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Biomedical subjects

G A Fraser

Publications and source records attributed to G A Fraser.

12 recordsLinked to original sources

The p36 isoform of BAG-1 is translated by internal ribosome entry following heat shock.

BAG-1 (also known as RAP46/HAP46) was originally identified as a 46 kDa protein that bound to and enhanced the anti-apoptotic properties of Bcl-2. BAG-1 exists as three major isoforms (designated p50, p46 and p36 or BAG-1L, BAG-1M and BAG-1S respectively) and one minor isoform (p29), which are translated from a common transcript. The differing amino terminus determines both the intracellular location and the repertoire of binding partners of the isoforms which play different roles in a variety of cellular processes including signal transduction, heat shock, apoptosis and transcription. Although in vitro data suggest that the four BAG-1 isoforms are translated by leaky scanning, the patterns of isoform expression in vivo, especially in transformed cells, do not support this hypothesis. We have performed in vivo analysis of the BAG-1 5' untranslated region and shown that translation initiation of the most highly expressed isoform (p36/BAG-1S) can occur by both internal ribosome entry and cap-dependent scanning. Following heat shock, when there is a downregulation of cap-dependent translation, the expression of the p36 isoform of BAG-1 is maintained by internal ribosome entry.

5' Untranslated Regions↗

Derivation of a structural model for the c-myc IRES.

We have derived a secondary structure model for the c-myc internal ribosome entry segment (IRES) by using information from chemical probing of the c-myc IRES RNA to constrain structure prediction programs. Our data suggest that the IRES is modular in nature, and can be divided into two structural domains linked by a long unstructured region. Both domains are required for full IRES function. Domain 1 is a complex element that contains a GNNRA apical loop and an overlapping double pseudoknot motif that is topologically unique amongst published RNA structures. Domain 2, the smaller of the two, contains an apical AUUU loop. We have located the ribosome landing site and have shown that ribosomes enter in a 16 nt region downstream of the pseudoknots in a situation similar to that observed in several viral IRESs. To test the structure, several key regions of the IRES were mutated and, interestingly, it appears that some of the structural elements that we have identified function to repress c-myc IRES function. This has profound implications for de-regulation of c-myc expression by mutations occurring in the IRES.

Base Sequence↗

Abuse histories in 102 cases of multiple personality disorder.

The authors interviewed 102 individuals with clinical diagnoses of multiple personality disorder at four centres using the Dissociative Disorders Interview Schedule. The patients reported high rates of childhood trauma: 90.2% had been sexually abused, 82.4% physically abused, and 95.1% subjected to one or both forms of child abuse. Over 50% of subjects reported initial physical and sexual abuse before age five. The average duration of both types of abuse was ten years, and numerous different perpetrators were identified. Subjects were equally likely to be physically abused by their mothers or fathers. Sexual abusers were more often male than female, but a substantial amount of sexual abuse was perpetrated by mothers, female relatives, and other females. Multiple personality disorder appears to be a response to chronic trauma originating during a vulnerable period in childhood.

Adolescent↗

Structured interview data on 102 cases of multiple personality disorder from four centers.

Patients with multiple personality disorder (N = 102) at four different centers were interviewed with the Dissociative Disorders Interview Schedule. The presenting characteristics of the patients at all four centers were very similar. The clinical profile that emerged included a history of childhood physical and/or sexual abuse in 97 (95.1%) of the cases. The subjects reported an average of 15.2 somatic symptoms, 6.4 Schneiderian symptoms, 10.2 secondary features of the disorder, 5.2 borderline personality disorder criteria, and 5.6 extrasensory experiences; their average score on the Dissociative Experiences Scale was 41.4. The results indicate that multiple personality disorder has a stable, consistent set of features.

Borderline Personality Disorder↗

Lumbar intervertebral disc prolapse in teenage twins. A case report and review of the literature.

We report the cases of teenage twin girls presenting within months of each other with severe symptoms from lumbosacral disc prolapses, requiring laminectomy in one and chemonucleolysis in the other. CT scans showed similarities in spinal configuration, including the presence of disc bulges at the L4-5 level. This suggests a strong hereditary factor in prolapse of intervertebral discs, but a review of the literature showed little information on that aspect.

Adolescent↗

Revision of the Charnley low-friction arthroplasty for recurrent or irreducible dislocation.

Twenty-one cases of the Charnley low-friction arthroplasty were revised because of recurrent or irreducible dislocation. Three main reasons for this revision, usually in combination, were identified: loss of the abductor mechanism due to trochanteric detachment; shortening of the limb due to high placement of the socket or low section of the femoral neck; and malorientation of the components. Sixteen patients had no further problems after revision. One patient had a single dislocation, four had more than one dislocation although they managed to cope with them and did not require a further revision.

Adult↗

Septic arthritis in childhood.

In the first 4 years (1974 to 1978) of operation of the Children's Hospital of Eastern Ontario, in Ottawa, 50 children were treated for septic arthritis. The neonatal group (birth to 6 months) of three patients had the most severe involvement and the worst prognosis. The early childhood group (6 months to 4 years) of 15 patients was characterized by sepsis due to Hemophilus influenzae. The 32 older children (4 to 16 years), more susceptible to staphylococcal infections, commonly presented with atypical and unusual symptoms. The erythrocyte sedimentation rate was the most reliable laboratory investigation. Positive joint cultures were obtained in 66% of patients. Arthrotomy with drainage was the most reliable form of treatment, particularly in cases of hip joint sepsis. Six patients have substantial residual joint damage with some degree of permanent disability. Early diagnosis of the condition and rapid removal of pus are mandatory for the survival of the joint.

Adolescent↗

A short encounter with Anna Freud at Berggasse 19.

This article discusses a short encounter with Dr. Anna Freud in her former consulting office in Vienna at 19 Berggasse in May 1977. Dr. Freud had gone to Vienna for the laying of a marble plaque at the site of the former BelleVue Hotel where Sigmund Freud had first started his work on the 'interpretation of dreams'. In 1900 Dr. Sigmund Freud had written to Wilhelm Fliess "Do you suppose that some day a marble tablet will be placed on the house, inscribed with the words: 'in this house on July 24, 1895, The Secret of Dreams was revealed to Dr. Sigmund Freud' At this moment I see little prospect of it". This request was realized on 6 May 1977 and the author who was present at the ceremonies, describes some of the events.

Austria↗

Schneiderian symptoms in multiple personality disorder and schizophrenia.

We report structured interview data from a series of 102 cases of multiple personality disorder (MPD) diagnosed in four centers. Schneiderian first-rank symptoms of schizophrenia were equally common in all four centers. The average MPD patient had experienced 6.4 Schneiderian symptoms. When these 102 cases are combined with two previously reported series of MPD cases, an average of 4.9 Schneiderian symptoms in 368 cases of MPD is noted. This compares with an average of 1.3 symptoms acknowledged by 1,739 schizophrenics in 10 published series. Schneiderian symptoms are more characteristic of MPD than of schizophrenia.

Adult↗

Retinoic acid stimulates the synthesis of a novel heat shock protein in the regenerating forelimb of the newt.

Morphogenetic effects of retinoic acid (RA) on the urodele amphibian limb regenerate pattern have been well documented, but little is known regarding the mechanism of this action of RA at the molecular level. Since exogenous RA, at concentrations sufficient to cause proximalization, represents a significant stress to newts and has been shown previously to elicit increased synthesis of heat shock proteins (HSPs) in mouse embryo limb buds, we investigated the effects of this putative morphogen on the synthesis of members of the 70-kilodalton (70-kDa) stress protein family in amputated forelimbs of the newt Notophthalmus viridescens. Injection (i.p.) of RA in dimethyl sulfoxide (DMSO), at a dose sufficient to cause significant proximal-distal reduplication of the pattern in 50% of animals treated, resulted in increased synthesis and accumulation of a 73-kDa protein with a pI of approximately 6.75. The synthesis of this same protein is increased in limb tissues as a result of a brief 35 degrees C heat shock. This protein is electrophoretically distinct from the newt HSP 70 family members, displays a different partial peptide map, and shows no immunological cross-reactivity with an anti-human HSP 70 monoclonal antibody. It may be a member of a separate family of 70- to 73-kDa HSPs. Interestingly, the synthesis of this protein is increased and it is more abundant in control, proximal moderate-early bud stage regenerates at 6 days after i.p. injection of DMSO than in similarly treated distal regenerates. This protein is, in addition, increased in distal regenerates to proximal levels by a prior injection of RA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amputation, Surgical↗