Research-based clinical practice.
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Biomedical subjects
Publications and source records attributed to D Forrest.
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Thyroid hormones and their receptors (TRs) have critical functions in development. Here we show that a chicken TR beta cDNA clone encodes a receptor with a novel, short N-terminal domain. In vitro-expressed TR beta protein bound thyroid hormone with similar affinity as the chicken TR alpha. Comparison of expression of TR alpha and TR beta mRNAs throughout chicken development until 3 weeks post-hatching revealed ubiquitous expression of TR alpha mRNAs (in 14 different tissues) with some variations in levels, from early embryonic stages. In contast, expression of TR beta mRNA was restricted, occurring notably in brain, eye, lung, yolk sac and kidney, and was subject to striking developmental control, especially in brain where levels increased 30-fold upon hatching. Levels also sharply increased in late embryonic lung, but were relatively high earlier in embryonic eye and yolk sac. RNase protection analyses detected no obvious mRNAs for alpha and beta TRs with variant C-termini as demonstrated previously for the rat TR alpha gene. The data suggest a general role for TR alpha and specific developmental functions for TR beta, and that thyroid-dependent development involves temporal and tissue-specific expression of the TR beta gene.
In contrast to the normal thyroid hormone receptor, the v-erbA product fails to bind hormone due to mutations in the C-terminal ligand binding domain and thus appears to represent a hormone-independent, oncogenic transcription factor. Therefore, we asked whether or not the C-terminal domain of v-erbA is required for its biological activity and putative transcriptional control functions by analysing mutants with altered C-termini. A v-erbA protein truncated in the C-terminal domain lacked detectable biological activity in transformed erythroblasts and its transcriptional repression function with respect to the band 3 gene was abolished. The protein displayed a nuclear location and could still bind to DNA, indicating that the N-terminal region retained DNA-binding activity but was insufficient to produce characteristic v-erbA changes in erythroblasts. Another biologically defective v-erbA variant with a small frameshift towards the extreme C-terminus also failed to repress band 3, indicating a requirement for a specific C-terminal structure in repression. However, this mutant retained partial biological activity, stimulating erythroblasts to grow at a higher rate than cells containing a completely inactive, deleted v-erbA gene. The results demonstrate that the mutated hormone-binding domain, in addition to the DNA-binding region, is critical for v-erbA biological and transcriptional control functions.
Caring is inextricably bound to the belief system and practice of nursing. Yet there is a lack of research on what caring is for the practising nurse. It was the purpose of this qualitative study to investigate the phenomenon of caring with 17 hospital staff nurses who, in taped sessions, described their subjective experiences of caring. Phenomenology, an inductive descriptive research method, was used with the data analysed according to Colaizzi's procedure. Thirty theme clusters, emerging from specific themes, fell into seven categories under two broad classifications; 'what is caring' and 'what affects caring'. The essential structure of caring is described and implications for nursing education, practice and research discussed.
Genetic analysis of the MAL6 locus has previously yielded mal6 mutants which fall into a single complementation group and which are noninducible for maltase and maltose permease. However, the strains used in these studies contained additional partially functional copies of MAL1 (referred to as MAL1g) and MAL3 (referred to as MAL3g). Using a strain lacking MALg genes, we have isolated two classes of mutants and these classes correspond to mutations in MAL63 and MAL61, two genes of the MAL6 complex. Disruptions of MAL63 are noninducible for maltase and maltose permease and for their corresponding mRNAs. The mal6 mutants are shown to map to MAL63. Inducer exclusion as a cause of the noninducible phenotype of the mal63 mutations has been eliminated by constructing a mal63 mutant in a strain constitutive for maltose permease; the strain remains noninducible. These results rigorously demonstrate that MAL63 is a regulatory gene which plays a positive role in the regulation of maltose fermentation.
We, and others, have recently shown that recombinant feline leukaemia viruses (FeLV) containing the myc gene (FeLV-myc) occur in up to 30% of naturally occurring cases of T-cell lymphosarcoma. Investigation of the disease spectrum of two FeLV-myc isolates showed that they induced clonal or oligoclonal T-cell tumours after a short latent period. The phenotypic pattern of the thymic tumours was restricted in that they all expressed the alpha and beta chains of the T-cell antigen receptor and could readily be established in culture in vitro without the addition of exogenous interleukin-2. Although helper FeLV was transmitted from infected cats to uninfected tracer cats, there was no evidence of horizontal transmission of FeLV-myc viruses, suggesting that these viruses arise de novo in individual cases of thymic lymphosarcoma.
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The composition of plume produced during carbon dioxide laser endoscopic treatment for endometriosis was examined to determine whether it represented a hazard to the surgical staff. A total of 32 plume samples were collected from 17 women undergoing laser laparoscopic treatment for endometriosis and/or adhesions. The smoke was found to consist of particles having a median aerodynamic diameter of 0.31 micron with a range of 0.10-0.80 micron. The size range has two consequences: 1) using a human red blood cell as a model for all cells, it can be stated with greater than 99.9999% certainty that no cell-size particles, including cancer cells, are present in the plume; 2) particles in this size range are too small to be effectively filtered by currently available surgical masks.
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The c-myc gene is rearranged in a subset of feline T-cell lymphosarcomas. Detailed mapping of c-myc rearrangements showed that some result from feline leukaemia virus (FeLV) proviral integration within or upstream of c-myc, but one case involves a complex 3' alteration and amplification which is apparently not directly virus-induced. S1 nuclease mapping of RNA from normal cells using c-myc probes revealed two presumptive 5' ends, each corresponding to a promoter-like sequence (P1 and P2), and a major 3' discontinuity which mapped to the 3'-most of two possible polyadenylation signals. Analysis of RNA from a series of tumours revealed different modes of c-myc expression. All tumours produced P1 and P2 transcripts with apparently normal structure except for one case where an insertion in intron 1 displaced exon 1 sequences. The abundance ratio of P1/P2 transcripts varied considerably and was high in tumours which carry a rearrangement adjacent to c-myc, but some other T-cell tumours with no apparent myc alteration displayed an equally high ratio. However, a consistent feature was the lack of detectable RNA from normal c-myc alleles in tumours which express a rearranged c-myc allele or a transduced FeLV v-myc gene. We suggest that this may prove to be a useful indicator of the presence of an oncogenically active myc gene, whether this is a rearranged c-myc or transduced v-myc sequence.
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We have cloned the normal feline c-myc locus and determined the nucleotide sequence of all three exons. The feline c-myc gene shows close homology to other mammalian c-myc genes, particularly human c-myc. The feline and human sequences are colinear within the open reading frame for the putative c-myc product but show insertions and deletions relative to each other outside this domain. We have also analyzed a cloned FeLV provirus, CT4, which contains the host-derived myc gene. In this provirus the v-myc sequences are located at the 3' end of the pol gene, replacing pol and env sequences. Nucleotide sequence analysis of CT4 shows an open reading frame for a v-myc gene product which may be expressed without fusion to any viral protein sequences. This contrasts with another FeLV v-myc (LC), in which myc and gag sequences were found to be fused. Unlike previously identified avian v-myc genes, the feline v-myc genes contain exon 1-derived sequences, but these have been truncated or internally deleted. The FeLV CT4 v-myc sequence shows very few coding changes relative to c-myc and the FeLV LC v-myc coding sequence is unchanged relative to c-myc apart from fusion to gag. These results are discussed in relation to the mechanism of transduction and activation of myc by FeLV.
Thirty-seven children admitted to hospital with a diagnosis of abuse at an average of 5.5 years previously were compared with 37 non-abused children matched for age, sex, ethnic group, school and social class. The mean age of the children with 8.9 years (range 4.6-14.0 years). Self-esteem in the children was assessed by means of a structured interview with the child and the Piers-Harris Self-Concept Scale. The abused children saw themselves as having significantly fewer friends than the comparison children and they played with friends less often. They were less ambitious than the non-abused children with regard to the sort of occupation they would like as adults and were significantly lower in self-concept on the Piers-Harris Self-Concept Scale. These results show that, as well as providing treatment for abusive parents, a long-term program which aims at improving interpersonal relationship skills and self-esteem is required for abused children.
Thirty-six mothers whose children had been abused were interviewed and compared with 36 mothers matched for social class and ethnic background. The abuse group mothers had lower self-esteem than the comparison mothers as judged by their desire that their children should not grow up to be like themselves or their partners. They were also less likely to discuss their problems with other people. They were less likely than the comparison mothers to have been brought up by their own parents. They had significantly more negative feelings than the comparison mothers towards their fathers when they were children and these negative feelings persisted into adult life. It is important that emphasis on treatment programs for these mothers should be placed on building up self-esteem and skills in interpersonal relationships.