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BIOLOGICAL CONTROL OF ARTHROPODS
758
and electromyography was abnormal in two-thirds.8 Sometimes plasma free fatty acids and triglycerides are highlO and on a high-fat diet the patient may then be unable to produce ketones (the normal response).10," The largest group of lipid-storage myopathies involves defects in the transport of long-chain fatty acids. In normal muscle, lipid is histologically most prominent in type-1 muscle fibres" and oxidation of this lipid can serve as the sole energy source in both cardiac and skeletal muscle. A key intermediary in fatty-acid transport into mitochondria, where p-oxidation occurs, is a carrier substance, carnitine.16,17 Carnitine is synthesised in the liver from the aminoacid lysine,18 released into blood, and transferred across the sarcolemmal membrane into the muscle cell. Fatty acids with a chain length of less than 12 carbon atoms are able to pass through the outer membrane of the mitochondria without a carrier. Longer-chain fatty acids, however, are first activated by attachment to coenzyme-A and next attached to carnitine to form acylcarnitine by the enzyme, carnitine palmityltransferase I, which is located on the mitochondrial membrane.",19 This step allows the fatty-acid ester to pass into the mitochondria where another enzyme, carnitine palmityltransferase II, located on the inner surface of the inner mitochondrial membrane, releases the fatty acid from carnitine. Thereafter the fatty acid undergoes p-oxidation, and acetylCoA released is further metabolised in the Krebs cycle. In 1972 Engel and Siekert1 described a woman of 24 with a lipid-storage myopathy who had two striking biochemical abnormalities-a very low carnitine in muscle obtained by biopsy and, in vitro, a considerable reduction in oxidation of fatty acids. Since then several other cases of carnitine deficiency have been recorded.’" The diagnosis depends on demonstration of a low carnitine level in muscle, 20 since serum-carnitine was normal in 4 of 7 cases. In one patient with carnitine deficiency, neutral fat also accumulated in leucocytes and in Schwann cells.9 Deficiency of carnitine may arise from either a failure of hepatic synthesis or a failure of transport from liver into muscle." Since the serum-carnitine level was normal in half the cases and the hepatic carnitine level was normal in the 1 patient who had a liver biopsy the evidence favours a failure of transport of carnitine into muscle, at least in some of these patients. In 2 other patients both muscle and liver (and in 1 patient, serum) carnitine levels were low. These patients had hepatomegaly and massive lipid storage in liver as well as muscle. In these, hepatic failure to synthesise carnitine seems likely. 4 other patients, 2 brothers and twin sisters,4,5 who all had myoglobinuria following exertion, had raised muscle-carnitine levels but there was a virtual absence of the enzyme, carnitine palmityltransferase. A. G., Watters, G., Allen, J., Rothman, S., Klassen, G., Mamer, O. A. Neurology, 1975, 25, 16. 12. Angelini, C., Lucke, S., Cantarutti, F. ibid. 1976, 26, 633. 13. Engel, A. G., Banker, B. Q., Eiben, R. M. J. Neurol. Neurosurg. Psychiat. 1977, 40, 313. 14. Whitaker, J. N., Dimauro, S., Solomon, S. S., Sabesin, S., Duckworth, W. C., Mendell, J. R. Am. J. Med. 1977, 63, 805. 15. Engel, W. K. Archs Neurol. 1970, 22, 97. 16. Fritz, I. B., Yue, K. T. N. J. Lipid Res. 1963, 4, 279. 17. Bremer, J. J. biol. Chem. 1963, 238, 2774. 18. Tanphaichitr, V., Broquist, H. P. ibid. 1973, 248, 2176. 19. Hoppel, C. L., Tomec, R. J. ibid. 1972, 247, 832. 20. Dimauro, S., Scott, C., Penn, A. S., Rowland, L. P. Archs Neurol. 1973, 28, 11.
Karpati, G., Carpenter, S., Engel,
186.
Lipid deposition
in muscle
was
only marginally
in-
creased in this group. Neutral fat can also accumulate in the absence of a demonstrable disorder in the carnitine-carrier system. In such cases there may be muscle wasting, a scaly skin disorder indistinguishable from ichthyosis, and lipid accumulation in most cells of the body, including fibroblasts maintained in tissue culture.2 Plasma-carnitine level is normal. These cases are easily recognised because of the striking vacuolation in blood leucocytes, including all the polymorph series and monocytes. (A possibly similar patient was described in Zurich as a congenital non-progressive lipid myopathy.8) In these cases the defect may lie in a failure of p-oxidation of lipid, but more precise data are lacking. Therapeutically, good responses have been obtained with corticosteroids:l,14 clinical benefit coincides with an impressive reduction in muscle lipid. Large doses of oral carnitine have also proved beneficial,l1,12 but the most severely affected patients do not live long. 13
BIOLOGICAL CONTROL OF ARTHROPODS THE birth of medical entomology has been dated from Patrick Manson’s discovery in 1877 that filariasis in man is caused by a pathogen which undergoes obligatory development in an insect vector. The next half-century brought major advances in knowledge of malaria, yellow fever, sleeping sickness, and many another vector-borne diseases. But a symposium marking the centenary of medical entomology also stressed the unsolved problems. now facing those who seek to control vector-borne diseases of man and animals.21 In 1955 the World Health Organisation adopted ambitious plans for malaria eradication ; these have now given way to more modest aims of malaria control, a compromise forced by the emergence of insecticide resistance and compounded by increasing concern over environmental hazards associated with chemical insecticides. In 1964 W.H.O. published an annotated list of parasites and diseases of vectors,22 and more recently, in recognition of the need for greater research in the area of biological control of insect vectors, the same body has published a review of "pathogens of medically important arthropods". 23 This contains comprehensive "host-pathogen" and "pathogen-host" lists together with some 1100 citations. The arthropods covered include mosquitoes, ticks, mites, midges, bugs, cockroaches, fleas, and various flies (black flies, horseflies, stable flies, sandflies, tsetse flies, house flies, and face flies). The pathogens include viruses, rickettsiae, bacteria, protozoa, microsporidia, fungi, Coelomomyces, and nematodes. Because of the special problems associated with the taxonomy of microsporidia the text includes a synonomy of the microsporidia which infect mosquitoes. This is a valuable publication, but one for the specialist. For the non-specialist there have been several recent reviews.24-27 Entomology Centenary. Edited by SHEILA WILLMOTT. Royal Society Tropical Medicine and Hygiene, London, 1978. £6. (£4 to Fellows). 22. Jenkins, D. W. Bull. Wld Hlth Org. 1964, 30, suppl. 23. Roberts, D. W., Strand, M. A. ibid. 1977, 55, suppl.. 24. Weiser, J. Adv. vet. Sci. comp. Med. 1975, 19, 47. 25. Davidson, G. Genetic Control of Insect Pests. London, 1974. 26. Gunn, D. L. in Pesticides and Human Welfare (edited by D. L. Gunn and J. G. R. Stevens). London, 1976. 27. Wright, J. W. Adv. envir. Sci. Technol. 1976, 6, 17. 21. Medical
for
and electromyography was abnormal in two-thirds.8 Sometimes plasma free fatty acids and triglycerides are highlO and on a high-fat diet the patient may then be unable to produce ketones (the normal response).10," The largest group of lipid-storage myopathies involves defects in the transport of long-chain fatty acids. In normal muscle, lipid is histologically most prominent in type-1 muscle fibres" and oxidation of this lipid can serve as the sole energy source in both cardiac and skeletal muscle. A key intermediary in fatty-acid transport into mitochondria, where p-oxidation occurs, is a carrier substance, carnitine.16,17 Carnitine is synthesised in the liver from the aminoacid lysine,18 released into blood, and transferred across the sarcolemmal membrane into the muscle cell. Fatty acids with a chain length of less than 12 carbon atoms are able to pass through the outer membrane of the mitochondria without a carrier. Longer-chain fatty acids, however, are first activated by attachment to coenzyme-A and next attached to carnitine to form acylcarnitine by the enzyme, carnitine palmityltransferase I, which is located on the mitochondrial membrane.",19 This step allows the fatty-acid ester to pass into the mitochondria where another enzyme, carnitine palmityltransferase II, located on the inner surface of the inner mitochondrial membrane, releases the fatty acid from carnitine. Thereafter the fatty acid undergoes p-oxidation, and acetylCoA released is further metabolised in the Krebs cycle. In 1972 Engel and Siekert1 described a woman of 24 with a lipid-storage myopathy who had two striking biochemical abnormalities-a very low carnitine in muscle obtained by biopsy and, in vitro, a considerable reduction in oxidation of fatty acids. Since then several other cases of carnitine deficiency have been recorded.’" The diagnosis depends on demonstration of a low carnitine level in muscle, 20 since serum-carnitine was normal in 4 of 7 cases. In one patient with carnitine deficiency, neutral fat also accumulated in leucocytes and in Schwann cells.9 Deficiency of carnitine may arise from either a failure of hepatic synthesis or a failure of transport from liver into muscle." Since the serum-carnitine level was normal in half the cases and the hepatic carnitine level was normal in the 1 patient who had a liver biopsy the evidence favours a failure of transport of carnitine into muscle, at least in some of these patients. In 2 other patients both muscle and liver (and in 1 patient, serum) carnitine levels were low. These patients had hepatomegaly and massive lipid storage in liver as well as muscle. In these, hepatic failure to synthesise carnitine seems likely. 4 other patients, 2 brothers and twin sisters,4,5 who all had myoglobinuria following exertion, had raised muscle-carnitine levels but there was a virtual absence of the enzyme, carnitine palmityltransferase. A. G., Watters, G., Allen, J., Rothman, S., Klassen, G., Mamer, O. A. Neurology, 1975, 25, 16. 12. Angelini, C., Lucke, S., Cantarutti, F. ibid. 1976, 26, 633. 13. Engel, A. G., Banker, B. Q., Eiben, R. M. J. Neurol. Neurosurg. Psychiat. 1977, 40, 313. 14. Whitaker, J. N., Dimauro, S., Solomon, S. S., Sabesin, S., Duckworth, W. C., Mendell, J. R. Am. J. Med. 1977, 63, 805. 15. Engel, W. K. Archs Neurol. 1970, 22, 97. 16. Fritz, I. B., Yue, K. T. N. J. Lipid Res. 1963, 4, 279. 17. Bremer, J. J. biol. Chem. 1963, 238, 2774. 18. Tanphaichitr, V., Broquist, H. P. ibid. 1973, 248, 2176. 19. Hoppel, C. L., Tomec, R. J. ibid. 1972, 247, 832. 20. Dimauro, S., Scott, C., Penn, A. S., Rowland, L. P. Archs Neurol. 1973, 28, 11.
Karpati, G., Carpenter, S., Engel,
186.
Lipid deposition
in muscle
was
only marginally
in-
creased in this group. Neutral fat can also accumulate in the absence of a demonstrable disorder in the carnitine-carrier system. In such cases there may be muscle wasting, a scaly skin disorder indistinguishable from ichthyosis, and lipid accumulation in most cells of the body, including fibroblasts maintained in tissue culture.2 Plasma-carnitine level is normal. These cases are easily recognised because of the striking vacuolation in blood leucocytes, including all the polymorph series and monocytes. (A possibly similar patient was described in Zurich as a congenital non-progressive lipid myopathy.8) In these cases the defect may lie in a failure of p-oxidation of lipid, but more precise data are lacking. Therapeutically, good responses have been obtained with corticosteroids:l,14 clinical benefit coincides with an impressive reduction in muscle lipid. Large doses of oral carnitine have also proved beneficial,l1,12 but the most severely affected patients do not live long. 13
BIOLOGICAL CONTROL OF ARTHROPODS THE birth of medical entomology has been dated from Patrick Manson’s discovery in 1877 that filariasis in man is caused by a pathogen which undergoes obligatory development in an insect vector. The next half-century brought major advances in knowledge of malaria, yellow fever, sleeping sickness, and many another vector-borne diseases. But a symposium marking the centenary of medical entomology also stressed the unsolved problems. now facing those who seek to control vector-borne diseases of man and animals.21 In 1955 the World Health Organisation adopted ambitious plans for malaria eradication ; these have now given way to more modest aims of malaria control, a compromise forced by the emergence of insecticide resistance and compounded by increasing concern over environmental hazards associated with chemical insecticides. In 1964 W.H.O. published an annotated list of parasites and diseases of vectors,22 and more recently, in recognition of the need for greater research in the area of biological control of insect vectors, the same body has published a review of "pathogens of medically important arthropods". 23 This contains comprehensive "host-pathogen" and "pathogen-host" lists together with some 1100 citations. The arthropods covered include mosquitoes, ticks, mites, midges, bugs, cockroaches, fleas, and various flies (black flies, horseflies, stable flies, sandflies, tsetse flies, house flies, and face flies). The pathogens include viruses, rickettsiae, bacteria, protozoa, microsporidia, fungi, Coelomomyces, and nematodes. Because of the special problems associated with the taxonomy of microsporidia the text includes a synonomy of the microsporidia which infect mosquitoes. This is a valuable publication, but one for the specialist. For the non-specialist there have been several recent reviews.24-27 Entomology Centenary. Edited by SHEILA WILLMOTT. Royal Society Tropical Medicine and Hygiene, London, 1978. £6. (£4 to Fellows). 22. Jenkins, D. W. Bull. Wld Hlth Org. 1964, 30, suppl. 23. Roberts, D. W., Strand, M. A. ibid. 1977, 55, suppl.. 24. Weiser, J. Adv. vet. Sci. comp. Med. 1975, 19, 47. 25. Davidson, G. Genetic Control of Insect Pests. London, 1974. 26. Gunn, D. L. in Pesticides and Human Welfare (edited by D. L. Gunn and J. G. R. Stevens). London, 1976. 27. Wright, J. W. Adv. envir. Sci. Technol. 1976, 6, 17. 21. Medical
for