Activation of the EGF receptor signaling pathway in airway epithelial cells exposed to Utah Valley PM.
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Exposure to ambient particulate matter (PM) in the Utah Valley has previously been associated with a variety of adverse health effects. To investigate intracellular signaling mechanisms for pulmonary responses to Utah Valley PM inhalation, human primary airway epithelial cells were exposed to aqueous extracts of PM collected from the year before (Y1), during (Y2), and after (Y3) the closure of a local steel mill located in the Utah Valley in this study. Transfection with kinase-deficient extracellular signal-regulated kinase (ERK) 1 constructs partially blocked Utah Valley PM-induced interleukin (IL)-8 promoter reporter activity. The mitogen-activated protein kinase/ERK kinase (MEK) activity inhibitor PD-98059 significantly abolished IL-8 released in response to Utah Valley PM, as did the epidermal growth factor (EGF) receptor kinase inhibitor AG-1478. Western blotting showed that Utah Valley PM induced phosphorylation of EGF receptor tyrosine, MEK1/2, and ERK1/2, which could be ablated with AG-1478 or PD-98059. For all findings, the potency of Utah Valley PM collected during Y2 was found to be lower relative to that of Y1 and Y3. These data demonstrate that Utah Valley PM can induce IL-8 expression partially through the activation of the EGF receptor signaling. (+info)
Consanguinity and prereproductive mortality in the Utah Mormon population.
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To test the effects of parental consanguinity on mortality among offspring, inbreeding coefficients were estimated for 303,675 members of the Utah Mormon population who were born between 1847 and 1945. Although consanguinity has been relatively rare in this population, the large sample size permitted the identification of more than 3,500 inbred offspring. Among the offspring of unrelated parents, 13.2% died before the age of 16. Significant elevations in prereproductive mortality were seen among the offspring of first-cousin marriages (22%) and among the offspring of closer unions (32%). The cor- responding relative risks are 1.70 (95% confidence limits = 1.52, 1.91) and 2.41 (95% confidence limits = 1.59, 3.41), respectively. Other categories of relationship did not produce significant elevations in offspring mortality. Similar results were obtained when a case-control approach was used to remove the effects of socioeconomic variation. Consistent with many other studies of populations with low consanguinity rates, this population experienced a relatively high absolute increase in mortality among the offspring of first-cousin marriages (9%). Preliminary evidence is offered for the hypothesis that mortality differentials are larger in populations with low inbreeding and low mortality because nongenetic causes of death do not obscure the effects of consanguinity. (+info)
Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level.
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Some previous studies have reported an improved prognosis in sporadic colon cancers with microsatellite instability, whereas others have not. In addition, relatively few of those reporting an improved prognosis controlled for tumor stage or were population-based. Therefore, we evaluated the relationship between microsatellite instability and prognosis, tumor stage, and other clinical variables in a population-based study of 1026 individuals. Microsatellite instability was determined by the noncoding mononucleotide repeat BAT-26 and the coding mononucleotide repeat in transforming growth factor-beta receptor type II. Significant relationships were seen between microsatellite instability and proximal tumor location, female gender, young and old age at diagnosis, poor histological differentiation, and low tumor stage (P < 0.01). There was a significant relationship between microsatellite instability and improved prognosis, even after adjusting for stage, with a reduction in the risk of death attributable to colon cancer of approximately 60%. Most of this risk reduction occurred in individuals with American Joint Committee on Cancer stage III tumors, although transforming growth factor-beta receptor type II mutations were associated with a significant reduction in colon cancer death in tumors with distant metastases. We conclude that microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. (+info)
Comparison of two methods based on cross-sectional data for correcting corpus uterine cancer incidence and probabilities.
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BACKGROUND: Two methods are presented for obtaining hysterectomy prevalence corrected estimates of invasive cancer incidence rates and probabilities of the corpus uterine. METHODS: The first method involves cross-sectional hysterectomy data from the Utah Hospital Discharge Data Base and mortality data applied to life-table methods. The second involves hysterectomy prevalence estimates obtained directly from the Utah Behavior Risk Factor Surveillance System (BRFSS) survey. RESULTS: Hysterectomy prevalence estimates based on the first method are lower than those obtained from the second method through age 74, but higher in the remaining ages. Correction for hysterectomy prevalence is greatest among women ages 75-79. In this age group, the uncorrected rate is 125 (per 100,000) and the corrected rate based on the life-table method is 223 using 1995-97 data, 243 using 1992-94 data, and 228 from the survey method. The uncorrected lifetime probability of developing corpus uterine cancer is 2.6%; the corrected probability from the life-table method using 1995-97 data is 4.2%, using 1992-94 data is 4.5%; and based on prevalence data from the survey method is 4.6%. CONCLUSIONS: Both methods provide reasonable hysterectomy prevalence estimates for correcting corpus uterine cancer rates and probabilities. Because of declining trends in hysterectomy in recent decades, corrected estimates from the life-table method are less pronounced than those based on the survey method. These methods may be useful for obtaining corrected uterine cancer rates and probabilities in areas of the world that do not have sufficient years of hysterectomy data to directly compute prevalence. (+info)
Functional consequences of naturally occurring mutations in human uroporphyrinogen decarboxylase.
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Functional consequences of 12 mutations-10 missense, 1 splicing defect, and 1 frameshift mutation-were characterized in the uroporphyrinogen decarboxylase (URO-D) gene found in Utah pedigrees with familial porphyria cutanea tarda (F-PCT). All but one mutation altered a restriction site in the URO-D gene, permitting identification of affected relatives using a combination of polymerase chain reaction and restriction enzyme digestion. In a bacterial expression system, 3 of the missense mutants were found in inclusion bodies, but 7 were expressed as soluble proteins. Enzymatic activity of soluble, recombinant mutant URO-D genes ranged from 29% to 94% of normal. URO-D mRNA levels in Epstein-Barr-virus transformed cells derived from patients were normal (with the exception of the frameshift mutation) even though protein levels were lower than normal, suggesting that missense mutations generally cause unstable URO-Ds in vivo. The crystal structures of 3 mutant URO-Ds were solved, and the structural consequences of the mutations were defined. All missense mutations reported here and by others were mapped to the crystal structure of URO-D, and structural effects were predicted. These studies define structural and functional consequences of URO-D mutations occurring in patients with F-PCT. (+info)
Coccidioidomycosis in workers at an archeologic site--Dinosaur National Monument, Utah, June-July 2001.
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Coccidioidomycosis is a fungal infection caused by inhalation of airborne Coccidioides immitis spores that are present in the arid soil of the southwestern United States, California, and parts of Central and South America. Infection with C. immitis previously has not been diagnosed in patients outside these areas, except in travelers returning from areas where the disease is endemic. This report describes an outbreak of coccidioidomycosis in workers at an archeologic site in northeastern Utah during June-July, 2001, and represents the first identification of coccidioidomycosis in northern Utah. Health-care providers should consider coccidioidomycosis in the differential diagnosis for patients with compatible illness who reside in or recently have traveled to this area. Interventions to minimize soil disturbance and dust inhalation can reduce the risk for coccidioidomycosis. (+info)
Prevalence of aneuploidy and additional anatomic abnormalities in fetuses and neonates with cleft lip with or without cleft palate: a population-based study in Utah.
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OBJECTIVE: To determine the prevalence of aneuploidy and additional major anatomic abnormalities in fetuses and neonates with cleft lip with or without cleft palate. METHODS: All cases of cleft lip with or without cleft palate (cleft lip/cleft palate) occurring in Utah from 1995 through 1999 were reviewed by using the Utah Birth Defect Network population-based surveillance system. All pregnancy outcomes are included (stillborn, live born, and termination) in this analysis. RESULTS: Of 263 cases of cleft lip/cleft palate, 72 (27.4%) were unilateral cleft lip, 112 (42.6%) were unilateral cleft lip and cleft palate, 12 (4.6%) were bilateral cleft lip, and 67 (25.5%) were bilateral cleft lip and cleft palate. Fifteen (5.7%) of the 263 fetuses and neonates were aneuploid. One (1.2%) with cleft lip (unilateral and bilateral combined) was aneuploid. Five (4.5%) of the fetuses and neonates with unilateral cleft lip and cleft palate were aneuploid compared with 9 (13.4%) of fetuses and neonates with bilateral cleft lip and cleft palate. In known or presumed euploid fetuses and neonates, additional sonographically occult major anatomic abnormalities occurred in 5 (7.0%) of 71 with unilateral cleft lip, 18 (16.8%) of 107 with unilateral cleft lip and cleft palate, 1 (8.3%) of 12 with bilateral cleft lip, and 12 (20.7%) of 58 with bilateral cleft lip and cleft palate. These abnormalities primarily involved the heart and the central nervous system. CONCLUSIONS: Amniocentesis for karyotype should be offered in all cases of cleft lip/cleft palate because of the risk of aneuploidy. Patients should be counseled that sonographically occult additional anatomic abnormalities might be present with all clefts. (+info)
Hypothermia-related deaths--Utah, 2000, and United States, 1979-1-998.
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Hypothermia is a medical emergency that is completely preventable. Hypothermia occurs when persons are exposed to ambient cold temperatures without appropriate protection for extended periods of time. The clinical definition of hypothermia is a core body temperature < or = 95 F (35 C). This report describes cases of hypothermia-related deaths in Utah during 2000 and describes unintentional hypothermia-related deaths in the United States during 1979-1998. The Utah cases illustrate risk factors and environmental conditions associated with hypothermia. (+info)