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HL-A ANTIGENS AND DIABETES MELLITUS
1153
dangerous influences, for they have no hold, protect, and cherish them.
evil and to
true
mother
Physicians can do nothing to prevent the battered baby; it is a fait accompli; nor can they rectify the education system producing maternal palsy; but a concerted effort by general practitioners, obstetricians, and poediatricians can prevent the warping effect on the offspring. The women need constant manipulation at every juncture of their mothering to correct their own perverse and rejecting bent, to draw them back from the influence of commercial fashion (facing-away prams and artificial laps), and fix them to the pattern of the cherishing, self-effacing, intimate, and intuitive mother that is the norm for the human being. Without that medical effort (and an eye on the associated nursing staff), the human, whose Being depends entirely on a lively, pre-adult-long, fast mother-child bond, will certainly cease to be. Selly Oak Hospital, LOUISE F. W. EICKHOFF. Birmingham B29 6JD.
risk of developing juvenile-onset insulin-dependent diabetes. The possibility of loci for immune response gene(s) predisposing to diabetes linked to the major HL-A loci is further strengthened by the study of HL-A antigens in families in which there are several members of a sibship with diabetes. We have studied four such families (an example is shown in the figure). The subjects II 4 and II 6 developed acute-onset diabetes simultaneously (age twentyone and thirteen years, respectively) after an influenza-like illness. II 5 developed diabetes two years previously. Standard 50 g. oral glucose-tolerance tests were normal in the remaining siblings apart from II 2 who showed unequivocal evidence of chemical diabetes. This individual and the three with clinical diabetes share the W29,8 haplotype. Within the families so far studied, the presence of diabetes is always associated with the inheritance by each affected sibling of a haplotype including either HL-8 or
W15,
or
both.
unlikely that susceptibility to this type of diabetes is directly related to these HL-A antigens, but more probable that particular immune-response genes are in linkage disequilibrium with HL-A8 and W15. Juvenile-onset3 diabetes is genetically heterogeneous. Tattersall and Pyke showed that approximately 50% of identical twins were discordant in respect of diabetes, suggesting variability in the importance of environmental and genetic factors. It would be of great interest to determine the frequencies of It is
HL-A ANTIGENS AND DIABETES MELLITUS SiR,—We have performed HL-A typing on 100 cases of diabetes mellitus in Liverpool (50 with an onset before the age of thirty years and 50 with an onset after this age). The data have been analysed both on their own and also in combination with the results from two earlier studies 1,2 and with the data of Dr Nerup and his colleagues from Denmark
(Oct. 12,
p.
864).
HL-A8 was present in 27 (54%) of the juvenile-onset diabetics compared with 74 out of 233 (31-8%) of the controls. The relative incidence is 2-52 (P =0-0056). When p is multiplied by the number of specificities tested, the probability becomes 0-129. In relation to W15, 9 (18%)
HL-A antigens, juvenile-onset diabetes, and abnormal oral glucose-tolerance tests in one family.
of the
juvenile-onset patients
were
positive
as
against 28
(12%) of controls. When the data are combined with those of the Danish workers and Finkelstein et al.l the combined relative risk for juvenile-onset diabetes is 2-41 CX3= 2559, 1 d.f.) for HL-A8, and 2-34 (X2=18-1, 1 d.f.) for W15, without evidence of heterogeneity between these studies. When data relating to insulin-dependent diabetics from our series and from the three other studies are combined, the relative risk for HL-A8 is 2-12 Cx2=26’74,1 d.f.) and for W15 the combined relative risk is 2-60 (XZ=3448, 1 d.f.), again without evidence of heterogeneity. Similar to the findings of Dr Nerup and his colleagues we found no significant disturbance of the HL-A frequencies in relation to maturity-onset diabetes. Thus, the evidence indicates that HL-A8 and W15 positive individuals have a 2-3 fold 1. 2.
Finkelstein, S., Zeller, E., Walford, R. L. Tissue Antigens, 1972, 2, 74. Singal, D. P., Blajchman, M. A. Diabetes, 1973, 22, 429.
HL-A8 and W15 in identical twins who are concordant and discordant for juvenile-onset diabetes mellitus. It is possible to speculate that the basis of the association of acute-onset juvenile diabetes with the HL-A system may be a defective immune response to a virus infection. Epidemiological and serological evidence has been put forward to suggest that infection with Coxsackie B virus may be a precipitating factor in acute-onset juvenile diabetes. 4.5 In addition, some variants of the encephalomyocarditis virus and Coxsackie B virus have been shown experimentally to produce islet-cell damage in mice.6.7 It would seem to be worth while to explore further the hypothesis that in a proportion of acute-onset juvenile diabetics virus infection may be involved and that the susceptibility to beta-cell damage may be influenced by genes in the HL-A chromosomal region. These genes might influence the virus-receptor sites or modify adversely the immune 8 response to certain viruses. Department of Medicine, University of Liverpool, A. G. CUDWORTH P.O. Box 147, Liverpool, L69 3BX. J. C. WOODROW.
VITAMIN C AND SCHIZOPHRENIA
SIR,-Dr Lee (Sept. 28, p. 775) cites two reports 9.10 the results of which appear " to demonstrate that schizophrenics have a greater than normal requirement for vitamin C, although neither paper gives any dietary information". In 1971 11 a colleague and I compared the buffy-layer ascorbic-acid levels of 32 schizophrenics and 24 controls in the same ward and on the same hospital diet (Claybury, Essex) and found significantly higher levels in the schizophrenic group. Furthermore, patients from 3. Tattersall, R. B., Pyke, D. A. Lancet, 1972, ii, 1120. 4. Gamble, D. R., Taylor, K. W. Br. med. J. 1969, iii, 631. 5. Gamble, D. R., Taylor, K. W., Cumming, H. ibid. 1973, iv, 260. 6. Craighead, J. E., McLane, M. F. Science, 1968, 162, 913. 7. Burch, G. E., Tsui, C. Y., Harb, J. M., Colcolough H. L. Archs intern. Med. 1971, 128, 40. 8. McDevitt, H. O., Bodmer, W. F. Lancet, 1974, i, 1269. 9. Milner, G. Br. J. Psych. 1963, 109, 294. 10. Pauling, L., et al. Orthomolecular Psychiatry. San Francisco, 1973. 11. Pitt, B., Pollitt, N. Br. J. Psych. 1971, 118, 227.
dangerous influences, for they have no hold, protect, and cherish them.
evil and to
true
mother
Physicians can do nothing to prevent the battered baby; it is a fait accompli; nor can they rectify the education system producing maternal palsy; but a concerted effort by general practitioners, obstetricians, and poediatricians can prevent the warping effect on the offspring. The women need constant manipulation at every juncture of their mothering to correct their own perverse and rejecting bent, to draw them back from the influence of commercial fashion (facing-away prams and artificial laps), and fix them to the pattern of the cherishing, self-effacing, intimate, and intuitive mother that is the norm for the human being. Without that medical effort (and an eye on the associated nursing staff), the human, whose Being depends entirely on a lively, pre-adult-long, fast mother-child bond, will certainly cease to be. Selly Oak Hospital, LOUISE F. W. EICKHOFF. Birmingham B29 6JD.
risk of developing juvenile-onset insulin-dependent diabetes. The possibility of loci for immune response gene(s) predisposing to diabetes linked to the major HL-A loci is further strengthened by the study of HL-A antigens in families in which there are several members of a sibship with diabetes. We have studied four such families (an example is shown in the figure). The subjects II 4 and II 6 developed acute-onset diabetes simultaneously (age twentyone and thirteen years, respectively) after an influenza-like illness. II 5 developed diabetes two years previously. Standard 50 g. oral glucose-tolerance tests were normal in the remaining siblings apart from II 2 who showed unequivocal evidence of chemical diabetes. This individual and the three with clinical diabetes share the W29,8 haplotype. Within the families so far studied, the presence of diabetes is always associated with the inheritance by each affected sibling of a haplotype including either HL-8 or
W15,
or
both.
unlikely that susceptibility to this type of diabetes is directly related to these HL-A antigens, but more probable that particular immune-response genes are in linkage disequilibrium with HL-A8 and W15. Juvenile-onset3 diabetes is genetically heterogeneous. Tattersall and Pyke showed that approximately 50% of identical twins were discordant in respect of diabetes, suggesting variability in the importance of environmental and genetic factors. It would be of great interest to determine the frequencies of It is
HL-A ANTIGENS AND DIABETES MELLITUS SiR,—We have performed HL-A typing on 100 cases of diabetes mellitus in Liverpool (50 with an onset before the age of thirty years and 50 with an onset after this age). The data have been analysed both on their own and also in combination with the results from two earlier studies 1,2 and with the data of Dr Nerup and his colleagues from Denmark
(Oct. 12,
p.
864).
HL-A8 was present in 27 (54%) of the juvenile-onset diabetics compared with 74 out of 233 (31-8%) of the controls. The relative incidence is 2-52 (P =0-0056). When p is multiplied by the number of specificities tested, the probability becomes 0-129. In relation to W15, 9 (18%)
HL-A antigens, juvenile-onset diabetes, and abnormal oral glucose-tolerance tests in one family.
of the
juvenile-onset patients
were
positive
as
against 28
(12%) of controls. When the data are combined with those of the Danish workers and Finkelstein et al.l the combined relative risk for juvenile-onset diabetes is 2-41 CX3= 2559, 1 d.f.) for HL-A8, and 2-34 (X2=18-1, 1 d.f.) for W15, without evidence of heterogeneity between these studies. When data relating to insulin-dependent diabetics from our series and from the three other studies are combined, the relative risk for HL-A8 is 2-12 Cx2=26’74,1 d.f.) and for W15 the combined relative risk is 2-60 (XZ=3448, 1 d.f.), again without evidence of heterogeneity. Similar to the findings of Dr Nerup and his colleagues we found no significant disturbance of the HL-A frequencies in relation to maturity-onset diabetes. Thus, the evidence indicates that HL-A8 and W15 positive individuals have a 2-3 fold 1. 2.
Finkelstein, S., Zeller, E., Walford, R. L. Tissue Antigens, 1972, 2, 74. Singal, D. P., Blajchman, M. A. Diabetes, 1973, 22, 429.
HL-A8 and W15 in identical twins who are concordant and discordant for juvenile-onset diabetes mellitus. It is possible to speculate that the basis of the association of acute-onset juvenile diabetes with the HL-A system may be a defective immune response to a virus infection. Epidemiological and serological evidence has been put forward to suggest that infection with Coxsackie B virus may be a precipitating factor in acute-onset juvenile diabetes. 4.5 In addition, some variants of the encephalomyocarditis virus and Coxsackie B virus have been shown experimentally to produce islet-cell damage in mice.6.7 It would seem to be worth while to explore further the hypothesis that in a proportion of acute-onset juvenile diabetics virus infection may be involved and that the susceptibility to beta-cell damage may be influenced by genes in the HL-A chromosomal region. These genes might influence the virus-receptor sites or modify adversely the immune 8 response to certain viruses. Department of Medicine, University of Liverpool, A. G. CUDWORTH P.O. Box 147, Liverpool, L69 3BX. J. C. WOODROW.
VITAMIN C AND SCHIZOPHRENIA
SIR,-Dr Lee (Sept. 28, p. 775) cites two reports 9.10 the results of which appear " to demonstrate that schizophrenics have a greater than normal requirement for vitamin C, although neither paper gives any dietary information". In 1971 11 a colleague and I compared the buffy-layer ascorbic-acid levels of 32 schizophrenics and 24 controls in the same ward and on the same hospital diet (Claybury, Essex) and found significantly higher levels in the schizophrenic group. Furthermore, patients from 3. Tattersall, R. B., Pyke, D. A. Lancet, 1972, ii, 1120. 4. Gamble, D. R., Taylor, K. W. Br. med. J. 1969, iii, 631. 5. Gamble, D. R., Taylor, K. W., Cumming, H. ibid. 1973, iv, 260. 6. Craighead, J. E., McLane, M. F. Science, 1968, 162, 913. 7. Burch, G. E., Tsui, C. Y., Harb, J. M., Colcolough H. L. Archs intern. Med. 1971, 128, 40. 8. McDevitt, H. O., Bodmer, W. F. Lancet, 1974, i, 1269. 9. Milner, G. Br. J. Psych. 1963, 109, 294. 10. Pauling, L., et al. Orthomolecular Psychiatry. San Francisco, 1973. 11. Pitt, B., Pollitt, N. Br. J. Psych. 1971, 118, 227.