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Biomedical subjects

P Denny

Publications and source records attributed to P Denny.

At least 19 recordsLinked to original sources
PubMed2005

The Oral Fluid MEMS/NEMS Chip (OFMNC): diagnostic and translational applications.

The ability to monitor health status, disease onset and progression, and treatment outcome through non-invasive means is a most desirable goal in health-care promotion and delivery. There are three prerequisites for this goal to be realized: specific biomarkers associated with a health or disease state, a non-invasive approach to detect and monitor the biomarkers, and the technologies to discriminate between and among the biomarkers. We present a roadmap to achieve these goals using oral fluids as the diagnostic medium to scrutinize the health and/or disease status of individuals. This is an ideal opportunity to bridge state-of-the-art micro-/nano-electromechanical system (MEMS/NEMS) sensors to oral fluid for diagnostic applications. As the "mirror of body", oral fluid is a perfect medium to be explored for health and disease surveillance. The translational applications and opportunities are enormous.

Biomarkers↗
PubMed2005

Potential of a tropical subsurface constructed wetland to remove phenol from pre-treated pulp and papermill wastewater.

The capacity of a pilot project subsurface flow constructed wetland in the tropics to remove phenol from pre-treated pulp and paper mill wastewater was studied under varying hydraulic retention times (HRT) with batch loading. Initial 15 months results indicate that removal efficiencies for phenol were variable but on average reached 60% at 5-day HRT and 77% at 3-day HRT. It was thought that the longer retention time might have caused oxygen and nutrient deficiencies, which may have reduced removal performance. Although phenol was sometimes not detectable in the wetland outflow, on average values over the experimental period did not meet set national guidelines. In the ongoing study, the impact of varying hydraulic retention time and/or loading rate on the removal of phenols will be evaluated and the main removal process established.

Ecosystem↗
PubMed2003

The effect of wastewater discharge on biomass production and nutrient content of Cyperus papyrus and Miscanthidium violaceum in the Nakivubo wetland, Kampala, Uganda.

The nutrient content of representative plant parts and biomass production in the Nakivubo wetland, correlation of these with the wastewater flow patterns and determination of nutrient uptake, storage and biomass production of Cyperus papyrus (papyrus) and Miscanthidium violaceum was studied. On average papyrus vegetation under the influence of wastewater had higher nutrient content in the above ground biomass (1.6% N and 0.23% P on dry weight basis) than those not affected (0.98% N and 0.18% P). The biomass varied between 3,529-5,844 g/m2 and 883-1,156 g/m2 in the two respective sites. The juvenile plants of papyrus and Miscanthidium had higher concentrations of P and N in their organs compared to the mature ones. Considering the nutrients stored by the dominant vegetation and the current flow patterns of wastewater in the Nakivubo wetland, harvesting of the above ground biomass once a year, would remove 7.7% of the N input and 15.8% of the P input of the annual total load entering the wetland. However, if the wetland is bio-manipulated and the wastewater flow distributed over the whole wetland, up to 70% nitrogen and 76% phosphorus would be removed by harvesting above ground papyrus biomass.

Biodegradation, Environmental↗
PubMed2001

Genetic, physical, and phenotypic characterization of the Del(13)Svea36H mouse.

The Del(13)Svea36H deletion was recovered from a radiation mutagenesis experiment and represents a valuable resource for investigating gene content and function at this region of mouse Chromosome (Chr) 13 and human Chr 6p21.3-23 and 6p25. In this paper we examine the physical extent of chromosome loss and construct an integrated genetic and radiation hybrid map of the deleted segment. We show that embryos which are homozygous for the deletion die at or before implantation and that heterozygotes are subviable, with a substantial proportion of carriers dying after mid-gestation but before weaning. The majority of viable carriers exhibit a variety of phenotypes including decreased size, eyes open at birth, corneal opacity, tail kinks, and craniofacial abnormalities. Both the heterozygous viability and the penetrance of the visible phenotypes vary with genetic background.

Animals↗
PubMed2001

The impact of alum discharges on a natural tropical wetland in Uganda.

Alum sludge discharge effects on a natural wetland on the shores of Lake Victoria at Gaba in Uganda has been investigated. The water quality in the swamp, the sediment chemistry and plant growth and productivity were monitored. The subsequent application of alum sludge discharges shows no immediate, noticeable, adverse overall effects on the water quality and sediment chemistry. A distinct effect on plant productivity was noted in Cyperus papyrus L. the dominant macrophyte in the Gaba swamp resulting in a low productivity rate of 5.1 g/m2 d and the apparent phasing out of this macrophyte in the swamp. Phragmites mauritianus (Kunth) exhibited better tolerance to alum sludge. Clear indications are cited of the ecosystem degrading and cumulative effects being marked over a longer time frame.

Alum Compounds↗
PubMed2001

High-resolution quantitative trait locus mapping for body weight in mice by recombinant progeny testing.

A major obstacle to the positional cloning of quantitative trait loci (QTLs) lies in resolving genetic factors whose allelic effects are blurred by environmental and background genetic variation. We investigate a fine-mapping approach that combines the use of an interval-specific congenic strain with progeny testing of recombinants for markers flanking a QTL. We apply the approach to map a murine QTL with an approximately 20% effect on growth rate by progeny testing 39 recombinants in a 12 cM region of the X chromosome. We use a likelihood analysis in an attempt to maximize the information on QTL map location and effect. The major X-linked effect is mapped to an approximately 2 cM region flanked by markers about 5 cM apart, outside which LOD support for the QTL drops extremely steeply by about 80. Nearly unambiguous assignment of the QTL genotypic state is obtained for each recombinant. The resolution of individual recombinants in the region is therefore sufficiently high to facilitate the positional cloning of the locus, although progress has been hampered because the genomic region containing the QTL shows an exceptionally low level of polymorphism in comparison with recent studies.

Alleles↗
PubMed2001

A radiation hybrid map of mouse genes.

A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome.

Animals↗
PubMed2001

Role of genetic resistance in invasive pneumococcal infection: identification and study of susceptibility and resistance in inbred mouse strains.

From a panel of nine inbred mice strains intranasally infected with Streptococcus pneumoniae type 2 strain, BALB/c mice were resistant and CBA/Ca and SJL mice were susceptible to infection. Further investigation revealed that BALB/c mice were able to prevent proliferation of pneumococci in the lungs and blood, whereas CBA/Ca mice showed no bacterial clearance. Rapidly increasing numbers of bacteria in the blood was a feature of CBA/Ca but not BALB/c mice. In the lungs, BALB/c mice recruited significantly more neutrophils than CBA/Ca mice at 12 and 24 h postinfection. Inflammatory lesions in BALB/c mice were visible much earlier than in CBA/Ca mice, and there was a greater cellular infiltration into the lung tissue of BALB/c mice at the earlier time points. Our data suggest that resistance or susceptibility to intranasal pneumococci may have an association with recruitment and/or function of neutrophils.

Animals↗
PubMed2001

[Contrast-enhanced MRA of the carotid arteries using 0.5 Tesla: comparison with selective digital angiography].

PURPOSE: To assess the feasability, the imaging quality and the effectiveness of contrast-enhanced MRA (CE MRA) using a 0.5 Tesla MR unit in the evaluation of internal carotid artery (ICA) stenosis. Materials and Methods. 29 patients underwent CE MRA and selective digital substraction angiography (DSA). All data were reviewed in a blinded fashion by 2 independant observers. Imaging quality was graded as good, moderate but interpretable, and insufficient. Stenosis was graded according to the NASCET classification from grade 1 to 4, with the following thresholds:<30%,<70%,<99% and occlusion. Inter and intra- observer agreement was evaluated using the kappa index. RESULTS: Imaging quality was good for 79 arteries, moderate for 24 and insufficient for 13 (k MRA=0.72 and 0.64 respectively for the right and left ICAs). Interobserver agreement was good with values for right/left ICA of 0.84/0.94, 0.72/0.74 respectively for CE-MRA and DSA. For the comparison between CE MRA and DSA, agreement was also good, with values of 0.74 and 0.64 for both readers. Sensitivity of CE MRA in the detection of hemodynamically significant stenosis (>70%) was of 0.95 and 0.94 and specifity of 0.91 and 0.89 respectively for reader n degrees 1 and reader n degrees 2. CONCLUSION: CE MRA using a 0.5T MR unit is a valuable technique in the evaluation of ICA stenosis.

Adult↗
PubMed2000

The effect of ageing on parenchymal cell populations in adult female mouse submandibular gland.

The submandibular gland shows an array of responses that accompany ageing, which are usually modest. However, the submandibular acinar-cell mucin shows a substantial decline in total amount per gland. In the submandibular gland, there is also a loss of secretory parenchyma. A number of factors that could influence either parenchymal loss or a change in its cellular composition were examined in three ages of adult female mice. The goal was to see if there are ageing-related cellular changes that might have an effect on mucin production or secretion. The factors examined included DNA, protein, rates of cell division and apoptosis, cell volume and cellular composition of the parenchymal population. The parenchymal cell composition showed significant differences during ageing, with a substantial decrease in the percentage of acinar cells and increases in the percentage of both types of ductal cell components. This decline in the proportion of acinar cells in the parenchyma also reflected an overall reduction in the total number of acinar cells in the gland. Thus, the change in proportions of cells may potentially be a direct cause of the ageing-related decline in the submandibular acinar-cell mucin. The alteration in cellular composition was not attributable to changes in the cell-division indices; however, there was an increased rate of apoptosis for acinar cells that was significantly different between 3 and 28 months. The apoptotic rate doubled for acinar cells but showed no significant change in ductal cells. This selective change in the rate of apoptosis with ageing suggests that it is one of the main reasons for the decline in the proportion of acinar cells in the submandibular gland.

Aging↗
PubMed2000

Mouse as the measure of man?

The humble house mouse's cohabitation with humans has been noted since the birth of agriculture, about 10 000 years ago, in the fertile flood plains of the Middle East. In recent times, however, the mouse has been elevated from pest to model for the study of human health and disease. Recent genomics and genetics initiatives will ensure the continued growth of the house mouse as a disease model.

Animals↗
PubMed2000

The NOD Idd9 genetic interval influences the pathogenicity of insulitis and contains molecular variants of Cd30, Tnfr2, and Cd137.

Previous analyses of NOD mice have shown that some genes control the development of both insulitis and diabetes, while other loci influence diabetes without reducing insulitis. Evidence for the existence of a gene only influencing diabetes, Idd9 on mouse chromosome 4, is provided here by the development of a novel congenic mouse strain, NOD.B10 Idd9. NOD.B10 Idd9 mice display profound resistance to diabetes even though nearly all develop insulitis. Subcongenic analysis has demonstrated that alleles of at least three B10 genes, Idd9.1, Idd9.2, and Idd9.3 are required to produce Idd9-mediated diabetes resistance. Candidate genes with amino acid differences between the NOD and B10 strains have been localized to the 5.6 cM Idd9.2 interval (Tnfr2, Cd30) and to the 2.0 cM Idd9.3 interval (Cd137).

Alleles↗
PubMed2000

Congenic mapping of the type 1 diabetes locus, Idd3, to a 780-kb region of mouse chromosome 3: identification of a candidate segment of ancestral DNA by haplotype mapping.

Type 1 diabetes in the nonobese diabetic (NOD) mouse arises as a consequence of T cell-mediated destruction of the insulin-producing beta cells of the pancreas. Although little is known of the events that initiate and subsequently drive beta-cell destruction it is clear that the entire process is under complex genetic control. At present 19 loci have been mapped that influence the development of diabetes either at the level of initiation of insulitis or at the level of progression from insulitis to overt diabetes, or both. Previously, we have mapped one of these loci, Idd3, to a 0.35-cM interval on proximal mouse chromosome 3. In the present study we have narrowed the map position of this locus to an interval of 0.15 cM by a combination of novel congenic strains and an ancestral haplotype analysis approach. We have constructed a physical contig in bacterial artificial chromosome (BAC) clones across the minimal interval. Restriction mapping of the BAC contig placed the maximum size of the Idd3 interval at 780 kb between the markers D3Nds36 and D3Nds76. To refine further the Idd3 interval we developed a series of novel single nucleotide polymorphisms (SNPs) and carried out haplotype analysis on DNA from mouse strains known to carry either Idd3 susceptibility or protective alleles. This haplotype analysis identified a 145-kb segment of ancestral DNA between the microsatellite marker D3Nds6 and the SNP 81.3. One haplotype of this ancestral segment of DNA is found in mouse strains carrying an Idd3 susceptibility allele and another is found in mouse strains carrying an Idd3 protective allelle. Within the 780-kb congenically defined interval this 145-kb segment represents the most likely location for Idd3. The Il2 gene, which encodes the cytokine interleukin 2 (IL2), maps to this interval and is a strong candidate for Idd3. To investigate whether sequence variation exists in the promoter region of the Il2 gene, which might alter its expression, we sequenced the promoter region of the Il2 gene from mouse strains carrying either an Idd3 susceptibility or resistance allele. Two sequence variants were identified, neither of which fell in known regulatory elements within the Il2 promoter. In agreement with this observation steady-state Il2 mRNA levels showed no variation between susceptible and resistant mouse strains. These data suggest that the profound protection from diabetes seen in congenic mice carrying an Idd3 protective allele is unlikely to be due to differences in the level of expression of the Il2 gene. Instead, all of the current data support our hypothesis that Idd3 corresponds to amino acid variation at the amino terminus of Il2.

Alleles↗
PubMed2000

Comparative genome sequence analysis of the Bpa/Str region in mouse and Man.

The progress of human and mouse genome sequencing programs presages the possibility of systematic cross-species comparison of the two genomes as a powerful tool for gene and regulatory element identification. As the opportunities to perform comparative sequence analysis emerge, it is important to develop parameters for such analyses and to examine the outcomes of cross-species comparison. Our analysis used gene prediction and a database search of 430 kb of genomic sequence covering the Bpa/Str region of the mouse X chromosome, and 745 kb of genomic sequence from the homologous human X chromosome region. We identified 11 genes in mouse and 13 genes and two pseudogenes in human. In addition, we compared the mouse and human sequences using pairwise alignment and searches for evolutionary conserved regions (ECRs) exceeding a defined threshold of sequence identity. This approach aided the identification of at least four further putative conserved genes in the region. Comparative sequencing revealed that this region is a mosaic in evolutionary terms, with considerably more rearrangement between the two species than realized previously from comparative mapping studies. Surprisingly, this region showed an extremely high LINE and low SINE content, low G+C content, and yet a relatively high gene density, in contrast to the low gene density usually associated with such regions.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Isolation and characterization of Suv39h2, a second histone H3 methyltransferase gene that displays testis-specific expression.

Higher-order chromatin has been implicated in epigenetic gene control and in the functional organization of chromosomes. We have recently discovered mouse (Suv39h1) and human (SUV39H1) histone H3 lysine 9-selective methyltransferases (Suv39h HMTases) and shown that they modulate chromatin dynamics in somatic cells. We describe here the isolation, chromosomal assignment, and characterization of a second murine gene, Suv39h2. Like Suv39h1, Suv39h2 encodes an H3 HMTase that shares 59% identity with Suv39h1 but which differs by the presence of a highly basic N terminus. Using fluorescent in situ hybridization and haplotype analysis, the Suv39h2 locus was mapped to the subcentromeric region of mouse chromosome 2, whereas the Suv39h1 locus resides at the tip of the mouse X chromosome. Notably, although both Suv39h loci display overlapping expression profiles during mouse embryogenesis, Suv39h2 transcripts remain specifically expressed in adult testes. Immunolocalization of Suv39h2 protein during spermatogenesis indicates enriched distribution at the heterochromatin from the leptotene to the round spermatid stage. Moreover, Suv39h2 specifically accumulates with chromatin of the sex chromosomes (XY body) which undergo transcriptional silencing during the first meiotic prophase. These data are consistent with redundant enzymatic roles for Suv39h1 and Suv39h2 during mouse development and suggest an additional function of the Suv39h2 HMTase in organizing meiotic heterochromatin that may even impart an epigenetic imprint to the male germ line.

Amino Acid Sequence↗