Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and bipolar affective disorder (BPAD) in comparison with control individuals have previously been reported, implying a possible etiological role for trinucleotide repeats in these diseases. Two unstable CAG/CTG repeats, SEF2-1B and ERDA1, have recently been cloned, and studies indicate that the majority of individuals with large repeats as detected by repeat-expansion detection (RED) have large repeat alleles at these loci. These repeats do not show association of large alleles with either BPAD or SCZ. Using RED, we have identified a BPAD individual with a very large CAG/CTG repeat that is not due to expansion at SEF2-1B or ERDA1. From this individual's DNA, we have cloned a highly polymorphic trinucleotide repeat consisting of (CTA)n (CTG)n, which is very long ( approximately 1,800 bp) in this patient. The repeat region localizes to chromosome 13q21, within 1.2 cM of fragile site FRA13C. Repeat alleles in our sample were unstable in 13 (5.6%) of 231 meioses. Large alleles (>100 repeats) were observed in 14 (1. 25%) of 1,120 patients with psychosis, borderline personality disorder, or juvenile-onset depression and in 5 (.7%) of 710 healthy controls. Very large alleles were also detected for Centre d'Etude Polymorphisme Humaine (CEPH) reference family 1334. This triplet expansion has recently been reported to be the cause of spinocerebellar ataxia type 8 (SCA8); however, none of our large alleles above the disease threshold occurred in individuals either affected by SCA or with known family history of SCA. The high frequency of large alleles at this locus is inconsistent with the much rarer occurrence of SCA8. Thus, it seems unlikely that expansion alone causes SCA8; other genetic mechanisms may be necessary to explain SCA8 etiology.

No abstract

1. An extract of Ginkgo biloba (EGb 761) has been reported to alleviate cerebrovascular problems. In the present study, we investigated the antithrombotic effects of EGb 761 in cerebral blood vessels of stroke-prone spontaneously hypertensive rats (SHRSP/Izm). 2. In the present study, EGb 761 was administered orally to SHRSP/Izm at 60 and 120 mg/kg each day for 3 weeks from the age of 7 weeks. The age-related increase in blood pressure observed in SHRSP was suppressed significantly by EGb 761 at both doses 3 weeks after treatment. 3. Thrombotic potential was assessed in vivo using a He-Ne laser-induced thrombosis model and was significantly suppressed by EGb 761. 4. The anti-oxidant effects of EGb 761 were determined by measurement of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). At 120 mg/kg, EGb 761 decreased 8-OHdG significantly compared with control animals. 5. Urinary nitrite/nitrate, nitric oxide (NO) metabolites, were increased significantly after administration of EGb 761. Expression of endothelial NO synthase (eNOS) mRNA was measured using a real-time quantitative reverse transcription-polymerase chain reaction method. The expression of eNOS mRNA in the EGb 761 group (120 mg/kg) was significantly higher than in the control group. 6. The results indicate that EGb 761 decreases blood pressure and mediates strong antithrombotic and anti-oxidant effects in SHRSP. These pharmacological activities may contribute to the beneficial properties of EGb 761 observed in clinical practice.

No abstract