- Email: [email protected]
Myotonic dystrophy gene identified
SCIENCE AND MEDICINE
Index predicts cardiac complications in pregnancy
R
esearchers in Canada have Women got one point for each predeveloped a risk index that can dictor present. The estimated predict the likelihood of cardiacchance of having cardiac-related related complications in pregnant complications in women with no women who have heart conditions. points, one point, or more than one Pregnancy in point was 5%, 27%, these women can and 75%, respecbe associated with tively. When the Rights were not serious maternal new index was granted to include and neonatal comapplied retrospecthis image in plications. tively to the women “Most women enrolled, it was electronic media. with heart disease able to define accuPlease refer to the have a low risk rately those at risk index and do well (Circulation 2001; printed journal. during pregnancy, 104: 515–21). with successful The index should outcomes for Most outcomes are successful help to avoid mothers and inappropriate reffetuses”, says Jack M Colman erral for mothers at low risk of (University of Toronto, Canada), complications. “Recommendations one of the investigators. “Some to avoid pregnancy are sometimes women and fetuses, however, do made on the basis of the presence of not do well, in spite of the best of any sort of maternal heart condicare. It is important to determine tion”, Colman told The Lancet. in advance which pregnancies are “We hope the data and risk index likely to be complicated, since it is described in our paper will provide these to which the majority of a basis for avoiding such unwarresources should be devoted.” ranted advice, and also for avoiding Over 5 years, Samuel C Siu investigations and treatments not and co-investigators prospectively required by mothers at low risk.” studied 562 women with congenital “There are hardly any prospecor acquired disorders of the heart, tive data to serve as guidelines for or arrhythmias, who became counselling pregnant patients with pregnant. The group identified four heart disease”, comments Verena predictors of cardiac events, which Stangl (Medizinische Klinik they then incorporated into a mit Schwerpunkt Kardiologie, revised risk index. The predictors Angiologie und Pneumologie, were: poor functional class (New Berlin, Germany). “We need such York Heart Association) or cyanosis; studies in order to better assess the previous cardiac event or arrhythmaternal and fetal risks.” mia; left heart obstruction; and left Abigail Pound ventricular systolic dysfunction.
Myotonic dystrophy gene identified he myotonic dystrophy type 1 (DM1) mutation on chromosome 19 was localised 9 years ago. Now, the DM2 mutation has been identified on chromosome 3. Both mutations are expanded nucleotide repeats in non-coding regions of DNA (Science 2001; 293: 864–67). “Liquori and co-workers present good evidence that the principal features of DM2 are caused by a huge expanded repeat in the ZNF9 gene”, says commentator Stephen Tapscott (Fred Hutchinson Cancer Research Center, Seattle, WA, USA). “The repeat is in the first intron of ZNF9, a region that is transcribed into RNA but not translated into protein.” How can a repeat expansion in a non-coding region produce the diverse symptoms of DM? Potentially the accumulation of mutant RNA transcripts in the nucleus could lead to the sequestration or activation of specific RNA binding proteins; the nucleotide expansion can be up to 15 kilobases in length for DM1 and 44 kilobases for DM2. “Accurate genetic diagnosis of DM2 will allow us to better manage the myriad clinical problems of this disease”, say John Day and Laura Ranum (Institute of Human Genetics, University of Minnesota, Minneapolis, MN, USA), two of the investigators. “Our discovery will help focus research on mechanisms directly involving RNA—an essential step to better understanding the biology of these disesases.”
T
Rebecca Love
Green tea extract may have neuroprotective effects in Parkinson’s disease esearchers from Israel have found that a phenolic compound in green tea is a strong neuroprotectant in two different models of Parkinson’s disease. The results were presented at the 14th International Congress on Parkinson’s Disease in Helsinki, Finland, on July 27. The investigators, led by Moussa Youdim (Technion-Faculty of Medicine, Haifa, Israel), used microarrays, or “gene chips”, to study the effects of epigallocatechin-3-gallate (EGCG), which comprises about a third of the polyphenol content of green tea extracts. They found that treating rodents with MPTP or 6-hydroxydopamine, the two classic inducers of experimental parkinsonism, causes a
R
THE LANCET • Vol 358 • August 4, 2001
suite of 51 genes to change their expression levels, in some cases increasing by 1000% or more. These include genes for NFB, and proinflammatory cytokines, such as interleukin 1. However, if the rodents receive oral EGCG for 2 days before treatment, these changes in gene expression are suppressed, and the rodents are protected from the harmful effects of each toxin. EGCG is a powerful iron chelator, which may partly explain its neuroprotective effects: iron accumulation has been implicated in a range of neurodegenerative diseases (see Lancet 2001; 358: 302), and iron accumulates in neurons in the substantia nigra of patients with Parkinson’s disease.
To test the applicability of EGCG in Parkinson’s disease, Youdim is currently using microarrays to see whether human brain with Parkinson’s disease also shares these genetic changes. However, Youdim cautions that a long line of putative neuroprotectants have been tried, and failed, in human beings (although he is optimistic enough to have applied for a patent on EGCG). But he also notes: “Cell death is not just one process; it’s a domino effect involving many pathways. I don’t believe we can protect neurons with one single drug; we’ll need a cocktail of agents to interrupt these different pathways.” Richard Robinson
391
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Index predicts cardiac complications in pregnancy
R
esearchers in Canada have Women got one point for each predeveloped a risk index that can dictor present. The estimated predict the likelihood of cardiacchance of having cardiac-related related complications in pregnant complications in women with no women who have heart conditions. points, one point, or more than one Pregnancy in point was 5%, 27%, these women can and 75%, respecbe associated with tively. When the Rights were not serious maternal new index was granted to include and neonatal comapplied retrospecthis image in plications. tively to the women “Most women enrolled, it was electronic media. with heart disease able to define accuPlease refer to the have a low risk rately those at risk index and do well (Circulation 2001; printed journal. during pregnancy, 104: 515–21). with successful The index should outcomes for Most outcomes are successful help to avoid mothers and inappropriate reffetuses”, says Jack M Colman erral for mothers at low risk of (University of Toronto, Canada), complications. “Recommendations one of the investigators. “Some to avoid pregnancy are sometimes women and fetuses, however, do made on the basis of the presence of not do well, in spite of the best of any sort of maternal heart condicare. It is important to determine tion”, Colman told The Lancet. in advance which pregnancies are “We hope the data and risk index likely to be complicated, since it is described in our paper will provide these to which the majority of a basis for avoiding such unwarresources should be devoted.” ranted advice, and also for avoiding Over 5 years, Samuel C Siu investigations and treatments not and co-investigators prospectively required by mothers at low risk.” studied 562 women with congenital “There are hardly any prospecor acquired disorders of the heart, tive data to serve as guidelines for or arrhythmias, who became counselling pregnant patients with pregnant. The group identified four heart disease”, comments Verena predictors of cardiac events, which Stangl (Medizinische Klinik they then incorporated into a mit Schwerpunkt Kardiologie, revised risk index. The predictors Angiologie und Pneumologie, were: poor functional class (New Berlin, Germany). “We need such York Heart Association) or cyanosis; studies in order to better assess the previous cardiac event or arrhythmaternal and fetal risks.” mia; left heart obstruction; and left Abigail Pound ventricular systolic dysfunction.
Myotonic dystrophy gene identified he myotonic dystrophy type 1 (DM1) mutation on chromosome 19 was localised 9 years ago. Now, the DM2 mutation has been identified on chromosome 3. Both mutations are expanded nucleotide repeats in non-coding regions of DNA (Science 2001; 293: 864–67). “Liquori and co-workers present good evidence that the principal features of DM2 are caused by a huge expanded repeat in the ZNF9 gene”, says commentator Stephen Tapscott (Fred Hutchinson Cancer Research Center, Seattle, WA, USA). “The repeat is in the first intron of ZNF9, a region that is transcribed into RNA but not translated into protein.” How can a repeat expansion in a non-coding region produce the diverse symptoms of DM? Potentially the accumulation of mutant RNA transcripts in the nucleus could lead to the sequestration or activation of specific RNA binding proteins; the nucleotide expansion can be up to 15 kilobases in length for DM1 and 44 kilobases for DM2. “Accurate genetic diagnosis of DM2 will allow us to better manage the myriad clinical problems of this disease”, say John Day and Laura Ranum (Institute of Human Genetics, University of Minnesota, Minneapolis, MN, USA), two of the investigators. “Our discovery will help focus research on mechanisms directly involving RNA—an essential step to better understanding the biology of these disesases.”
T
Rebecca Love
Green tea extract may have neuroprotective effects in Parkinson’s disease esearchers from Israel have found that a phenolic compound in green tea is a strong neuroprotectant in two different models of Parkinson’s disease. The results were presented at the 14th International Congress on Parkinson’s Disease in Helsinki, Finland, on July 27. The investigators, led by Moussa Youdim (Technion-Faculty of Medicine, Haifa, Israel), used microarrays, or “gene chips”, to study the effects of epigallocatechin-3-gallate (EGCG), which comprises about a third of the polyphenol content of green tea extracts. They found that treating rodents with MPTP or 6-hydroxydopamine, the two classic inducers of experimental parkinsonism, causes a
R
THE LANCET • Vol 358 • August 4, 2001
suite of 51 genes to change their expression levels, in some cases increasing by 1000% or more. These include genes for NFB, and proinflammatory cytokines, such as interleukin 1. However, if the rodents receive oral EGCG for 2 days before treatment, these changes in gene expression are suppressed, and the rodents are protected from the harmful effects of each toxin. EGCG is a powerful iron chelator, which may partly explain its neuroprotective effects: iron accumulation has been implicated in a range of neurodegenerative diseases (see Lancet 2001; 358: 302), and iron accumulates in neurons in the substantia nigra of patients with Parkinson’s disease.
To test the applicability of EGCG in Parkinson’s disease, Youdim is currently using microarrays to see whether human brain with Parkinson’s disease also shares these genetic changes. However, Youdim cautions that a long line of putative neuroprotectants have been tried, and failed, in human beings (although he is optimistic enough to have applied for a patent on EGCG). But he also notes: “Cell death is not just one process; it’s a domino effect involving many pathways. I don’t believe we can protect neurons with one single drug; we’ll need a cocktail of agents to interrupt these different pathways.” Richard Robinson
391
For personal use. Only reproduce with permission from The Lancet Publishing Group.