483
baseline23 has provided evidence that low dietary magnesium is predictive of IHD. 7-day weighed dietary records were kept by 665 men.4 Prevalent heart disease was identified by the London School of Hygiene and Tropical Medicine questionnaire and by electrocardiography, with standard criteria,5 and men were divided into those with symptomatic heart disease (previous myocardial infarction and/or current angina; 97 men) and those with no relevant symptoms (568 men). Incident heart disease events were identified during the following 5 years. These consisted of deaths certified as due to IHD (ICD 410-414) and non-fatal myocardial infarctions that fulfilled World Health Organisation criteria .6 Mean daily intakes of magnesium were: Quantitative HIV-1 and HHV-6 PCR assays on maternal and fetal PBMC DNA. DNA submitted to PCR was serially five-fold diluted from 100 ng (lane to 0-03 ng (lane 6) for maternal PBMCs and from 5 Jlg (lane 7) to 1 6 pg (lane 12) for fetal PBMCs HIV-1 amplification was done with the primers P3/P46 and HHV-6 PCR with the primers 022/023, the sequences of which are located m the major capstde protein gene (022: 5’-GCG TGA ATC AAA CCT CGC TCG-3’; 023. 5’GCC TTA CTC GGA ATC TAC TGC-3’)." Amplified products were analysed on agarose gel, transferred on nylon membranes, and hybridised with ’P-labelled
No of men
/Vo symptomatic IHD //D at af baseline /)aNe//ne No incident event An IHD event af baseline &ae//ne Sy/npfo/TMf/c //-/0 at No incident event An IHD event
Nosymptomatic Symptomatic IHD
1)
oligomer probes. Our results show that HHV-6 can be transmitted in utero in association with maternal viraemia. The absence of maternal HHV-6 IgM antibodies indicates that transmission can occur even when the mother has previous immunity to the virus, but this remains to be confirmed. Intrauterine transmission strengthens even more the relation of HHV-6 to human cytomegalovirus which is also supported by the comparison of genomic organisation8 and antiviral susceptibility.9
JEAN-THIERRY AUBIN Bactériologie-Virologie, CERVI, Hôpital Pitié-Salpétrière, 75651 Paris, France
LAURENT POIREL HENRI AGUT JEAN-MARIE HURAUX
Centre d’Hémobiologie Périnatale, Hôpital Saint-Antoine, Paris
CHRISTIANE BIGNOZZI YVES BROSSARD
Laboratoire d’Embryoilogie Pathologique, et de Cytogénétique, Hôpital Saint-Antoine, Paris
NICOLE MULLIEZ JOELLE ROUME
Service de
FABRICE LECURU ROLAND TAURELLE
Laboratoire de
Gynécologie-Obstétrique, Hôpital Boucicaut, Paris
K, Okuno T, Shiraki K, et al. Identification of human herpesvirus-6 as causal agent for exanthem subitum. Lancet 1988; i: 1065-67. 2 Prusksananonda P, Breese Hall C, Insel RA, et al. Primary human herpesvirus 6 infection in young children. N Engl J Med 1992; 32: 1445-50. 3. Ueda K, Kusuhara K, Hirose M, et al. Exanthem subitum and antibody to human herpesvirus-6. J Infect Dis 1989; 159: 750-52. 4 Aubin JT, Collandre H, Candotti D, et al. Several groups among human herpesvirus 6 can be distinguished by southern blotting and polymerase chain reaction. J Clin Microbiol 1991; 29: 367-72 5. Ou CY, Kwok S, Mitchell SW, et al DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science 1988, 239: 295-97. 6 Laure F, Courgnaud V, Rouzioux C, et al. Detection of HIV-1 DNA in infants and children by means of polymerase chain reaction. Lancet 1988; ii: 538-40. 7 Robert C, Agut H, Aubin JT, et al. Detection of antibodies to human herpesvirus 6 using immunofluorescence assay. Res Virol 1990; 141: 545-55. 8 Lawrence GL, Chee M, Craxton MA, Compels UA, Honess RW, Barrell BG. Human herpesvirus 6 is closely related to human cytomegalovirus. J Virol 1990; 64: 287-99. 9. Agut H, Aubin JT, Huraux JM. Homogeneous susceptibility of distinct human herpesvirus 6 to antivirals in vitro. J Infect Dis 1991; 163: 1382-83. 1 Yamanishi
Dietary magnesium and prediction
of heart
disease SIR,-The LIMIT-2 trial (June 27, p 1553) makes a most important contribution to a confused topic-ie, the relevance of magnesium to ischaemic heart disease (IHD). This new evidence establishes the value of magnesium in the treatment of myocardial mfarction. But what is its role in prevention before infarction? Magnesium has long been of interest in relation to IHD. One observation consistent with an aetiological role is reduced amounts in the myocardium of subjects whose deaths had been certified as due to heart disease, even when death had been "sudden". The Caerphilly Heart Disease study of men aged 45-59 years at
540 28 87 10
Mean intake
(SD) (mg Mgjday) 310 310 (105) 274 (81) 283 283 (91) (91)
248 (86)
The mean daily intake of magnesium was about 12 % lower in men who later had an IHD event, both in those with IHD at baseline and those without. Overall, the intake was lower by 38-9 mg (95% confidence interval [CI] 5 3-72mg) in those who had an event, and adjustment for the presence or absence of baseline symptoms reduces this difference to 35-6 mg daily (95% CI 2-0-691).
MRC
Epidemiology Unit (South Wales), Llandough Hospital, Penarth, South Glamorgan CF6 1XX, UK
P. C. ELWOOD A. M. FEHILY P. M. SWEETNAM J. W. G. YARNELL
1. Elwood
2.
3.
4. 5.
6.
PC, Sweetnam PM, Beasley WH, Jones D, France R. Magnesium and calcium in the myocardium: cause of death and area differences. Lancet 1980; ii: 720-22. Caerphilly and Speedwell Collaborative Group Caerphilly and Speedwell collaborative heart disease studies. J Epidemiol Community Health 1984; 38: 259-62. The Caerphilly Collaborative Heart Disease Studies. Project description and manual of operations. Cardiff: MRC Epidemiology Unit, 1985. Fehily AM, Yarnell JWG, Butland BK. Diet and ischaemic heart disease in the Caerphilly study. Human Nutr Appl Nutr 1987; 41A: 319-26. Bainton D, Baker IA, Sweetnam PM, Yarnell JWG, Elwood PC. Prevalence of ischaemic heart disease: the Caerphilly and Speedwell Surveys. Br Heart J 1988; 59: 201-06. Yarnell JWG, Baker IA, Sweetnam PM, et al. Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease: the Caerphilly and Speedwell Collaborative Heart Disease Studies. Circulation 1991; 83: 836-14.
Striking identity between HIV-1 envelope glycoprotein gp120 and its CD4 receptor SIR,--Oligopeptides, such as the pentapeptides homoregulatory peptide and epidermal pentapeptide,l are involved in many biological processes.1-s Some have been mapped in the HIV-1 envelope.4,5 On the basis of the homology that they share with immunoregulatory molecules such as interleukin-2 receptorbinding domain or a-interferon-p I 5E, they are likely to have a role in the immune dysregulation observed in AIDS.4,5 We have designed software (Automat) to find systematically all peptidic homologies between proteins in a bank and a given protein.5 Scanning the HIV-1 envelope sequences revealed a pentapeptide identity (SLWDQ) with the CD4 molecule at positions 110-114 in the HIV-1envelope and 60-64 in CD4. Exploration of the MIPS data bank revealed the pentapeptide sequence in only one other protein, the aminotransferase A64988. The sequence is perfectly conserved among all HIV-1strains (but is lacking in HIV-2 and simian immunodeficiency virus) and in human and chimpanzee CD4. The SLWDQ pentapeptide is located in the N-terminal part of the gpl20 external membrane protein of HIV-1. This segment lies on an accessible loop of the first domain of CD4,6 and is the epitope for the OKT4a monoclonal antibody.’ Moreover this region has an important function in the CD4 molecule since OKT4a monoclonal antibodies (specifically directed towards this region) can block T4 cell immune activation,8 and a W-to-C mutation suppresses the binding of HIV-1.’ In agreement with the above mentioned biological characteristics, the
baseline23 has provided evidence that low dietary magnesium is predictive of IHD. 7-day weighed dietary records were kept by 665 men.4 Prevalent heart disease was identified by the London School of Hygiene and Tropical Medicine questionnaire and by electrocardiography, with standard criteria,5 and men were divided into those with symptomatic heart disease (previous myocardial infarction and/or current angina; 97 men) and those with no relevant symptoms (568 men). Incident heart disease events were identified during the following 5 years. These consisted of deaths certified as due to IHD (ICD 410-414) and non-fatal myocardial infarctions that fulfilled World Health Organisation criteria .6 Mean daily intakes of magnesium were: Quantitative HIV-1 and HHV-6 PCR assays on maternal and fetal PBMC DNA. DNA submitted to PCR was serially five-fold diluted from 100 ng (lane to 0-03 ng (lane 6) for maternal PBMCs and from 5 Jlg (lane 7) to 1 6 pg (lane 12) for fetal PBMCs HIV-1 amplification was done with the primers P3/P46 and HHV-6 PCR with the primers 022/023, the sequences of which are located m the major capstde protein gene (022: 5’-GCG TGA ATC AAA CCT CGC TCG-3’; 023. 5’GCC TTA CTC GGA ATC TAC TGC-3’)." Amplified products were analysed on agarose gel, transferred on nylon membranes, and hybridised with ’P-labelled
No of men
/Vo symptomatic IHD //D at af baseline /)aNe//ne No incident event An IHD event af baseline &ae//ne Sy/npfo/TMf/c //-/0 at No incident event An IHD event
Nosymptomatic Symptomatic IHD
1)
oligomer probes. Our results show that HHV-6 can be transmitted in utero in association with maternal viraemia. The absence of maternal HHV-6 IgM antibodies indicates that transmission can occur even when the mother has previous immunity to the virus, but this remains to be confirmed. Intrauterine transmission strengthens even more the relation of HHV-6 to human cytomegalovirus which is also supported by the comparison of genomic organisation8 and antiviral susceptibility.9
JEAN-THIERRY AUBIN Bactériologie-Virologie, CERVI, Hôpital Pitié-Salpétrière, 75651 Paris, France
LAURENT POIREL HENRI AGUT JEAN-MARIE HURAUX
Centre d’Hémobiologie Périnatale, Hôpital Saint-Antoine, Paris
CHRISTIANE BIGNOZZI YVES BROSSARD
Laboratoire d’Embryoilogie Pathologique, et de Cytogénétique, Hôpital Saint-Antoine, Paris
NICOLE MULLIEZ JOELLE ROUME
Service de
FABRICE LECURU ROLAND TAURELLE
Laboratoire de
Gynécologie-Obstétrique, Hôpital Boucicaut, Paris
K, Okuno T, Shiraki K, et al. Identification of human herpesvirus-6 as causal agent for exanthem subitum. Lancet 1988; i: 1065-67. 2 Prusksananonda P, Breese Hall C, Insel RA, et al. Primary human herpesvirus 6 infection in young children. N Engl J Med 1992; 32: 1445-50. 3. Ueda K, Kusuhara K, Hirose M, et al. Exanthem subitum and antibody to human herpesvirus-6. J Infect Dis 1989; 159: 750-52. 4 Aubin JT, Collandre H, Candotti D, et al. Several groups among human herpesvirus 6 can be distinguished by southern blotting and polymerase chain reaction. J Clin Microbiol 1991; 29: 367-72 5. Ou CY, Kwok S, Mitchell SW, et al DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science 1988, 239: 295-97. 6 Laure F, Courgnaud V, Rouzioux C, et al. Detection of HIV-1 DNA in infants and children by means of polymerase chain reaction. Lancet 1988; ii: 538-40. 7 Robert C, Agut H, Aubin JT, et al. Detection of antibodies to human herpesvirus 6 using immunofluorescence assay. Res Virol 1990; 141: 545-55. 8 Lawrence GL, Chee M, Craxton MA, Compels UA, Honess RW, Barrell BG. Human herpesvirus 6 is closely related to human cytomegalovirus. J Virol 1990; 64: 287-99. 9. Agut H, Aubin JT, Huraux JM. Homogeneous susceptibility of distinct human herpesvirus 6 to antivirals in vitro. J Infect Dis 1991; 163: 1382-83. 1 Yamanishi
Dietary magnesium and prediction
of heart
disease SIR,-The LIMIT-2 trial (June 27, p 1553) makes a most important contribution to a confused topic-ie, the relevance of magnesium to ischaemic heart disease (IHD). This new evidence establishes the value of magnesium in the treatment of myocardial mfarction. But what is its role in prevention before infarction? Magnesium has long been of interest in relation to IHD. One observation consistent with an aetiological role is reduced amounts in the myocardium of subjects whose deaths had been certified as due to heart disease, even when death had been "sudden". The Caerphilly Heart Disease study of men aged 45-59 years at
540 28 87 10
Mean intake
(SD) (mg Mgjday) 310 310 (105) 274 (81) 283 283 (91) (91)
248 (86)
The mean daily intake of magnesium was about 12 % lower in men who later had an IHD event, both in those with IHD at baseline and those without. Overall, the intake was lower by 38-9 mg (95% confidence interval [CI] 5 3-72mg) in those who had an event, and adjustment for the presence or absence of baseline symptoms reduces this difference to 35-6 mg daily (95% CI 2-0-691).
MRC
Epidemiology Unit (South Wales), Llandough Hospital, Penarth, South Glamorgan CF6 1XX, UK
P. C. ELWOOD A. M. FEHILY P. M. SWEETNAM J. W. G. YARNELL
1. Elwood
2.
3.
4. 5.
6.
PC, Sweetnam PM, Beasley WH, Jones D, France R. Magnesium and calcium in the myocardium: cause of death and area differences. Lancet 1980; ii: 720-22. Caerphilly and Speedwell Collaborative Group Caerphilly and Speedwell collaborative heart disease studies. J Epidemiol Community Health 1984; 38: 259-62. The Caerphilly Collaborative Heart Disease Studies. Project description and manual of operations. Cardiff: MRC Epidemiology Unit, 1985. Fehily AM, Yarnell JWG, Butland BK. Diet and ischaemic heart disease in the Caerphilly study. Human Nutr Appl Nutr 1987; 41A: 319-26. Bainton D, Baker IA, Sweetnam PM, Yarnell JWG, Elwood PC. Prevalence of ischaemic heart disease: the Caerphilly and Speedwell Surveys. Br Heart J 1988; 59: 201-06. Yarnell JWG, Baker IA, Sweetnam PM, et al. Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease: the Caerphilly and Speedwell Collaborative Heart Disease Studies. Circulation 1991; 83: 836-14.
Striking identity between HIV-1 envelope glycoprotein gp120 and its CD4 receptor SIR,--Oligopeptides, such as the pentapeptides homoregulatory peptide and epidermal pentapeptide,l are involved in many biological processes.1-s Some have been mapped in the HIV-1 envelope.4,5 On the basis of the homology that they share with immunoregulatory molecules such as interleukin-2 receptorbinding domain or a-interferon-p I 5E, they are likely to have a role in the immune dysregulation observed in AIDS.4,5 We have designed software (Automat) to find systematically all peptidic homologies between proteins in a bank and a given protein.5 Scanning the HIV-1 envelope sequences revealed a pentapeptide identity (SLWDQ) with the CD4 molecule at positions 110-114 in the HIV-1envelope and 60-64 in CD4. Exploration of the MIPS data bank revealed the pentapeptide sequence in only one other protein, the aminotransferase A64988. The sequence is perfectly conserved among all HIV-1strains (but is lacking in HIV-2 and simian immunodeficiency virus) and in human and chimpanzee CD4. The SLWDQ pentapeptide is located in the N-terminal part of the gpl20 external membrane protein of HIV-1. This segment lies on an accessible loop of the first domain of CD4,6 and is the epitope for the OKT4a monoclonal antibody.’ Moreover this region has an important function in the CD4 molecule since OKT4a monoclonal antibodies (specifically directed towards this region) can block T4 cell immune activation,8 and a W-to-C mutation suppresses the binding of HIV-1.’ In agreement with the above mentioned biological characteristics, the
