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ANTIGENIC CHANGES IN MOUSE-ADAPTED INFLUENZA VIRUS STRAINS
1229 which is a potent reversible, competitive inhibitor both of a-amylase and of a-glycoside hydrolases. Acarbose 200 mg taken immediately before a test meal of 50 g starch flattened the glycaemic response by 80-t7% and delayed its peak rise.1 Serial measurements of breath hydrogen, as an index of malabsorption, showed no change and the subjects reported no symptoms suggestive of malabsorption. There was a significant reduction in insulin and gastric inhibitory peptide responses2and a significant rise in the enteroglucagon response2,3 after acarbose compared with placebo given with a test breakfast. Motilin release is4 also significantly increased by acarbose, independent of the dose.4 This evidence indicates, firstly, that this amylase inhibitor can reduce the blood glucose response markedly without causing malabsorption of carbohydrate. Secondly, from the gut hormone responses it is clear that the slowed digestive and absorptive activity following a meal with an amylase inhibitor occurs further down the small intestine. Thus absorption is spread both in time and space but is complete, though the rise in blood glucose may be very small. Meyer et al, raise the important point that the timing and presentation of the inhibitor may be critical. In Garrow’s study the inhibitors were given 10 min before the starch meal and their results showed no difference in carbohydrate oxidation rate (n 5) or blood glucose and insulin responses (n = 2). Bo-Linn et al, gave two thirds of their inhibitors at the start of the meal and the remaining third halfway through the meal and showed no difference in excretion of faecal calories.5 Most of these inhibitors are polypeptides which may well be inactivated by gastric acid and pepsin. Equally, if given before the meal, they may pass into the small intestine ahead of the amylase released by the test meal and so not inhibit the amylase involved in digestion of the meal. By mixing their inhibitor with fat, Meyer et al, have obviously protected it from inactivation and delivered it effectively to its site of action intimately mixed with ’the
pseudotetrasaccharide
=
carbohydrate. These inhibitors of intestinal enzymes are of considerable scientific interest but their therapeutic role remains to be evaluated fully. The attenuated blood glucose response which they produce may have some value in management of diabetes but the accumulated evidence suggests that they have no place in the treatment of obesity. Indeed a state of iatrogenically induced malabsorption, which is the only way caloric uptake can be reduced, could have hazardous long term consequences. Department of Gastroenterology and Nutrition, Central Middlesex Hospital, London NW10 7NS
RODNEY H. TAYLOR HELEN M. BARKER
ANTIGENIC CHANGES IN MOUSE-ADAPTED INFLUENZA VIRUS STRAINS
SIR,-Many antigenic variants of influenza virus circulate in human and other animal populations. A factor contributing to this variation in viral surface antigens is the selective pressure from the immune human population. The introduction of human virus strain into an animal population leads to a prolonged conservation of the antigenic specificity of the viral haemagglutinin.b However, we do not know whether adaptation to a new host may be in itself a factor affecting the immunological properties of haemagglutinin. To study the problem experimentally we have adapted two human influenza strains of HI subtype (A/USSR/90/77 and A/USSR/50/79) to mice by consecutive passages with the use of intranasal inoculation: the strains acquired an ability to kill mice at 1. Jenkins DJA, Taylor RH, Goff, et al. Scope and specificity of acarbose in slowing carbohydrate absorption in man. Diabetes 1981; 30: 951-54. 2. Taylor RH, Jenkins DJA, Goff DV, et al. Gut hormone response to carbohydrate with acarbose and guar. In: Creutzfeldt W, ed. Proceedings of 1st International Symposium on Acarbose. Amsterdam; Excerpta Medica, 1982: 206-09. 3. Taylor RH, Jenkins DJA, Goff DV, Nineham R, Bloom SR, Sarson D. Enteroglucagon release stimulated by carbohydrate malabsorption. Gut 1980; 21: A449. 4 Uttenthal LO, Ukponmwan OO, Ghatei MA, Bloom SR. Acute and short term effects of intestinal alpha-glucosidase inhibition on gut hormone responses in man. Gut 1983; 24: A461-62. 5. Bo-Linn GW, Santa Ana CA, Morawski SG, Fordtran JS. Starch blockers: Their effect on calorie absorption from a high starch meal. N Engl J Med 1982, 307: 1413-36. 6. Kilbourne ED, ed. Influenza viruses and influenza. New York: Academic Press, 1975: 483.
REACTIVITY OF MONOCLONAL ANTIBODIES WITH MOUSE-ADAPTED INFLUENZA VIRUS STRAINS
the l lth and 8th passage, respectively. The original strains, after isolation from man, underwent three passages in chick embryos. The original strains and the mouse-adapted variants were tested by haemagglutination-inhibition (HAI) against a panel of seven antiHIA monoclonal antibodies raised against a closely related strain (A/Brazil/11/78). The antibodies were kindly donated by Dr J. J. Skehel and Dr A. Douglas (National Institute for Medical
Research, London). The results
(table) reveal a characteristic change in the reactivity
pattern in the course of the adaptation, virtually identical for both virus strains. The change is not a result of host-induced since both original and mouse-adapted variants were in chick embryos and the virus-containing allantoic fluid was used as antigen in the HAI test. The uniformity of the change in both strains suggests that it is not a result of a chance variation. Rather, ’it reflects the change in the receptor zone of the haemagglutinin associated with the adaptation to a new host
modification,
propagated
species.
Host-species-related antigenic groups within subtypes have been reported for avian influenza by H. Fukushi and colleagues (Arch Virol 1982; 72: 217). However, our data are the first, to our knowledge, to register a change in the immunological specificity of influenza haemagglutinin during the crossing of an interspecies barrier.
DI Ivanovsky Institute of Virology, USSR Academy of Medical Sciences, Moscow 123098, USSR
A. K. GITELMAN N. V. KAVERIN I. G. KHARITONENKOV I. A. RUDNEVA V. M. ZHDANOV
CARBAMAZEPINE-INDUCED NON-HEREDITARY ACUTE PORPHYRIA
SiR,—I found Dr Yeung Laiwah and colleagues’ report (April 9, p 790) of a case of non-hereditary acute porphyria induced by combined treatment with carbamazepine and several other antiepileptic drugs interesting but unconvincing. The clinical and biochemical evidence provided does suggest an acute attack of porphyria, but the conclusion that this was a chemically induced syndrome in the absence of genetic predisposition is not well founded. These workers
rest their case on two observations-erythrocyte uroporphyrinogen i synthetase activity rose to normal after withdrawal of carbamazepine therapy, and there was no family history. However, there is a significant overlap in the range of erythrocyte uroporphyrinogen I synthetase between patients with acute intermittent porphyria (AIP) and normal subjects, so a
normal result obtained after withdrawal of carbamazepine does not rule out AIP. How thorough was the family history? The father and mother had normal erythrocyte uroporphyrinogen i synthetase activity, but what about other relatives? If the family study was not exhaustive it cannot be regarded as conclusive. 1. Sassa S, Granick S, Bickers DR, Bradlow HL, Kappas A. A microassay for uroporphyrinogen I synthase, one of three abnormal enzyme activities in acute intermittent prophyria, and its application to the study of the genetics of this disease. Proc Natl Acad Sci USA 1974; 71: 732-36.
pseudotetrasaccharide
=
carbohydrate. These inhibitors of intestinal enzymes are of considerable scientific interest but their therapeutic role remains to be evaluated fully. The attenuated blood glucose response which they produce may have some value in management of diabetes but the accumulated evidence suggests that they have no place in the treatment of obesity. Indeed a state of iatrogenically induced malabsorption, which is the only way caloric uptake can be reduced, could have hazardous long term consequences. Department of Gastroenterology and Nutrition, Central Middlesex Hospital, London NW10 7NS
RODNEY H. TAYLOR HELEN M. BARKER
ANTIGENIC CHANGES IN MOUSE-ADAPTED INFLUENZA VIRUS STRAINS
SIR,-Many antigenic variants of influenza virus circulate in human and other animal populations. A factor contributing to this variation in viral surface antigens is the selective pressure from the immune human population. The introduction of human virus strain into an animal population leads to a prolonged conservation of the antigenic specificity of the viral haemagglutinin.b However, we do not know whether adaptation to a new host may be in itself a factor affecting the immunological properties of haemagglutinin. To study the problem experimentally we have adapted two human influenza strains of HI subtype (A/USSR/90/77 and A/USSR/50/79) to mice by consecutive passages with the use of intranasal inoculation: the strains acquired an ability to kill mice at 1. Jenkins DJA, Taylor RH, Goff, et al. Scope and specificity of acarbose in slowing carbohydrate absorption in man. Diabetes 1981; 30: 951-54. 2. Taylor RH, Jenkins DJA, Goff DV, et al. Gut hormone response to carbohydrate with acarbose and guar. In: Creutzfeldt W, ed. Proceedings of 1st International Symposium on Acarbose. Amsterdam; Excerpta Medica, 1982: 206-09. 3. Taylor RH, Jenkins DJA, Goff DV, Nineham R, Bloom SR, Sarson D. Enteroglucagon release stimulated by carbohydrate malabsorption. Gut 1980; 21: A449. 4 Uttenthal LO, Ukponmwan OO, Ghatei MA, Bloom SR. Acute and short term effects of intestinal alpha-glucosidase inhibition on gut hormone responses in man. Gut 1983; 24: A461-62. 5. Bo-Linn GW, Santa Ana CA, Morawski SG, Fordtran JS. Starch blockers: Their effect on calorie absorption from a high starch meal. N Engl J Med 1982, 307: 1413-36. 6. Kilbourne ED, ed. Influenza viruses and influenza. New York: Academic Press, 1975: 483.
REACTIVITY OF MONOCLONAL ANTIBODIES WITH MOUSE-ADAPTED INFLUENZA VIRUS STRAINS
the l lth and 8th passage, respectively. The original strains, after isolation from man, underwent three passages in chick embryos. The original strains and the mouse-adapted variants were tested by haemagglutination-inhibition (HAI) against a panel of seven antiHIA monoclonal antibodies raised against a closely related strain (A/Brazil/11/78). The antibodies were kindly donated by Dr J. J. Skehel and Dr A. Douglas (National Institute for Medical
Research, London). The results
(table) reveal a characteristic change in the reactivity
pattern in the course of the adaptation, virtually identical for both virus strains. The change is not a result of host-induced since both original and mouse-adapted variants were in chick embryos and the virus-containing allantoic fluid was used as antigen in the HAI test. The uniformity of the change in both strains suggests that it is not a result of a chance variation. Rather, ’it reflects the change in the receptor zone of the haemagglutinin associated with the adaptation to a new host
modification,
propagated
species.
Host-species-related antigenic groups within subtypes have been reported for avian influenza by H. Fukushi and colleagues (Arch Virol 1982; 72: 217). However, our data are the first, to our knowledge, to register a change in the immunological specificity of influenza haemagglutinin during the crossing of an interspecies barrier.
DI Ivanovsky Institute of Virology, USSR Academy of Medical Sciences, Moscow 123098, USSR
A. K. GITELMAN N. V. KAVERIN I. G. KHARITONENKOV I. A. RUDNEVA V. M. ZHDANOV
CARBAMAZEPINE-INDUCED NON-HEREDITARY ACUTE PORPHYRIA
SiR,—I found Dr Yeung Laiwah and colleagues’ report (April 9, p 790) of a case of non-hereditary acute porphyria induced by combined treatment with carbamazepine and several other antiepileptic drugs interesting but unconvincing. The clinical and biochemical evidence provided does suggest an acute attack of porphyria, but the conclusion that this was a chemically induced syndrome in the absence of genetic predisposition is not well founded. These workers
rest their case on two observations-erythrocyte uroporphyrinogen i synthetase activity rose to normal after withdrawal of carbamazepine therapy, and there was no family history. However, there is a significant overlap in the range of erythrocyte uroporphyrinogen I synthetase between patients with acute intermittent porphyria (AIP) and normal subjects, so a
normal result obtained after withdrawal of carbamazepine does not rule out AIP. How thorough was the family history? The father and mother had normal erythrocyte uroporphyrinogen i synthetase activity, but what about other relatives? If the family study was not exhaustive it cannot be regarded as conclusive. 1. Sassa S, Granick S, Bickers DR, Bradlow HL, Kappas A. A microassay for uroporphyrinogen I synthase, one of three abnormal enzyme activities in acute intermittent prophyria, and its application to the study of the genetics of this disease. Proc Natl Acad Sci USA 1974; 71: 732-36.