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Biomedical subjects

R Bremner

Publications and source records attributed to R Bremner.

At least 19 recordsLinked to original sources
PubMed1998

The effects of programmatic change on resident motivation.

BACKGROUND: Critical to any resident's success is that individual's commitment and desire to succeed. Rarely do surgical educators consider the impact of a programmatic change on a resident's motivation. Recently much attention has centered around the impact of IL-372 on medical practice. In this article we instead focus on the impact that a programmatic change can have on resident motivation and use IL-372 as an example. METHODS: This article is a review of literature on motivation relevant to surgical education. RESULTS: Motivation theory can help surgical educators understand resident (1) choice to engage in an activity, (2) the quantity of effort someone invests, and (3) the willingness to persist at tasks. It can also help educators identify and understand positive and negative behavioral reactions that can occur when there is a mismatch between a resident's belief about his or her ability and expectations in the operating room. CONCLUSIONS: This article concludes with a number of strategies to improve resident motivation.

Attitude of Health Personnel↗
PubMed1997

Deletion of RB exons 24 and 25 causes low-penetrance retinoblastoma.

A deletion in the tumor-suppressor gene, RB, discovered by quantitative multiplex PCR, shows low penetrance (LP), since only 39% of eyes at risk in this family develop retinoblastoma. The 4-kb deletion spanning exons 24 and 25 (delta24-25) is the largest ever observed in an LP retinoblastoma family. Unlike the usual RB mutations, which cause retinoblastoma in 95% of at-risk eyes and yield no detectable protein, the delta24-25 allele transcribed a message splicing exon 23 to exon 26, resulting in a detectable protein (pRBdelta24-25) that lacks 58 amino acids from the C-terminal domain, proving that this domain is essential for suppression of retinoblastoma. Two functions were partially impaired by delta24-25-nuclear localization and repression of E2F-consistent with the idea that LP mutations generate "weak alleles" by reducing but not eliminating essential activities. However, delta24-25 ablated interaction of pRB with MDM2. Since a homozygous LP allele is considered nontumorigenic, the pRB/MDM2 interaction may be semi- or nonessential for suppressing retinoblastoma. Alternatively, some homozygous LP alleles may not cause tumorigenesis because an additional event is required (the "three-hit hypothesis"), or the resulting imbalance in pRB function may cause apoptosis (the "death allele hypothesis"). pRBdelta24-25 was also completely defective in suppressing growth of Saos-2 osteosarcoma cells. Targeting pRBdelta24-25 to the nucleus did not improve Saos-2 growth suppression, suggesting that C-terminal domain functions other than nuclear localization are essential for blocking proliferation in these cells. Since delta24-25 behaves like a null allele in these cells but like an LP allele in the retina, pRB may use different mechanisms to control growth in different cell types.

Canada↗
PubMed1995

Large group community-based parenting programs for families of preschoolers at risk for disruptive behaviour disorders: utilization, cost effectiveness, and outcome.

A significant percentage of children with disruptive behavior disorders do not receive mental health assistance. Utilization is lowest among groups whose children are at greatest risk. To increase the availability, accessibility, and cost efficacy of parent training programs, this prospective randomized trial compared a large group community-based parent training program to a clinic-based individual parent training (PT) programs. All families of junior kindergartners in the Hamilton public and separate school boards were sent a checklist regarding problems at home. Those returning questionnaires above the 90th percentile were block randomly assigned to: (1) a 12-week clinic-based individual parent training (Clinic/Individual), (2) a 12-week community-based large group parent training (Community/Group), or (3) a waiting list control condition. Immigrant families, those using English as a second language, and parents of children with severe behaviour problems were significantly more likely to enroll in Community/Groups than Clinic/Individual PT. Parents in Community/Groups reported greater improvements in behaviour problems at home and better maintenance of these gains at 6-month follow-up. A cost analysis showed that, with groups of 18 families, Community/Groups are more than six times as cost effective as Clinic/Individual programs.

Child Behavior Disorders↗
PubMed1995

Direct transcriptional repression by pRB and its reversal by specific cyclins.

It was recently shown that the E2F-pRB complex is a negative transcriptional regulator. However, it was not determined whether the whole complex or pRB alone is required for repression. Here we show that pRB and the related protein p107 are capable of direct transcriptional repression independent of E2F. When fused to the DNA binding domain of GAL4, pRB or p107 represses transcription of promoters with GAL4 binding sites. Thus, E2F acts as a tether for pRB or p107 but is not actively involved in repression of other enhancers. This function of pRB maps to the pocket and is abrogated by mutation of this domain. This result suggests an intriguing model in which the pocket has a dual function, first to bind E2F and second to repress transcription directly, possibly through interaction with other proteins. We also show that direct transcriptional repression by pRB is regulated by phosphorylation. Mutations which render pRB constitutively hypophosphorylated potentiate repression, while phosphorylation induced by cyclin A or E reduces repression ninefold.

Base Sequence↗
PubMed1994

Induction of different genetic changes by different classes of chemical carcinogens during progression of mouse skin tumors.

By analysis of skin tumors from F1 hybrid mice we demonstrated that the genetic events that occur during tumor progression depend on the type of chemical carcinogenesis protocol used to induce tumor growth. More than 95% of tumors induced by initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) exhibited mutations in Ha-ras and trisomy of chromosome 7. Carcinomas induced with multiple DMBA treatments had a lower frequency of alterations on chromosome 7 (50%), but only in tumors with Ha-ras mutations, and had a much wider spectrum of alterations, including trisomy, mitotic recombination, deletion, and gene duplication. Carcinomas induced with multiple N-methyl-N'-nitro-N-nitrosoguanidine treatments only rarely exhibited alterations on chromosome 7 (8%), even if they contained mutant Ha-ras. More frequent numerical alterations of chromosome 11 were also seen in TPA-promoted tumors (23%) than in tumors induced by multiple carcinogen treatments (8%). These results show that postinitiation events are nonrandom and fit a model in which promoting agents induce numerical chromosomal alterations but in which mutagens cause more directed mutational events.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

A revised map position for the Ha-ras gene on mouse chromosome 7: implications for analysis of genetic alterations in rodent tumors.

The mouse Ha-ras gene has previously been mapped to the central region of chromosome 7, 31 cM from the centromere, using an interspecific Mus musculus/Mus spretus backcross (Saunders AM, Seldin MF, Genomics 8:525-535, 1990). However, analysis of mitotic recombinations in mouse skin tumors from intraspecific F1 hybrid mice suggested a more distal location for the Ha-ras gene on chromosome 7 (Bremner R, Balmain A, Cell 61:407-417, 1990). In the study reported here, we demonstrated, by analysis of Ha-ras gene mutations in skin tumors from interspecific M. spretus/M. musculus F1 hybrids, the existence only in M. spretus of a pseudogene or other Ha-ras-related sequence that is probably the sequence originally mapped by Saunders and Seldin. The functional Ha-ras gene maps to the distal region of chromosome 7, and it is this sequence that acquires mutations in chemically induced tumors.

Animals↗
PubMed1993

Coping modeling problem solving versus mastery modeling: effects on adherence, in-session process, and skill acquisition in a residential parent-training program.

This trial compared two approaches used to introduce parenting skills in a residential staff training program. Fifty staff were randomly assigned to: mastery modelling in which videotaped models demonstrated new skills, coping modelling problem solving (CMPS) in which participants formulated their own solutions to the errors depicted by videotaped models, or a waiting-list control group. In both, leaders used modelling, role playing, and homework projects to promote mastery and transfer of new skills. The skills of all groups improved, but CMPS participants attended more sessions, were late to fewer sessions, completed more homework, engaged in more cooperative in-session interaction, rated the program more positively, and reported higher job accomplishment scores. These data suggest that CMPS allowing participants to formulate their own solutions may enhance adherence and reduce the resistance observed in more didactic programs.

Adaptation, Psychological↗
PubMed1993

A bipartite nuclear localization signal in the retinoblastoma gene product and its importance for biological activity.

The retinoblastoma gene product, p110RB1, appears to regulate cell growth by modulating the activities of nuclear transcription factors. The elements that specify the transport of p110RB1 into the nucleus have not yet been explored. We now report the identification of a basic region, KRSAEGGNPPKPLKKLR, in the C terminus of p110RB1, which has sequence similarity to known bipartite nuclear localization signals (NLSs). A two-amino-acid mutation introduced into this putative NLS [to give mutant NLS(NQ)] or deletion of the entire NLS (delta NLS) abrogated exclusive nuclear localization, yielding proteins which were distributed either equally throughout the cell or predominantly in the cytoplasm. A mutant protein [NLS(NQ)/delta 22] containing both the mutated NLS and a deletion of exon 22, previously shown to disrupt the interaction of p110RB1 with several cellular transcription factors and oncoproteins, accumulated only in the cytoplasm. When fused to the C terminus of Escherichia coli beta-galactosidase, the RB1 NLS directed this protein to the nucleus, indicating that the motif is not only necessary but also sufficient for nuclear transport. Neither NLS(NQ) nor delta NLS was hyperphosphorylated in vivo, but both retained their abilities to interact, in vitro, with simian virus 40 large T antigen, adenovirus E1a, and the cellular transcription factor E2F. When transfected at multiple copy number, the NLS mutant alleles displayed reduced biological activity, measured by inhibition of growth of the osteogenic sarcoma cell line Saos-2, which has no wild-type RB1. Naturally occurring mutations and deletions in exon 25 of RB1 which disrupt the NLS may lead to partial or complete inactivation of p110RB1 and may be responsible for some retinoblastoma and other tumors.

Amino Acid Sequence↗
PubMed1991

Genetic changes during mouse skin tumorigenesis.

This paper describes specific genetic changes involving chromosome 7 in mouse skin tumors, the most important consequence of which appears to be an alteration in the allelic balance of normal and mutant H-ras genes. The use of restriction-fragment-length polymorphisms in F1 hybrid mice demonstrates that trisomy of chromosome 7 is an early event preceding papilloma formation, and further events, such as mitotic recombination, seem to occur during progression to malignant carcinomas. There is some evidence of a tumor-suppressor locus situated on chromosome 7.

Alleles↗
PubMed1991

Loss of heterozygosity and mutational alterations of the p53 gene in skin tumours of interspecific hybrid mice.

Functional alterations or loss of tumor-suppressor genes are an important feature of neoplastic progression in humans. The employment of suitable animal model systems would greatly facilitate the detection and manipulation of such genes. We describe here an experimental approach to this problem based on the analysis of skin tumors induced in F1 hybrids between Mus musculus and Mus spretus mice. The results show that loss of heterozygosity on chromosome 11 occurred in 4/13 mouse skin carcinomas, but not in premalignant papillomas. Since the murine p53 gene is located on this chromosome, immunoprecipitation and DNA-sequencing studies were carried out on tumorigenic cell lines and primary tumor DNA respectively to determine the status of p53 alleles. These studies revealed the presence of p53 mutations, both frameshifts and missense, some of which are identical to those found in human tumors. Loss of normal p53 function is found in well-differentiated squamous-cell carcinomas and thus does not appear to be directly responsible for further progression to an undifferentiated spindle cell phenotype.

Amino Acid Sequence↗
PubMed1990

Genetic changes in skin tumor progression: correlation between presence of a mutant ras gene and loss of heterozygosity on mouse chromosome 7.

Initiation of tumorigenesis in mouse skin can be accomplished by mutagenesis of the H-ras gene by treatment with chemical carcinogens. A mouse model system has been developed to study the additional genetic events that take place during tumor progression. Skin carcinomas were induced in F1 hybrid mice exhibiting restriction fragment length polymorphisms at multiple chromosomal loci. Analysis of loss of heterozygosity in such tumors showed that imbalance of alleles on mouse chromosome 7, on which the H-ras gene is located, occurs very frequently in skin carcinomas. The chromosomal alterations detected, which included both nondisjunction and mitotic recombination events, were only seen in tumors that have activated ras genes. We conclude that gross chromosomal alterations that elevate the copy number of mutant H-ras and/or lead to loss of normal H-ras are a consistent feature of mouse skin tumor development.

Alleles↗
PubMed1989

A follow-up study of high-functioning autistic children.

It is well known that IQ is an important prognostic variable in the outcome of autistic children. There are, however, very few data available on the outcome of nonretarded autistic children as adults. We identified 16 such probands from records and followed them up between 11 and 27 years since discharge from a center specializing in the assessment of autistic children. There were 12 males and 4 females, average age was 26, and mean IQ was 92 (range 68-110). Although the majority were functioning poorly in terms of occupational-social outcome and psychiatric symptoms, a surprising number (4) had a very good outcome and might be considered recovered. The severity of early autistic behavior was a poor predictor of outcome, but neuropsychologic measures of nonverbal problem solving were highly correlated with outcomes. The results of the study indicate that a small percentage of nonretarded autistic children can be expected to recover to a substantial degree.

Adolescent↗
PubMed1989

Asperger's syndrome and autism: comparison of early history and outcome.

The authors compared children with Asperger syndrome (AS) with high-functioning autistic children and psychiatric outpatient controls on measures of early history and outcome. In terms of their early history, the autistic probands showed more social impairment, a higher frequency of echolalia and pronoun reversal, and a more restricted range of activities than the AS group. Cluster analysis suggested refinements to the diagnostic criteria, which resulted in larger differences between the groups on these early history measures. In terms of their outcome, the autistic probands spent more time in special education classes but developed fewer accessory psychiatric symptoms than the AS children. It was clear, however, that there were no substantive, qualitative differences between the AS and autistic groups, indicating that AS should be considered a mild form of high-functioning autism. The inclusion of AS among the autistic spectrum of disorders has implications both for aetiological studies and for prevalence estimates of the pervasive developmental disorders.

Autistic Disorder↗
PubMed1989

Asperger's syndrome: a review of clinical features.

The term Asperger's Syndrome (AS) refers to a clinical picture characterized by social isolation in combination with odd and eccentric behaviour. While the syndrome has been recognized for some time, diagnostic criteria for the disorder have not yet been established or evaluated. The objective of this paper is to describe some of the clinical features of AS. Twenty-eight children and adolescents with AS were compared to a group of psychiatric outpatients (matched on age and sex) who were also socially impaired. The AS subjects showed a range of social impairments essentially different than those seen in the control group. The sex ratio, family history, and presence of neurologic disease in some AS cases, suggest that the etiology of the disorder is similar to that in autism. The methodological limitations of the study are discussed, and a revised set of diagnostic criteria are proposed for AS.

Adolescent↗