Search PubMed⌕ Search

Biomedical subjects

Thomas E Johnson

Publications and source records attributed to Thomas E Johnson.

At least 37 records · Page 2Linked to original sources
PubMed2006

Noninfectious complications due to vascular access ports (VAPs) in Yucatan minipigs (Sus scrofa domestica).

Vascular access ports (VAPs) for studies requiring intermittent or continuous infusion and frequent sampling are well accepted and widely used in large animal species. However, the use of medical devices such as VAPs to facilitate sample collection can lead to complications. Noninfectious complications of VAP implantation can result from thrombotic or mechanical obstructions, other mechanical problems, and animal-associated complications. To facilitate our research, we surgically implanted VAPs in the right external jugular vein of 6 adult male and 3 female Yucatan miniswine (age, 12 mo) to enable collection of blood samples every 30 min for 8 h and then every 8 h for as long as 60 d. The VAPs were operational an average of 35.6 d (range, 29 to 56 d) and had an overall success rate of 77.8% with 7 of 9 VAPs functional. In these 7 animals, 53.1 samples on average (range, 28 to 95 samples) were collected from each VAP. Rates of noninfectious complications were 60% for thrombotic events and 40% for nonthrombotic events over the course of this study.

Animals↗
PubMed2006

Particulate matter in animal rooms housing mice in microisolation caging.

Reactions to allergens created by laboratory animals are among the most frequently encountered occupational illnesses associated with research animals. Personnel are exposed to these allergens through airborne particulate matter. Although the use of microisolation caging systems can reduce particulate matter concentrations in rooms housing mice, the operating parameters of ventilated caging systems vary extensively. We compared room air in mouse rooms containing 5 different types of caging: 1) individually ventilated caging under positive pressure with filtered intake air and exhaust air returned to the room (VCR+), 2) individually ventilated caging under negative pressure with exhaust air returned to the room (VCR-), 3) individually ventilated caging under positive pressure with exhaust air returned to the heating, ventilation, and air-conditioning (HVAC) system, 4) individually ventilated caging under negative pressure with exhaust air returned to the HVAC system, and 5) static microisolation cages. We found that rooms under VCR conditions had fewer large particles than did those under other conditions, but the numbers of 0.3 microm particles did not differ significantly among systems. Static, positive or negative pressure applied to caging units as well as route of air exhaust were found to have little influence on the total number of particles in the atmosphere. Therefore, considering the heat load, odor, and overall particulate concentration in the room, placing individually ventilated caging under negative pressure with exhaust air returned to the HVAC system appears to be the optimal overall choice when using microisolation housing for rodents.

Air Pollutants, Occupational↗
PubMed2005

Genetics of body weight in the LXS recombinant inbred mouse strains.

This is the first phenotypic analysis of 75 new recombinant inbred (RI) strains derived from ILS and ISS progenitors. We analyzed body weight in two independent cohorts of female mice at various ages and in males at 60 days. Body weight is a complex trait which has been mapped in numerous crosses in rodents. The LXS RI strains displayed a large range of weights, transgressing those of the inbred progenitors, supporting the utility of this large panel for mapping traits not selected in the progenitors. Numerous QTLs for body weight mapped in single- and multilocus scans. We assessed replication between these and previously reported QTLs based on overlapping confidence intervals of published QTLs for body weight at 60 days and used meta-analyses to determine combined p values for three QTL regions located on Chromosomes 4, 5, and 11. Strain distribution patterns of microsatellite marker genotypes, weight, and other phenotypes are available on WebQTL (http://www.webqtl.org/search.html ) and allow genetic mapping of any heritable quantitative phenotype measured in these strains. We report one such analysis, correlating brain and body weights. Large reference panels of RI strains, such as the LXS, are invaluable for identifying genetic correlations, GXE (Gene X Environment) interactions, and replicating previously identified QTLs.

Animals↗
PubMed2005

A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans.

When both genotype and environment are held constant, 'chance' variation in the lifespan of individuals in a population is still quite large. Using isogenic populations of the nematode Caenorhabditis elegans, we show that, on the first day of adult life, chance variation in the level of induction of a green fluorescent protein (GFP) reporter coupled to a promoter from the gene hsp-16.2 predicts as much as a fourfold variation in subsequent survival. The same reporter is also a predictor of ability to withstand a subsequent lethal thermal stress. The level of induction of GFP is not heritable, and GFP expression levels in other reporter constructs are not associated with differences in longevity. HSP-16.2 itself is probably not responsible for the observed differences in survival but instead probably reflects a hidden, heterogeneous, but now quantifiable, physiological state that dictates the ability of an organism to deal with the rigors of living.

Animals↗
PubMed2005

Genes, phenes, and dreams of immortality: the 2003 Kleemeier Award lecture.

The 2002 Kleemeier Award from the Gerontological Society of America was awarded to Thomas E. Johnson, PhD, of the University of Colorado at Boulder. Dr. Johnson was the pioneer who first applied genetic analyses to the study of the aging processes in Caenorhabditis elegans and who introduced the nematode as an aging model. Longer life span was chosen as a surrogate marker for slowed aging. Here Dr. Johnson describes his role(s) in the isolation of age-1, the first longevity mutant, which can more than double the life span and which slows the rate of aging more than twofold. He also reviews research suggesting conservation of function and applicability to intervention by pharmacological targeting of the Age-1 pathway. Current work by biotechnology companies targets this and other basic discoveries in an attempt to postpone human aging.

Aging↗
PubMed2005

Dietary restriction in the nematode Caenorhabditis elegans.

The first observation of the positive effect of reduced food intake on mammalian life span was made 70 years ago. In the decades that followed, researchers successfully applied this method to increase the life span of a very wide range of animals. The nematode Caenorhabditis elegans is an excellent model organism for studying the aging process. However, relatively little effort has been made to study the effects of dietary restriction in C. elegans. In this review we discuss the difficulties of subjecting C. elegans to dietary restriction, the effects of dietary restriction on metabolism and stress defense, and the potential role of different signaling pathways in DR-induced life extension. Recent experiments suggest that the TOR (target of rapamycin) pathway, rather than insulin-like signaling, might be involved in mediating the life-extending effect of dietary restriction.

Aging↗
PubMed2005

Norepinephrine transporter: a candidate gene for initial ethanol sensitivity in inbred long-sleep and short-sleep mice.

BACKGROUND: Altered noradrenergic neurotransmission is associated with depression and may contribute to drug abuse and alcoholism. Differential initial sensitivity to ethanol is an important predictor of risk for future alcoholism, making the inbred long-sleep (ILS) and inbred short-sleep (ISS) mice a useful model for identifying genes that may contribute to alcoholism. METHODS: In this study, molecular biological, neurochemical, and behavioral approaches were used to test the hypothesis that the norepinephrine transporter (NET) contributes to the differences in ethanol-induced loss of righting reflex (LORR) in ILS and ISS mice. RESULTS: We used these mice to investigate the NET as a candidate gene contributing to this phenotype. The ILS and ISS mice carry different DNA haplotypes for NET, showing eight silent differences between allelic coding regions. Only the ILS haplotype is found in other mouse strains thus far sequenced. Brain regional analyses revealed that ILS mice have 30 to 50% lower [3H]NE uptake, NET binding, and NET mRNA levels than ISS mice. Maximal [3H]NE uptake and NET number were reduced, with no change in affinity, in the ILS mice. These neurobiological changes were associated with significant influences on the behavioral phenotype of these mice, as demonstrated by (1) a differential response in the duration of ethanol-induced LORR in ILS and ISS mice pretreated with a NET inhibitor and (2) increased ethanol-induced LORR in LXS recombinant inbred (RI) strains, homozygous for ILS in the NET chromosomal region (44-47 cM), compared with ISS homozygous strains. CONCLUSIONS: This is the first report to suggest that the NET gene is one of many possible genetic factors influencing ethanol sensitivity in ILS, ISS, and LXS RI mouse strains.

Animals↗
PubMed2005

Conjunctival cytology features of giant papillary conjunctivitis associated with ocular prostheses.

PURPOSE: In this study, the conjunctival cytology features of giant papillary conjunctivitis (GPC) associated with ocular prosthesis wear was examined. METHODS: In a prospective study, 12 consecutive patients diagnosed with GPC associated with ocular prosthesis wear were examined. Impression cytology specimens were taken from the upper eyelid tarsal conjunctiva, the bulbar conjunctiva, and the lower eyelid tarsal conjunctiva of each socket, with the contralateral eye serving as a matched control. RESULTS: The randomized impression cytology specimens showed no significant change in goblet cell density or epithelial cell morphology when comparing the GPC and control specimens. The GPC specimens did have a statistically significant increase in conjunctival inflammation and mucous strands on all three sample areas. In addition, the GPC specimens from the upper and lower tarsal conjunctiva had a honeycomb pattern consistent with giant papillae. CONCLUSIONS: This is the first report to describe the honeycomb pattern created by giant papillae on impression cytology and the changes of GPC on the lower tarsal conjunctiva.

Adolescent↗
PubMed2005

Reduced expression of frataxin extends the lifespan of Caenorhabditis elegans.

Defects in the expression of the mitochondrial protein frataxin cause Friedreich's ataxia, an hereditary neurodegenerative syndrome characterized by progressive ataxia and associated with reduced life expectancy in humans. Homozygous inactivation of the frataxin gene results in embryonic lethality in mice, suggesting that frataxin is required for organismic survival. Intriguingly, the inactivation of many mitochondrial genes in the nematode Caenorhabditis elegans by RNAi extends lifespan. We therefore investigated whether inactivation of frataxin by RNAi-mediated suppression of the frataxin homolog gene (frh-1) would also prolong lifespan in the nematode. Frataxin-deficient animals have a small body size, reduced fertility and altered responses to oxidative stress. Importantly, frataxin suppression by RNAi significantly extends lifespan in C. elegans.

Animals↗
PubMed2005

A microarray analysis of potential genes underlying the neurosensitivity of mice to propofol.

Establishing the mechanism of action of general anesthetics at the molecular level is difficult because of the multiple targets with which these drugs are associated. Inbred short sleep (ISS) and long sleep (ILS) mice are differentially sensitive in response to ethanol and other sedative hypnotics and contain a single quantitative trait locus (Lorp1) that accounts for the genetic variance of loss-of-righting reflex in response to propofol (LORP). In this study, we used high-density oligonucleotide microarrays to identify global gene expression and candidate genes differentially expressed within the Lorp1 region that may give insight into the molecular mechanism underlying LORP. Microarray analysis was performed using Affymetrix MG-U74Av2 Genechips and a selection of differentially expressed genes was confirmed by semiquantitative reverse transcription-polymerase chain reaction. Global expression in the brains of ILS and ISS mice revealed 3423 genes that were significantly expressed, of which 139 (4%) were differentially expressed. Analysis of genes located within the Lorp1 region showed that 26 genes were significantly expressed and that just 2 genes (7%) were differentially expressed. These genes encoded for the proteins AWP1 (associated with protein kinase 1) and "BTB (POZ) domain containing 1," whose functions are largely uncharacterized. Genes differentially expressed outside Lorp1 included seven genes with previously characterized neuronal functions and thus stand out as additional candidate genes that may be involved in mediating the neurosensitivity differences between ISS and ILS.

Anesthetics, Intravenous↗
PubMed2005

The ex vivo pig eye as a replacement model for laser safety testing.

The purpose of this study was to evaluate the viability of ex vivo pig eyes as a replacement model for in vivo testing in the establishment of laser eye safety standards. Previous studies of pulsed energy absorption at 3.8 microm were performed using rhesus monkey cornea at pulse durations two orders of magnitude shorter than the 8-micros pulses used in the current study. Ex vivo pig eyes were exposed to laser pulses of various energies and then evaluated to establish the statistical threshold for corneal damage. Tissue analysis (histologic evaluation) was used to determine the extent of damage to the cornea. These results can be used in the establishment of safety standards for laser use; our findings also suggest that ex vivo pig eyes are suitable models for this purpose.

Animals↗
PubMed2004

Isolation of long-lived mutants in Caenorhabditis elegans using selection for resistance to juglone.

The accumulation of molecular damage from attack by reactive oxygen species is one cause of aging. Therefore, some mutant organisms showing increased resistance to reactive oxygen species should live longer. We show that selection for Caenorhabditis elegans mutants that are resistant to juglone, a reactive oxygen species-generating compound, leads to the identification of long-lived mutants. Indeed, four of six resistant mutants isolated were also long-lived. This study illustrates once more the strong relationship between oxidative stress and the aging processes.

Aging↗
PubMed2004

Genetic structure of the LXS panel of recombinant inbred mouse strains: a powerful resource for complex trait analysis.

The set of LXS recombinant inbred (RI) strains is a new and exceptionally large mapping panel that is suitable for the analysis of complex traits with comparatively high power. This panel consists of 77 strains-more than twice the size of other RI sets--and will typically provide sufficient statistical power (beta = 0.8) to map quantitative trait loci (QTLs) that account for approximately 25% of genetic variance with a genomewide p < 0.05. To characterize the genetic architecture of this new set of RI strains, we genotyped 330 MIT microsatellite markers distributed on all autosomes and the X Chromosome and assembled error-checked meiotic recombination maps that have an average F2-adjusted marker spacing of approximately 4 cM. The LXS panel has a genetic structure consistent with random segregation and subsequent fixation of alleles, the expected 3-4 x map expansion, a low level of nonsyntenic association among loci, and complete independence among all 77 strains. Although the parental inbred strains-Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS)--were derived originally by selection from an 8-way heterogeneous stock selected for differential sensitivity to sedative effects of ethanol, the LXS panel is also segregating for many other traits. Thus, the LXS panel provides a powerful new resource for mapping complex traits across many systems and disciplines and should prove to be of great utility in modeling the genetics of complex diseases in human populations.

Alleles↗
PubMed2004

Lower body temperature as a potential mechanism of life extension in homeotherms.

Although best known for his studies on the anti-aging effects of dietary restriction, Dr Roy Walford began his career by studying the anti-aging effects of lowering body temperature. As a tribute to his long and productive career, we review these pioneering studies and the singular influence these have had on our own thinking about the potential for lower body temperature to extend the life span of homeotherms. We show our results from a study of six classical inbred strains of mice that depict marked strain variation in the body temperature response to dietary restriction. In addition, we show a genome scan from a recombinant inbred strain panel in which we identified a significant quantitative trait locus on murine chromosome 9 and a provisional locus on chromosome 17 that specify variation in the response of body temperature to dietary restriction. These discoveries suggest that we can now extend the studies of Dr Walford to critically test whether lower body temperature can prolong the life span of mammals.

Aging↗
PubMed2004

The Collaborative Cross, a community resource for the genetic analysis of complex traits.

The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

Animals↗
PubMed2004

Quantitative trait Loci specifying the response of body temperature to dietary restriction.

Dietary restriction (DR) retards aging and mortality across a variety of taxa. In homeotherms, one of the hallmarks of DR is lower mean body temperature (T(b)), which might be directly responsible for some aspects of DR-mediated life extension. We conducted a quantitative trait locus (QTL) analysis of the response of T(b) to DR in mice using a panel of 22 LSXSS recombinant inbred strains, tested in two cohorts. T(b) in response to DR had a significant genetic component, explaining approximately 35% of the phenotypic variation. We mapped a statistically significant QTL to chromosome 9 and a provisional QTL to chromosome 17, which together accounted for about two thirds of the genetic variation. Such QTLs could be used to critically test whether the response of T(b) to DR also affects the response of life extension. In addition, this study demonstrates the feasibility of trying to map QTLs that affect other physiological responses to DR, including the life extension response. Importantly, the genes underlying such QTLs would be causal factors affecting these responses and could be identified by positional cloning.

Aging↗