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Biomedical subjects

P Hinds

Publications and source records attributed to P Hinds.

At least 37 records · Page 2Linked to original sources

Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation.

Previous experiments have brought into question which amino acid sequence of the p53 oncogene product should be considered wild type and whether the normal protein is capable of cooperating with the ras oncogene to transform cells in culture. To address these questions, a series of p53 cDNA-genomic hybrid clones have been compared for the ability to cooperate with the ras oncogene in transformation assays. From these experiments, it has become clear that the amino acid alanine at position 135, in either the genomic clone or the cDNA clone, failed to produce a p53 protein that cooperated with the ras oncogene and transformed cells. Replacing alanine with valine at this position in either the genomic or the cDNA clone activated for transformation in this assay. Using restriction enzyme polymorphisms in the p53 gene, it was shown that normal mouse DNA encodes alanine at position 135 in the p53 protein. Thus, mutation is required to activate the p53 protein for cooperation with the ras oncogene. After cotransfection with the activated ras gene, the genomic p53 DNA clone always produced more transformed cell foci (1.7-fold) than similar cDNA clones and these foci were more readily cloned (3.6-fold) into permanent cell lines. A series of deletion mutants of the genomic p53 clone were employed to show that the presence of intron 4 in the p53 gene was sufficient to provide much enhanced clonability of transformed foci from culture dishes. The presence of introns in the p53 gene constructions also resulted in elevated levels of p53 protein in the p53-plus-ras-transformed cell lines. Thus, qualitative changes in the p53 protein are required to activate p53 for transformation with the oncogene ras. Quantitative improvements of transformation frequencies are associated with the higher expression levels of altered p53 protein that are provided by having one of the p53 introns in the transforming plasmid.

Amino Acid Sequence↗

Cellular gene expression in papillomas of the choroid plexus from transgenic mice that express the simian virus 40 large T antigen.

Transgenic mice that contain the simian virus 40 (SV40) enhancer-promoter and large tumor (T) antigen gene develop papillomas of the choroid plexus. The tumors remain well differentiated on histological examination and express normal levels of tissue-specific mRNAs for transthyretin (TTR) and the 5-HT1C serotonin receptor, two differentiated cell markers. Both Northern (RNA) blot analysis and in situ cytohybridization have been used to monitor the steady-state levels of the mRNAs from the viral oncogene (T antigen) and from several cellular oncogenes. In situ hybridization demonstrated, in serial sections, increased levels of both T antigen mRNA and p53 mRNA localized in the tumor tissue but not in the normal brain tissue. The ratios of the steady-state levels of mRNA for p53/TTR and p53/L32, a ribosomal protein gene, were 2- to 20-fold higher in the tumor tissue than in the normal choroid plexus tissue. Several other oncogenes did not show elevated levels of mRNA in these tumors. p53 protein levels were not detectable in normal brain tissue, but p53 levels were very high in tumor tissue in which all of the p53 was found in a complex with the SV40 large T antigen. These data continue to show a close relationship between SV40 T-antigen-mediated tumorigenesis and the role of p53 in these tumors.

Animals↗

Modifications in deaf children's vowel production: perceptual evidence.

This study examined the perceived changes in vowel articulation by profoundly deaf children as a function of the method of teaching: with visual feedback provided by the Computer Vowel Trainer (CVT) vs conventional methods. The assessment carried out by experienced listeners consisted in marking the sounds heard on the vowel quadrilateral. It was found that changes in perception were feedback and age dependent: younger children taught with the CVT were perceived as displaying more mobility in articulation and they approximated more closely the target vowels than their control counterparts or older children. Progress was evident in particular for back and central vowels. Analysis of perceived discrepancies between target and judged vowels, too, suggested that visual feedback was beneficial: perception of experimental children's utterances showed a marked reduction in substitutions with central vowels, a characteristic pattern of deaf speech. Comparison of these findings with the results yielded by the judgement of the same items by naive listeners indicated broad agreement between the two categories of assessors. Results were discussed in terms of the perceptual and articulatory intervening variables with reference to the specific advantages and constraints imposed by evaluating vowel quality on the vowel plane.

Articulation Disorders↗

Vowel-learning and the vowel system of deaf children: age and feedback-related differences.

A study comparing perceptual judgments of vowels produced by deaf children taught to speak by using a computer-based aid (experimental group, E) and by conventional techniques (control group, C) revealed feedback-related differences. These concerned the ability to reorganise articulatory performance, intelligibility of vowels after training, and the strength of the memory trace, which all showed an advantage for the E group. A phoneme-by-phoneme analysis indicated that the E group improved consistently on back and central vowels, whereas no consistent trend was found in the C group. The modifications observed were also age-dependent, more progress was found in the younger than in the older children's performance. An error analysis showed that asymmetric vowel confusions were predominant and that the major factor accounting for all errors was the small difference between second formant values. The findings are discussed in terms of the articulatory and perceptual variables intervening in the vowel intelligibility of deaf children.

Age Factors↗

Acquisition of frication by severely hearing-impaired children.

The ability of severely deaf school children to master fricative production and the fricative-affricate distinction was studied over a period of 6 months. The children were given daily speech therapy and half of them received, in addition, visual feedback from a microprocessor-based speech training aid - the 'Fricative and Timing Aid'. The speech of a third group of children, who received no training from us, was also monitored. Results were analysed in terms of the acquisition of fricatives and affricates, and of their position in a word. Results yielded by perceptual tests showed a substantial increase in the intelligibility of all trained children for almost all phonemes at the end of the training programme. Retention scores, i.e. intelligibility scores obtained by re-testing the children after a 2-moth period of non-practice, showed that practically no forgetting of articulatory skills occurred during this interval. Comparisons between children trained with or without visual feedback in general showed no difference between them; however, the former were more intelligible when producing affricates. No improvement in intelligibility was found when no systematic speech training was available. It was concluded that while frication may not be acquired spontaneously, it is a task within the reach of severely deaf children when adequately trained.

Adolescent↗

Acquisition of the voicing distinction by profoundly hearing-impaired children.

The ability of profoundly deaf schoolchildren to learn the voicing distinction was studied over a period of 6 months. The children were given daily speech therapy and half of them received, in addition, visual feedback from a microprocessor-based speech training aid - the Fricative and Timing Aid. Their performance was analysed in terms of the acquisition of voiced v. voiceless stop consonants and of their position in a word. Results yielded by perceptual tests showed a substantial increase in the intelligibility of stop consonants at the end of the training programme. Retention scores, i.e. intelligibility scores obtained by re-testing the children after a 2-month period of non-practice, showed that practically no articulatory skills were forgotten during this interval. Measurements of vowel duration in word-final stop consonants indicated a considerable decrease in vowel length with training, and although this remained higher than for hearing children it probably contributed to higher intelligibility scores. Comparisons between children trained with or without visual feedback showed a definite advantage for the former. No improvement in intelligibility was found when no systematic speech training was available. It was concluded that while the voicing distinction may not be acquired spontaneously, it is a skill within reach of profoundly deaf children when they are trained adequately.

Adolescent↗

Teaching vowel articulation with the computer vowel trainer. Methodology and results.

The Computer Vowel Trainer (CVT) uses linear prediction to estimate and display the shape of the speaker's vocal tract during an utterance. The assessment of the CVT was carried out over a period of three years with 14 profoundly deaf children divided into an experimental and a matched control group. Two main results were obtained: (a) children learning to articulate with the CVT achieve consistently higher articulation scores than those trained with conventional methods; (b) the younger the children, the greater their progress in vowel learning, retention and generalization.

Age Factors↗

Response bias in the perception of deaf speech by experienced and naive listeners.

A comparative study of the attempts of naive listeners and listeners familiar with deaf speech to identify utterances of young deaf speakers showed that there were no differences between the intelligibility scores of the two groups. Significant differences emerged, however, in the type of errors made by each group, the naive listeners making more errors of omission and the listeners familiar with deaf speech more substitution errors. It is suggested that these results indicate different response biases towards the evaluation task, but fail to support the hypothesis that familiarity with the speaker confers a substantial advantage in understanding the speech of the deaf, in the absence of other clues.

Analysis of Variance↗

A model to integrate hospital board and health office functions at district level.

Proposals to integrate the administrative responsibilities of a hospital board and a district health office, are described. Relevant literature advocating the combination of some of the operational functions of these two agencies is reviewed, as is the situation in the Gisborne district as it was at the time that the proposals were formulated. Possible constraints that may obstruct the implementation of the proposals are also discussed, and the need for empowering legislation to allow further development to proceed is emphasised.

Hospital Administration↗

The role of EMS systems in public health emergencies.

INTRODUCTION: Until now, the public health response to the threat of an epidemic has involved coordination of efforts between federal agencies, local health departments, and individual hospitals, with no defined role for prehospital emergency medical services (EMS) providers. METHODS: Representatives from the local health department, hospital consortium, and prehospital EMS providers developed an interim plan for dealing with an epidemic alert. The plan allowed for the prehospital use of appropriate isolation procedures, prophylaxis of personnel, and predesignation of receiving hospitals for patients suspected of having infection. Additionally, a dual notification system utilizing an EMS physician and a representative from the Office of Infectious Diseases from the hospital group was implemented to ensure that all potential cases were captured. Initially, the plan was employed only for those cases arising from the Centers for Disease Control and Prevention (CDC)/Public Health Service (PHS) quarantine unit at the airport, but its use later was expanded to include all potential cases within the 9-1-1 system. RESULTS: In the two test situations in which it was employed, the plan incorporating the prehospital EMS sector worked well and extended the "surveillance net" further into the community. During the Pneumonic Plague alert, EMS responded to the quarantine facilities at the airport five times and transported two patients to isolation facilities. Two additional patients were identified and transported to isolation facilities from calls within the 9-1-1 system. In all four isolated cases, Pneumonic Plague was ruled out. During the Ebola alert, no potential cases were identified. CONCLUSIONS: The incorporation of the prehospital sector into an already existing framework for public health emergencies (i.e., epidemics), enhances the reach of the public safety surveillance net and ensure that proper isolation is continued from identification of a possible case to arrive at a definitive treatment facility.

Disease Outbreaks↗

From dawn to dusk.

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Community Health Nursing↗