Search PubMed⌕ Search

Biomedical subjects

J Lewis

Publications and source records attributed to J Lewis.

At least 19 recordsLinked to original sources

Craniospinal irradiation using a forward planned segmented field technique.

Craniospinal irradiation is technically demanding due to the complex shape of the planning target volume (PTV). Radiotherapy treatment techniques have evolved over time as imaging and radiotherapy treatment technology have improved. However, most are variations on a class solution utilizing a prone patient position with two shaped lateral cranial portals and a matched posterior spinal portal with moving junctions. Major areas of difficulty remain with the accurate definition of the PTV and achieving a homogeneous dose within it, especially at the junctions. We describe a three-dimensionally (3D) planned craniospinal radiation technique that permits rapid image acquisition with reduced localization time, simplified spinal PTV definition and standardized cranial PTV definition. Improved dose homogeneity within the PTV is achieved by use of a segmented "field-in-field" technique (forward planned intensity-modulated radiotherapy (IMRT)) in place of customized compensators. This has negated the requirement for constructing physical compensators. Autosequencing for field delivery enables the junction to be "moved" during a single fraction and reduces the overall treatment time, an important consideration when treating very young patients.

Brain Neoplasms↗

Tau suppression in a neurodegenerative mouse model improves memory function.

Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy.

Aging↗

Development and mapping of microsatellite (SSR) markers in wheat.

Microsatellite DNA markers are consistently found to be more informative than other classes of markers in hexaploid wheat. The objectives of this research were to develop new primers flanking wheat microsatellites and to position the associated loci on the wheat genome map by genetic linkage mapping in the ITMI W7984 x Opata85 recombinant inbred line (RIL) population and/or by physical mapping with cytogenetic stocks. We observed that the efficiency of marker development could be increased in wheat by creating libraries from sheared rather than enzyme-digested DNA fragments for microsatellite screening, by focusing on microsatellites with the [ATT/TAA]n motif, and by adding an untemplated G-C clamp to the 5'-end of primers. A total of 540 microsatellite-flanking primer pairs were developed, tested, and annotated from random genomic libraries. Primer pairs and associated loci were assigned identifiers prefixed with BARC (the acronym for the USDA-ARS Beltsville Agricultural Research Center) or Xbarc, respectively. A subset of 315 primer sets was used to map 347 loci. One hundred and twenty-five loci were localized by physical mapping alone. Of the 222 loci mapped with the ITMI population, 126 were also physically mapped. Considering all mapped loci, 126, 125, and 96 mapped to the A, B, and D genomes, respectively. Twenty-three of the new loci were positioned in gaps larger than 10 cM in the map based on pre-existing markers, and 14 mapped to the ends of chromosomes. The length of the linkage map was extended by 80.7 cM. Map positions were consistent for 111 of the 126 loci positioned by both genetic and physical mapping. The majority of the 15 discrepancies between genetic and physical mapping involved chromosome group 5.

Base Sequence↗

Impact of Cre1, Cre8 and Cre3 genes on cereal cyst nematode resistance in wheat.

The cereal cyst nematode (CCN; Heterodera avenae), a root disease of cereal crops, is a major economic constraint in many wheat (Triticum aestivum)-growing areas of the world. The objective of this study was to assess the impact of the Cre1, Cre8 and Cre3 genes on CCN resistance. A population of 92 doubled-haploid (DH) lines derived from a cross between wheat cvs. Frame and Silverstar as well as 1,851 wheat breeding lines were screened for CCN resistance at the Primary Industries Research Victoria (PIRVic). A second population of 9,470 wheat breeding lines was screened at the South Australian Research and Development Institute (SARDI). Cre3 had the largest impact on reducing the number of female cysts, followed by Cre1 and Cre8. There was no significant difference in number of cysts between DH lines with or without the Cre8 marker, suggesting that the marker is not perfectly linked to Cre8. The estimated heritabilities were 0.32 in the DH population, 0.48 in the PIRVic data set and 0.32 in the SARDI data set, which confirm that this is a trait of low heritability. The repeatability of CCN resistance improved with an increase in the number of plants assessed per line-up to ten. However, 85-88% of the improvement was achieved with the assessments of the first five plants.

Animals↗

The Mouse Genome Database (MGD): from genes to mice--a community resource for mouse biology.

The Mouse Genome Database (MGD) forms the core of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a model organism database resource for the laboratory mouse. MGD provides essential integration of experimental knowledge for the mouse system with information annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genotype (sequence) through phenotype information, including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships among genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent improvements in MGD discussed here include the enhancement of phenotype resources, the re-development of the International Mouse Strain Resource, IMSR, the update of mammalian orthology datasets and the electronic publication of classic books in mouse genetics.

Animals↗

Autoimmune ovarian disease in day 3-thymectomized mice: the neonatal time window, antigen specificity of disease suppression, and genetic control.

Discovery of the CD4+CD25+ T cells has stemmed from investigation of the AOD in the d3tx mice. Besides CD4+CD25+ T cell depletion, d3tx disease induction requires effector T cell activation prompted by lymphopenia. This is supported by other neonatal AOD models in which T cell-mediated injury has been found to be triggered by immune complex or Ag immunization. In addition, there is growing evidence that support a state of neonatal propensity to autoimmunity, which depends on concomitant endogenous antigenic stimulation, concomitant nematode infection, resistance to CD4+CD25+ T cell regulation, and participation of the neonatal innate system. The suppression of d3tx disease by polyclonal CD4+CD25+ T cells appears to be dependent on endogenous Ag and the persistence of regulatory T cells. Thus, suppression of AOD occurs in the ovarian LN, and AOD emerges upon ablation of the input regulatory T cells; and in AIP, the hormone-induced expression of prostate Ag in the CD4+CD25+ T cell donors rapidly enhances the capacity to suppress disease over Ag negative donors. Finally, genetic analysis of AOD and its component phenotypes has uncovered seven Aod loci. As the general themes that emerged, significant epistatic interactions among the loci play a role in controlling disease susceptibility, the majority of the Aod loci are linked to susceptibility loci of other autoimmune diseases, and the genetic intervals encompass candidate genes that are differentially expressed between CD4+CD25+ T cells and other T cells. The candidate genes include Pdcd1, TNFR superfamily genes, H2, Il2, Tgfb, Nalp5 or Mater, an oocyte autoAg that reacts with autoantibody in sera of d3tx mice.

Animals↗

Trigeminal uptake and clearance of inhaled manganese chloride in rats and mice.

Inhaled manganese (Mn) can enter the olfactory bulbs via the olfactory epithelium, and can then be further transported trans-synaptically to deeper brain structures. In addition to olfactory neurons, the nasal cavity is innervated by the maxillary division of the trigeminal nerve that projects to the spinal trigeminal nucleus. Direct uptake and transport of inhaled metal particles in the trigeminal system has not been investigated previously. We studied the uptake, deposition, and clearance of soluble Mn in the trigeminal system following nose-only inhalation of environmentally relevant concentrations. Rats and mice were exposed for 10-days (6 h/day, 5 days/week) to air or MnCl2 aerosols containing 2.3 +/- 1.3 mg/m3 Mn with mass median aerodynamic diameter (MMAD) of 3.1 +/- 1.4 microm for rats and 2.0 +/- 0.09 mg/m3 Mn MnCl2 with MMAD of 1.98 +/- 0.12 microm for mice. Mn concentrations in the trigeminal ganglia and spinal trigeminal nucleus were measured 2 h (0-day), 7-, 14-, or 30-days post-exposure using proton induced X-ray emission (PIXE). Manganese-exposed rats and mice showed statistically elevated levels of Mn in trigeminal ganglia 0-, 7- and 14-days after the 10-days exposure period when compared to control animals. The Mn concentration gradually decreased over time with a clearance rate (t1/2) of 7-8-days. Rats and mice were similar in both average accumulated Mn levels in trigeminal ganglia and in rates of clearance. We also found a small but significant elevation of Mn in the spinal trigeminal nucleus of mice 7-days post-exposure and in rats 0- and 7-days post-exposure. Our data demonstrate that the trigeminal nerve can serve as a pathway for entry of inhaled Mn to the brain in rodents following nose-only exposure and raise the question of whether entry of toxicants via this pathway may contribute to development of neurodegenerative diseases.

Administration, Inhalation↗

The retinal degeneration (rd) gene seriously impairs spatial cognitive performance in normal and Alzheimer's transgenic mice.

To determine the effects of the recessive retinal degeneration (rd) gene on behavioral performance, three Alzheimer's transgenic lines (APPsw, P301L, APPsw + P301L) and non-transgenic littermates were evaluated in a comprehensive behavioral battery between 5 and 8.5 months of age. For all four genotypes collectively, rd homozygosity resulted in profound impairment in spatial cognitive tasks requiring visual acuity (Morris maze, platform recognition, and radial arm water maze). Non-transgenic and P301L mutant tau mice contributed most to this rd effect since heterozygous and wild type mice performed well. By contrast, spatial cognitive performance of both APPsw-expressing lines was often impaired, irrespective of rd status. Sensorimotor performance was unaffected by rd homozygosity, while rd effects on anxiety were genotype-dependent (less anxiety in NT, APPsw; more anxiety in P301L, APPsw + P301L). Our results strongly encourage rd screening of genetically manipulated mouse lines produced from rd-carrying strain backgrounds to avoid serious potential confounds in the interpretation of spatially based cognitive performance.

Alzheimer Disease↗

The Mouse Genome Database (MGD): integrating biology with the genome.

The Mouse Genome Database (MGD) is one component of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a community database resource for the laboratory mouse. MGD strives to provide a comprehensive knowledgebase about the mouse with experiments and data annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genetic, genotype (sequence) and phenotype information including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships between genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent developments in MGD discussed here include an extensive integration of the mouse sequence data and substantial revisions in the presentation, query and visualization of sequence data.

Animals↗

Phantoms in rheumatology.

This paper examines rheumatology pain and how it may relate to amputee phantom limb pain (PLP), specifically as experienced in rheumatoid arthritis, fibromyalgia and complex regional pain syndrome (CRPS). Clinical findings, which suggest cortical sensory reorganization, are discussed and illustrated for each condition. It is proposed that this sensory reorganization generates pain and altered body image in rheumatology patients in the same manner as has previously been hypothesized for amputees with PLP; that is via a motor/sensory conflict. The correction of this conflict through the provision of appropriate visual sensory input, using a mirror, is tested in a population of patients with CRPS. Its analgesic efficacy is assessed in those with acute, intermediate and chronic disease. Finally, the hypothesis is taken to its natural conclusion whereby motor/sensory conflict is artificially generated in healthy volunteers and chronic pain patients to establish whether sensory disturbances can be created where no pain symptoms exists and exacerbated when it is already present. The findings of our studies support the hypothesis that a mismatch between motor output and sensory input creates sensory disturbances, including pain, in rheumatology patients and healthy volunteers. We propose the term 'ominory' to describe the central monitoring mechanism and the resultant sensory disturbances as a dissensory state.

Adult↗

Experience of post-pyloric feeding in seriously ill patients in clinical practice.

BACKGROUND: Maintaining nutrition is an integral part of patient care and when it is possible enteral nutrition is regarded as superior to parenteral nutrition. Post-pyloric feeding may enable enteral feeding to be maintained in patients who cannot tolerate nasogastric feeding. The success of post-pyloric feeding in routine clinical practice is uncertain. METHODS: One hundred and forty six consecutive patients who had 150 separate episodes of post-pyloric feeding were identified. Casenotes were reviewed to assess indication for post-pyloric feeding, prior use of alternative methods of feeding, success of achieving nutritional requirements and patient outcome. RESULTS: A post-pyloric tube was successfully placed in 138 (92%) and nutritional requirements were met by post-pyloric feeding alone in 124 (83%). Post-pyloric feeding was used for between 2 and 254 days (median 14 days). Conditions for which post-pyloric feeding was used to administer nutritional support included burn injury, pancreatitis, sepsis, post-operative gastric stasis, bone marrow transplantation and chemotherapy induced vomiting. Fifty (33%) patients had an attempt at nasogastric feeding and 33 (22%) were on total parenteral nutrition before post-pyloric feeding was commenced. There was one major complication of a jejunal ulcer bleed in the series. Minor complications included displacement of the nasojejunal tube and failure to absorb feed related to gastrointestinal dysfunction. CONCLUSIONS: Post-pyloric feeding can be successfully used to maintain enteral nutrition in patients who would otherwise require parenteral nutrition.

Critical Illness↗

Are patients with chronic low back pain or chronic neck pain fatigued?

OBJECTIVES: The objectives of this study were the following: to determine if fatigue is present in chronic low back pain (LBP) and chronic neck pain patients to a greater extent than in controls (nonpatients); to determine which variables are associated with the presence of fatigue; and to determine which of the above chronic pain patient (CPP) groups is more fatigued. To the authors' knowledge, this is the first such study in the literature. DESIGN: Totals of 175 chronic LBP and 33 chronic neck pain patients completed the Multidimensional Fatigue Inventory (MFI), Neuropathic Pain Scale (NPS), and Beck Depression Inventory rating scales on admission. In addition, an information tool was completed on each CPP and contained the following information: demographics, primary and secondary pain diagnoses, DSM-IV psychiatric diagnoses assigned, pain location, pain precipitating event, type of injury, years in pain, number of surgeries, types of surgery, type of pain pattern, opioids consumed per day in morphine equivalents, workers' compensation status, and whether, according to the clinical examination, the pain did or did not have a neuropathic component. Scores on the MFI were then compared with published norms for controls (nonpatients) via chi-squared tests. Bivariate analyses were conducted between the MFI subscales and the variables selected for analysis. Pearson correlations, analyses of variance, and t-tests were used to test for relationships between MFI scale scores and the appropriate variables. In the next step of the analysis, stepwise regression analyses were used to predict each of the MFI subscale scores using the variables that were found to be significantly (P < 0.05) related to fatigue by the preceding analysis. In the final analysis, the variables that were significant predictors of the fatigue subscales were controlled for as covariates in an analysis of variance in order to determine if chronic LBP patients had scores on the MFI subscales that were significantly different from those of chronic neck pain patients. SETTING: Multidisciplinary pain facility. PATIENTS: Chronic LBP and chronic neck pain patients. RESULTS: Chronic LBP and chronic neck pain patients were found to be significantly more fatigued than controls (nonpatients). Most of the MFI subscale scores could be predicted by four major variables: presence of neuropathic pain, female gender, presence of depression, and total number of DSM-IV diagnoses. Chronic LBP patients were as fatigued as chronic neck pain patients. CONCLUSIONS: The complaint of fatigue appears to be a significant problem for chronic LBP and chronic neck pain patients. This complaint may be associated with neuropathic pain, female gender, and psychiatric comorbidities.

Chronic Disease↗

Evaluation of Xenostrip-Tv, a rapid diagnostic test for Trichomonas vaginalis infection.

An immunochromatographic strip test, Xenostrip-Tv, was compared to wet mount and PCR for the diagnosis of Trichomonas vaginalis infection in women. Of 428 specimens tested, 54 (12.6%) were positive by an "expanded gold standard," defined as either a positive wet mount and PCR test with primers TVK3 and TVK7 and/or a positive PCR test confirmed by a second PCR assay with primers TVA5-1 and TVA6; 26 (6%) were positive by wet mount, and 36 (8.4%) were positive by Xenostrip-Tv test. Since the Xenostrip-Tv test is rapid and easy to perform and proved to be more sensitive than wet mount, it should be considered as an alternative to wet mount for point-of-care diagnosis of trichomoniasis, especially in settings where microscopy is impractical.

Animals↗

Modafinil for the treatment of pain-associated fatigue: review and case report.

Fatigue is a symptom that is frequently found in chronic pain patients with low back pain and/or neck pain. At the present time, no specific psychopharmacological treatment for this problem has been identified. Modafinil is a wakefulness-promoting agent that the FDA has approved for the treatment of excessive daytime sleepiness associated with narcolepsy. There have been reports on the use of modafinil for the treatment of fatigue in various neurological syndromes. This literature is reviewed. As such, modafinil treatment was initiated for a patient with severe fatigue associated with chronic low back pain and neck pain. There was dramatic improvement in fatigue and associated function. This case is described. It is the first such case report in the literature. The significance of this finding to the treatment of pain-associated fatigue is discussed.

Adult↗