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Biomedical subjects

David King

Publications and source records attributed to David King.

At least 19 recordsLinked to original sources

Nonrandom processes maintain diversity in tropical forests.

An ecological community's species diversity tends to erode through time as a result of stochastic extinction, competitive exclusion, and unstable host-enemy dynamics. This erosion of diversity can be prevented over the short term if recruits are highly diverse as a result of preferential recruitment of rare species or, alternatively, if rare species survive preferentially, which increases diversity as the ages of the individuals increase. Here, we present census data from seven New and Old World tropical forest dynamics plots that all show the latter pattern. Within local areas, the trees that survived were as a group more diverse than those that were recruited or those that died. The larger (and therefore on average older) survivors were more diverse within local areas than the smaller survivors. When species were rare in a local area, they had a higher survival rate than when they were common, resulting in enrichment for rare species and increasing diversity with age and size class in these complex ecosystems.

Biodiversity↗

Uptake and persistence of the vertebrate pesticide, sodium monofluoroacetate (compound 1080), in plants of cultural importance.

Field research was undertaken to determine if naturally occurring plants utilised by a Maori (the indigenous people of New Zealand) community for food and medicine would take up the toxin sodium monofluoroacetate (Compound 1080) from baits used to control the brush-tailed possum Trichosurus vulpecula. Single baits were placed at the base of individual plants of two species, pikopiko (Asplenium bulbiferum) and karamuramu (Coprosma robusta). Plants were sampled at various times up to 56 days, and samples analyzed for 1080 content. No 1080 was detected in any of the pikopiko samples, whereas 1080 was detected in karamuramu, at a maximum concentration of 5 ppb after 7 days, and 2.5 ppb after 14 days. This concentration decreased to zero at 28 days, indicating that while karamuramu was shown to take up 1080, it was not persistent. The results of this study suggest there is negligible risk of humans being poisoned by consuming plants that have taken up 1080 from baits. To allay community concerns that minute concentrations of 1080 might influence the medicinal properties of plants, it is suggested a withholding period of 30 days after 1080 control operations could be adopted.

Animals↗

No effect of 85 mT permanent magnets on laser-Doppler measured blood flow response to inspiratory gasps.

Although no effects of permanent magnets on resting skin blood flow (SBF) in humans have yet been demonstrated, the possibility that magnet related effects might modify dynamic SBF changes has not been previously studied. We hypothesized that magnets may alter local neurovascular mechanisms to cause changes in normal SBF vasoactive responses. To test this, we studied the effects of a magnet on SBF reductions induced by sympathetic reflexes associated with deep inspirations. SBF was continuously monitored by a dual channel laser-Doppler flowmeter with probes on the middle finger dorsum of both hands of 24 healthy subjects. In the first of two successive intervals, each of the fingers rested on sham ceramic magnets (control interval). Subsequently, one finger rested on an active magnet and the other finger on a sham (experimental interval). Skin temperatures were also measured. The magnet was a 37 mm diameter x 14 mm thick ceramic magnet with a surface field strength of 85 mT measured in the geometrical center of the magnet. Field strength at the finger dorsum, 13 mm above magnet, was 31.5 mT. During each interval, three deep breaths were used to elicit SBF reductions. Responses were calculated as the percent reduction in SBF from its prior 20 s average. Breaths in each interval were spaced 3 min apart to permit full recovery between responses. The experimental interval started after an active magnet was in place for 20 min. Results showed no significant difference in either vasoconstrictive responses or skin temperature due to the magnet. We conclude that magnets of the type, strength and duration used, have no significant effect on vasoconstrictive processes associated with this sympathetic reflex in this group of healthy subjects.

Adult↗

A genetically encoded photocaged amino acid.

We have developed a second orthogonal tRNA/synthetase pair for use in yeast based on the Escherichia coli tRNALeu/leucyl tRNA-synthetase pair. Using a novel genetic selection, we have identified a series of synthetase mutants that selectively charge the amber suppresor tRNA with the C8 amino acid, alpha-aminocaprylic acid, and the photocaged amino acid, o-nitrobenzyl cysteine, allowing them to be inserted into proteins in yeast in response to the amber nonsense codon, TAG.

Base Sequence↗

Bioactivation and cell targeting of semiconductor CdSe/ZnS nanocrystals with phytochelatin-related peptides.

Synthetic phytochelatin-related peptides are used as an organic coat on the surface of colloidal CdSe/ZnS semiconductor nanocrystals synthesized from hydrophobic coordinating trioctyl phosphine oxide (TOPO) solvents. The peptides are designed to bind to the nanocrystals via a C-terminal adhesive domain. This adhesive domain, composed of multiple repeats of cysteines pairs flanked by hydrophobic 3-cyclohexylalanines, is followed by a flexible hydrophilic linker domain to which various bio-affinity tags can be attached. This surface coating chemistry results in small, buffer soluble, monodisperse peptide-coated nanoparticles with high colloidal stability and ensemble photophysical properties similar to those of TOPO-coated nanocrystals. Various peptide coatings are used to modulate the nanocrystal surface properties and to bioactivate the nanoparticles. CdSe/ZnS nanocrystals coated with biotinylated peptides efficiently bind to streptavidin and are specifically targeted to GPI-anchored avidin-CD14 chimeric proteins expressed on the membranes of live HeLa cells. This peptide coating surface chemistry provides a novel approach for the production of biocompatible photoluminescent nanocrystal probes.

Adhesiveness↗

Phase I trial of the polyamine analog N1,N14-diethylhomospermine (DEHSPM) in patients with advanced solid tumors.

BACKGROUND: This phase I study was conducted to determine maximal tolerated dose (MTD) and dose-limiting toxicities (DLT) in patients with advanced solid tumors treated with the polyamine analog N1, N14-diethylhomospermine (DEHSPM). METHODS: Patients were treated with DEHSPM administered as a subcutaneous (SC) injection daily for five consecutive days repeated every 4 weeks. Three dose levels were examined starting at 12.5 mg/m2/day, escalating to 37.5 mg/m2/day. RESULTS: A total of 15 patients were enrolled. Dose limiting toxicities (grade 3 or 4) included nausea, vomiting, constipation, ileus, elevations of aspartate aminotransferase (AST) and alkaline phosphatase, hyperbilirubinemia, and ventricular bigeminy. CONCLUSION: DEHSPM given as a SC injection is overall well tolerated at lower doses, but significant toxicities were observed at the 37.5mg/m2/day dose level. MTD was established at 25 mg/m2/day but further investigation with this study drug is not recommended secondary to the potential for neurotoxicities and hepatic damage as a result of cumulative doses.

Aged↗

Fatal subacute cytomegalovirus encephalitis associated with hypogammaglobulinemia and thymoma.

Parathymic syndromes are systemic disorders that occur in association with thymoma. One such parathymic syndrome, hypogammaglobulinemia, was initially identified by Good in 1954 and has been referred to as Good syndrome. Patients with this syndrome develop a variety of recurrent infections due to the associated immunodeficiency. We describe a patient with cytomegalovirus encephalitis associated with Good syndrome and discuss the pathologic findings present on autopsy. The possibility of a cytomegalovirus infection should be considered early in the evaluation of patients with Good syndrome if appropriate clinical symptoms are present.

Agammaglobulinemia↗

Fatigue and endocrine disorders. Causes and comorbidities.

BACKGROUND: Most causes of fatigue are ill defined, self limiting or elude diagnosis. Many endocrine disorders present with nonspecific features including fatigue, so are difficult to differentiate on clinical grounds. However, avoiding diagnostic delay is vital to prevent significant morbidity and mortality. Thus, a high index of suspicion and knowledge of appropriate investigations is important. Endocrine disorders predispose the individual to developing related disorders; fatigue may be one sign of associated comorbidity. OBJECTIVE: This article discusses the endocrine disorders that commonly present with or develop fatigue as a prominent feature, with emphasis on particular challenges for diagnosis, investigation or management. Screening recommendations for comorbid disease was generated by an extensive review of current evidence. DISCUSSION: The identification of endocrine disorders can be both challenging--due to patterns of presentation--and rewarding for doctors and patients alike, due to importance and effectiveness of treatment.

Adult↗

Cytoplasmic and/or nuclear accumulation of the beta-catenin protein is a frequent event in human osteosarcoma.

The molecular events that precede the development of osteosarcoma, the most common primary malignancy of bone, are unclear, and concurrent molecular and genetic alterations associated with its pathogenesis have yet to be identified. Recent studies suggest that activation of beta-catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of beta-catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for beta-catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the beta-catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of beta-catenin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, suggesting that other regulatory mechanisms may play an important role in activating beta-catenin signaling in osteosarcoma. In our survival analysis, beta-catenin deregulation conferred a hazard ratio of 1.05, indicating that beta-catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, beta-catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of beta-catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma.

Adult↗

Biological consequences of antigen and cytokine co-expression by recombinant Streptococcus gordonii vaccine vectors.

To test the effect of co-expression of immunomodulatory molecules, together with target antigen, two recombinant Streptococcus gordonii strains were constructed which secreted either murine interleukin-2 (IL-2) or interferon-gamma (IFN-gamma) in addition to a surface anchored test antigen (the conserved C-repeat region (CRR) of the M6 protein of Streptococcus pyogenes). The secretion of functional cytokines by S. gordonii was achieved by in-frame fusion of sequences encoding mature IL-2 or IFN-gamma to the sequences encoding the leader signal of the M6 protein. Expression of the M protein CRR region from a separate chromosomal site produced double recombinants expressing a secreted cytokine and the M protein CRR region anchored to the surface. Protein expression was verified by streak blot, immunoblot, and ELISA on both the single and double recombinants. A cytokine bioassay using HT-2 cells verified biological activity of recombinant IL-2 secreted from S. gordonii. When mice were immunized subcutaneously with the different S. gordonii expression strains, cytokine co-expression apparently modulated the systemic immune response. These results show that streptococci can deliver biologically active molecules such as cytokines along with antigens to the immune system. These results demonstrate that a cytokine-secreting, noninvasive, bacterial vaccine vector can be used to modulate immune responses to a co-expressed antigen.

Animals↗

Outcomes associated with restored and unrestored deciduous molar teeth.

INTRODUCTION: Most dental treatment for children in the United Kingdom (UK) is provided by general dental practitioners (GDPs) working in the National Health Service (NHS). A working party of the British Society of Paediatric Dentistry, in a special publication from the Dental Practice Board, has suggested that failure to provide restorative care for the deciduous dentition is unacceptable, yet GDPs are filling fewer teeth in young children. The study aimed to evaluate the health outcomes obtained from restoring carious deciduous molar teeth. METHOD: The dental records of 677 children cared for by 50 GDPs in the north west of England were analysed. RESULTS: The results showed that 18.8% of deciduous molars with unrestored caries and 17.0% with a history of restorative care went on to be extracted because of pain or sepsis. CONCLUSION: The results suggest that the risk of carious deciduous molars being extracted is similar whether these teeth receive restorative care or not.

Dental Caries↗

Immunophenotypic variability of B-cell non-Hodgkin lymphoma: a retrospective study of cases analyzed by flow cytometry.

Flow cytometric analysis is important in the diagnosis, classification, and follow-up of non-Hodgkin lymphoma. It is assumed that the lymphoma phenotype for each patient remains unchanged over time and is consistent from one specimen to another. To determine the variability in expression of lymphoid antigens, we reviewed 211 flow cytometry specimens of malignant lymphoma from 81 patients. Some antigens showed a stable pattern of expression such as CD5, CD10, CD19, CD20, and HLA-DR. In contrast, CD21, CD22, CD23, and CD25 showed more variability from one specimen to another. We believe several factors affect the stability of antigen expression. True differences in expression most probably are related to the biology and function of the different antigens. For instance, CD19 and CD20 are essential in cell maturation and function and, therefore, are present on the majority of cells. In contrast, CD22 has a role during B-cell activation and, therefore, is more variable. Lack of standardization inflow cytometry procedures also is responsible for some variability. Instrument settings for adequate compensation and the criteria used to determine when an antigen is reported as positive are important considerations when evaluating flow cytometry histograms.

Antibodies, Monoclonal↗

Simultaneous intrastriatal and intranigral fetal dopaminergic grafts in patients with Parkinson disease: a pilot study. Report of three cases.

The main neural transplantation strategy in Parkinson disease (PD) has been focused on reinnervating the striatum. The clinical results reported in patients who receive transplants have been limited and do not justify the use of neural transplantation as a routine therapeutic procedure for PD. Identifying the optimal target for transplantation may be one of the critical factors for optimizing clinical outcomes. Evidence from preclinical studies indicates that simultaneous intrastriatal and intranigral grafts (double grafts) may produce a more complete functional recovery. The authors report the clinical and positron emission tomography (PET) scanning results in three patients enrolled in a safety and feasibility pilot study who received double grafts and who have been followed for up to 13 months posttransplantation. Patients included in the study had idiopathic PD. All patients underwent detailed assessments before and after surgery, in accordance with the Core Assessment Program for Intracerebral Transplantation. The patients received implants of fetal mesencephalic cell suspensions in the putamen and substantia nigra (SN) bilaterally. There were no intraoperative or perioperative complications. Follow-up PET scans demonstrated an increase in the mean fluorodopa uptake constant values in the putamen and SN 12 months postsurgery. Improvements were also noted in the total Unified Parkinson's Disease Rating Scale, Hoehn and Yahr, Schwab and England, and pronation/supination scores after transplantation. The authors demonstrate the feasibility of reinnervating the SN and striatum by using a double transplant strategy in humans.

Cells, Cultured↗