Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “multiple exposures”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources
PubMed2005

Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy.

Among the diverse experimental vaccines evaluated in various animal lentivirus models, live attenuated vaccines have proven to be the most effective, thus providing an important model for examining critical immune correlates of protective vaccine immunity. We previously reported that an experimental live attenuated vaccine for equine infectious anemia virus (EIAV), based on mutation of the viral S2 accessory gene, elicited protection from detectable infection by virulent virus challenge (F. Li et al., J. Virol. 77:7244-7253, 2003). To better understand the critical components of EIAV vaccine efficacy, we examine here the relationship between the extent of virus attenuation, the maturation of host immune responses, and vaccine efficacy in a comparative study of three related attenuated EIAV proviral vaccine strains: the previously described EIAV(UK)DeltaS2 derived from a virulent proviral clone, EIAV(UK)DeltaS2/DU containing a second gene mutation in the virulent proviral clone, and EIAV(PR)DeltaS2 derived from a reference avirulent proviral clone. Inoculations of parallel groups of eight horses resulted in relatively low levels of viral replication (average of 10(2) to 10(3) RNA copies/ml) and a similar maturation of EIAV envelope-specific antibody responses as determined in quantitative and qualitative serological assays. However, experimental challenge of the experimentally immunized horses by our standard virulent EIAV(PV) strain by using a low-dose multiple exposure protocol (three inoculations with 10 median horse infective doses, administered intravenously) revealed a marked difference in the protective efficacy of the various attenuated proviral vaccine strains that was evidently associated with the extent of vaccine virus attenuation, time of viral challenge, and the apparent maturation of virus-specific immunity.

Animals↗
PubMed1976

Unexplained hepatitis following halothane.

Full clinical and laboratory details of 203 patients with postoperative jaundice were submitted to a panel of hepatologists. All patients whose jaundice may have had an identifiable cause were excluded, which left 76 patients with unexplained hepatitis following halothane anaesthesia (UHFH). Hepatitis in 95% of these cases followed multiple exposure to halothane, with repeated exposure within four weeks in 55% of cases. Twenty-nine patients were obese, 52 were aged 41-70, and 53 were women. Thirteen patients died in acute hepatic failure. Rapid onset of jaundice after anaesthesia, male sex, and obesity in either sex were poor prognostic signs. Of the clinical stigmata of hypersensitivity, only eosinophilia was impressive. The UHFH group had a much greater incidence of liver kidney microsomal (LKM) and thyroid antibodies and autoimmune complement fixation than those patients whose jaundice related to identifiable factors. Thirteen of the 19 patients with LKM antibodies also had thyroid antibodies. In six patients retested two to three years later LKM antibodies had disappeared, although thyroid antibodies persisted. Rapidly repeated exposure to halothane may cause hepatitis, but such a complication is probably rare. Possibly obese women with a tendency to organ-specific autoimmunity may be more at risk. Nevertheless, the comparative risks of rapidly repeated halothane or non-halothane anaesthesia cannot be determined from the present data. If alternative satisfactory agents are available halothane should be avoided in patients with unexplained hepatitis after previous exposure, although in three to five patients with UHFH who were re-exposed to halothane jaundice did not recur.

Adolescent↗
PubMed1984

The metabolism of insecticides: the role of monooxygenase enzymes.

In summary, it can be said that advances have been made in understanding the range and significance of monooxygenase reactions involving insecticides in both target and non-target species and that some specific aspects emerge that should command the attention of insecticide toxicologists and others in the immediate future. The role of co-oxidation of insecticides during prostaglandin synthesis has just emerged as an issue but, if we can extrapolate from other xenobiotics (126), we can predict with some confidence that it will assume major proportions. It is also apparent that both activation and detoxication reactions are catalyzed by the FAD-containing monooxygenase and that many of these reactions were formerly attributed to the cytochrome P-450-dependent monooxygenase system. Since any particular substrate may be oxidized by either or both of these two routes, it is essential that studies be conducted to define their relative contributions to xenobiotic oxidation in microsomal preparations and ultimately in vivo. The area of interactions and the mechanisms behind them is also of importance, from the public health point of view in the case of multiple exposures, and from the practical viewpoint in the case of insecticide synergists. While the above aspects are not the only ones of future importance, they should contribute to the ultimate goal of insecticide toxicology: practical, safe use of chemicals for the control of insect pests.

Amines↗
PubMed1975

Elbow Arthrography with the Application of Tomography.

The intra-articular structure of the elbow joint was studied in 18 patients with double contrast arthrography and tomography. All tomographic examinations were made with the hypocycloid motion. The authors feel that the disadvantages of the method, i.e., getting access to tomographic equipment, the 30 to 45 minutes required to complete the examination, and the radiation from multiple exposures needed for tomographic sections are obviated by the results: the arthrographic findings were confirmed in all 7 patients who later underwent surgery.

Adolescent↗
PubMed2000

Stretch-activated ion channels contribute to membrane depolarization after eccentric contractions.

We tested the hypothesis that eccentric contractions activate mechanosensitive or stretch-activated ion channels (SAC) in skeletal muscles, producing increased cation conductance. Resting membrane potentials and contractile function were measured in rat tibialis anterior muscles after single or multiple exposures to a series of eccentric contractions. Each exposure produced a significant and prolonged (>24 h) membrane depolarization in exercised muscle fibers. The magnitude and duration of the depolarization were related to the number of contractions. Membrane depolarization was due primarily to an increase in Na(+) influx, because the estimated Na(+)-to-K(+) permeability ratio was increased in exercised muscles and resting membrane potentials could be partially repolarized by substituting an impermeant cation for extracellular Na(+) concentration. Neither the Na(+)/H(+) antiport inhibitor amiloride nor the fast Na(+) channel blocker TTX had a significant effect on the depolarization. In contrast, addition of either of two nonselective SAC inhibitors, streptomycin or Gd(3+), produced significant membrane repolarization. The results suggest that muscle fibers experience prolonged depolarization after eccentric contractions due, principally, to the activation of Na(+)-selective SAC.

Amiloride↗
PubMed2003

Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity.

Reflexes arising from the carotid bodies may play an important role in cardiorespiratory changes evoked by chronic intermittent hypoxia (CIH). In the present study, we examined whether CIH affects the hypoxic sensing ability of the carotid bodies and, if so, by what mechanisms. Experiments were performed on adult male rats (Sprague-Dawley, 250-300 g) exposed to two paradigms of CIH for 10 days: 1) multiple exposures to short durations of intermittent hypoxia per day (SDIH; 15 s of 5% O(2) + 5 min of 21% O(2), 9 episodes/h, 8 h/day) and 2) single exposure to longer durations of intermittent hypoxia per day [LDIH; 4 h of hypobaric hypoxia (0.4 atm/day) + 20 h of normoxia]. Carotid body sensory response to graded isocapnic hypoxia was examined in both groups of animals under anesthetized conditions. Hypoxic sensory response was significantly enhanced in SDIH but not in LDIH animals. Similar enhancement in hypoxic sensory response was also elicited in ex vivo carotid bodies from SDIH animals, suggesting that the effects were not secondary to cardiovascular changes. SDIH, however, had no significant effect on the hypercapnic sensory response. The effects of SDIH on the hypoxic sensory response completely reversed after SDIH animals were placed in a normoxic environment for an additional 10 days. Previous treatment with systemic administration of O(2)(-)* radical scavenger prevented SDIH-induced augmentation of the hypoxic sensory response. These results demonstrate that SDIH but not LDIH results in selective augmentation of the hypoxic response of the carotid body and O(2)(-)* radicals play an important role in SDIH-induced sensitization of the carotid body.

Animals↗
PubMed2005

Intraindividual variability in arsenic methylation in a U.S. population.

Several recent investigations have reported associations between a reduced capacity to fully methylate inorganic arsenic and increased susceptibility to arsenic-caused cancer. In these studies, methylation patterns were based on a single assessment of urinary arsenic metabolites collected at the time of cancer diagnosis. However, the latency of arsenic-caused cancer may be several decades, and the extent to which a recent measurement can be used to estimate a person's past methylation pattern is unknown. In this investigation, the distribution of urinary inorganic arsenic, monomethylarsonate, and dimethylarsinate was used to assess intraindividual variation in methylation capacity in 81 subjects with low to moderate arsenic exposures. Multiple urine samples were collected from each subject over a 1-year period. Duplicate analyses done on 27 samples were used to assess laboratory measurement imprecision. The intraclass correlation coefficients (ICC) for the proportion of urinary arsenic as inorganic arsenic, monomethylarsonate, and dimethylarsinate in samples taken an average of 258 days apart, were 0.45 [95% confidence interval (95% CI), 0.23-0.63] 0.46 (95% CI, 0.24-0.64), and 0.49 (95% CI, 0.28-0.66). In analyses of duplicate samples, ICCs for the concentration of arsenic species ranged from 0.87 to 0.93, whereas ICCs for species proportions ranged from 0.63 to 0.76. These data suggest that individual methylation patterns remain fairly stable over time, although variability due to measurement imprecision or intraindividual changes over time does occur. This variability could lead to misclassification of methylation patterns and could bias relative risk estimates in studies of methylation and cancer towards the null.

Aged↗
PubMed2005

Polymorphisms of the dopamine receptor gene DRD2 and colorectal cancer risk.

Sporadic colorectal cancer is considered a multifactorial disease in which multiple exposures interact with the individual genetic background resulting in risk modulation. Recent experimental data suggest a role of dopamine and dopamine receptors in the control of proliferation of the cells of colon and gastrointestinal tract. To investigate whether polymorphisms within dopamine receptors genes could have a role in modulating the risk of sporadic colorectal cancer, we did a case-control association study and genotyped 370 cases and 327 controls for seven single-nucleotide polymorphisms (SNP) of DRD2 (-141Cdel, 957T>C, TaqIB, TaqIA, 1412A>G, S311C, and 3208G>T) by a microarray-based technique. Three SNPs within DRD2 were associated with colorectal cancer, with a maximum odds ratio of 2.28 (95% confidence interval, 1.38-3.76) for carriers of the functional SNP -141Cdel. The haplotype which includes -141Cdel, together with the variants 957C and 1412G, shows an odds ratio of 2.86 (95% confidence interval, 1.58-5.18), as compared with the most frequent haplotype. The SNPs within DRD2 associated with colorectal cancer are known to be related to reduced levels of D2 dopamine receptor. Thus, our data point to a possible role of dopamine receptor DRD2 in modulating the risk of colorectal cancer. Future studies on dopamine receptor-mediated signal transduction may provide new insight into the mechanisms of colorectal cancer and suggest new therapeutic strategies.

Adult↗
PubMed2001

Does higher concordance in monozygotic twins than in dizygotic twins suggest a genetic component?

It is widely regarded that twins can be used as a natural experiment to subject hypotheses to empirical testing regarding the contributions of genetic factors to phenotypic variability in human traits, especially behavioral traits. In genetic epidemiology, a higher concordance rate in monozygotic (MZ) twins than in dizygotic (DZ) twins is often taken as prima facie evidence for a genetic component. While twins studies have been used to estimate the contributions of genetic factors to phenotypic variability in human traits, the corresponding methodology that allows the estimation entails several crucial assumptions. The most critical is that MZ and DZ twins are equally similar environmentally. Although MZ twins are genetically more similar than DZ twins, they are often environmentally more similar. This paper demonstrates that, even in the complete absence of any genetic factor and of any biases, the greater environmental similarity alone in MZ twins can result in higher concordance rate in MZ twins than in DZ twins. This is especially true when there are multiple environmental factors, which may have multiple exposure levels and/or interact strongly, although each of them may be of low risk. This may serve as a sobering antidote to the uncritical reliance on twin studies without examining the validity of the underlying assumptions.

Environment↗
PubMed1996

Evaluation of the long-term safety and efficacy of 311C90 in the treatment of migraine.

311C90 is an orally active 5-HT1D agonist with both central and peripheral actions that is currently being developed as an acute antimigraine treatment. Several studies have demonstrated the safety and efficacy of 311C90 in the treatment of a single migraine headache. The objectives of this open study are to assess the safety and efficacy of 311C90 when used for a period of up to one year. Patients can treat as many migraine headaches as desired with an oral treatment regimen of 311C90. An initial 5 mg dose for treatment of the migraine headache may be followed with a second 5 mg dose to treat recurrence should it develop. Safety assessments include electrocardiograms, the frequency, intensity and duration of adverse experiences, and routine haematology, urinalysis and clinical chemistry measures. Data presented here are an interim view of the database as of August 1995 and should be considered as preliminary observations. No clinically significant serious adverse experiences have been reported. The adverse experience and efficacy profile appears to be consistent with previous 311C90 studies and this dosing regimen of 311C90 was well tolerated during multiple exposures. Notably, response rates are as good after both initial and repeated exposure (up to 5 migraines).

Acute Disease↗
PubMed1995

Influence on lenticular glutathione research.

Otto Hockwin influenced the early research career in ophthalmic biochemistry of William Rathbun in several ways. These included multiple exposures via symposia to the European research community, providing editorial experience and encouragement to expand fundamental glutathione enzyme research to the problems of aging, species variation and anti-cataract drug development.

Aging↗
PubMed1980

Surgical approaches in fetal radiography and the study of skeletal age in Macaca mulatta.

The fetal surgery and fetal radiography utilized in longitudinal radiographic study of bone maturation in Macaca mulatta and their implications for fetal surgery are discussed. The novel technique of serial uterotomies and multiple exposure of the same fetus (two-week intervals) starting on 120 days of gestation as well as anesthesia and surgical procedures are presented.

Abortion, Veterinary↗
PubMed2005

Occupational asthma.

Substantial epidemiologic and clinical evidence indicates that agents inhaled at work can induce asthma. In industrialized countries, occupational factors have been implicated in 9 to 15% of all cases of adult asthma. Work-related asthma includes (1) immunologic occupational asthma (OA), characterized by a latency period before the onset of symptoms; (2) nonimmunologic OA, which occurs after single or multiple exposures to high concentrations of irritant materials; (3) work-aggravated asthma, which is preexisting or concurrent asthma exacerbated by workplace exposures; and (4) variant syndromes. Assessment of the work environment has improved, making it possible to measure concentrations of several high- and low-molecular-weight agents in the workplace. The identification of host factors, polymorphisms, and candidate genes associated with OA is in progress and may improve our understanding of mechanisms involved in OA. A reliable diagnosis of OA should be confirmed by objective testing early after its onset. Removal of the worker from exposure to the causal agent and treatment with inhaled glucocorticoids lead to a better outcome. Finally, strategies for preventing OA should be implemented and their cost-effectiveness examined.

Adult↗
PubMed1985

Colonization of the human oral cavity by a strain of Streptococcus mutans.

Streptococcus mutans strain JH1001 produces a bacteriocin that can kill virtually all other strains of this micro-organism. The ability of JH1001 to colonize the human oral cavity was tested in a study involving five subjects and three different infection regimens, all of which involved multiple exposures to large numbers of organisms. Two and one-half years after infection, JH1001 was found to have persistently colonized three of the subjects. The indigenous S. mutans in one subject were reduced below the level of detection. Levels of (total) S. mutans and S. sanguis were not affected in persistently colonized subjects. Mutants of indigenous S. mutans resistant to the bacteriocin were not observed. The results indicate the importance of host variability and infection regimen for superinfection by this strain of S. mutans. The efficient replacement of indigenous S. mutans by JH1001 in one subject lends support to the eventual application of replacement therapy to the prevention of dental caries.

Bacteriocins↗
PubMed1987

Colonization of the human oral cavity by a Streptococcus mutans mutant producing increased bacteriocin.

Streptococcus mutans strain JH1005 is a mutant that produces levels of bacteriocin activity three-fold-elevated than those produced by its parent, JH1001. A single infection regimen with JH1005 was found to result in persistent colonization of the teeth of all three adult subjects tested. This is a significant improvement over JH1001, which required multiple exposures in order to colonize the teeth of humans reliably. The levels of total cultivable bacteria and indigenous S. sanguis were not affected by JH1005 colonization. In two of the three subjects, total (indigenous plus JH1005) S. mutans levels were significantly decreased. The results provide additional support for the role of bacteriocin production as an ecological determinant in colonization by S. mutans. They also indicate that a practical regimen for infection by an effector strain might be achieved for use in the replacement therapy of dental caries.

Adult↗
PubMed1992

Assessment of the effects of dentifrices on plaque acidogenesis via intra-oral measurement of plaque acids.

Dionex ion chromatography was used for identification and quantification of the plaque acids (formate, lactate, acetate, and propionate) formed in vivo following a sucrose rinse. Consistent with other literature reports, lactate and acetate were the predominant acid species generated by plaque. This micro-analytical technique was used for investigation of the effects of dentifrice formulations containing NaF, xylitol, or NaF/xylitol on plaque acid metabolism. Neither a single nor multiple exposures (three times daily for one week) to the experimental dentifrices significantly altered the profiles of the individual acids or total plaque acidity relative to the placebo dentifrice. The lack of an effect of fluoride and xylitol on plaque acid metabolism is attributed to the variability of dental plaque and the low concentrations of active ingredients reaching the plaque. However, we believe that, with further improvement in sampling technique and study design, this approach may prove useful for the study of the effects of active ingredients (i.e., anticaries agents) on plaque acidogenesis.

Acetates↗
PubMed2001

Stability of nitroblue tetrazolium-based alkaline phosphatase substrates.

This report demonstrates the stability of NBT substrate after multiple exposures to alkaline phosphatase. Perhaps more important than the ability to reuse substrates, the report provides some insight into the mechanisms by which tetrazoliums are reduced and evidence for the formation of an intermediary product, i.e., a half-formazan that is reduced more rapidly. (J Histochem Cytochem 49:1189-1190, 2001)

Alkaline Phosphatase↗
PubMed1989

Four cases of progressive supranuclear palsy in patients exposed to organic solvents.

Four cases are described in which Progressive Supranuclear Palsy (PSP) is associated with the use of organic solvents. Two of them are a housewife and an exbanker who had multiple exposure to insecticides (with organic solvent base), followed years later with a diagnosis of PSP. The other two are of lithographers, both of whom worked at the same industrial firm where solvent exposure took place with subsequent development of PSP. The hypothesis that PSP is linked to an environmental toxin is supported by these cases.

Aged↗