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Biomedical subjects

S Hawkins

Publications and source records attributed to S Hawkins.

At least 37 records · Page 2Linked to original sources

Effects of head and neck radiation therapy on vocal function.

OBJECTIVE: Radiotherapy (RT) is used to treat a variety of head and neck malignancies. The larynx may receive high radiation doses even in the absence of disease. The effects of RT on the nondiseased larynx are unknown. This study will evaluate subjective and objective parameters of vocal function in patients treated with RT for nonlaryngeal malignancies. DESIGN: Cross-sectional observational study. METHODS: Videostroboscopic, aerodynamic, and acoustic analyses were performed. Results were compared to age- and gender-matched controls. Self-assessment of voice quality was measured using the Voice Handicap Index. RESULTS: A majority of patients demonstrated increased supraglottal activity (i.e., ventricular fold constriction) during stroboscopic evaluation. Significant differences compared to normative data were found in many aerodynamic and acoustic parameters. A substantial proportion (27%) of patients reported significant voice handicap. Younger patients reported greater handicap, and voice quality was worse with time. CONCLUSIONS: Significant objective and subjective changes in vocal function occur in patients radiated for nonlaryngeal head and neck malignancies. Young patients may have the worst impact, and vocal dysfunction may increase with time. A prospective study of this patient population should include a baseline voice quality assessment.

Adult↗

Feature selection for examining behavior by pathology laboratories.

Australia has a universal health insurance scheme called Medicare, which is managed by Australia's Health Insurance Commission. Medicare payments for pathology services generate voluminous transaction data on patients, doctors and pathology laboratories. The Health Insurance Commission (HIC) currently uses predictive models to monitor compliance with regulatory requirements. The HIC commissioned a project to investigate the generation of new features from the data. Feature generation has not appeared as an important step in the knowledge discovery in databases (KDD) literature. New interesting features for use in predictive modeling are generated. These features were summarized, visualized and used as inputs for clustering and outlier detection methods. Data organization and data transformation methods are described for the efficient access and manipulation of these new features.

Artificial Intelligence↗

Loss of expression of the beta subunit of soluble guanylyl cyclase prevents nitric oxide-mediated inhibition of DNA synthesis in smooth muscle cells of old rats.

We compared the effects of NO donors and cGMP analogues on the growth of aortic smooth muscle cells (SMCs) derived from newborn, adult (aged 3 months), and old (aged 2 years) rats. We found that the NO donor S-nitroso-N-acetylpenicillamine failed to block DNA synthesis in SMCs from old rats but was effective in SMCs from newborn and adult rats. However, cGMP analogues were inhibitory in all 3 SMC types. We demonstrated that in SMCs from old rats, NO was unable to increase the concentration of intracellular cGMP, suggesting that either cGMP synthesis was defective or cGMP degradation was enhanced. Western blot analysis revealed that SMCs from old rats do not express the beta subunit of soluble guanylyl cyclase. To confirm the importance of this observation in vivo, we balloon-injured the carotid arteries of adult and old rats. Whereas soluble guanylyl cyclase was expressed at the same level in the media of injured vessels and uninjured vessels of both groups, its expression in the intimas of old rats was reduced by 70% compared with intimas from adult animals. Furthermore, N(omega)-nitro-L-arginine, an inhibitor of NO synthesis, enhanced the intimal thickening in injured vessels in adult rats but not in old rats. We conclude that the loss of NO responsiveness in aged rats is due to the lack of the beta subunit of soluble guanylyl cyclase, and we speculate that this defect contributes to the enhanced intimal thickening in response to injury in old animals.

Aging↗

Early onset of Friedreich's ataxia in a compound heterozygote.

Friedreich's ataxia (FA) is an autosomal recessive condition caused by a GAA trinucleotide repeat expansion in the X25 gene on chromosome 9. We describe an unusual form of "pseudodominant" inheritance to illustrate how a diagnosis of FA in a parent does not preclude the diagnosis in the child.

Age of Onset↗

Overexpression of CCAAT displacement protein represses the promiscuously active proximal gp91(phox) promoter.

CCAAT displacement protein (CDP) is a transcriptional repressor that restricts expression of the gp91(phox) gene to mature myeloid cells. CDP interacts with multiple sites within the -450 to +12 bp human gp91(phox) promoter, and down-regulation of CDP DNA-binding activity is required for induction of gp91(phox) transcription in mature phagocytes. Truncation of the gp91(phox) promoter to -102 to +12 bp removes 4 CDP-binding sites and reveals a promiscuous promoter activity that is active in some nonphagocytic cells. A cis-element at -90 bp is required for derepressed transcription and serves as a binding site for multiple transcriptional activators. We now report that this element also serves as a binding site for CDP. The affinity of CDP for this element is relatively weak compared with upstream CDP-binding sites within the promoter, consistent with the promiscuous transcriptional activity exhibited by the -102 to +12 bp gp91(phox) promoter fragment. Further analysis of the proximal promoter reveals an additional weak-affinity CDP-binding site centered at approximately -20 bp. Overexpression of cloned CDP represses the -102 to +12 bp gp91(phox) promoter, indicating that these proximal CDP-binding sites are functionally significant. The constellation of transcriptional activators and a repressor that interacts with the -90 bp cis-element is identical to that observed for a promoter element at -220 bp, reflecting the highly modular organization of the gp91(phox) promoter. These studies illustrate the complex interplay between transcriptional activators and a repressor that contribute to the myeloid-restricted expression of the gp91(phox) gene.

Cell Differentiation↗

Biochemical characterization, molecular cloning and expression of laccases - a divergent gene family - in poplar.

The nature of the enzyme(s) involved in the dehydrogenative polymerization of lignin monomers is still a matter of debate. Potential candidates include laccases which have recently received attention due to their capacity to oxidize lignin monomers and close spatial and temporal correlation with lignin deposition. We have characterized two H2O2-independent phenoloxidases with approximate molecular masses of 90 kDa and 110 kDa from cell walls of Populus euramericana xylem that are capable of oxidizing coniferyl alcohol. The 90-kDa protein was purified to apparent homogeneity and extensively characterized at the biochemical and structural levels. To our knowledge, this is the first report of a plant laccase purified to homogeneity from a lignifying tissue of an angiosperm. The cDNA clones corresponding to the 90-kDa and 110-kDa proteins, lac90 and lac110, were obtained by a PCR-based approach using specific oligonucleotides derived from peptide sequences. Sequence analysis indicated that lac90 and lac110 encoded two distinct laccases. In addition, heterologous screening using an Acer pseudoplatanus laccase cDNA enabled us to obtain three additional cDNAs (lac1, lac2, lac3) that did not correspond to lac90 and lac110. The five laccase cDNAs correspond to a highly divergent multigene family but Northern analysis with gene-specific probes indicated that all of the genes are exclusively and abundantly expressed in stems. These results highlight the polymorphism of plant laccases by an integrated biochemical and molecular approach, and provide the tools that will enable us to clearly determine the function of these enzymes in plants by molecular and genetic approaches.

Acrolein↗

Immunolocalization of cinnamyl alcohol dehydrogenase 2 (CAD 2) indicates a good correlation with cell-specific activity of CAD 2 promoter in transgenic poplar shoots.

Cinnamyl alcohol dehydrogenase 2 (CAD 2) localization and the cell-specific activity of the eucalyptus CAD 2 promoter were investigated by CAD 2 immunogold localization and promoter beta-glucuronidase (GUS) histochemistry in apical and mature parts of stable transformed poplar (Populus tremula x P. alba) stems. Both CAD 2 protein and GUS activity were found to be confined in the same types of cells in the shoot apices, particularly in the determined meristematic cells in leaf axils and shell zones, procambium and developing tracheids. Within mature stems, CAD 2 and GUS were also identified in cambium and in fully or partially lignified cells derived from it (young xylem, developing phloem fibres, chambered parenchyma cells around phloem). Additionally, GUS activity was found in the scale leaves of apical shoot buds and in the roots (namely in the procambium, cambium, phellogen, young xylem, pericycle) of transformed plants. By employing immunogold cytochemistry, CAD 2 was shown to be localized in the cytoplasm within cambial, ray and young xylem cells in stems, the gold particles being randomly attached to endoplasmic reticulum and Golgi-derived vesicles. These results support a crucial role for CAD 2 in lignification and indicate a new role for this enzyme in branching events within the shoot apex and during lateral root formation.

Alcohol Oxidoreductases↗

Changes in the male voice at puberty: vocal fold length and its relationship to the fundamental frequency of the voice.

Ultrasound measurements of the vocal folds were taken for a number of boys passing through puberty. The boys were grouped according to their pubertal stage as defined by Tanner and there was a gradual increase in the length of the vocal folds as puberty progressed. The fundamental frequency of the boys' speaking voice was recorded via laryngography and a good correlation between the length of the vocal folds and the frequency of the voice was seen. The sudden drop in frequency seen between Tanner stages 3 and 4 did not correlate with similar changes in the length of the vocal folds at this time but stroboscopic findings suggest a change in the structure and mass of the vocal folds at this time of maximum frequency change.

Adolescent↗

Cinnamoyl CoA reductase, the first committed enzyme of the lignin branch biosynthetic pathway: cloning, expression and phylogenetic relationships.

Cinnamoyl CoA:NADP oxidoreductase (CCR, EC 1.2.1.44) catalyzes the conversion of cinnamoyl CoA esters to their corresponding cinnamaldehydes, i.e. the first specific step in the synthesis of the lignin monomers. The cloning of a cDNA encoding CCR in Eucalyptus gunnii (EUCCR) is reported here. The identity of the EUCCR cDNA was demonstrated by comparison with peptide sequence data from purified CCR and functional expression of the recombinant enzyme in Escherichia coli. Sequence analysis revealed remarkable homologies with dihydroflavonol-4-reductase (DFR), the first enzyme of the anthocyanin biosynthetic pathway. Moreover, significant similarities were found with mammalian 3 beta-hydroxysteroid dehydrogenase and bacterial UDP-galactose-4-epimerase, suggesting that CCR shared a common ancestor with these enzymes and can therefore be considered as a new member of the mammalian 3 beta-hydroxysteroid dehydrogenase/ plant dihydroflavonol reductase superfamily. In Eucalyptus gunnii, CCR is encoded by one gene containing four introns whose positions are similar to those of introns I, II, III and V in DFR genes from dicots. In agreement with the involvement of CCR in lignification, the CCR transcript was shown to be expressed in lignified organs, i.e. root and stem tissues, and was localized mainly in young differentiating xylem. On the other hand, its abundance in Eucalyptus leaves suggests that monolignols may be precursors of end products other than lignins. This first characterization of a gene corresponding to CCR opens new possibilities to genetically engineer plants with lower lignin content. This is particularly important for woody plants such as Eucalyptus which are used for pulp making.

Aldehyde Oxidoreductases↗

Tail-gut cyst.

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Adult↗

Changes in the male voice at puberty.

The changes in the male voice in relation to the biological characteristics of puberty were assessed longitudinally in 26 boys. Speaking and singing fundamental frequencies were analysed in relation to the Tanner staging of puberty, saliva testosterone levels, and the Cooksey classification of voice analysis. There were abrupt changes in voice characteristics between Tanner stages G3 and G4 and more gradually from stages C3 to C5 of Cooksey. Although testosterone concentrations were not predictive of the changes, there was a correlation with testis volume. Voice fundamental frequencies were seen to change abruptly in late puberty, in contrast with previous studies. There is a good correlation between the Tanner and Cooksey methods of classification during male puberty.

Adolescent↗

Databases.

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Databases, Bibliographic↗

The impact of heart health promotion on coronary heart disease lifestyle risk factors in schoolchildren: lessons learnt from a community-based project.

A community health promotion project called Action Heart was undertaken in two electoral wards in Rotherham to try to change lifestyles of people. Schools were included within the project. Coronary heart disease lifestyle risk factors were measured at baseline and after a three year period in the intervention area and a similar control area. Lifestyle factors in schoolchildren were measured separately from adults using a different instrument. The post intervention survey of adults and economic evaluation demonstrated that Action Heart had achieved cost-effective estimated health gains. In the schoolchildren however, a mixture of positive and negative risk factor changes in both areas was demonstrated. Significant changes in lifestyle risk factors in schoolchildren were not elicited using this approach. The possible reasons for the lack of impact on lifestyle risk factors in schoolchildren are examined and the implications for further work explored.

Adolescent↗

Barium enema preparation: a study of low-residue diet, "Picolax' and 'Kleen-Prep'.

A prospective, randomized three-arm trial is presented of 150 consecutive patients attending for double-contrast barium enema (BE). This compares 'Picolax' (a combined stimulant and osmotic agent), 'Picolax' following a 3 day low-residue diet and 'Kleen-Prep' (a polyethylene-glycol osmotic agent). Faecal clearance, mucosal coating and colon fluid were scored in four colonic segments by two radiologists working independently and blinded to the preparation used. Analyses of an elderly subgroup and of side effects was performed. Low-residue diet conferred no benefit to Picolax preparation, which was satisfactory (ability to exclude 5 mm polyps) in 80% of patients. Kleen-Prep failed to achieve adequate preparation in 46%, due to excess fluid and poor mucosal coating. Kleen-Prep caused more patient nausea, abdominal bloating and pain than Picolax. Patients 70 years and older had similar results. Low-residue diet need not be used in addition to Picolax. Kleen-Prep as a single agent is not recommended for BE preparation.

Aged↗