Mood disorders linked to site In prefrontal cortex

THE LANCET

SCIENCE AND MEDICINE

Mood disorders linked to site In prefrontal cortex imaging may identify children at risk. trait-like abnormalities seen on The team are also imaging dopamine repeated MRIs, even after drug therreceptors to see whether abnormal apy and regardless of whether a binding correlates with grey matter patient is in the manic or remitted abnormalities. In all, phase”. The finding the work may explain is “particularly excitwhy episodes tend to ing”, because the recur when medicasubgenual prefrontal tion is stopped, and cortex connects with may take away brain areas thought some of the stigma to be involved associated with the in responses to recurrences. “Bipolar emotional stimuli. illness is a brain Preliminary evidisease that affects dence from ongoing structures related to work suggests that It’s all in the mind region emotional regulation people with the and processing, not the result of bad greatest abnormalities in grey matter parenting or character weakness or are most prone to developing anything like that”, Drevets asserts. psychotic symptoms during manic or depressive episodes, adds Drevets. If the abnormalities are inherited, then Marilynn Larkin Wellcome Institute Library, London

S researchers have identified a brain region, the subgenual prefrontal cortex, that is both smaller and less active in people with hereditary depression than in nondepressed people. These persistent, “robust abnormalities” may have “clinical correlates”, says Wayne Drevets (University of Pittsburgh, PA, USA), lead author of the study. Drevets and his colleagues used positron emission tomography and magnetic resonance imaging (MRI) techniques to examine brain activity and volume of grey matter in bipolar and unipolar depressives (Nature 1997; 386: 824–27). They found decreased blood flow and metabolism in the region, and volume reductions in grey matter of 39–48% in patients compared with controls. Says Drevets, “These are stable,

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HIV-1 fusion mechanism could be target for new drugs

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IV-1 infects cells by using its envelope glycoprotein, gp41, to fuse viral and cellular membranes. The structure of gp41, reported this week, suggests how membrane fusion occurs and could be a good starting point for developing new therapies for HIV-1 infection. The HIV-1 envelope glycoprotein complex consists of gp41 and gp120. Initially, gp120 binds to target-cell receptors. This interaction induces gp41 to change shape from the native state to the fusogenic state. A hydrophobic fusion peptide on gp41 is then exposed and inserts into the target-cell membrane. David Chan, Peter Kim, and co-workers from the Whitehead Institute and the

Howard Hughes Medical Institute (Cambridge, MA, USA) studied two key peptides, N36 and C34, that interact to form the core of the gp41 fusogenic structure (Cell 1997; 89: 263–73). The gp41 core structure was solved by X-ray crystallography. It consists of three N36 helices coiled to form a central cylinder, with three C34 helices wrapping round this central coil. The fusion peptide sits on top of this protein scaffold, which is surprisingly similar to influenza virus haemagglutinin in its fusion-active state, says Chan. “It is only when the ’flu virus is triggered to fuse . . . that the fusion peptide, which is buried in the core,

springs out. A similar structural change may happen in HIV-1.” “Other people have shown that adding C-peptides [similar to C34] disrupts the ability of HIV-1 to fuse with membranes and infect cells. The remarkable thing we found is that the contact points between the C34 peptide and the central coil are highly conserved between HIV-1 and simian immunodeficiency virus. It may be possible to develop peptides or design small-molecule drugs to block this interaction. This would hopefully be effective in stalling infection in a wide range of HIV-1 strains”, adds Chan. Kelly Morris

Revised guidelines for colposcopy aired in Glasgow evised guidelines for the UK cervical screening programme are to be published later this year. Changes to the current guidelines include recommendations that colposcopy should now be considered after a woman’s first mildly dyskaryotic cervical smear and that annual follow-up smears should be continued for 10 years (rather than 5) after treatment for CIN 3. Other aspects of the revised guidelines were discussed by Ian Duncan (Ninewells Hospital, Dundee, UK) at the Silver Jubilee conference of the British Society for Colposcopy and

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Vol 349 • April 26, 1997

Cervical Pathology (Glasgow, UK; April 17–19). “There is no justification for taking a cervical smear in an immunocompetent teenager. Also, a lot of resources are being wasted totally unnecessarily on additional smears in symptomatic women and those starting hormonal contraception. If a woman is symptomatic it would be more appropriate to pursue immediate gynaecological referral.” Brendan Bolger (Gateshead Hospital, Newcastle upon Tyne, UK) made the controversial suggestion that many women with early invasive cervical cancer are undergoing

unnecessary hysterectomies. A study looking at women treated by loop diathermy, who were unexpectedly found to have early cancer, suggests that if the loop margins are free of disease, there is a high likelihood that the tumour has been completely excised. In those cases where the loop margins are not clear, a second loop—“looping the loop”—may be sufficient treatment. More studies are required, however, before a major change of practice is contemplated, cautioned Bolger. Anne Szarewski

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