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Biomedical subjects

J White

Publications and source records attributed to J White.

At least 145 records · Page 8Linked to original sources

Investigation of a large-area phased array for focused ultrasound surgery through the skull.

Non-invasive treatment of brain disorders using ultrasound would require a transducer array that can propagate ultrasound through the skull and still produce sufficient acoustic pressure at a specific location within the brain. Additionally, the array must not cause excessive heating near the skull or in other regions of the brain. A hemisphere-shaped transducer is proposed which disperses the ultrasound over a large region of the skull. The large surface area covered allows maximum ultrasound gain while minimizing undesired heating. To test the feasibility of the transducer two virtual arrays are simulated by superposition of multiple measurements from an 11-element and a 40-element spherically concave test array. Each array is focused through an ex vivo human skull at four separate locations around the skull surface. The resultant ultrasound field is calculated by combining measurements taken with a polyvinylidene difluoride needle hydrophone providing the fields from a 44-element and a 160-element virtual array covering 88% and 33% of a hemisphere respectively. Measurements are repeated after the phase of each array element is adjusted to maximize the constructive interference at the transducer's geometric focus. An investigation of mechanical and electronic beam steering through the skull is also performed with the 160-element virtual array, phasing it such that the focus of the transducer is located 14 mm from the geometric centre. Results indicate the feasibility of focusing and beam steering through the skull using an array spread over a large surface area. Further, it is demonstrated that beam steering through the skull is plausible.

Bone and Bones↗

Caregiver quality of life after autologous bone marrow transplantation.

Bone marrow transplantation (BMT) is a unique cancer therapy characterized by its novelty, intensity, and toxicity. Although families have been identified as having a critical influence on patient adaptation during the acute phase of BMT, minimal attention has been paid to their experiences during extended survivorship. This article reviews findings from a descriptive study on quality of life in primary caregivers of adult autologous bone marrow transplantation (AuBMT) survivors after acute hospitalization. Caregiver perceptions of their survival are delineated in an effort to characterize the dynamics of family recovery after BMT. Specifically, caregivers of AuBMT survivors require ongoing assistance to maintain their primary support role after BMT.

Adaptation, Psychological↗

Bites and stings from venomous animals: a global overview.

Venomous and poisonous animals are a significant cause of global morbidity and mortality. This Seminar will cover selected aspects of these animals, their venoms/poisons, and their clinical impact on humankind, from a global perspective, but with a distinctive Australian flavor and a clinical emphasis. Venomous snakes are found throughout most of the world, including many oceans, and have evolved a variety of highly effective toxins and methods of delivery. Their impact on humans is considerable, most current data suggesting they cause in excess of 3 million bites per year with more than 150,000 deaths. Particularly in the rural tropics, snakebite morbidity and mortality has a significant human medical and economic toll. The major groups of snakes causing bites are the vipers, the elapids (cobra type), the sea snakes, the side-fanged vipers, and the back-fanged colubrids. Australian venomous snakes are nearly all elapids and have evolved some of the most toxic of all snake venoms. Their effects include potent procoagulants and anticoagulants, neurotoxins, myotoxins, and nephrotoxins, but a distinct absence of the major local necrotoxins found in some non-Australian elapids and many vipers. The effect of these toxins on humans is not limited to envenoming, for the toxins are proving invaluable as research tools and diagnostic agents, and may even have a future as precursors of therapeutic agents. Because of the high toxicity and diversity of Australian elapids, a variety of monovalent antivenoms have been developed. There is also a venom detection kit to determine the type of snake and allow targeted antivenom therapy. The kit has also increased information available on diagnostic patterns of envenoming for each species. Australia is also home to the world's most lethal spiders, the funnel webs of eastern Australia, as well as the red back spider, the single most common reason for antivenom treatment in Australia. The latter spiders have been accidently exported to Japan. Within the marine environment exist a vast array of toxic animals, both poisonous and venomous, which not only cause morbidity and mortality in humans, but offer an incredibly rich array of valuable toxins. Australian waters contain some of the most lethal and medically problematic species, presenting a diverse range of clinical problems.

Animals↗

Microarray analysis of developing Arabidopsis seeds.

To provide a broad analysis of gene expression in developing Arabidopsis seeds, microarrays have been produced that display approximately 2,600 seed-expressed genes. DNA for genes spotted on the arrays were selected from >10,000 clones partially sequenced from a cDNA library of developing seeds. Based on a series of controls, sensitivity of the arrays was estimated at one to two copies of mRNA per cell and cross hybridization was estimated to occur if closely related genes have >70% to 80% sequence identity. These arrays have been hybridized in a series of experiments with probes derived from seeds, leaves, and roots of Arabidopsis. Analysis of expression ratios between the different tissues has allowed the tissue-specific expression patterns of many hundreds of genes to be described for the first time. Approximately 25% of the 2, 600 genes were expressed at ratios > or =2-fold higher in seeds than leaves or roots and 10% at ratios > or =10. Included in this list are a large number of proteins of unknown function, and potential regulatory factors such as protein kinases, phosphatases, and transcription factors. The Arabidopsis arrays were also found to be useful for transcriptional profiling of mRNA isolated from developing oilseed rape (Brassica napus) seeds and expression patterns correlated well between the two species.

Arabidopsis↗

Structure of Cu6PbO8

First-principles quantum mechanical calculations based on density functional theory were performed for Cu6PbO8, hexacopper lead octaoxide, murdochite. The computed lattice parameter, density and bond lengths at ambient pressure are in good agreement with experimental data for murdochite. At about 18 GPa a phase transition is predicted, when a polymorph with a Suzuki-type structure, i.e. a close-packed structure with ordered vacancies, is proposed to become stable. The pressure dependence of the structural parameters has been calculated for the two polymorphs and their bulk moduli have been predicted. It is argued that the incorporation of halogen atoms is not a precondition for the stability of murdochite.

Journal Article↗

Potent and selective activity of a combination of thymidine and 1843U89, a folate-based thymidylate synthase inhibitor, against Plasmodium falciparum.

Unlike mammalian cells, malarial parasites are completely dependent on the de novo pyrimidine pathway and lack the enzymes to salvage preformed pyrimidines. In the present study, first, it is shown that 1843U89, even without polyglutamylation, is a potent folate-based inhibitor of purified malarial parasite thymidylate synthase. The binding was noncompetitive with respect to methylenetetrahydrofolate, and 1843U89 had a K(i) of 1 nM. The compound also had potent antimalarial activity in vitro. Plasmodium falciparum cells in culture were inhibited by 1843U89, with a 50% inhibitory concentration of about 70 nM. The compound was effective against drug-sensitive as well as drug-resistant clones of P. falciparum. As predicted by the biochemistry of the parasite, the potent inhibition of parasite proliferation by 1843U89 could not be reversed with 10 microM thymidine. In contrast, in the presence of 10 microM thymidine, mammalian cells were unaffected by 1843U89 even at concentrations as high as 0.1 mM, thus offering a selectivity window of more than 1,000-fold. On this basis, folate-based thymidylate synthase inhibitors may represent a powerful additional tool that can be used to combat drug-resistant malaria.

Animals↗

Nitric oxide modulation of TNF-alpha-induced cardiac contractile dysfunction is concentration dependent.

Whereas previous studies suggest that tumor necrosis factor-alpha (TNF-alpha) induces cardiac contraction-relaxation deficits, the mechanisms remain unclear. Our recent studies have implicated cardiac-derived nitric oxide (NO). This study examined the detrimental and protective effects of NO donors S-nitroso-N-acetyl-penicillamine (SNAP) or (Z)-1- [N-(3-ammonio-propyl)-N-(n-propyl)amino]diazen-1-ium- 1,2diolate (PAPA/NO) on TNF-alpha-related changes in cardiac contractile function (Langendorff), cellular injury, and intracellular myocyte Ca(2+) concentration ([Ca(2+)](i)). Myocytes were incubated in the presence/absence of TNF-alpha (200-500 pg/ml x 10(5) cells) for 3 h; subsets of myocytes were incubated with one of several concentrations of SNAP or PAPA/NO (0.1, 0.3, 0.5, and 1.5 mM) for 15 min before TNF-alpha challenge. Supernatant creatine kinase (CK), cell viability (Trypan blue dye exclusion), and myocyte [Ca(2+)](i) (fura 2-acetoxymethyl ester) were measured. In parallel experiments, cardiac function (Langendorff) was examined after TNF-alpha challenge in the presence or absence of SNAP or PAPA/NO (0.1 and 1.5 mM). TNF-alpha in the absence of an NO donor impaired cardiac contraction and relaxation and produced cardiomyocyte injury. Pretreating perfused hearts or isolated cardiomyocytes with a low concentration of either SNAP or PAPA/NO decreased TNF-alpha-mediated cardiac injury and improved contractile dysfunction, whereas high concentrations of NO donor exacerbated TNF-alpha-mediated cardiac effects. These data provide one explanation for the conflicting reports of beneficial versus detrimental effects of NO in the face of inflammation and suggest that the effects of NO on organ function are concentration dependent; low concentrations of NO are cardioprotective, whereas high concentrations of NO are deleterious.

Animals↗

The efficacy, safety and tolerance of calcitriol 3 microg/g ointment in the treatment of plaque psoriasis: a comparison with short-contact dithranol.

OBJECTIVE: A comparison of efficacy, safety and tolerance of a twice-daily application of calcitriol 3 microg/g ointment with dithranol cream. METHODS: The study was an 8-week, prospective, randomised, open, parallel-group trial with 114 patients. Subjects received either 3 microg/g calcitriol ointment (twice daily) or 0. 25-2% dithranol cream (once daily for 30 min). Results were measured using global improvement, global severity, PASI, quality of life (QOL) and Psoriasis Disability Index scores. Safety was determined from reports of adverse events and blood chemistry analysis. RESULTS: At final assessment, calcitriol and dithranol were comparably efficacious. Skin irritation was reported by 5% of calcitriol and 72% of dithranol patients. Patients rated QOL and overall acceptability of calcitriol more highly. CONCLUSIONS: Twice-daily calcitriol ointment (3 microg/g) is equally effective as a once-daily, short-contact dithranol regimen. However, calcitriol is better tolerated than dithranol, and provides a better QOL and a greater patient acceptability.

Administration, Topical↗

Effects of lead counseling for children with lead levels > or = 20 microgram/dL: impact on parental knowledge, attitudes, and behavior.

The purpose of this study was to assess parental knowledge, attitudes, and behavior concerning lead reduction counseling. Of 108 children with confirmed venous lead levels > or = 20 microg/dL, 75 (69%) of the parents were interviewed by telephone 6-9 months later. The majority of parents recalled being given specific lead reduction strategies. Knowledge of cleaning interventions was associated with parents who could state the lead level, who perceived a benefit from knowing it was elevated, and whose children were referred to a specialty lead clinic. Recall of nutritional interventions was associated with parents who could state the lead level and whose children were referred to a specialty lead clinic. Although 79% of parents thought that it was beneficial to know their child's lead level was elevated, only 65% reported implementing lead reduction strategies. The majority of parents recalled receiving lead reduction counseling but reported low compliance with lead reduction strategies. Further research is needed to determine the causes of the discrepancy between knowledge and making the behavior changes necessary to comply with lead reduction interventions.

Child, Preschool↗

Cytochrome P450RAI(CYP26) promoter: a distinct composite retinoic acid response element underlies the complex regulation of retinoic acid metabolism.

The catabolism of retinoic acid (RA) is an essential mechanism for restricting the exposure of specific tissues and cells to RA. We recently reported the identification of a RA-inducible cytochrome P450 [P450RAI(CYP26)], in zebrafish, mouse, and human, which was shown to be responsible for RA catabolism. P450RAI exhibits a complex spatiotemporal pattern of expression during development and is highly inducible by exogenous RA treatment in certain tissues and cell lines. Sequence analysis of the proximal upstream region of the P450RAI promoter revealed a high degree of conservation between zebrafish, mouse, and human. This region of the promoter contains a canonical retinoic acid response element (5'-AGT-TCA-(n)5-AGTTCA-3'), embedded within a 32-bp region (designated R1), which is conserved among all three species. Electrophoretic mobility shift assays using this element demonstrated the specific binding of murine retinoic acid receptor-gamma (RARgamma) and retinoid X receptor-alpha (RXRalpha) proteins. Transient transfection experiments with the mouse P450RAI promoter fused to a luciferase reporter gene showed transcriptional activation in the presence of RA in HeLa, Cos-1, and F9 wild-type cells. This activation, as well as basal promoter activity, was abolished upon mutation of the RARE. Deletion and mutational analyses of the P450RAI promoter, as well as DNase I footprinting studies, revealed potential binding sites for several other proteins in conserved regions of the promoter. Also, two conserved 5'-TAAT-3' sequences flanking the RARE were investigated for their potential importance in P450RAI promoter activity. Moreover, these studies revealed an essential requirement for a G-rich element (designated GGRE), located just upstream of the RARE, for RA inducibility. This element was demonstrated to form complexes with Sp1 and Sp3 using nuclear extracts from either murine F9 or P19 cells. Together, these results indicate that the P450RAI-RARE is atypical in that conserved flanking sequences may play a very important role in regulating RA inducibility and expression of P450RAI(CYP26).

Animals↗

Worm tales.

Explore the source record for details and available documents.

Animals↗

Application of redD, the transcriptional activator gene of the undecylprodigiosin biosynthetic pathway, as a reporter for transcriptional activity in Streptomyces coelicolor A3(2) and Streptomyces lividans.

redD encodes the transcriptional activator of the biosynthetic pathway for undecylprodigiosin, a red-pigmented, mycelium-bound antibiotic made by Streptomyces coelicolor A3(2) and Streptomyces lividans. A promoterless version of redD preceded by the efficiently used tuf1 ribosome binding site was inserted into two different plasmid vectors, providing a convenient reporter of transcriptional activity in both species. One plasmid, plJ2587, replicates autonomously in both Escherichia coli and streptomycetes, while the other, plJ2585, replicates in E. coli and can be transferred to streptomycetes by conjugation or transformation, whereupon it integrates stably at the chromosomal attachment site for the temperate phage phiC31. The utility of the plasmids in detecting not only transcriptional activity, but also its regulation, was confirmed using the rrnAp, ermEp*, and glnRp promoters. The ability to screen visually and spectrophotometrically for red pigmentation should make the vectors particularly attractive for analysing the regulation of gene expression, and for the isolation of mutants, in both S. coelicolor and S. lividans.

Amino Acid Sequence↗

An integrative contextual developmental model of male stalking.

This article evaluates current research and theory on stalking as a form of male violence against women. The integrative contextual developmental model (White & Kowalski, 1998) suggests that stalking, as legally defined, is best understood as a multiply determined form of violence, with variables identifiable at several levels, the sociocultural, interpersonal, dyadic, situational and intrapersonal. The model also serves as a framework for identifying gaps in current research and suggests directions for further work.

Fear↗