H. Ibid, 1951, 49, 463. Sanger, F., Smith, L. F., Kital, R. Ibid, 1954, 58, vi. 8. Paladini. A., Craig, L. C. J. Amer. chem. Soc. 1954, 76, 688. 9. Brockmann, H., Bohusack, G., Franck, B., Gröne, H., Muxfeldt, H., Süling. C. Angew. Chem. 1956, 68, 70. 10. Lancet, 1954, ii, 1315. 11. Composting. By HAROLD B. GOTAAS. World Hlth Org. Monogr. Ser. 1956, no. 31. World Health Organisation : Geneva. (Obtainable from H.M. Stationery Office, P.O. Box 569. 25s. London, S.E.1.) Pp. 205.
occupied ; but the fabric, particularly the fl woodwork, is in urgent need of repair. A committee, representing the East Kilbride
Corporation, the University of Glasg Royal Faculty of Physicians and Surgeons, Western Regional Hospital Board, has been to raise enough money to repair the house and it..E3500 is needed urgently for repairs and of th E3000 has already been raised in Scotland. T mittee is now crossing the Border and appe doctors everywhere to help it to raise another to form an endowment fund. It plans to have a ment
trustees to maintain the house as a memorial, a and a possible research centre. The medical members of the committee a G. M. Wishart, Prof. J. D. Mackie, Prof. Stanle, Prof. Andrew Allison, -Alr. Walter Galbrai Alexander Miller, and Dr. Alexander Smith (ho tary). Donations should be sent to the hon. t
Royal
Faculty
Vincent Street, 12.
of Physicians Glasgow, C.2.
and
Surgeons,
Rudolfs, W., Falk, L. L., Ragotzkie, R. A. Wastes, 1951, 23, 253.
Sewag
megaloblasts began
to
megaloblasts.
"
Until the
divide, lymphocytes wandered at
random around the megaloblasts, showing no affinity for them. and wandering away again when they made contact. As soon as a megaloblast has entered into mitosis, and the stage has been reached where only a - mail bridge of cytoplasm unites the daughter cells, a lymphocyte is seen to dive upon them and to cross exactly midway. This behaviour is too often seen to be accidental; it produces a ludicrous appearance of the rutting of an umbilical cord. When it is appreciated that in many preparations there are comparatively few lymphocytes, that in all cases the preparations only thrive if the cells are well flattened out and separated, and that the zone of circulation of an individual lymphocyte is small, the frequency of this phenomenon indicates a purposive, concentrated and probably essential function." Lymphocytes thus show a remarkable affinity for cells and for cells in mitosis-that is, for activelygrowing and dividing cells. Humble and his colleagues suggest that the lymphocyte is a " mobile source of enzymes or metabolites which are particularly ill demand by actively growing and dividing cells." If this is so, malignant cells accumulate in lymph-nodes because, when they are brought there by lymphatic or Hood channels, they find a site particularly suitable for their growth and multiplication. So the lymphocyte functions in malignant disease as an agent hostile to the interests of the host since normally it furthers the growth and division of cells, regardless of their nature." Humble et al. note that in their serum-agar preparations 90% of the cells from inoculated primary tumours died within the first hour, whereas in preparations from secondary growths in bone-marrow or lymph-nodes 90% of the malignant cells survived. Another point they mention is that radiotherapy is known to cause a diminution in the number of lymphocytes in the blood and this may help, not hinder, the cessation of malignant
malignant
growth. The cultures in which these phenomena have been observed are, like all cultures, artificial affairs ; they differ mainly in that the cells are under some pressure from the superimposed coverslip. Changes in the lymphocytes like those described have not been observed in qbilli-clot cultures on slides or in roller tubes. But that does not mean that the observations are incorrect ;they are of much interest, and the ideas they stimulate about the function of the lymphocyte deserve further
exploration.
that the larger vessels do not undergo permanent changes. Most surgeons would treat the condition by decompression of the anterior tibial compartment, although few cases have been recognised early enough to assess the merits of this operation. Mavor 3 has lately identified what he takes to be a chronic form of this condition. His patient, a footballer, had pain in the front of the calf after exercise. There was no evidence of circulatory disorder, but two small muscle herniae were present over the upper part of the anterior tibial muscles on each side. After excision of the fascia over this muscle, the defect was repaired by a graft of fascia lata, and the patient’s symptoms subsided. Biopsy of the tibialis anterior showed no evidence of necrosis, and the diagnosis must remain uncertain. Nevertheless, there can be little doubt that attacks of pain in this region are common among athletes in training, who refer to them as shin splints." Whether they ever precede an acute attack is not clear, but muscle tenderness and swelling and redness of the overlying skin may all be present and subside with rest. The reluctance of athletes to seek medical advice when difficulties arise during training may account for the absence of recorded accounts of this chronic form. Thus, Woodward4 says " the only answer is to build up the tone of the muscle more gradually and the pain will die away." But were this unsuccessful, decompression of the anterior tibial compartment might be undertaken. "
OXYTOCIN
THE completion of chemical investigations of one of the polypeptide hormones of the posterior pituitary gland was recognised this year by the award of the Nobel prize for chemistry to Prof. Vincent du Vigneaud, of Cornell University Medical College, New York. du Vigneaud’s group have isolated, determined the structure of, and synthesised, oxytocin, the hormone responsible for uterine contraction and milk ejection. 5 6 The isolation of the factor was in itself a notable achievement, since the material is present in minute quantities in the gland and is unstable ; and each stage of purification had to be controlled by tedious and time-consuming bio-assays. Starting from some hundreds of thousands of hog and beef glands, the hormone was eventually isolated in an apparently homogeneous form by the techniques of counter-current distribution and electro-
phoresis. Total hydrolysis yielded a mixture of eight amino-acids and ammonia ; further degradative studies revealed that the components were arranged in peptide linkageas follows :
THE ANTERIOR TIBIAL SYNDROME 1B its acute form the anterior tibial
syndrome is now in the front of the leg Severe dearly recognised. pain afterexercise is associated with a firm swelling of the corsiflexors of the ankle and weakness or complete paralysis of these muscles. Barham Carter et al.1 described ’ patients with this syndrome in 1949. They regarded the condition as one of primary swelling of the muscles within the anterior fascial compartment of the leg, pro:.’ ing secondary ischæmia. The anterior tibial nerve often affected, and there was also paralysis of the mensor digitorum brevis and anaesthesia of the first ligital cleft. The necrosis of the muscles was rarely followed bs shortening-a feature distinguishing the consharply from Volkmann’s contracture. Hughes2 desneed3 cases of this type. After an investigation of the :-uppiy of the anterior compartment of the leg, he ’..l,1ed that spasm of the anterior tibial artery was the kely cause of the ischaemia. It is generally agreed .
.
ii, 928. B., Richards,
1. Carter, A. 2.
Hughes, J. R.
R. L., Zachary, R. B.
J. Bone Jt Surg. 1948, 30B, 581.
Lancet, 1949,
An important biological and chemical property is the reversible opening of the 20-membered ring by reduction of the -S-S- link of cystine to the -SH HS- form (i.e.,
cysteine residues). The synthesis was accomplished by condensing the protected tetrapeptide of cysteine-proline-leucine-glycinamide with the tripeptide isoleucine-glutamine-asparagine and then the product with the protected dipeptide Reductive removal of protective cysteine-tyrosine. the open chain ( -SH HS- ) form of the groupings gave hormone, and aeration in aqueous solution at neutrality gave natural oxytocin. The synthetic hormone had every chemical and biological property shown by the natural 3. Mavor, G. E. Ibid, 1956, 38B, 513. 4. Woodward, C. Sports Injuries. London, 1954. 5. du Vigneaud, V. Science, 1956, 123, 967. 6. du Vigneaud, V. Symposium on Peptide Chemistry, Chemical Society. London, 1955 ; p. 49.
454 and also showed very slight avian depressor, antidiadnuretic activity. These last three a are shown to properties high degree by another posterior pituitary hormone, vasopressin, which conversely has traces of oxytocin activity. As might have been expected, the hormones are chemically similar, the leucine and isoleucine residues of oxytocin being replaced by phenylalanine and arginine in vasopressin. The 20-membered ring is again present and can be reversibly opened by mild reduction. This 20-membered-ring type of structure is also present in insulin,7 and du Vigneaud feels that, although the insulin molecule is of a higher order of complexity than that of oxytocin, insulin, too, may be synthesised in the future. Furthermore, the antibiotic tyrocydin A also contains a large polypeptide ring,8 as does actinomycin D,9 in which the ring is attached to a heterocyclic ring
longer be martyrs to worms o faeces among the growing lettuces i obvious source of infection that the reformers hav Yet there is evidence that the mo no further. polluted water may be used for irrigating crop with impunity.12 Those races most plagued by infections and infestations have other more habits than the use of night-soil which may expla If they are to be of their misfortune. their excreta they must be given a r compost quantitative estimate of the benefits to be Equally it would be unwise to put too much tru freedom of composted excreta from all pa parasites. Such a claim may be made quite fair produce of a large mechanised plant, but th the scale of operations the less likely is the k complete. From the nature of the material i difficult to devise a process as efficient as a milk ising plant-which have been known to fail. typhoid bacillus in the wrong place can probabl
peptide,
would
pressor,
Undigested
system (phenazine). COMPOSTING
of human and animal excreta to increase the fertility of the land is a custom older than history. Mixed with vegetable matter they add humus to the soil, and, thanks to S. A. Waksman, we now know something of the scientific basis of this traditional practice. It would clearly be sound economy to turn to this purpose the THE
no
pers
an
epidemic.
use
nitrogenous wastes which are now discharged improvidently into the all-engulfing sea.10 The Borough of Southwark and the County of Dumfries have been pioneers of large-scale composting in this island and have little reason to regret their ventures. A recent monograph from the World Health Organisation suggests that there urban
few countries where similar or more ambitious proare not under trial or already established.11 It is an admirable book which, after a clear exposition of the principles of bacterial digestion, illustrates their application on a small as well as on a large scale. There is even a chapter on the production of methane for heating or lighting as a by-product of the communal village latrine. But the author (and others who have written on the same subject) would perhaps carry a little more conviction if he gave more attention to the objections to this process. Municipal authorities and farmers are those primarily interested. The former seldom neglect any source of income for the benefit of the ratepayers ; the latter welcome any source of profitable fertility. But there are in fact grave mechanical and financial impediments to the wide use of composted town wastes. These will be overcome in time, and when this economical practice has become the rule we shall have reason to be grateful to the quasi-religious fervour of its champions. (That is if we survive so long. Some of the more inflamed disciples of the compost-heap prophesy our speedy end from murrains and want, if we continue to poison So far the our fields with almost pure chemicals. figures of the Registrar-General do not support this
THE HUNTERS’ HOUSE
AN opportunity has come to acquire and pre house at Long Calderwood, East Kilbride, Lana where William Hunter was born in 1718 and hi John ten years later. It is, as our picture shows I Scots farm-house, typical of its period.
are
jects
thesis.) As doctors we are mainly concerned with the risks to health arising from using as a fertiliser faeces which may contain pathogenic bacteria or helminth ova. A major claim for composting is that the heat evolved is lethal to these ; and if the practice were adopted in those countries where night-soil is used on the growing crops-and that includes a large part of rural England-the inhabitants 7. Sanger, F., Thompson, E. O. P. Biochem. J. 1953, 53, 353. Sanger, F., Tuppy, H. Ibid, 1951, 49, 463. Sanger, F., Smith, L. F., Kital, R. Ibid, 1954, 58, vi. 8. Paladini. A., Craig, L. C. J. Amer. chem. Soc. 1954, 76, 688. 9. Brockmann, H., Bohusack, G., Franck, B., Gröne, H., Muxfeldt, H., Süling. C. Angew. Chem. 1956, 68, 70. 10. Lancet, 1954, ii, 1315. 11. Composting. By HAROLD B. GOTAAS. World Hlth Org. Monogr. Ser. 1956, no. 31. World Health Organisation : Geneva. (Obtainable from H.M. Stationery Office, P.O. Box 569. 25s. London, S.E.1.) Pp. 205.
occupied ; but the fabric, particularly the fl woodwork, is in urgent need of repair. A committee, representing the East Kilbride
Corporation, the University of Glasg Royal Faculty of Physicians and Surgeons, Western Regional Hospital Board, has been to raise enough money to repair the house and it..E3500 is needed urgently for repairs and of th E3000 has already been raised in Scotland. T mittee is now crossing the Border and appe doctors everywhere to help it to raise another to form an endowment fund. It plans to have a ment
trustees to maintain the house as a memorial, a and a possible research centre. The medical members of the committee a G. M. Wishart, Prof. J. D. Mackie, Prof. Stanle, Prof. Andrew Allison, -Alr. Walter Galbrai Alexander Miller, and Dr. Alexander Smith (ho tary). Donations should be sent to the hon. t
Royal
Faculty
Vincent Street, 12.
of Physicians Glasgow, C.2.
and
Surgeons,
Rudolfs, W., Falk, L. L., Ragotzkie, R. A. Wastes, 1951, 23, 253.
Sewag