Identifying novel genetic determinants of hemostatic balance

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73734/1/j.1538-7836.2005.01461.x.pd

The association between subjective memory complaint and objective cognitive function in older people with previous major depression

The goal of this study is to investigate associations between subjective memory complaint and objective cognitive performance in older people with previous major depression-a high-risk sample for cognitive impairment and later dementia. A cross-sectional study was carried out in people aged 60 or over with previous major depression but not fulfilling current major depression criteria according to DSM-IV-TR. People with dementia or Mini-Mental State Examination score less than 17 were excluded. Subjective memory complaint was defined on the basis of a score ≧4 on the subscale of Geriatric Mental State schedule, a maximum score of 8. Older people aged equal or over 60 without any psychiatric diagnosis were enrolled as healthy controls. Cognitive function was evaluated using a series of cognitive tests assessing verbal memory, attention/speed, visuospatial function, verbal fluency, and cognitive flexibility in all participants. One hundred and thirteen older people with previous major depression and forty-six healthy controls were enrolled. Subjective memory complaint was present in more than half of the participants with depression history (55.8%). Among those with major depression history, subjective memory complaint was associated with lower total immediate recall and delayed verbal recall scores after adjustment. The associations between subjective memory complaint and worse memory performance were stronger in participants with lower depressive symptoms (Hamilton Depression Rating Scale score<7). The results suggest subjective memory complaint may be a valid appraisal of memory performance in older people with previous major depression and consideration should be given to more proactive assessment and follow-up in these clinical samples

Single Nucleotide Polymorphism in Gene Encoding Transcription Factor Prep1 Is Associated with HIV-1-Associated Dementia

BACKGROUND: Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. METHODS: We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. RESULTS: The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2 × 10(-5)). Prep1 has recently been identified as a transcription factor preferentially binding the -2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. CONCLUSION: These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders

The role of factor XI in thrombin generation induced by low concentrations of tissue factor.

SummaryThrombin generation has been studied in the plasma of severely factor XI deficient patients under conditions in which contact activation did not play a role. In platelet-rich as well as platelet-poor plasma, thrombin generation was dependent upon the presence of factor XI at tissue factor concentrations of between 1 and 20 pg/ml i.e. ~ 0.01 to 0.20% of the concentration normally present in the thromboplastin time determination. The requirement for factor XI is low; significant thrombin generation was seen at 1% factor XI; at 10%, thrombin formation was nearly normalised. A suspension of normal platelets in severely factor XI deficient plasma did not increase thrombin generation. This implies that there is no significant factor XI activity carried by normal platelets, although the presence of factor XI and factor XI inhibitors in platelets cannot be ruled out

Combined factors V and VIII deficiency — the solution

Combined deficiency of coagulation factor V and factor VIII is an autosomal recessive disorder which has been observed in a number of populations around the world. However, this disease appears to be most common in the Mediterranean basin, particularly in Jews of Sephardic and Middle Eastern origin living in Israel. We have taken a positional cloning approach toward identifying the gene responsible for this disorder. We initially studied 14 affected individuals from nine unrelated Jewish families using a panel of polymorphic genetic markers spaced throughout the human genome. The combined factors V and VIII deficiency gene was mapped to a locus on the long arm of chromosome 18 with a maximal LOD score of 13.22. A detailed genetic analysis identified two distinct haplotypes among these families, suggesting two independent founders or, alternatively, a single ancient founder with a more recent split of these subpopulations. Further work to identify and characterize the gene responsible for combined factors V and VIII deficiency should provide important insights into the biosynthesis of these homologous proteins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73279/1/j.1365-2516.1998.440677.x.pd