- Email: [email protected]
MALARIA, MOSQUITO CONTROL, AND PRIMARY HEALTH CARE
511
with many other disorders that stimulate macrophage activity—eg, AIDS24 (and in individuals who are at risk of AIDS25); tuberculosis;26 malaria and other
protozoal disorders ;27 graft-versus-host disease;4 Crohn’s disease;28 ulcerative colitis ;29 rheumatoid
arthritis;coeliac disease;31 various malignancies,33 including carcinoma of the cervix;32and immunemediated liver disease.33 This work documented a positive correlation between neopterin concentrations and other indices of disease activity, and led to the proposal that neopterin assays should be used more
widely in clinical practice. Despite many published reports, of which those listed above are but a small selection, it is not easy to assess the clinical value of neopterin measurements. Since neopterins rise in response to common and clinically unimportant infections, the concentrations may exceed those attributable to the disorder being studied. There is a consistent overlap between neopterin results in patients and in controls, and the differences between patients with "severe" and "mild" disease have generally been small (even though statistically highly significant). The wide range of stimuli that increase neopterin concentration and the high frequency of false-positive and falsenegative results would seem to argue against the introduction of routine neopterin assays. Perhaps the most promising clinical application of neopterin measurement is in monitoring progress in bone-marrow transplant recipients.4Depletion of immunocompetent cells by means of drug therapy or irradiation leads to a fall in neopterin concentrations; if the graft is successful, neopterin concentrations rise at least 48 hours before other signs of engraftment. However, a rise in neopterin also heralds infection or graft-versus-host disease, and therapy (including drugs with antifolate activity) may influence pterin levels.34 Because of the kidney’s role in pterin metabolism, the neopterin changes following renal transplantation are even more CoMpleX.20 24 Wachter H, Fuchs D, Hausen A, et al Elevated urinary neopterin levels in patients with the acquired immuno-deficiency syndrome (AIDS). Hoppe Seylers Z Physiol Chem 1983, 364: 1345-46. 25 Wachter H, Fuchs D, Hausen A, Reibnegger G, Werner ER, Dierich MP. Who will get AIDS? Lancet 1986, ii: 1215-17 26. Fuchs D, Hausen A, Kofler M, Osanowski H, Reibnegger G, Wachter H. Neopterin as an index of immune response in patients with tuberculosis. Lung 1984; 162: 337-46. 27. Schutzhard E, Fuchs D, Hausen A, Reibnegger G, Wachter H. Neopterin ein neuer Parameter in der malariadiagnostik? Mit Oster Tropenmed Parasitol 1985; 72: 63-70. 28 Prior Ch, Bollbach R, Fuchs D, et al. Urinary neopterin, a marker of clinical activity in patients with Crohn’s disease Clin Chim Acta 1986; 155: 11-22. 29. Niederwieser D, Fuchs D, Hausen A, et al. Neopterin as a new biochemical marker in the clinical assessment of ulcerative colitis. Immunobiol 1985; 170: 320-26. 30 Reibnegger G, Egg D, Fuchs D, et al Urinary neopterin reflects clinical activity in patients with rheumatoid arthritis. Arthritis Rheum 1986; 29: 1063-70. 31 Fuchs D, Granditsch G, Hausen A, Reibnegger G, Wachter H. Urinary neopterin excretion in coeliac disease. Lancet 1983; ii: 463-64. 32. Reibnegger GJ, Bichler AH, Dapunt O, et al. Neopterin as a prognostic indicator in patients with carcinoma of the uterine cervix. Cancer Res 1986; 46: 950-55. 33. Pnor Ch, Fuchs D, Hausen A, et al. Potential of urinary neoptenn excretion in differentiating chronic non-A, non-B hepatitis from fatty liver Lancet 1987; ii: 1235-37 34. Fink M, Zeigler I, Rokos H. Pteridines in bone marrow transplantation the problem of pharmacological interactions In Wachter H, Curtius H-Ch, Pfleiderer W, eds. Biochemical and clinical aspects of pteridines. Berlin Walter de Gruyter, 1985: 383-401
Maybe neopterin assays will be useful in the management of patients who require frequent monitoring of cellular immunity, or will occasionally help to distinguish immune-mediated from metabolic tissue damage. Better designed studies are needed to determine whether the neopterin results can influence clinical decisions (rather than simply correlate with other indices of disease activity). The question of whether measurements of NH2 and of biopterins, as well as of neopterin, would provide a more sensitive and informative measure of changes in cellular immunity also requires examination. What of the biological significance of the neopterin changes? Does the increased synthesis and breakdown of GTP to NH2 and phosphate by macrophages serve any useful purpose, or have any pathological consequences? Nothing is known, but the possibility has been raised of
effect of NH2 on folate metabolism in microorganisms,35 and in the host;the possible effects of biopterins produced during immune stimulation also need to be considered in view of the close links between pterin and folate metabolism that have been revealed by the studies in patients with DHPR deficiency.13,23 Much remains to be learned about the metabolic changes during immune stimulation; neopterins are likely to be of interest to clinical scientists for some time to come. an
MALARIA, MOSQUITO CONTROL, AND PRIMARY HEALTH CARE MALARIA vaccines are unlikely to come into widespread for several years. Meanwhile, prevention of mortality and morbidity from the disease will depend on chemotherapy, chemoprophylaxis, and vector control. There has lately been a move away from large, centrally run malaria control programmes towards community-based projects integrated into primary health care. Communitybased primary health care workers can assist in the control of malaria in three main ways: they can provide a handy source of treatment for clinical attacks; they can administer chemoprophylaxis to at-risk groups such as pregnant women; and they can encourage their community to adopt measures that will reduce exposure to vector mosquitoes. Some of the ways in which vector control can be incorporated into primary health care have now been considered by a World Health Organisation scientific
use
working groUp.1 Exposure to malaria can be reduced either by destruction of vector mosquitoes or by prevention of man/mosquito contact. In some ecological situations it is possible to reduce vector breeding sites, resting sites, or both by simple measures such as filling in ponds, digging drains, or clearing bush; communities can be encouraged to undertake these tasks with their own resources. However, in many situations there are too many potential breeding sites for this approach 35 Nathan CF. Peroxide and
pteridine a hypothesis on the regulation of macrophage anti-microbial activity by interferon-&ggr;. Interferon 1986; 7: 125-43. 36. Smith I, Howells DW, Kendall B, Levinsky R, Hyland K. Folate deficiency and demyelination in AIDS Lancet 1987; ii: 215. 1. World Health Organisation. Vector control in primary health care. Geneva: WHO, 1987
512 be effective. Several species of fish feed on mosquito larvae and culture of larvivorous fish is a method of malaria control that is well suited to the primary health care approach. Both herbivorous and larvivorous fish are used as components of a successful, integrated programme in Pondicherry.2 Herbivorous fish reduce pond weed, making mosquito larvae more accessible to their predators, and they provide a source of food and cash. Larvivorous fish have proved to be especially effective in parts of Somalia, where mosquito breeding takes place mainly in large cisterns (barkits).3 Household spraying with insecticides is now used less frequently because of the emergence of insecticide resistance, cost, and community resistance to the intrusion of spray teams. This method of malaria control is likely to be more acceptable and effective when spraying is carried out by members of the community. Man/mosquito contact can be reduced in various ways. The position and design of a house are both important in determining the exposure of its inhabitants to mosquitoes.4 Even small differences in house design-eg, leaving an open space between the walls and roof-can have a pronounced effect on the number of mosquitoes that enter a house. Primary health care workers can encourage their community to undertake simple measures such as the filling-in of eaves, which will reduce exposure to vector mosquitoes. Many communities have traditional methods for keeping mosquitoes at bay. In West Africa, wood is burnt to provide a repellent smoke; in other communities commercial mosquito coils are used widely for this purpose.5 Both methods are effective at preventing mosquito bites. In some malaria endemic areas bed (mosquito) nets are used extensively to protect against mosquitoes and other insects. Intact bed nets undoubtedly reduce mosquito bites6 but nets with holes become mosquito traps and a fruitful source of specimens for entomologists. The effectiveness of bed nets can be greatly enhanced by impregnating them with safe, persistent insecticides.’ Nets treated with synthetic pyrethroids provide considerable protection against mosquito bites,8 even when holed, and also protect against lice and bed-bugs. Trials of the efficacy of insecticidetreated bed nets in preventing malaria are now under way in several countries. Reductions in the prevalence of splenomegaly and parasitaemia, and in the incidence of clinical malaria have been reported.9,1O In communities where bed nets are not used widely, impregnated door and eave curtains provide a suitable alternative." Treatment of nets is simple-they are immersed in an insecticide solution of known concentration and left to dry-so this control measure is well suited to community participation.
, Any attempt to incorporate control of malaria vectors into
to
2.
3 4. 5.
6. 7.
8.
Panicker KN, Das PK. Control of malaria and filariasis vectors in South India Parasitol Today 1987, 3: 233-41. Alio AY, Isaq A, Delfini LF Using fish against mosquito-borne diseases. Wld Hlth Forum 1985; 6: 320-21. Schofield CJ, White GB House design and domestic vectors of disease. Trans R Soc Trop Med Hyg 1984, 78: 285-92. Chadwick PR. Mosquito coils protect against malaria Parasitol Today 1985, 1: 90-91. Port GR, Boreham PFL. The effect of bed nets on feeding by Anopheles gambiae Giles (Diptera:Culicidae) Bull Ent Res 1982; 72: 483-88. Schreck CE, Self LS. Bed nets that kill mosquitoes Wld Hlth Forum 1985, 6: 342-44. Lines JD, Myamba J, Curtis CF. Experimental hut trials of permethrin-impregnated mosquito nets and eave curtains against malana vectors m Tanzania. Med Vet Ent
Rajagopalan PK,
1987; 1: 37-51 et al Use of mosquito nets impregnated with deltamethrin in mosquito control. 1984 Abstracts of XI International Congress on Tropical Medicine and Malaria, Calgary, Canada 124 10 Snow RW, Rowan KM, Greenwood BM A trial of permethrin-treated bed nets in the prevention of malaria in Gambian children. Trans R Soc Trop Med Hyg 1987; 81:
9.
Ranque P, Toure TY, Soula G,
primary health care programme must be based on sound local knowledge. The clinical pattern of malaria, the nature and behaviour of the dominant vector mosquito, and the nature of any anti-mosquito measures already in use in the community must be carefully documented before any intervention is planned. Whenever possible the control measure adopted should build on any measures that are already in use—eg, upon an existing appreciation of the value of bed nets. Community leaders as well as primary health care workers must be fully involved in all stages of the planning of the programme and in its evaluation. Any approach to the control of malaria through the primary health care system must be evaluated as rigorously as for other control programmes. Unfortunately, such standards have seldom been achieved. In areas, such as much of tropical Africa, where malaria vector mosquitoes are highly successful and the pressure of infection is intense, very large reductions in mosquito numbers are required to reduce malaria transmission. Thus methods of vector control most applicable to primary health care programmes, such as destruction of breeding sites and use of bed nets and mosquito coils, are unlikely to reduce man/mosquito contact enough to make a significant impact on malaria transmission, although they may make a contribution to an integrated malaria control programme. In areas where mosquitoes are less efficient, vector control at the primary health care level alone may have some success in reducing mortality and morbidity from malaria.
a
DNA TOPOISOM ERASES—NEW TWISTS TO TUMOUR THERAPY EACH mammalian chromosome contains on average 5 cm of helical DNA that must be packaged into a nucleus which is generally 5-10 nm in diameter. In order to accomplish this feat, several higher orders of structure are imposed on the basic double helix:1 it is wrapped around histone proteins to form nucleosomes; the nucleosomes themselves are packaged into a regular repetitive array known as the 30 nm chromatin fibre; the 30 nm fibre is further organised into looped domains that project from the backbone of the chromosome; and an even higher order of structure is suggested by the cytogenetic banding pattern observed in mitotic chromosomes. Add to this scenario the fact that many fundamental cellular processes, including DNA replication, chromatid separation, and gene transcription necessitate an unravelling of the double helix and it becomes clear that mechanisms must exist to circumvent the resultant torsional stresses and other mechanical obstacles. DNA topoisomerases are nuclear enzymes that play a central role in resolving these problems by means of their ability to catalyse the interconversion of topological isomers of DNA (hence their name). Two types are recognised: type I introduces single strand DNA breaks, and type II cleaves both strands of a DNA helix. As reviewed by Dr Epstein in this issue (p 521), both enzymes have lately been transformed from abstruse laboratory phenomena into subjects of intense clinical interest; it has been shown that topoisomerases act as the molecular target for certain
563-67 11
Majori G, Sabatinelli G, Coluzzi M. Efficacy of permethrin-impregnated malaria vector control. Med Vet Ent 1987; 1: 185-92
curtains
for
B, Bray D, Lewis J, Raff M, Roberts K, Watson JD Molecular biology of the cell. New York. Garland, 1983
1. Alberts
with many other disorders that stimulate macrophage activity—eg, AIDS24 (and in individuals who are at risk of AIDS25); tuberculosis;26 malaria and other
protozoal disorders ;27 graft-versus-host disease;4 Crohn’s disease;28 ulcerative colitis ;29 rheumatoid
arthritis;coeliac disease;31 various malignancies,33 including carcinoma of the cervix;32and immunemediated liver disease.33 This work documented a positive correlation between neopterin concentrations and other indices of disease activity, and led to the proposal that neopterin assays should be used more
widely in clinical practice. Despite many published reports, of which those listed above are but a small selection, it is not easy to assess the clinical value of neopterin measurements. Since neopterins rise in response to common and clinically unimportant infections, the concentrations may exceed those attributable to the disorder being studied. There is a consistent overlap between neopterin results in patients and in controls, and the differences between patients with "severe" and "mild" disease have generally been small (even though statistically highly significant). The wide range of stimuli that increase neopterin concentration and the high frequency of false-positive and falsenegative results would seem to argue against the introduction of routine neopterin assays. Perhaps the most promising clinical application of neopterin measurement is in monitoring progress in bone-marrow transplant recipients.4Depletion of immunocompetent cells by means of drug therapy or irradiation leads to a fall in neopterin concentrations; if the graft is successful, neopterin concentrations rise at least 48 hours before other signs of engraftment. However, a rise in neopterin also heralds infection or graft-versus-host disease, and therapy (including drugs with antifolate activity) may influence pterin levels.34 Because of the kidney’s role in pterin metabolism, the neopterin changes following renal transplantation are even more CoMpleX.20 24 Wachter H, Fuchs D, Hausen A, et al Elevated urinary neopterin levels in patients with the acquired immuno-deficiency syndrome (AIDS). Hoppe Seylers Z Physiol Chem 1983, 364: 1345-46. 25 Wachter H, Fuchs D, Hausen A, Reibnegger G, Werner ER, Dierich MP. Who will get AIDS? Lancet 1986, ii: 1215-17 26. Fuchs D, Hausen A, Kofler M, Osanowski H, Reibnegger G, Wachter H. Neopterin as an index of immune response in patients with tuberculosis. Lung 1984; 162: 337-46. 27. Schutzhard E, Fuchs D, Hausen A, Reibnegger G, Wachter H. Neopterin ein neuer Parameter in der malariadiagnostik? Mit Oster Tropenmed Parasitol 1985; 72: 63-70. 28 Prior Ch, Bollbach R, Fuchs D, et al. Urinary neopterin, a marker of clinical activity in patients with Crohn’s disease Clin Chim Acta 1986; 155: 11-22. 29. Niederwieser D, Fuchs D, Hausen A, et al. Neopterin as a new biochemical marker in the clinical assessment of ulcerative colitis. Immunobiol 1985; 170: 320-26. 30 Reibnegger G, Egg D, Fuchs D, et al Urinary neopterin reflects clinical activity in patients with rheumatoid arthritis. Arthritis Rheum 1986; 29: 1063-70. 31 Fuchs D, Granditsch G, Hausen A, Reibnegger G, Wachter H. Urinary neopterin excretion in coeliac disease. Lancet 1983; ii: 463-64. 32. Reibnegger GJ, Bichler AH, Dapunt O, et al. Neopterin as a prognostic indicator in patients with carcinoma of the uterine cervix. Cancer Res 1986; 46: 950-55. 33. Pnor Ch, Fuchs D, Hausen A, et al. Potential of urinary neoptenn excretion in differentiating chronic non-A, non-B hepatitis from fatty liver Lancet 1987; ii: 1235-37 34. Fink M, Zeigler I, Rokos H. Pteridines in bone marrow transplantation the problem of pharmacological interactions In Wachter H, Curtius H-Ch, Pfleiderer W, eds. Biochemical and clinical aspects of pteridines. Berlin Walter de Gruyter, 1985: 383-401
Maybe neopterin assays will be useful in the management of patients who require frequent monitoring of cellular immunity, or will occasionally help to distinguish immune-mediated from metabolic tissue damage. Better designed studies are needed to determine whether the neopterin results can influence clinical decisions (rather than simply correlate with other indices of disease activity). The question of whether measurements of NH2 and of biopterins, as well as of neopterin, would provide a more sensitive and informative measure of changes in cellular immunity also requires examination. What of the biological significance of the neopterin changes? Does the increased synthesis and breakdown of GTP to NH2 and phosphate by macrophages serve any useful purpose, or have any pathological consequences? Nothing is known, but the possibility has been raised of
effect of NH2 on folate metabolism in microorganisms,35 and in the host;the possible effects of biopterins produced during immune stimulation also need to be considered in view of the close links between pterin and folate metabolism that have been revealed by the studies in patients with DHPR deficiency.13,23 Much remains to be learned about the metabolic changes during immune stimulation; neopterins are likely to be of interest to clinical scientists for some time to come. an
MALARIA, MOSQUITO CONTROL, AND PRIMARY HEALTH CARE MALARIA vaccines are unlikely to come into widespread for several years. Meanwhile, prevention of mortality and morbidity from the disease will depend on chemotherapy, chemoprophylaxis, and vector control. There has lately been a move away from large, centrally run malaria control programmes towards community-based projects integrated into primary health care. Communitybased primary health care workers can assist in the control of malaria in three main ways: they can provide a handy source of treatment for clinical attacks; they can administer chemoprophylaxis to at-risk groups such as pregnant women; and they can encourage their community to adopt measures that will reduce exposure to vector mosquitoes. Some of the ways in which vector control can be incorporated into primary health care have now been considered by a World Health Organisation scientific
use
working groUp.1 Exposure to malaria can be reduced either by destruction of vector mosquitoes or by prevention of man/mosquito contact. In some ecological situations it is possible to reduce vector breeding sites, resting sites, or both by simple measures such as filling in ponds, digging drains, or clearing bush; communities can be encouraged to undertake these tasks with their own resources. However, in many situations there are too many potential breeding sites for this approach 35 Nathan CF. Peroxide and
pteridine a hypothesis on the regulation of macrophage anti-microbial activity by interferon-&ggr;. Interferon 1986; 7: 125-43. 36. Smith I, Howells DW, Kendall B, Levinsky R, Hyland K. Folate deficiency and demyelination in AIDS Lancet 1987; ii: 215. 1. World Health Organisation. Vector control in primary health care. Geneva: WHO, 1987
512 be effective. Several species of fish feed on mosquito larvae and culture of larvivorous fish is a method of malaria control that is well suited to the primary health care approach. Both herbivorous and larvivorous fish are used as components of a successful, integrated programme in Pondicherry.2 Herbivorous fish reduce pond weed, making mosquito larvae more accessible to their predators, and they provide a source of food and cash. Larvivorous fish have proved to be especially effective in parts of Somalia, where mosquito breeding takes place mainly in large cisterns (barkits).3 Household spraying with insecticides is now used less frequently because of the emergence of insecticide resistance, cost, and community resistance to the intrusion of spray teams. This method of malaria control is likely to be more acceptable and effective when spraying is carried out by members of the community. Man/mosquito contact can be reduced in various ways. The position and design of a house are both important in determining the exposure of its inhabitants to mosquitoes.4 Even small differences in house design-eg, leaving an open space between the walls and roof-can have a pronounced effect on the number of mosquitoes that enter a house. Primary health care workers can encourage their community to undertake simple measures such as the filling-in of eaves, which will reduce exposure to vector mosquitoes. Many communities have traditional methods for keeping mosquitoes at bay. In West Africa, wood is burnt to provide a repellent smoke; in other communities commercial mosquito coils are used widely for this purpose.5 Both methods are effective at preventing mosquito bites. In some malaria endemic areas bed (mosquito) nets are used extensively to protect against mosquitoes and other insects. Intact bed nets undoubtedly reduce mosquito bites6 but nets with holes become mosquito traps and a fruitful source of specimens for entomologists. The effectiveness of bed nets can be greatly enhanced by impregnating them with safe, persistent insecticides.’ Nets treated with synthetic pyrethroids provide considerable protection against mosquito bites,8 even when holed, and also protect against lice and bed-bugs. Trials of the efficacy of insecticidetreated bed nets in preventing malaria are now under way in several countries. Reductions in the prevalence of splenomegaly and parasitaemia, and in the incidence of clinical malaria have been reported.9,1O In communities where bed nets are not used widely, impregnated door and eave curtains provide a suitable alternative." Treatment of nets is simple-they are immersed in an insecticide solution of known concentration and left to dry-so this control measure is well suited to community participation.
, Any attempt to incorporate control of malaria vectors into
to
2.
3 4. 5.
6. 7.
8.
Panicker KN, Das PK. Control of malaria and filariasis vectors in South India Parasitol Today 1987, 3: 233-41. Alio AY, Isaq A, Delfini LF Using fish against mosquito-borne diseases. Wld Hlth Forum 1985; 6: 320-21. Schofield CJ, White GB House design and domestic vectors of disease. Trans R Soc Trop Med Hyg 1984, 78: 285-92. Chadwick PR. Mosquito coils protect against malaria Parasitol Today 1985, 1: 90-91. Port GR, Boreham PFL. The effect of bed nets on feeding by Anopheles gambiae Giles (Diptera:Culicidae) Bull Ent Res 1982; 72: 483-88. Schreck CE, Self LS. Bed nets that kill mosquitoes Wld Hlth Forum 1985, 6: 342-44. Lines JD, Myamba J, Curtis CF. Experimental hut trials of permethrin-impregnated mosquito nets and eave curtains against malana vectors m Tanzania. Med Vet Ent
Rajagopalan PK,
1987; 1: 37-51 et al Use of mosquito nets impregnated with deltamethrin in mosquito control. 1984 Abstracts of XI International Congress on Tropical Medicine and Malaria, Calgary, Canada 124 10 Snow RW, Rowan KM, Greenwood BM A trial of permethrin-treated bed nets in the prevention of malaria in Gambian children. Trans R Soc Trop Med Hyg 1987; 81:
9.
Ranque P, Toure TY, Soula G,
primary health care programme must be based on sound local knowledge. The clinical pattern of malaria, the nature and behaviour of the dominant vector mosquito, and the nature of any anti-mosquito measures already in use in the community must be carefully documented before any intervention is planned. Whenever possible the control measure adopted should build on any measures that are already in use—eg, upon an existing appreciation of the value of bed nets. Community leaders as well as primary health care workers must be fully involved in all stages of the planning of the programme and in its evaluation. Any approach to the control of malaria through the primary health care system must be evaluated as rigorously as for other control programmes. Unfortunately, such standards have seldom been achieved. In areas, such as much of tropical Africa, where malaria vector mosquitoes are highly successful and the pressure of infection is intense, very large reductions in mosquito numbers are required to reduce malaria transmission. Thus methods of vector control most applicable to primary health care programmes, such as destruction of breeding sites and use of bed nets and mosquito coils, are unlikely to reduce man/mosquito contact enough to make a significant impact on malaria transmission, although they may make a contribution to an integrated malaria control programme. In areas where mosquitoes are less efficient, vector control at the primary health care level alone may have some success in reducing mortality and morbidity from malaria.
a
DNA TOPOISOM ERASES—NEW TWISTS TO TUMOUR THERAPY EACH mammalian chromosome contains on average 5 cm of helical DNA that must be packaged into a nucleus which is generally 5-10 nm in diameter. In order to accomplish this feat, several higher orders of structure are imposed on the basic double helix:1 it is wrapped around histone proteins to form nucleosomes; the nucleosomes themselves are packaged into a regular repetitive array known as the 30 nm chromatin fibre; the 30 nm fibre is further organised into looped domains that project from the backbone of the chromosome; and an even higher order of structure is suggested by the cytogenetic banding pattern observed in mitotic chromosomes. Add to this scenario the fact that many fundamental cellular processes, including DNA replication, chromatid separation, and gene transcription necessitate an unravelling of the double helix and it becomes clear that mechanisms must exist to circumvent the resultant torsional stresses and other mechanical obstacles. DNA topoisomerases are nuclear enzymes that play a central role in resolving these problems by means of their ability to catalyse the interconversion of topological isomers of DNA (hence their name). Two types are recognised: type I introduces single strand DNA breaks, and type II cleaves both strands of a DNA helix. As reviewed by Dr Epstein in this issue (p 521), both enzymes have lately been transformed from abstruse laboratory phenomena into subjects of intense clinical interest; it has been shown that topoisomerases act as the molecular target for certain
563-67 11
Majori G, Sabatinelli G, Coluzzi M. Efficacy of permethrin-impregnated malaria vector control. Med Vet Ent 1987; 1: 185-92
curtains
for
B, Bray D, Lewis J, Raff M, Roberts K, Watson JD Molecular biology of the cell. New York. Garland, 1983
1. Alberts