1350
findings. The ethical implications do not negate the importance of our work. Aluminium does appear in the brains of patients with hepatic failure and metastatic carcinoma but these are not long-term conditions so this cannot be used as an argument against a role for aluminium in AD. Aluminium accumulation in renal failure is very different; such patients have an acute exposure with greatly increased body levels of silicon which may protect them from the effects of aluminium, though neuropathological changes similar to those of AD develop in some.12,13 Department of Nephrology and Biochemistry, London Hospital and London Hospital Medical College, London E1 1BB, UK; and Division of Biology, Pharmaceutical Sciences, University of Aston, Birmingham
PAUL ALTMANN GILLIAN FARRAR SIMON WELCH JOHN A. BLAIR
1. Morris CM, Court JA, Moshtaghie AA, et al. Transferrin and transferrin receptors in normal brain and in Alzheimer’s disease. Biochem Soc Trans 1987; 15: 891-92. 2. Hams DC, Aisen P. Physical biochemistry ofthe transferrins. In: Loehr TM, ed. Iron carriers and iron proteins. New York: VCH, 1989. 3. Dacie JV, Lewis SM, Hoffbrand AV. Investigation of megaloblastic and irondeficiency anaemias. In: Practical haematology. Edinburgh: Churchill Livingstone, 1984. 4. Legget BA. Prevalence of haemochromatosis amongst asymptomatic Australians. Br J Haematol 1990; 74: 525-30. 5. Goya N, Miyazaki S, Kodate S, Ushio B. A family of congenital atransferrinaemia. Blood 1972; 40: 239-45. 6. Kaplan J, Craven C, Alexander J, et al. Regulation of the distribution of tissue iron. Ann NY Acad Sci 1988; 526: 124-35. 7. Candy JM, Oakley AE, Klinowsky J, et al. Aluminosilicates and senile plaque formation in Alzheimer’s disease. Lancet 1986; i: 354-57. 8. Martyn CN, Barker DJP, Osmond C, Hams EC, Edwardson JA, Lacey RF. Geographical relation between Alzheimer’s disease and aluminium in drinking water. Lancet 1989; i: 59-62. 9. Kellett JM, Taylor A, Oram JJ. Aluminosilicates and Alzheimer’s disease. Lancet 1986; i: 682. 10. Barlow PJ, Francois PE, Goldberg I, et al. Trace metal abnormalities in long-stay hyperactive mentally handicapped children and agitated senile dements. J R Soc Med 1986; 79: 581-83. 11. Cochran M, Neoh S, Stephens E. Aluminium interactions with 67Ga uptake by human plasma and transferrin. Clin Chim Acta 1983; 132: 199-203. 12. Brun A, Dictor M. Senile plaques and tangles in dialysis dementia. Acta Pathol Microbiol Scand 1981; 89: 193-98. 13. Scholtz CL, Swash M, Gray A, Kogeorgos J, Marsh F. Neurofibrillary neuronal degeneration in dialysis dementia: a feature of aluminium toxicity. Clin Neuropathol 1987; 6: 93-97.
Guillain-Barré syndrome and Campylobacter jejuni infection SIR,-A high rate of Campylobacter jejuni infection has been reported in patients with the Guillain-Barre syndrome (GBS).1-s Although several possibilities have been suggested, we still have no direct evidence that GBS might be caused by this organism. We report the possibility that C jejuni infection could cause GBS by stimulating the production of antibodies that react with human peripheral nerve-myelin. Myelin proteins were extracted by Norton and Poduslo’s method6 from human sciatic nerve tissues, which were obtained within 24 h of death in patients with non-demyelinating diseases. In crude tissue extracts several protein-bands were electrophoresed and in the purified myelin fraction two main protein-bands at 35 kD and 145 kD and a faint band at 21 5kD were detected. From their migrating position in the gel they were identified as the myelin specific proteins PO, P2, and PI, respectively. An antiserum for C jejuni strain OH4384, a clinical isolate from a patient with GBS, was made in mice by intraperitoneal injection of whole viable bacterial cells. On immunoblotting the antiserum reacted strongly with PO, faintly but significantly with P2, but not with PI protein. This patient’s serum was not available for testing. But we identified these myelin-reactive antibodies in serum from another GBS patient, from whom C jejuni was not isolated, by immunoblotting. These results suggest that there are some protein(s) in Cjejuni which have similar antigenic properties to myelin protein PO and P2. This observation helps to explain the possible pathogenic relation between GBS and C jejuni infection. Studies of experimental allergic neuritis (an animal model of GBS) showed
that immunisation with the P2 protein can induce allergic neutitis.’-9 In addition, Carlo et al10 reported that the antigens to which the sensitised lymphocytes respond are the PO and P2 proteins. The crossreactive antibodies to PO and P2 proteins induced by C jejuni infection possibly cause neural diseases such as GBS. The nature of a crossreactive protein(s) of C jejuni, whether specific on a specific serotype or not, its location on the cell, and the presence of this antibody in cerebrospinal fluid of GBS patients needs to be determined. Department of Bacteriology, Faculty of Medicine, Kyushu University, Maedashi 3-1-1, Fukuoka, Japan
SHUJI FUJIMOTO KAZUNOBU AMAKO
1. Ropper AH. Campylobacter diarrhea and Guillain-Barré syndrome. Arch Neurol 1988; 45: 655-56. 2. Speed BR, Kaldor J, Watosn J, et al. Gampylobacter jejum/Campylobacter coliassociated Guillain-Barré syndrome: immunoblot confirmation of the serological response. Med J Aust 1987; 147; 13-16. 3. Kaldor J, Speed BR. Guillain-Barré syndrome Campylobacter jejuni: a serological study. Br MedJ 1984; 288: 1867-70 4. Molnar GK, Mertsola J, Erkko M. Guillain-Barré syndrome associated with Campylobacter infection. Br MedJ 1982; 285: 652. 5. Rhodes KM, Tattersfield AE. Guillain-Barrié syndrome associated with Campylobacter infection. Br Med J 1982; 285: 173-74. 6. Norton WT, Poduslo SE. Myelination in rat brain: method of myelin isolation. J Neurochem 1973; 21: 749-57. 7. Suzuki M, Kitamura K, Uyemura K, et al. Neuritogenic activity of peripheral nerve myelin proteins in Lewis rats. Neurosci Lett 1980; 19: 353-58. 8. Weise MJ, Hsieh D, Hoffman PM, et al. Bovine peripheral nervous system myelin P2 protein: chemical and immunological characterization of the cyanogen bromide peptides. J Neurochem 1980; 35: 393-99. 9. Kadlubowski M, Hughes RAC. Identification of the neuritogen for experimental allergic neuritis. Nature 1979; 277: 140-41. 10. Carlo DJ, Karkhanis YD, Bailey PJ, et al. Experimantal allergic neuritis: evidence for the involvement of the P0 and P2 proteins. Brain Res 1975; 88: 580-84.
Induction of von Willebrand disease type I by valproic acid SIR,-Under valproic acid (VPA) therapy most patients remain symptom-free but some have shown severe hepatotoxicity.l Haematological reactions2 include haemorrhagic diatheses, thrombocytopenia, and decreases in fibrinogen. 3,4 In our outpatient clinic we have frequently observed haemorrhage in children treated with VPA. Among 83 children on VPA we often found haemorrhagic disorders combined with a decrease in factor VIII/von Willebrand factor (vWF)-complex. Because the laboratory findings resembled those of congenital von Willebrand disease (vWD) we continued our observations in 30 children selected at random. These children (aged 1-18 years; 16 male and 14 female) were studied from March, 1985, until January, 1987. The daily dose was 300-2500 mg (typically 20-30 mg/kg) and the children had been on the drug for 6 months to 14 years. These children had not previously had a defect in haemostasis and they had no family history of bleeding disorders. We compared data in these children with those in 43 children (30 male and 13 female, aged 7 months to 14 years) with congenital vWD, excluding
Fig 1-Distribution of bleeding time among children treated with VPA and children with congenital vWD.
findings. The ethical implications do not negate the importance of our work. Aluminium does appear in the brains of patients with hepatic failure and metastatic carcinoma but these are not long-term conditions so this cannot be used as an argument against a role for aluminium in AD. Aluminium accumulation in renal failure is very different; such patients have an acute exposure with greatly increased body levels of silicon which may protect them from the effects of aluminium, though neuropathological changes similar to those of AD develop in some.12,13 Department of Nephrology and Biochemistry, London Hospital and London Hospital Medical College, London E1 1BB, UK; and Division of Biology, Pharmaceutical Sciences, University of Aston, Birmingham
PAUL ALTMANN GILLIAN FARRAR SIMON WELCH JOHN A. BLAIR
1. Morris CM, Court JA, Moshtaghie AA, et al. Transferrin and transferrin receptors in normal brain and in Alzheimer’s disease. Biochem Soc Trans 1987; 15: 891-92. 2. Hams DC, Aisen P. Physical biochemistry ofthe transferrins. In: Loehr TM, ed. Iron carriers and iron proteins. New York: VCH, 1989. 3. Dacie JV, Lewis SM, Hoffbrand AV. Investigation of megaloblastic and irondeficiency anaemias. In: Practical haematology. Edinburgh: Churchill Livingstone, 1984. 4. Legget BA. Prevalence of haemochromatosis amongst asymptomatic Australians. Br J Haematol 1990; 74: 525-30. 5. Goya N, Miyazaki S, Kodate S, Ushio B. A family of congenital atransferrinaemia. Blood 1972; 40: 239-45. 6. Kaplan J, Craven C, Alexander J, et al. Regulation of the distribution of tissue iron. Ann NY Acad Sci 1988; 526: 124-35. 7. Candy JM, Oakley AE, Klinowsky J, et al. Aluminosilicates and senile plaque formation in Alzheimer’s disease. Lancet 1986; i: 354-57. 8. Martyn CN, Barker DJP, Osmond C, Hams EC, Edwardson JA, Lacey RF. Geographical relation between Alzheimer’s disease and aluminium in drinking water. Lancet 1989; i: 59-62. 9. Kellett JM, Taylor A, Oram JJ. Aluminosilicates and Alzheimer’s disease. Lancet 1986; i: 682. 10. Barlow PJ, Francois PE, Goldberg I, et al. Trace metal abnormalities in long-stay hyperactive mentally handicapped children and agitated senile dements. J R Soc Med 1986; 79: 581-83. 11. Cochran M, Neoh S, Stephens E. Aluminium interactions with 67Ga uptake by human plasma and transferrin. Clin Chim Acta 1983; 132: 199-203. 12. Brun A, Dictor M. Senile plaques and tangles in dialysis dementia. Acta Pathol Microbiol Scand 1981; 89: 193-98. 13. Scholtz CL, Swash M, Gray A, Kogeorgos J, Marsh F. Neurofibrillary neuronal degeneration in dialysis dementia: a feature of aluminium toxicity. Clin Neuropathol 1987; 6: 93-97.
Guillain-Barré syndrome and Campylobacter jejuni infection SIR,-A high rate of Campylobacter jejuni infection has been reported in patients with the Guillain-Barre syndrome (GBS).1-s Although several possibilities have been suggested, we still have no direct evidence that GBS might be caused by this organism. We report the possibility that C jejuni infection could cause GBS by stimulating the production of antibodies that react with human peripheral nerve-myelin. Myelin proteins were extracted by Norton and Poduslo’s method6 from human sciatic nerve tissues, which were obtained within 24 h of death in patients with non-demyelinating diseases. In crude tissue extracts several protein-bands were electrophoresed and in the purified myelin fraction two main protein-bands at 35 kD and 145 kD and a faint band at 21 5kD were detected. From their migrating position in the gel they were identified as the myelin specific proteins PO, P2, and PI, respectively. An antiserum for C jejuni strain OH4384, a clinical isolate from a patient with GBS, was made in mice by intraperitoneal injection of whole viable bacterial cells. On immunoblotting the antiserum reacted strongly with PO, faintly but significantly with P2, but not with PI protein. This patient’s serum was not available for testing. But we identified these myelin-reactive antibodies in serum from another GBS patient, from whom C jejuni was not isolated, by immunoblotting. These results suggest that there are some protein(s) in Cjejuni which have similar antigenic properties to myelin protein PO and P2. This observation helps to explain the possible pathogenic relation between GBS and C jejuni infection. Studies of experimental allergic neuritis (an animal model of GBS) showed
that immunisation with the P2 protein can induce allergic neutitis.’-9 In addition, Carlo et al10 reported that the antigens to which the sensitised lymphocytes respond are the PO and P2 proteins. The crossreactive antibodies to PO and P2 proteins induced by C jejuni infection possibly cause neural diseases such as GBS. The nature of a crossreactive protein(s) of C jejuni, whether specific on a specific serotype or not, its location on the cell, and the presence of this antibody in cerebrospinal fluid of GBS patients needs to be determined. Department of Bacteriology, Faculty of Medicine, Kyushu University, Maedashi 3-1-1, Fukuoka, Japan
SHUJI FUJIMOTO KAZUNOBU AMAKO
1. Ropper AH. Campylobacter diarrhea and Guillain-Barré syndrome. Arch Neurol 1988; 45: 655-56. 2. Speed BR, Kaldor J, Watosn J, et al. Gampylobacter jejum/Campylobacter coliassociated Guillain-Barré syndrome: immunoblot confirmation of the serological response. Med J Aust 1987; 147; 13-16. 3. Kaldor J, Speed BR. Guillain-Barré syndrome Campylobacter jejuni: a serological study. Br MedJ 1984; 288: 1867-70 4. Molnar GK, Mertsola J, Erkko M. Guillain-Barré syndrome associated with Campylobacter infection. Br MedJ 1982; 285: 652. 5. Rhodes KM, Tattersfield AE. Guillain-Barrié syndrome associated with Campylobacter infection. Br Med J 1982; 285: 173-74. 6. Norton WT, Poduslo SE. Myelination in rat brain: method of myelin isolation. J Neurochem 1973; 21: 749-57. 7. Suzuki M, Kitamura K, Uyemura K, et al. Neuritogenic activity of peripheral nerve myelin proteins in Lewis rats. Neurosci Lett 1980; 19: 353-58. 8. Weise MJ, Hsieh D, Hoffman PM, et al. Bovine peripheral nervous system myelin P2 protein: chemical and immunological characterization of the cyanogen bromide peptides. J Neurochem 1980; 35: 393-99. 9. Kadlubowski M, Hughes RAC. Identification of the neuritogen for experimental allergic neuritis. Nature 1979; 277: 140-41. 10. Carlo DJ, Karkhanis YD, Bailey PJ, et al. Experimantal allergic neuritis: evidence for the involvement of the P0 and P2 proteins. Brain Res 1975; 88: 580-84.
Induction of von Willebrand disease type I by valproic acid SIR,-Under valproic acid (VPA) therapy most patients remain symptom-free but some have shown severe hepatotoxicity.l Haematological reactions2 include haemorrhagic diatheses, thrombocytopenia, and decreases in fibrinogen. 3,4 In our outpatient clinic we have frequently observed haemorrhage in children treated with VPA. Among 83 children on VPA we often found haemorrhagic disorders combined with a decrease in factor VIII/von Willebrand factor (vWF)-complex. Because the laboratory findings resembled those of congenital von Willebrand disease (vWD) we continued our observations in 30 children selected at random. These children (aged 1-18 years; 16 male and 14 female) were studied from March, 1985, until January, 1987. The daily dose was 300-2500 mg (typically 20-30 mg/kg) and the children had been on the drug for 6 months to 14 years. These children had not previously had a defect in haemostasis and they had no family history of bleeding disorders. We compared data in these children with those in 43 children (30 male and 13 female, aged 7 months to 14 years) with congenital vWD, excluding
Fig 1-Distribution of bleeding time among children treated with VPA and children with congenital vWD.
