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 541 records · Page 30Linked to original sources
PubMed1996

Contribution of passive immunity to porcine respiratory coronavirus to protection against transmissible gastroenteritis virus challenge exposure in suckling pigs.

OBJECTIVE: To determine the ability of porcine respiratory coronavirus (PRCV) infections to induce passive immunity in suckling pigs to transmissible gastroenteritis virus (TGEV) challenge exposure. DESIGN AND ANIMALS: 4 TGEV seronegative sows and their litters (group A) served as controls, whereas 2 other groups (B and C) of sows (also TGEV seronegative) were oronasally inoculated with live PRCV during 1 or 2 subsequent pregnancies, respectively. PROCEDURE: Effectiveness of passive immunity provided to pigs via colostrum and milk was assessed after TGEV challenge exposure, and TGEV antibody responses in colostrum and milk were analyzed. RESULTS: Mortality in the 3 groups of young pigs correlated with severity of clinical signs of TGEV infection and was highest in control litters (86% in group-A pigs) and lowest in litters of sows inoculated with PRCV in 2 subsequent pregnancies (14% in group-C pigs). Virus-neutralization and IgA and IgG TGEV antibody titers of milk collected from sows at challenge exposure had significant positive correlation with litter survival. Significantly higher numbers of TGEV-specific IgA and IgG antibody-secreting cells were found in group-A pigs than in group-C pigs, suggesting that high titer of maternal antibodies (induced in group-C sows multiply exposed to PRCV) may interfere with active antibody responses. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that, in PRCV-infected pig herds, multiple exposures of pregnant sows are associated with higher IgA and IgG antibody titers to TGEV in milk, and these titers contribute to protection against TGEV infection.

Animals↗
PubMed1987

Intraoperative carotid arteriography. A comparison of two techniques.

Routine intraoperative completion carotid arteriography was performed in 225 patients from January 1980 to December 1985 to detect technical problems. In the first 100 patients, standard common carotid artery puncture was used. In the last 125 patients, catheter technique through the superior thyroid artery was compared with the needle technique to evaluate quality of images, completeness of the study, number of exposures required, and complications from these two techniques. The needle technique resulted in complete visualization of the extracranial and intracranial circulations in 94 patients (94 percent). The catheter technique was similarly successful in 123 of 125 patients (98 percent). The proportions of complete visualization were not statistically different in the two groups (p = 0.16). Six patients (6 percent) in the needle technique group and three patients (2 percent) in the catheter technique group required multiple exposures. When the complications incurred by the two techniques were compared, there was no statistical difference between the two techniques (p = 0.39). Two complications occurred in the needle technique group (2 percent), one resulting in dissection and the other, extravasation. There were no complications in the catheter technique group. Due to technical ease of performance, the catheter technique is preferred, although statistical data did not reveal superiority of one technique over the other.

Carotid Arteries↗
PubMed1990

Pulmonary bombesin and calcitonin in hamsters during exposure to hyperoxia and diethylnitrosamine.

Combined exposure of hamsters to 60% hyperoxia and the carcinogen diethylnitrosamine for 6 wk resulted in the development of lung tumors. This was associated with progressive loss of body weight as well as increases in the pulmonary-associated peptides, mammalian bombesin (MB) and immunoreactive calcitonin (iCT). After 3 wk of exposure, multiple bronchial epithelial hyperplastic foci were noted, along with increased lung levels of MB and iCT as well as increased serum levels of MB. At this time, immunocytochemistry revealed the presence of MB and iCT within hyperplastic pulmonary neuroendocrine (PNE) cells. In addition, the localization of MB to alveolar type II cells was noted, along with the presence of lamellar bodies and secretion granules in these cells on electron microscopy. After 6 wk of exposure, distinctive microscopic pulmonary tumorlets were seen. These tumorlets were associated with a marked increase in lung and serum MB, and to a lesser extent lung and serum iCT. At this time, MB and iCT were localized exclusively to these abnormal PNE cell sites. These results, which may have relevance in humans, suggest that endogenous peptides may be important components in the process of development of neuroendocrine cancer.

Animals↗
PubMed2000

Environmental influence on reproductive health.

A rise in industrialization and the consequent environmental pollution, an increase in the use of synthetic chemicals and repeated exposure to hazardous compounds at the workplace and at home adversely affects reproductive health. Biohazardous compounds, some of which act as endocrine disrupters, are being increasingly implicated in infertility, menstrual irregularities, spontaneous abortions, birth defects, endometriosis and breast cancer. In some cases, women are at a greater risk than men, especially with the rise in environmental estrogens. Only a fraction of these chemicals have been adequately examined for toxicity and for synergistic effects due to multiple exposures. There is a need for a greater awareness and vigilance of the effects of environmental pollution on reproductive health.

Abortion, Spontaneous↗
PubMed1997

Pathophysiology of premature skin aging induced by ultraviolet light.

BACKGROUND: Long-term exposure to ultraviolet irradiation from sunlight causes premature skin aging (photoaging), characterized in part by wrinkles, altered pigmentation, and loss of skin tone. Photoaged skin displays prominent alterations in the collagenous extracellular matrix of connective tissue. We investigated the role of matrix-degrading metalloproteinases, a family of proteolytic enzymes, as mediators of collagen damage in photoaging. METHODS: We studied 59 whites (33 men and 26 women, ranging in age from 21 to 58 years) with light-to-moderate skin pigmentation, none of whom had current or prior skin disease. Only some of the participants were included in each of the studies. We irradiated their buttock skin with fluorescent ultraviolet lights under standard conditions and obtained skin samples from irradiated and nonirradiated areas by keratome or punch biopsy. In some studies, tretinoin and its vehicle were applied to skin under occlusion 48 hours before ultraviolet irradiation. The expression of matrix metalloproteinases was determined by in situ hybridization, immunohistology, and in situ zymography. Irradiation-induced degradation of skin collagen was measured by radioimmunoassay of soluble cross-linked telopeptides. The protein level of tissue inhibitor of matrix metalloproteinases type 1 was determined by Western blot analysis. RESULTS: A single exposure to ultraviolet irradiation increased the expression of three matrix metalloproteinases -- collagenase, a 92-kd gelatinase, and stromelysin -- in skin connective tissue and outer skin layers, as compared with nonirradiated skin. The degradation of endogenous type I collagen fibrils was increased by 58 percent in irradiated skin, as compared with nonirradiated skin. Collagenase and gelatinase activity remained maximally elevated (4.4 and 2.3 times, respectively) for seven days with four exposures to ultraviolet irradiation, delivered at two-day intervals, as compared with base-line levels. Pretreatment of skin with tretinoin (all-trans-retinoic acid) inhibited the induction of matrix metalloproteinase proteins and activity (by 70 to 80 percent) in both connective tissue and outer layers of irradiated skin. Ultraviolet irradiation also induced tissue inhibitor of matrix metalloproteinases-1, which regulates the enzyme. Induction of the inhibitor was not affected by tretinoin. CONCLUSIONS: Multiple exposures to ultraviolet irradiation lead to sustained elevations of matrix metalloproteinases that degrade skin collagen and may contribute to photoaging. Treatment with topical tretinoin inhibits irradiation-induced matrix metalloproteinases but not their endogenous inhibitor.

Administration, Cutaneous↗
PubMed2001

Pharmacological determinants of 9-aminocamptothecin cytotoxicity.

The camptothecins are a group of anticancer agents with a unique mechanism of action: poisoning of eukaryotic DNA topoisomerase I. 9-aminocamptothecin (9-AC), a potent water-insoluble derivative of camptothecin, is currently undergoing clinical testing. The kinetics of the active derivative 9-AC lactone in cell culture media was defined, and then 9-AC cytotoxicity against human breast (MCF-7), bladder (MGH-U1), and colon (HT-29) cancer cell lines was studied. The relationship between cytotoxic effects, drug concentration, and exposure time was then explored. For all of the three cell lines, 9-AC cytotoxicity increased with both higher drug concentrations and longer exposure times. However, when the duration of exposure was less than 24 h, cytotoxicity was limited and less than 1 log of cell killing occurred, even with very high drug concentrations. Minimal cell killing was also observed unless 9-AC concentrations exceeded a threshold of 2.7 nM. No fixed relationship between the survival fraction and the area under the drug concentration-time curve could be modeled that would fit all of the three cell lines. However, data for the three cell lines from the multiple exposure time experiments were fitted very well to the pharmacodynamic model C(n)t = k (r2, 0.90-0.99), where C is the drug concentration, n is the drug concentration coefficient, and t is the exposure time. For the three cell lines, to kill 1 log of cells, 0.30 < n < 0.85, which indicated that duration of exposure was more important than concentration. Our data support the use of 9-AC by infusion for 24 h or longer in clinical studies providing target plasma concentrations can be achieved.

Antineoplastic Agents↗
PubMed1983

Alterations of human endometrial stromal cells produced by N-methyl-N'-nitro-N-nitrosoguanidine.

Stromal cell cultures obtained from human endometrium were treated repetitively with N-methyl-N'-nitro-N-nitrosoguanidine in vitro at concentrations ranging from 0.5 to 4.0 micrograms/ml, and alterations in growth potential and morphology were analyzed. A single exposure to the carcinogen resulted in morphological evidence of toxicity and reductions in growth rates, plating efficiency, and saturation density as compared to solvent-treated control cells. Cytotoxicity was reduced after additional exposures to the carcinogen. Following repetitive treatments with N-methyl-N'-nitro-N-nitrosoguanidine, human endometrial stromal cells developed enhanced growth potential, the capacity to form macroscopic colonies in soft agar, and elevated gamma-glutamyltranspeptidase activity. Carcinogen-treated cells displayed atypical morphology characterized by irregularities in cell and nuclear size and shape, large bizarre nucleoli, increased nuclear:cytoplasmic ratios, and cellular crowding. Control cells did not display altered morphology or growth parameters even following multiple exposures to solvent and repetitive subculturing. These alterations in growth potential and morphology suggest that the cells are progressing towards preneoplastic and perhaps neoplastic transformation in vitro.

Agar↗
PubMed2005

Impact of childhood traumatic events, trauma-related guilt, and avoidant coping strategies on PTSD symptoms in female survivors of domestic violence.

This investigation utilized path analyses to examine the direct and indirect effects of experiences of potentially traumatic events in childhood, trauma-related guilt, and the use of avoidant coping strategies on level of PTSD symptomatology among a sample of female survivors of domestic violence. The results of this investigation indicated that individuals with more extensive histories of potentially traumatic events in childhood were more likely to report the experience of trauma-related guilt after exposure to domestic violence victimization in adulthood. Further, the path model indicated that experiencing trauma-related guilt was associated with greater use of avoidant coping strategies. Trauma-related guilt was related to increased PTSD symptomatology both directly and indirectly through the use of avoidant coping strategies. These findings highlight the importance of attending to guilt-based affective and cognitive reactions, maladaptive coping strategies, and the association between these constructs when treating survivors of relationship violence with multiple exposures to potentially traumatic events.

Adaptation, Psychological↗
PubMed2000

Acute toxicity to rats and trout with a focus on inhalation and aquatic exposures.

Due to limitations in toxicity data, extrapolations are often performed within and between species. In this context, median lethal concentration (LC(50)) and dose (LD(50)) for 231 chemicals, along with physicochemical factors, were log-transformed and compared across several exposure routes in rats (i.e., oral, dermal, intraperitoneal, inhalation, intravenous, subcutaneous) and rainbow trout (i.e., aquatic, oral, dermal, intraperitoneal). Molecular weight (MW), octanol-water partition coefficient (K(ow)), vapor pressure (VP), and water solubility (S) were intercorrelated (Bonferroni P<0.05). MW (7 of 10 cases) and K(ow) (3 of 10 cases) were inversely correlated to toxicity endpoints, whereas VP (5 of 10 cases) was positively correlated (Bonferroni P< 0.05). Interspecies correlations were observed in toxicity endpoints over multiple exposure routes (10 of 24 cases), in addition to intraspecies correlations within rat (13 of 15 cases) and within trout (3 of 5 cases) (Bonferroni P<0.05). It was hypothesized that rat inhalation LC(50) and trout LC(50) would be associated, since air and water exposures correspond to each organism's respiratory medium. This hypothesis was supported by their correlation (r=0.68, Bonferroni P<0.05), characterized by a median molar ratio near 1, and further analyzed via regression methods. Comparison of acute toxicity endpoints can, therefore, assist in identifying appropriate extrapolations, likely based on similar toxicokinetics.

Administration, Inhalation↗
PubMed1976

An assessment of investigations conducted in the USA on Brucella abortus strain 45/20 bacterins.

The results of five investigations in cattle using 45/20 Bacterins are presented and evaluated. Seemingly contradictory results may be the result of one or more modifications in project design or in procedures. In these trials, there appeared to be no significant difference in the level of protection for cattle when using either intramuscular or subcutaneous routes of injection or when 10 or 12 week intervals between doses were used in cattle 6 months of age or older. Also, the relative resistance to subsequent exposure was not significantly different in which only 45/20 Bacterins were administered. There were apparent differences in protection between cattle receiving one versus two doses of 45/20 Bacterin or initially vaccinated with 45/20 Bacterin at 3 months of age and again 15 weeks later compared to older age groups vaccinated at 10 or 12 week intervals between doses. The disproportionate infection rate among 45/20 vaccinated animals in the last completed investigation suggests that cattle in infected herds subjected to multiple exposures to virulent organisms do not develop adequate resistance. Local and systemic reactions following the administration of 45/20 Bacterin were also noted in some groups.

Animals↗
PubMed2000

Radiation injury from x-ray exposure during brachytherapy localization.

Two patients developed skin ulcers secondary to high doses of diagnostic-energy x rays received during localization procedures as part of brachytherapy treatments. Both were morbidly obese and diabetic. The obesity led to the delivery of estimated skin doses of 83 Gy in one case and 29 Gy in the other in attempts to produce readable images on localization radiographs. This report discusses the factors leading to the injuries, the progression of the injuries over time, and the variables involved in the localization procedures with the aim of preventing future mishaps. The greatest contribution to the large skin dose was the need, with the equipment available, to use multiple exposures to produce a single film, because of the effect of the resultant reciprocity failure.

Brachytherapy↗
PubMed2003

The effects of storage conditions on viability of Clostridium difficile vegetative cells and spores and toxin activity in human faeces.

AIMS: Clostridium difficile is a common nosocomial pathogen and as such diagnostic and research methods may necessitate storage of faecal specimens for long periods, followed by subsequent re-examination. This study investigated the effects of storage conditions upon the viability of this organism and its toxin. METHODS: Three genotypically distinct strains of C difficile (two clinical isolates including the UK epidemic strain, and an environmental isolate) were grown anaerobically at 37 degrees C for 72 hours in a pool of five faecal emulsions. Aliquots of each emulsion were stored at either -20 degrees C (frozen) or 4 degrees C (refrigerated). Emulsions were assayed for viable cells, spores, and cytotoxin titre before storage and at days 1, 3, 5, 7, 14, 28, and 56. An aliquot of each emulsion was also removed, assayed, and replaced in storage at each time point to investigate the effects of multiple freezing/refrigeration/thawing. RESULTS: Neither storage temperature nor multiple cycles of refrigeration/freezing and thawing adversely affected the viability of C difficile vegetative cells or spores. Single and multiple exposures of samples to 4 degrees C had little effect upon the C difficile toxin titre. Toxin titres of multiply frozen and thawed faeces became significantly lower than for refrigerated faeces (p < 0.01) by day 5 of the experiment in two of the three strains, and in all strains by day 28. Toxin titres of singly frozen faeces became significantly lower than for refrigerated faeces (p < 0.01) by day 56 of the experiment in two of the three strains. CONCLUSION: Storage temperature and multiple cycles of freezing (refrigeration)/thawing had minimal effects upon the viability of C difficile or its spores. Storage at 4 degrees C has no discernible effect on C difficile cytotoxin. However, storage at -20 degrees C has a detrimental effect upon C difficile cytotoxin, and multiple cycles of freezing and thawing may further adversely effect toxin titres.

Aged↗
PubMed2002

Phase shift of coupled oscillator model with feedbacks in response to multiple bright light exposure.

Human temperature rhythm was reported to have type 0 phase response curve (PRC) to multiple bright light exposure; however, mechanisms underlying this finding could not be clarified easily in a theoretical framework, and has not yet been confirmed by other researchers. In this paper, under reproduced photic exposure, phase response properties of a coupled three oscillator model were investigated to identify the possible mechanism underlying the experimental finding. The resulting phase shift of an oscillator reached approximately 12 h, and changed its sign acutely at the cross-over point of an original PRC of the oscillator. This type 0-like phase shift was produced by an accumulated phase response during the oscillator's re-entrainment process to the photic exposure. The organization of coupled oscillators affected the total amount of this phase shift.

Body Temperature↗
PubMed2005

Proximity to pollution sources and risk of amphibian limb malformation.

The cause of limb deformities in wild amphibian populations remains unclear, even though the apparent increase in prevalence of this condition may have implications for human health. Few studies have simultaneously assessed the effect of multiple exposures on the risk of limb deformities. In a cross-sectional survey of 5,264 hylid and ranid metamorphs in 42 Vermont wetlands, we assessed independent risk factors for nontraumatic limb malformation. The rate of nontraumatic limb malformation varied by location from 0 to 10.2%. Analysis of a subsample did not demonstrate any evidence of infection with the parasite Ribeiroia. We used geographic information system (GIS) land-use/land-cover data to validate field observations of land use in the proximity of study wetlands. In a multiple logistic regression model that included land use as well as developmental stage, genus, and water-quality measures, proximity to agricultural land use was associated with an increased risk of limb malformation (odds ratio = 2.26; 95% confidence interval, 1.42-3.58; p < 0.001). The overall discriminant power of the statistical model was high (C = 0.79). These findings from one of the largest systematic surveys to date provide support for the role of chemical toxicants in the development of amphibian limb malformation and demonstrate the value of an epidemiologic approach to this problem.

Agriculture↗
PubMed1994

Alteration of G protein levels in antigen-challenged guinea pigs.

To elucidate the mechanism(s) of altered responses of various receptors observed in asthma, we examined levels of G proteins in lung membranes isolated from guinea pigs at various stages of experimental asthma. We found that levels of Gi2 alpha and Gq alpha increase after multiple exposures to aerosolized antigen but not after a single exposure. Levels of Gi1 alpha, Gs alpha and G beta did not change under these experimental conditions. Tracheas from these animals exhibited hyperresponsive muscarinic bronchoconstriction and hyporesponsive beta adrenoceptor-mediated relaxation of endothelin-preconstricted tracheas as measured by an ex vivo isometric assay. No changes in numbers or affinities of membrane M3 muscarinic and beta-2 adrenergic receptors were detected as measured by binding of [3H]QNB and [125I]CYP, respectively. The impairment of beta adrenoceptor-mediated relaxation of tracheas isolated from animals treated by multiple challenges was reversed by the pretreatment of tracheas with pertussis toxin. On the other hand, the carbamylcholine-stimulated GTPase activity was higher in lung membranes isolated from animals in the multiple challenge group and was blocked by anti-Gq alpha protein antibody. Taken together, our present observations suggest that an underlying mechanism of altered receptor responses associated with asthma is in part due to increased expression of Gi2 alpha and Gq alpha proteins, leading to altered coupling of receptors to effector systems.

Acetylcholine↗
PubMed1993

Retrovirus-mediated gene transfer to cystic fibrosis airway epithelial cells: effect of selectable marker sequences on long-term expression.

Retrovirus-mediated gene transfer offers the potential for stable long-term expression of transduced genes in host cells subsequent to integration of vector DNA into the host genome. Using a murine amphotropic retrovirus vector containing an interleukin-2 receptor (IL-2R) gene as a reporter and a neomycin phosphotransferase (neor) gene as a dominant selectable marker, we measured the efficiency of retrovirus-mediated gene transfer and the stability of transduced gene expression in a cystic fibrosis tracheal epithelial cell line (CFT1). The use of the IL-2R cell surface marker as a reporter of infection permitted both quantitation of vector gene expression and flow cytometric sorting of cells transduced with the vector. In initial studies, the optimal conditions for retrovirus-mediated gene transfer were determined. The presence of a polycation was required for optimal transduction efficiency. The efficiency of infection of CFT1 cells was increased by repetitive exposure to virus such that it was possible to transduce approximately 80% of the cells following three successive daily exposures. The long-term stability of expression of the non-selected IL-2R gene was also evaluated. A slow decline in the percentage of cells expressing IL-2R was seen with cells that were maintained under constant selection pressure for expression of the neor gene, which was expressed from an internal promoter. Similar results were obtained when cultures were selected initially for neor gene expression and maintained without selection thereafter. In contrast, stable expression was observed in CFT1 cells for at least one year following multiple infections in the absence of G418 selection. In conclusion, (i) transduction of foreign genes into human airway epithelial cells using an amphotropic retrovirus vector can be highly efficient in the presence of appropriate polycations and multiple exposures; and (ii) stable expression of a non-selected gene in these epithelial cells is better maintained without selection.

Cell Line↗
PubMed1994

Olfactory toxicity resulting from dermal application of 2,6-dichlorobenzonitrile (dichlobenil) in the C57Bl mouse.

2,6-Dichlorobenzonitrile (dichlobenil) is an herbicide which has previously been reported by other investigators to be toxic to the olfactory mucosa following intraperitoneal administration. The objective of this study was to determine whether a more occupationally-relevant route of pesticide exposure, namely dermal exposure to dichlobenil, also resulted in olfactory system damage. Male C57Bl mice were clipped and administered 0-200 mg/kg dichlobenil dermally in acetone either as a single dose or for five consecutive days. In addition, olfactory bulb glial fibrillary acidic protein (GFAP) analysis was performed in order to determine whether the damage in the olfactory mucosa translated into damage which could be measured as an astroglial increase in GFAP concentration in the olfactory bulb, a marker of central nervous system neuronal loss. Olfactory mucosal histology revealed that single or multiple exposures to 50, 100, 150 and 200 mg/kg dichlobenil dermally caused olfactory epithelial damage (primarily sensory cell loss) in the epithelium lining the dorsal medial meatus of the nasal cavity. While the olfactory epithelial lesions were much less severe than those caused by i.p. administration of dichlobenil, GFAP was significantly elevated in both the 150 and 200 mg/kg treatment groups, demonstrating that relatively minor damage to a portion of the olfactory mucosa in the nasal cavity can be detected in the central nervous system.

Administration, Cutaneous↗
PubMed1999

Entry-into-human study with the novel immunosuppressant SDZ RAD in stable renal transplant recipients.

AIMS: To evaluate the tolerability of single oral SDZ RAD doses in stable renal transplant recipients and the pharmacokinetics of ascending SDZ RAD doses when coadministered with steady-state cyclosporin A microemulsion (Neoral). METHODS: This randomized, double-blind, placebo-controlled, sequential study involved 54 patients in six treatment groups; a different SDZ RAD dose (0.25, 0. 75, 2.5, 7.5, 15, 25 mg) was assessed in each group. Patients received a single oral dose of SDZ RAD (n=6) or placebo (n=3) with their usual Neoral dose. SDZ RAD and cyclosporin A pharmacokinetic parameters were determined. RESULTS: All SDZ RAD doses were well tolerated, with no discontinuations due to adverse events, serious adverse events, or deaths. Similar proportions of patients receiving SDZ RAD and placebo had at least one adverse event (44% and 50%, respectively). Mean changes in laboratory variables (baseline to endpoint) showed no clinically meaningful differences between SDZ RAD and placebo groups. SDZ RAD was absorbed rapidly and showed dose-proportional pharmacokinetics (dose: 2.5-25 mg), based on systemic exposure. Multiple postabsorptive phases in the pharmacokinetic profile indicate tissue distribution. The elimination half-life ranged from 24 to 35 h across the five highest dose groups. Pharmacokinetics were similar in men and women. Co-administration of escalating single oral SDZ RAD doses did not affect steady-state cyclosporin A pharmacokinetics. CONCLUSIONS: SDZ RAD was well tolerated; safety profiles of SDZ RAD and placebo were similar. SDZ RAD pharmacokinetics were dose-proportional across the range 2.5-25 mg in conjunction with cyclosporin A-based therapy, according to systemic exposure. Cyclosporin A pharmacokinetics were not affected by coadministration of single oral doses of 0.25-25 mg SDZ RAD.

Adolescent↗