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K R Smith

Publications and source records attributed to K R Smith.

At least 37 records · Page 2Linked to original sources
PubMed2000

Genetic testing, adverse selection, and the demand for life insurance.

The dramatic increase in genetic testing for adult-onset diseases has created a debate regarding whether or not insurance companies should be able to use genetic test results in underwriting. We use data from women who have been tested for the BRCA1 gene mutation along with data from otherwise comparable untested women to assess the potential for adverse selection in the life insurance market when tested individuals know their genetic test results but insurers do not. Our analyses show that women who test positive for the BRCA1 gene mutation do not capitalize on their informational advantage by purchasing more life insurance than those women who have not undergone genetic testing.

Adolescent↗
PubMed2000

Attitudes toward the genetic testing of children among adults in a Utah-based kindred tested for a BRCA1 mutation.

Advances in molecular biology and genetics have led to the identification of the breast/ovarian cancer susceptibility genes BRCA1 and BRCA2, along with tests to detect mutations in these genes. Although the appropriateness of BRCA1/2 genetic testing for children has been debated in the literature, little is known about the attitudes of individuals who have undergone cancer susceptibility testing. The present study focused on attitudes toward BRCA1 testing for children among 218 adults from a Utah-based kindred who had received BRCA1 test results. Results indicated that approximately one-fourth of the participants would permit BRCA1 testing for children under the age of 18. General attitudes about genetic testing were predictive of attitudes toward the testing of children. In addition, men and individuals without a BRCA1 mutation were more likely to agree that minors should be allowed BRCA1 testing. Individuals whose mother had been affected with breast cancer were less likely to permit testing for minors. Among parents of minor children, less than one-fifth indicated that they would want BRCA1 testing for their own children; carrier status was not predictive of attitudes toward testing their own children. As breast/ovarian cancer susceptibility testing continues to be disseminated into clinical settings, there may be an increase in the number of test requests for minors. The findings of the present study represent an important step in exploring attitudes about genetic testing of children among individuals who have received cancer susceptibility test results.

Adolescent↗
PubMed2000

Characteristics of women associated with continuing instruction in the Creighton Model Fertility Care System.

Effective use of natural family planning is strongly dependent upon adequate instruction. The Creighton Model Fertility Care System (CrMS) has a standardized protocol for instruction of new users that includes individual follow-up visits in the first year of use. This study evaluated the number of follow-up visits completed by new CrMS users from eight CrMS centers in the United States. Four follow-up visits were completed by 75.7% of women. Women who continued instruction were more likely to be educated, Catholic, and white, and to have a more challenging reproductive status (discontinuing oral contraceptives, or breastfeeding). These results suggest that the number of follow-up visits needed varies among new CrMS users. Future research should address the optimal length of instruction for adequate use of the CrMS by women with different characteristics and needs.

Adolescent↗
PubMed2000

Interleukin-8 levels in human lung epithelial cells are increased in response to coal fly ash and vary with the bioavailability of iron, as a function of particle size and source of coal.

Particulate air pollution contains iron, and some of the pathological effects after inhalation may be due to radical species produced by iron-catalyzed reactions. We tested the hypothesis that iron present in coal fly ash (CFA) could induce the expression and synthesis of the inflammatory cytokine interleukin-8 (IL-8). CFA, containing as much as 14% iron, was used as a model combustion source particle. Three coal types were used to generate three size fractions enriched in particles [submicron (<1 micrometer), fine (<2.5 micrometer), or coarse (2.5-10 micrometer]), as well as the fraction of >10 micrometer. Treatment of human lung epithelial (A549) cells for 4 h with CFA from Utah enriched in <1 micrometer particles (20 microgram/cm(2)) resulted in a 2.6-fold increase in mRNA levels for IL-8. IL-8 levels were increased in the medium by as much as 8-fold when cells were treated with the fraction enriched in the smallest size Utah CFA for 24 h. IL-8 production was completely inhibited when the CFA was pretreated with the metal chelator desferrioxamine B, suggesting that a transition metal was responsible for the induction, probably iron. Treatment with a soluble form of iron, ferric ammonium citrate (FAC), mimicked the IL-8 level increase observed with CFA. There was a direct relationship, above a threshold level of bioavailable iron, between the levels of IL-8 and bioavailable iron in A549 cells treated with CFA or FAC. Further, the relationship between IL-8 and bioavailable iron for CFA was indistinguishable from that for FAC. These results strongly suggest that iron can induce IL-8 in A549 cells and that iron was the likely component of CFA that induced IL-8. CFA-induced IL-8 production was inhibited by tetramethylthiourea or dimethyl sulfoxide, suggesting that radical species were involved in the induction. These results demonstrate that iron present in CFA may be responsible for production and release of inflammatory mediators by the lung epithelium through generation of radical species and suggest that iron may contribute to the exacerbation of respiratory problems by particulate air pollution.

Biological Availability↗
PubMed2000

Mobilization of iron from coal fly ash was dependent upon the particle size and source of coal: analysis of rates and mechanisms.

The observed iron mobilization rate from size-fractionated coal fly ash is consistent with the model predictions for a limiting case of mass transfer where the dominant resistance is diffusion through a layer of depleted solid between the surface of spherical particles and a shrinking core of unreacted material. The rate of mobilization of iron from coal fly ash under physiologically relevant conditions in vitro was previously shown to depend on the size of the ash particles and on the source of the coal, and these in vitro measurements have been shown to correlate with indirect measurements of excess iron in cultured cells. Existing iron mobilization data were compared to mathematical models for mass transfer and chemical reaction in solid-liquid heterogeneous systems. Liquid-phase diffusion resistance can be ruled out as the rate-limiting mechanism for iron mobilization as the model predictions for this case are clearly inconsistent with the measurements. Other plausible hypotheses, such as a rate limited by a heterogeneous surface reaction, cannot be conclusively ruled out by the available data. These mathematical analysis methods are applicable to the design of future experiments to determine the rate-limiting mechanism for the mobilization of iron and of other transition metals from both ambient air samples and surrogates for major sources of particulate air pollution.

Air Pollutants↗
PubMed2000

Mössbauer spectroscopy indicates that iron in an aluminosilicate glass phase is the source of the bioavailable iron from coal fly ash.

Iron speciation by Mössbauer spectroscopy indicates that ferric iron in an aluminosilicate glass phase is the source of the bioavailable iron in coal fly ash and that this iron species is associated with combustion particles, but not with crustal dust derived from soil minerals. Urban particulate has been shown to be a source of bioavailable iron and has been shown to be able to induce the formation of reactive species in cell culture experiments. Crustal dust and laboratory-generated coal fly ash have been studied as surrogates for two sources of metal-bearing particles in ambient air. As much as a 60-fold difference in the amount of iron mobilized by the chelator citrate was observed between fly ash and crustal dust samples with similar total iron contents. The extent of iron mobilization by citrate in vitro has been shown to correlate with indirect measures of excess iron in cultured cells and with assays for reactive oxygen species generation in vitro. Mössbauer spectroscopy of coal fly ash, before and after treatment with the chelator desferrioxamine B, showed that the iron in an aluminosilicate glass phase was preferentially removed. The removal of the glass-phase iron greatly reduced the amount of iron that could be mobilized by citrate and prevented the particles from inducing interleukin-8 in cultured human lung epithelial (A549) cells. Ferric iron in aluminosilicate glass is associated with particles formed at high temperatures followed by rapid cooling. The observation that ferric iron in aluminosilicate glass is the source of bioavailable iron in coal fly ash suggests that particles from ambient sources and other specific combustion sources should be examined for the presence of this potential source of bioavailable iron.

Air Pollutants↗
PubMed2000

Particulate matter and carbon monoxide in highland Guatemala: indoor and outdoor levels from traditional and improved wood stoves and gas stoves.

Area 22-h average carbon monoxide (CO), total suspended particulates (TSP), particles less than 10 microns in diameter (PM10), and particles less than 2.5 microns in diameter (PM2.5) measurements were made in three test homes of highland rural Guatemala in kitchens, bedrooms, and outdoors on a longitudinal basis, i.e. before and after introduction of potential exposure-reducing interventions. Four cookstove conditions were studied sequentially: background (no stove in use); traditional open woodstove, improved woodstove with flue (plancha), and bottled-gas (LPG) stove. With nine observations each, kitchen PM2.5 levels were 56 micrograms/m3 under background conditions, 528 micrograms/m3 for open fire conditions, 96 micrograms/m3 for plancha conditions, and 57 micrograms/m3 for gas stove conditions. Corresponding PM10/TSP levels were 173/174, 717/836, 210/276, 186/218 micrograms/m3. Corresponding CO levels were 0.2, 5.9, 1.4, 1.2 ppm. Comparisons with other studies in the area indicate that the reductions in indoor concentrations achieved by improved wood-burning stoves deteriorate with stove age. Mother and child personal CO and PM2.5 measurements for each stove condition demonstrate the same trend as area measurements, but with less differentiation.

Adult↗
PubMed2000

Bioavailability of iron from coal fly ash: mechanisms of mobilization and of biological effects.

Particulate air pollution contains iron that may be involved in the pathological effects after inhalation. This article reviews work demonstrating that ambient particulate samples (Standard Reference Material [SRM] 1648 and SRM 1649, from the National Institute of Science and Technology) contain iron that can be mobilized from the particle in vitro and inside human lung epithelial (A549) cells. The mobilized iron can then catalyze the formation of reactive oxygen species (ROS). Work is also reviewed on the generation and size fractionation of coal fly ash (CFA) from three commercially important coal types, as well as size fractionation of three types of noncombustion particles. The availability of iron from these particles to A549 cells was measured by citrate mobilization in vitro and induction of the iron storage protein ferritin in particle-treated cells. The amount of bioavailable iron decreased with increasing particle size. The ability of particles to induce synthesis of the proinflammatory cytokine interleukin-8 (IL-8) was also determined. As with the bioavailability of iron, there was an inverse correlation with size. Further work showed that iron in CFA is responsible for IL-8 induction. Mössbauer spectroscopy of a CFA sample before and after desferrioxamine B treatment to remove bioavailable iron showed that the bioavailable iron was associated with the glassy aluminosilicate fraction of the particle. In conclusion, this work shows that bioavailable iron is responsible for ROS production by SRMs and IL-8 induction by CFA in A549 cells. The source of this bioavailable iron in CFA is glassy aluminosilicates, which are found at higher levels in smaller sizes of CFA.

Air Pollutants↗
PubMed2000

Genetic variation in the spread of Drosophila subobscura from a nonequilibrium population.

Drosophila subobscura was first identified in North America in the early 1980s, and a newer D. subobscura population in Utah appears to have been established more than 10 years later. In this study, we use nuclear microsatellite allele frequencies, mitochondrial restriction fragment length polymorphism (RFLP) allele frequencies, and computer simulations to investigate possible scenarios of how this species has spread across North America. Our method develops a 95% confidence interval for the maximum and minimum number of founders that could have colonized the new population given various scenarios for spread. Unlike many other methods, it may be applied to nonequilibrium source populations given certain conditions. We find that observed allele frequency differences between newer and older D. subobscura populations are consistent with very few inseminated females being transported east from the coast in a single step or with larger numbers of colonizers invading after several intermediate steps. They are not consistent with a large, panmictic population of D. subobscura colonizing Utah in a single step.

Animals↗
PubMed2000

Indoor air pollution in developing countries and acute lower respiratory infections in children.

BACKGROUND: A critical review was conducted of the quantitative literature linking indoor air pollution from household use of biomass fuels with acute respiratory infections in young children, which is focused on, but not confined to, acute lower respiratory infection and pneumonia in children under two years in less developed countries. Biomass in the form of wood, crop residues, and animal dung is used in more than two fifths of the world's households as the principal fuel. METHODS: Medline and other electronic databases were used, but it was also necessary to secure literature from colleagues in less developed countries where not all publications are yet internationally indexed. RESULTS: The studies of indoor air pollution from household biomass fuels are reasonably consistent and, as a group, show a strong significant increase in risk for exposed young children compared with those living in households using cleaner fuels or being otherwise less exposed. Not all studies were able to adjust for confounders, but most of those that did so found that strong and significant risks remained. CONCLUSIONS: It seems that the relative risks are likely to be significant for the exposures considered here. Since acute lower respiratory infection is the chief cause of death in children in less developed countries, and exacts a larger burden of disease than any other disease category for the world population, even small additional risks due to such a ubiquitous exposure as air pollution have important public health implications. In the case of indoor air pollution in households using biomass fuels, the risks also seem to be fairly strong, presumably because of the high daily concentrations of pollutants found in such settings and the large amount of time young children spend with their mothers doing household cooking. Given the large vulnerable populations at risk, there is an urgent need to conduct randomised trials to increase confidence in the cause-effect relationship, to quantify the risk more precisely, to determine the degree of reduction in exposure required to significantly improve health, and to establish the effectiveness of interventions.

Acute Disease↗
PubMed2000

Use of radiographic atlases in a mass fatality.

In May and June of 1996, a forensic anthropology team from the C.A. Pound Human Identification Laboratory at the University of Florida identified 9 of 10 juveniles from the crash of ValuJet 592. The team relied primarily on a radiographic atlas developed and used by clinical practitioners to determine skeletal age. Postmortem radiographs of the juvenile victims were compared with radiographic standards to determine skeletal age. Skeletal age was then compared to a passenger list indicating the sex, weight, height, and chronological age of each individual. Tentative identifications based on the atlas method were organized into an exclusion matrix. Final identifications were based on this assessment in conjunction with other anthropological data such as appearance and fusion of ossification centers and estimation of stature.

Accidents, Aviation↗
PubMed1999

Low levels of arsenic trioxide stimulate proliferative signals in primary vascular cells without activating stress effector pathways.

Chronic human exposure to low levels of inorganic arsenic increases the incidence of vascular diseases and specific cancers. Exposure of endothelial cells to environmentally relevant concentrations of arsenic trioxide (arsenite) induces oxidant formation, activates the transcription factor NF-kappaB, and increases DNA synthesis (Barchowsky et al., Free Radic. Biol. Med. 21, 783-790, 1996). We show, in the current study, that arsenite induces concentration-dependent cell proliferation or death in primary porcine aortic endothelial cells. Low concentrations caused cell proliferation and were associated with increased superoxide and H(2)O(2) accumulation, cSrc activity, H(2)O(2)-dependent tyrosine phosphorylation, and NF-kappaB-dependent transcription. These concentrations were insufficient to activate MAP kinases. However, the MAP kinases, extracellular signal-regulated kinase and p38, were activated in response to levels of arsenite that caused cell death. These data suggest that arsenite-induced oxidant accumulation and subsequent activation of tyrosine phosphorylation represent a MAPK-independent pathway for phenotypic change and proliferation in vascular cells.

Animals↗
PubMed1999

Biomass cooking fuels and prevalence of tuberculosis in India.

OBJECTIVES: To examine the relation between use of biomass cooking fuels (wood or dung) and prevalence of active tuberculosis in India. METHODS: The analysis is based on 260,162 persons age 20 and over in India's 1992-93 National Family Health Survey. Logistic regression is used to estimate the effects of biomass fuel use on prevalence of active tuberculosis, as reported by household heads, after controlling for a number of potentially confounding variables. RESULTS: Persons living in households that primarily use biomass for cooking fuel have substantially higher prevalence of active tuberculosis than persons living in households that use cleaner fuels (odds ratio [OR] = 3.56; 95% confidence interval [CI] = 2.82-4. 50). This effect is reduced somewhat when availability of a separate kitchen, house type, indoor crowding, age, gender, urban or rural residence, education, religion, caste or tribe, and geographic region are statistically controlled (OR = 2.58; 95% CI = 1.98-3.37). Fuel type also has a large effect when the analysis is done separately for men (OR = 2.46; 95% CI = 1.79-3.39) and women (OR = 2. 74; 95% CI = 1.86-4.05) and separately for urban areas (OR = 2.29; 95% CI = 1.61-3.23) and rural areas (OR = 2.65; 95% CI = 1.74-4.03). The analysis also indicates that, among persons age 20 years and over, 51% of the prevalence of active tuberculosis is attributable to cooking smoke. CONCLUSIONS: Results strongly suggest that use of biomass fuels for cooking substantially increases the risk of tuberculosis in India.

Adult↗
PubMed1999

In vitro effects of coal fly ashes: hydroxyl radical generation, iron release, and DNA damage and toxicity in rat lung epithelial cells.

Oxygen radical generation due to surface radicals, inflammation, and iron release has been suggested as the mechanism of adverse effects of quartz, such as emphysema, fibrosis, and carcinogenic effects. Therefore, we measured iron release, acellular generation of hydroxyl radicals, and oxidative DNA damage and cytotoxicity in rat lung epithelial (RLE) cells by different coal fly ashes (CFA) that contain both quartz and iron. Seven samples of CFA with different particle size and quartz content (up to 14.1%) were tested along with silica (alpha-quartz), ground coal, and coal mine dust (respirable) as positive control particles, and fine TiO(2) (anatase) as a negative control. Five test samples were pulverized fuel ashes (PFA), two samples were coal gasification (SCG) ashes (quartz content <0.1%), and one sample was a ground coal. No marked differences between SCG and PFA fly ashes were observed, and toxicity did not correlate with physicochemical characteristics or effect parameters. Stable surface radicals were only detected in the reference particles silica and coal mine dust, but not in CFA. On the other hand, hydroxyl radical generation by all fly ashes was observed in the presence of hydrogen peroxide, which was positively correlated with iron mobilization and inhibited by deferoxamine, but not correlated with iron or quartz content. Also a relationship between acellular hydroxyl radical generation and oxidative DNA damage in RLE cells by CFA was observed. Differences in hydroxyl radical generation and oxidative damage by the CFA were not related to iron and quartz content, but the respirable ashes (MAT023, 38, and 41) showed a very extensive level of hydroxyl radical generation in comparison to nonrespirable fly ashes and respirable references. This radical generation was clearly related to the iron mobilization from these particles. In conclusion, the mechanisms by which CFA and the positive references (silica, coal mine dust) affect rat lung epithelial cells seem to be different, and the data suggest that quartz in CFA does not act the same as quartz in silica or coal mine dust. On the other hand, the results indicate an important role for size and iron release in generation and subsequent effects of reactive oxygen species caused by CFA.

Animals↗
PubMed1999

Sperm cell mediated transgenesis: a review.

Transgenesis would be greatly streamlined if sperm cells could be used as transgene vectors. Attempts to 'force' sperm cells to take up transgenes may be more worthy of further study than 'autouptake' attempts. However, thorough proof of its effectiveness will be required if sperm cell-mediated gene transfer is to be accepted, given the evolutionary implications associated with the possibility of sperm cells being able to transfer exogenous DNA.

Animals↗