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26.  Children's rights 
doi:10.1136/adc.2004.064899
PMCID: PMC1720271
27.  A general paediatrician's practice in children's rights 
Archives of Disease in Childhood  2005;90(2):178-181.
doi:10.1136/adc.2004.064014
PMCID: PMC1720252  PMID: 15665177
28.  Maternal undernutrition and the ovine acute phase response to vaccination 
Background
The acute phase response is the immediate host response to infection, inflammation and trauma and can be monitored by measuring the acute phase proteins (APP) such as haptoglobin (Hp) or serum amyloid A (SAA). The plane of nutrition during pregnancy is known to affect many mechanisms including the neuroendocrine and neuroimmune systems in neonatal animals but effects on the APP are unknown. To investigate this phenomenon the serum concentration of Hp and SAA was initially determined in non-stimulated lambs from 3 groups (n = 10/group). The dams of the lambs of the respective groups were fed 100% of requirements throughout gestation (High/High; HH); 100% of requirements for the first 65 d of gestation followed by 70% of requirements until 125 d from when they were fed 100% of requirements (High/Low; HL); 65% of liveweight maintenance requirements for the first 65 d gestation followed by 100% of requirements for the remainder of pregnancy (Low/High; LH). The dynamic APP response in the lambs was estimated by measuring the concentration of Hp and SAA following routine vaccination with a multivalent clostridial vaccine with a Pasteurella component, Heptavac P™ following primary and secondary vaccination.
Results
The Hp and SAA concentrations were significantly lower at the time of vaccination (day 8–14) than on the day of birth. Vaccination stimulated the acute phase response in lambs with increases found in both Hp and SAA. Maternal undernutrition led to the SAA response to vaccination being significantly lower in the HL group than in the HH group. The LH group did not differ significantly from either the HH or HL groups. No significant effects of maternal undernutrition were found on the Hp concentrations. A significant reduction was found in all groups in the response of SAA following the second vaccination compared to the response after the primary vaccination but no change occurred in the Hp response.
Conclusion
Decreased SAA concentrations, post-vaccination, in lambs born to ewes on the HL diet shows that maternal undernutrition prior to parturition affects the innate immune system of the offspring. The differences in response of Hp and SAA to primary and secondary vaccinations indicate that the cytokine driven APP response mechanisms vary with individual APP.
doi:10.1186/1746-6148-4-1
PMCID: PMC2233616  PMID: 18197966
29.  Acute phase protein response in an experimental model of ovine caseous lymphadenitis 
Background
Caseous lymphadenitis (CLA) is a disease of small ruminants caused by Corynebacterium pseudotuberculosis. The pathogenesis of CLA is a slow process, and produces a chronic rather than an acute disease state. Acute phase proteins (APP) such as haptoglobin (Hp) serum amyloid A (SAA) and α1 acid glycoprotein (AGP) are produced by the liver and released into the circulation in response to pro-inflammatory cytokines. The concentration of Hp in serum increases in experimental CLA but it is not known if SAA and AGP respond in parallel or have differing response profiles.
Results
The concentration in serum of Hp, SAA and AGP in 6 sheep challenged with 2 × 105 cells of C. pseudotuberculosis showed significant increases (P < 0.05) compared to 3 unchallenged control sheep. By day 7 post infection. (p.i.) the Hp and SAA concentrations reached mean (± SEM) values of 1.65 ± 0.21 g/L and 18.1 ± 5.2 mg/L respectively. Thereafter, their concentrations fell with no significant difference to those of the control sheep by day 18 p.i.. In contrast, the serum AGP concentration in infected sheep continued to rise to a peak of 0.38 ± 0.05 g/L on day 13 p.i., after which a slow decline occurred, although the mean concentration remained significantly higher (P < 0.05) than the control group up to 29 days p.i.. Specific IgG to phospholidase D of C. pseudotuberculosis became detectable at 11 days p.i. and continued to rise throughout the experiment.
Conclusion
The serum concentrations of Hp, SAA and AGP were raised in sheep in an experimental model of CLA. An extended response was found for AGP which occurred at a point when the infection was likely to have been transforming from an acute to a chronic phase. The results suggest that AGP could have a role as a marker for chronic conditions in sheep.
doi:10.1186/1746-6148-3-35
PMCID: PMC2235841  PMID: 18093286
31.  Preclinical Evaluation of Microneedle Technology for Intradermal Delivery of Influenza Vaccines▿  
Clinical and Vaccine Immunology  2007;14(4):375-381.
Recent clinical studies have suggested that, for certain strains of influenza virus, intradermal (i.d.) delivery may enable protective immune responses using a lower dose of vaccine than required by intramuscular (i.m.) injection. Here, we describe the first preclinical use of microneedle technology for i.d. administration of three different types of influenza vaccines: (i) a whole inactivated influenza virus, (ii) a trivalent split-virion human vaccine, and (iii) a plasmid DNA encoding the influenza virus hemagglutinin. In a rat model, i.d. delivery of the whole inactivated virus provided up to 100-fold dose sparing compared to i.m. injection. In addition, i.d. delivery of the trivalent human vaccine enabled at least 10-fold dose sparing for the H1N1 strain and elicited levels of response across the dose range similar to those of i.m. injection for the H3N2 and B strains. Furthermore, at least fivefold dose sparing from i.d. delivery was evident in animals treated with multiple doses of DNA plasmid vaccine, although such effects were not apparent after the first immunization. Altogether, the results demonstrate that microneedle-based i.d. delivery elicits antibody responses that are at least as strong as via i.m. injection and that, in many cases, dose sparing can be achieved by this new immunization method.
doi:10.1128/CVI.00387-06
PMCID: PMC1865614  PMID: 17329444
32.  Comparison of C. elegans and C. briggsae Genome Sequences Reveals Extensive Conservation of Chromosome Organization and Synteny 
PLoS Biology  2007;5(7):e167.
To determine whether the distinctive features of Caenorhabditis elegans chromosomal organization are shared with the C. briggsae genome, we constructed a single nucleotide polymorphism–based genetic map to order and orient the whole genome shotgun assembly along the six C. briggsae chromosomes. Although these species are of the same genus, their most recent common ancestor existed 80–110 million years ago, and thus they are more evolutionarily distant than, for example, human and mouse. We found that, like C. elegans chromosomes, C. briggsae chromosomes exhibit high levels of recombination on the arms along with higher repeat density, a higher fraction of intronic sequence, and a lower fraction of exonic sequence compared with chromosome centers. Despite extensive intrachromosomal rearrangements, 1:1 orthologs tend to remain in the same region of the chromosome, and colinear blocks of orthologs tend to be longer in chromosome centers compared with arms. More strikingly, the two species show an almost complete conservation of synteny, with 1:1 orthologs present on a single chromosome in one species also found on a single chromosome in the other. The conservation of both chromosomal organization and synteny between these two distantly related species suggests roles for chromosome organization in the fitness of an organism that are only poorly understood presently.
Author Summary
The importance of chromosomal organization in the fitness of a species is only poorly understood. The publication of the C. elegans genome sequence in 1998 revealed features of higher level organization that suggested its chromosomes were organized into distinct domains. Chromosome arms were accumulating changes more rapidly than the centers of chromosomes. In this paper, we have compared the organization of the nematode C. briggsae genome with that of C. elegans. By building a genetic map based on DNA variations between two strains of C. briggsae, and by using that map to organize the draft genome sequence of C. briggsae published in 2003, we found the following: (1) Intrachromosomal rearrangements are frequent within and even between arms but are less common within central regions and between arms and centers. (2) Genes have remained overwhelmingly on the same chromosomes. (3) The distinctive features that distinguish C. elegans arms from centers also are seen in C. briggsae chromosomes. The conservation of these features between these two species, despite the approximately 100 million years since their most recent common ancestor, provides clear evidence of the selective advantages of the domain architecture of chromosomes. The continuing association of genes on the same chromosomes suggests that this may also be advantageous.
The conservation of both chromosomal organization and synteny between two distantly related species suggests roles for chromosome organization in the fitness of an organism.
doi:10.1371/journal.pbio.0050167
PMCID: PMC1914384  PMID: 17608563
33.  Social capital: a key factor in child health inequalities 
Archives of Disease in Childhood  2004;89(5):456-459.
doi:10.1136/adc.2002.024422
PMCID: PMC1719915  PMID: 15102639
34.  Paediatrics in primary care 
doi:10.1136/adc.2003.046235
PMCID: PMC1719779  PMID: 14736618
35.  Codon usage patterns in Nematoda: analysis based on over 25 million codons in thirty-two species 
Genome Biology  2006;7(8):R75.
A codon usage table for 32 nematode species is presented and suggests that total genomic GC content drives codon usage.
Background
Codon usage has direct utility in molecular characterization of species and is also a marker for molecular evolution. To understand codon usage within the diverse phylum Nematoda, we analyzed a total of 265,494 expressed sequence tags (ESTs) from 30 nematode species. The full genomes of Caenorhabditis elegans and C. briggsae were also examined. A total of 25,871,325 codons were analyzed and a comprehensive codon usage table for all species was generated. This is the first codon usage table available for 24 of these organisms.
Results
Codon usage similarity in Nematoda usually persists over the breadth of a genus but then rapidly diminishes even within each clade. Globodera, Meloidogyne, Pristionchus, and Strongyloides have the most highly derived patterns of codon usage. The major factor affecting differences in codon usage between species is the coding sequence GC content, which varies in nematodes from 32% to 51%. Coding GC content (measured as GC3) also explains much of the observed variation in the effective number of codons (R = 0.70), which is a measure of codon bias, and it even accounts for differences in amino acid frequency. Codon usage is also affected by neighboring nucleotides (N1 context). Coding GC content correlates strongly with estimated noncoding genomic GC content (R = 0.92). On examining abundant clusters in five species, candidate optimal codons were identified that may be preferred in highly expressed transcripts.
Conclusion
Evolutionary models indicate that total genomic GC content, probably the product of directional mutation pressure, drives codon usage rather than the converse, a conclusion that is supported by examination of nematode genomes.
doi:10.1186/gb-2006-7-8-r75
PMCID: PMC1779591
36.  AceTree: a tool for visual analysis of Caenorhabditis elegans embryogenesis 
BMC Bioinformatics  2006;7:275.
Background
The invariant lineage of the nematode Caenorhabditis elegans has potential as a powerful tool for the description of mutant phenotypes and gene expression patterns. We previously described procedures for the imaging and automatic extraction of the cell lineage from C. elegans embryos. That method uses time-lapse confocal imaging of a strain expressing histone-GFP fusions and a software package, StarryNite, processes the thousands of images and produces output files that describe the location and lineage relationship of each nucleus at each time point.
Results
We have developed a companion software package, AceTree, which links the images and the annotations using tree representations of the lineage. This facilitates curation and editing of the lineage. AceTree also contains powerful visualization and interpretive tools, such as space filling models and tree-based expression patterning, that can be used to extract biological significance from the data.
Conclusion
By pairing a fast lineaging program written in C with a user interface program written in Java we have produced a powerful software suite for exploring embryonic development.
doi:10.1186/1471-2105-7-275
PMCID: PMC1501046  PMID: 16740163
37.  Investigating hookworm genomes by comparative analysis of two Ancylostoma species 
BMC Genomics  2005;6:58.
Background
Hookworms, infecting over one billion people, are the mostly closely related major human parasites to the model nematode Caenorhabditis elegans. Applying genomics techniques to these species, we analyzed 3,840 and 3,149 genes from Ancylostoma caninum and A. ceylanicum.
Results
Transcripts originated from libraries representing infective L3 larva, stimulated L3, arrested L3, and adults. Most genes are represented in single stages including abundant transcripts like hsp-20 in infective L3 and vit-3 in adults. Over 80% of the genes have homologs in C. elegans, and nearly 30% of these were with observable RNA interference phenotypes. Homologies were identified to nematode-specific and clade V specific gene families. To study the evolution of hookworm genes, 574 A. caninum / A. ceylanicum orthologs were identified, all of which were found to be under purifying selection with distribution ratios of nonsynonymous to synonymous amino acid substitutions similar to that reported for C. elegans / C. briggsae orthologs. The phylogenetic distance between A. caninum and A. ceylanicum is almost identical to that for C. elegans / C. briggsae.
Conclusion
The genes discovered should substantially accelerate research toward better understanding of the parasites' basic biology as well as new therapies including vaccines and novel anthelmintics.
doi:10.1186/1471-2164-6-58
PMCID: PMC1112591  PMID: 15854223
38.  Community paediatrics and change 
Archives of Disease in Childhood  2002;86(4):227-229.
doi:10.1136/adc.86.4.227
PMCID: PMC1719153  PMID: 11919089
39.  TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model 
British Journal of Cancer  2004;90(6):1279-1284.
doi:10.1038/sj.bjc.6601670
PMCID: PMC2409655  PMID: 15026813
TNF; melanoma; metastasis
40.  Poverty and child health 
doi:10.1136/adc.85.4.349
PMCID: PMC1718949
41.  Advocating for children's health: a US and UK perspective 
Archives of Disease in Childhood  2001;85(3):180-182.
doi:10.1136/adc.85.3.180
PMCID: PMC1718917  PMID: 11517094
43.  Work, family socioeconomic status, and growth among working boys in Jordan 
Archives of Disease in Childhood  2001;84(4):311-314.
AIMS—To describe the work, family socioeconomic characteristics, and growth of a representative sample of working children in Jordan.
METHODS—In a cross sectional survey of growth and health, 135 working children (aged 10-16 years) were studied in the areas of Irbid, Jarash, and North Jordan Valley. The children and their parents were interviewed and data collected on length of working week, income earned by the child, duration of work in years, age of starting work, type of work, child's smoking status, and family socioeconomic status.
RESULTS—The mean age of the children was 13.3 years; 14.8% had started work before the age of 10 and 12.6% had been working for more than four years. Mean income was 34 Jordanian Dinars but 6.7% were unwaged; 34% were working more than 60 hours per week, and 85.9% more than 40 hours. Monthly income and working hours were positively correlated with the age of the child. There was no correlation between age and smoking status; 37.8% smoked more than five cigarettes per day. Mean height and weight z scores were −0.365 and −0.081 of the UK standard respectively. Packed cell volume was within the anaemic range in 34.1% of children.
CONCLUSIONS—In Jordan many children start work at an early age and work long hours for little or no income. Stunting and anaemia are common and many are established smokers. Relevance of these findings for social policy and health care of working children in Jordan and elsewhere is discussed.


doi:10.1136/adc.84.4.311
PMCID: PMC1718738  PMID: 11259229
44.  Nematode.net: a tool for navigating sequences from parasitic and free-living nematodes 
Nucleic Acids Research  2004;32(Database issue):D423-D426.
Nematode.net (www.nematode.net) is a web- accessible resource for investigating gene sequences from nematode genomes. The database is an outgrowth of the parasitic nematode EST project at Washington University’s Genome Sequencing Center (GSC), St Louis. A sister project at the University of Edinburgh and the Sanger Institute is also underway. More than 295 000 ESTs have been generated from >30 nematodes other than Caenorhabditis elegans including key parasites of humans, animals and plants. Nematode.net currently provides NemaGene EST cluster consensus sequence, enhanced online BLAST search tools, functional classifications of cluster sequences and comprehensive information concerning the ongoing generation of nematode genome data. The long-term goal of nematode.net is to provide the scientific community with the highest quality sequence information and tools for studying these diverse species.
doi:10.1093/nar/gkh010
PMCID: PMC308745  PMID: 14681448
46.  Tertiary paediatrics needs a disability model 
doi:10.1136/adc.83.1.35
PMCID: PMC1718402  PMID: 10868997
47.  Exploring the scope for advocacy by paediatricians 
doi:10.1136/adc.82.5.428e
PMCID: PMC1718303  PMID: 10836938
48.  Analysis and functional classification of transcripts from the nematode Meloidogyne incognita 
Genome Biology  2003;4(4):R26.
As an entrée to characterizing plant parasitic nematode genomes, 5,700 expressed sequence tags (ESTs) from the infective second-stage larvae (L2) of the root-knot nematode Meloidogyne incognita have been analyzed. In addition to identifying putative nematode-specific and Tylenchida-specific genes, sequencing revealed previously uncharacterized horizontal gene transfer candidates in Meloidogyne with high identity to rhizobacterial genes.
Background
Plant parasitic nematodes are major pathogens of most crops. Molecular characterization of these species as well as the development of new techniques for control can benefit from genomic approaches. As an entrée to characterizing plant parasitic nematode genomes, we analyzed 5,700 expressed sequence tags (ESTs) from second-stage larvae (L2) of the root-knot nematode Meloidogyne incognita.
Results
From these, 1,625 EST clusters were formed and classified by function using the Gene Ontology (GO) hierarchy and the Kyoto KEGG database. L2 larvae, which represent the infective stage of the life cycle before plant invasion, express a diverse array of ligand-binding proteins and abundant cytoskeletal proteins. L2 are structurally similar to Caenorhabditis elegans dauer larva and the presence of transcripts encoding glyoxylate pathway enzymes in the M. incognita clusters suggests that root-knot nematode larvae metabolize lipid stores while in search of a host. Homology to other species was observed in 79% of translated cluster sequences, with the C. elegans genome providing more information than any other source. In addition to identifying putative nematode-specific and Tylenchida-specific genes, sequencing revealed previously uncharacterized horizontal gene transfer candidates in Meloidogyne with high identity to rhizobacterial genes including homologs of nodL acetyltransferase and novel cellulases.
Conclusions
With sequencing from plant parasitic nematodes accelerating, the approaches to transcript characterization described here can be applied to more extensive datasets and also provide a foundation for more complex genome analyses.
doi:10.1186/gb-2003-4-4-r26
PMCID: PMC154577  PMID: 12702207

Results 26-50 (152)