Association between functional psychosis and expanded CAG/CTG repeats is not explained by health stratification.

A number of studies have reported an association between large CAG/CTG repeats and both schizophrenia and bipolar disorder. Recently, we reported an inverse correlation between CAG/CTG repeat size and age in a health-selected population, raising the possibility that selection of control groups for physical health was a confounding factor in our previous association studies. We investigated this by health-selection of patients with schizophrenia and bipolar disorder.

The organization and evolution of the spinach stress 70 molecular chaperone gene family.

The stress 70 molecular chaperones of plants are localized and function in all of the major subcellular compartments of the cell. Collectively, all of the various forms are encoded by a multigene family in the nucleus. At least 12 members of this family have been found, and sequence and DNA blot analyses provide an emerging description of the diversity of gene structure organization for this family of evolutionarily conserved proteins in spinach.

Characterization of a gene for spinach CAP160 and expression of two spinach cold-acclimation proteins in tobacco.

The cDNA sequence for CAP160, an acidic protein previously linked with cold acclimation in spinach (Spinacia oleracea L.), was characterized and found to encode a novel acidic protein of 780 amino acids having very limited homology to a pair of Arabidopsis thaliana stress-regulated proteins, rd29A and rd29B. The lack of similarity in the structural organization of the spinach and Arabidopsis genes highlights the absence of a high degree of conservation of this cold-stress gene across taxonomic boundaries.

Linked polymorphisms upstream of exons 1 and 2 of the human cholecystokinin gene are not associated with schizophrenia or bipolar disorder.

The evidence for a significant genetic contribution to the functional psychoses (schizophrenia and bipolar disorder) is now well established. However, in both cases, the non-mendelian mode of inheritance has made the identification of susceptibility loci particularly challenging. The neuropeptide cholecystokinin (CCK) is present both in the gut and the CNS.

No evidence for expanded polyglutamine sequences in bipolar disorder and schizophrenia.

Several recent studies have suggested that expanded CAG repeats may contribute to the genetic transmission of bipolar disorder and schizophrenia. In all known disorders associated with expanded CAG repeats, the repeat sequence is translated into glutamine. Therefore the simplest hypothesis is that one or more proteins with expanded polyglutamine sequences are involved in the pathogenesis of bipolar disorder and schizophrenia.

Expanded CAG/CTG repeats in bipolar disorder: no correlation with phenotypic measures of illness severity.

The hypothesis that expanded trinucleotide repeats (TNRs) contribute to the pathogenesis of bipolar disorder has received strong support from recent studies showing that, on average, bipolar patients carry larger repeat sequences of the TNR motif CAG/CTG than do controls. It has been postulated that intergenerational expansion of a TNR may be responsible for the tendency for age of onset to become earlier in younger generations (anticipation) observed in some bipolar pedigrees, and that length polymorphism may account for variability in clinical phenotype. We have used the method of repeat expansion detection to examine these predictions in a sample of 133 Caucasian DSM-III-R bipolar I probands from the British Isles.

Exclusion of expansion of 50 CAG/CTG trinucleotide repeats in bipolar disorder.

Objective: The purpose of this study was to identify the specific expanded CAG/CTG trinucleotide repeat associated with bipolar disorder.

Method: The study employed an efficient multistage approach for using a genomic CAG/CTG screening set.

Results: The authors found no evidence of expanded repeats at 43 polymorphic autosomal loci and seven X chromosomal loci.

Real-time magnetic three-dimensional imaging of flexible endoscopy.

Because of the variability of the colonic anatomy from patient to patient, colonoscopy may be technically difficult to perform and teach, and lesions may be localized inaccurately by the endoscopist. Endoscopists understandably have abandoned fluoroscopy as an adjunct because of its expense, complexity, and potential hazard. The authors have developed a novel method of magnetic imaging that gives real-time views in simulated three dimensions of the endoscope configuration and the location of its tip in the abdomen.

Do enflurane and isoflurane interfere with the release, action, or stability of endothelium-derived relaxing factors?

Purpose: The volatile anaesthetics enflurane and isoflurane inhibit the endothelium dependent-relaxation in some in vitro preparations. To determine their site of action on the endothelium-derived relaxing factor/nitric oxide (EDRF/NO) pathway, experiments were conducted in a bioassay system.

Method: Continuously perfused cultured bovine aortic endothelial cells (BAEC) were the source of EDRF/NO while a phenylephrine-precontracted denuded rabbit aortic ring, directly superfused by the BAEC effluent served to detect EDRF/NO.

Exclusion of CAG/CTG trinucleotide repeat loci which map to chromosome 4 in bipolar disorder and schizophrenia.

The hypothesis that expanded trinucleotide repeats contribute to the pathogenesis of schizophrenia and bipolar disorder has been recently supported by three independent studies which have shown that patients with either disorder tend to have larger CAG/CTG repeat expansion detection products than controls. In an attempt to identify the specific expanded CAG/CTG locus or loci which are associated with schizophrenia and bipolar disorder, we determined the repeat size at CAG/CTG loci mapping to candidate regions for psychosis. In this study we report our findings from eight loci which map to chromosome 4.

Bias in the genomic distribution of CAG and CTG trinucleotide repeats.

We investigated the hypothesis that the trinucleotide repeat CAG is disproportionately located in exons in genomic DNA by analyzing unbiased genomic sequences with the Gene Recognition and Analysis Internet Link program (http@avalon.epm.ornl.

Motion specific responses from a blind hemifield.

In a previous study we showed that fast moving stimuli activate V5, an area specialized for motion, at very short latencies through a pathway that reaches it without passing through V1. Using the same technique of visual evoked responses, we have tested our conclusions by studying patient GY, whose V1 is damaged but whose V5 is intact. In spite of the contralateral hemi-blindness due to his V1 lesion, GY has a residual visual capacity that allows him to perceive, consciously, fast but not slow moving stimuli presented in his affected hemifield.

Expanded CAG/CTG repeats in schizophrenia. A study of clinical correlates.

Background: Schizophrenia is associated with expanded CAG/CTG trinucleotide repeats. We wished to determine whether the presence of such expansions correlated with specific subsyndromes or other clinical features of schizophrenia.

Method: Seventy patients from England and Wales and 44 patients from Portugal with a DSM-III-R diagnosis of schizophrenia were rated on the OPCRIT checklist.

Confirmation of association between expanded CAG/CTG repeats and both schizophrenia and bipolar disorder.

Recent studies have suggested that expanded CAG/CTG repeats contribute to the genetic aetiology of schizophrenia and bipolar disorder. However, the nature of this contribution is uncertain and difficult to predict from other known trinucleotide repeat diseases that display much simpler patterns of inheritance. We have sought to replicate and extend earlier findings using Repeat Expansion Detection in an enlarged sample of 152 patients with schizophrenia, 143 patients with bipolar disorder, and 160 controls.

Expansion of 50 CAG/CTG repeats excluded in schizophrenia by application of a highly efficient approach using repeat expansion detection and a PCR screening set.

Studies of the transmission of schizophrenia in families with affected members in several generations have suggested that an expanded trinucleotide repeat mechanism may contribute to the genetic inheritance of this disorder. Using repeat expansion detection (RED), we and others have previously found that the distribution of CAG/CTG repeat size is larger in patients with schizophrenia than in controls. In an attempt to identify the specific expanded CAG/CTG locus or loci associated with schizophrenia, we have now used an approach based on a CAG/CTG PCR screening set combined with RED data.

Molecular cloning and developmental expression of mouse p130, a member of the retinoblastoma gene family.

With sequence homology to the SV40 T antigen-binding domain of the retinoblastoma protein (Rb), p107 and p130 constitute two additional members of the Rb family. To explore the potential function of p130 in mouse development, we cloned the full-length mouse cDNA for p130 and characterized p130 mRNA expression in mice. The deduced mouse p130 protein sequence shares a higher degree of similarity with mouse p107 than with mouse Rb.

Detection of cytosine methylation and mapping of a gene influencing cytosine methylation in the genome of Citrus.

A new method was developed to detect DNA methylation in the Citrus genome using random amplification coupled with restriction enzyme digestion. Genomic DNA from Citrus grandis (L.) Osb.

Activated neu induces rapid tumor progression.

Expression of the activated neu oncogene in transgenic mice has been associated with both the synchronous (single-step) and the stochastic (multistep) transformation of the mammary epithelium. To determine the basis for these conflicting observations, additional strains of transgenic mice carrying the activated neu oncogene under the transcriptional control of the mouse mammary tumor virus promoter/enhancer were produced. Activated neu transgene expression, as measured by in situ hybridization and ribonuclease protection assays, resulted in rapid conversion of the normal mammary epithelium to malignant phenotype in three independent strains of mice.

E2F-1 blocks terminal differentiation and causes proliferation in transgenic megakaryocytes.

The transcription factor E2F-1 plays a central role in the cell cycle through its ability to activate genes involved in cell division. E2F-1 activity is regulated by a number of proteins, including the retinoblastoma susceptibility gene product, cyclin-dependent kinases, and their inhibitors, proteins that have been implicated in the control of certain developmental processes. To investigate a potential role of E2F-1 in differentiation, we assayed the ability of megakaryocytes to form platelets in an in vivo transgenic model.