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Biomedical subjects

J Gallagher

Publications and source records attributed to J Gallagher.

At least 19 recordsLinked to original sources
PubMed1995

32P-postlabeling and HPLC separation of DNA adducts formed by diesel exhaust extracts in vitro and in mouse skin and lung after topical treatment.

Diesel exhaust extracts contain many carcinogenic compounds which have been shown to form polycyclic aromatic hydrocarbon (PAH)- and nitrated PAH-DNA adducts in rodent skin and lung. The aim of this study was to characterize by 32P-postlabeling, TLC and HPLC the primary postlabeled PAH-DNA adduct(s) formed in vitro and in vivo by diesel extracts. The diesel particle extracts had known concentrations of benzo[a]pyrene, benzo[b,j,k]-fluoranthenes (B[b,j,k]F) and chrysene. DNA adducts were analyzed in calf thymus DNA incubated in vitro with PAHs activated by S9 mix and in skin and lung DNA from topically treated mice. The main diesel-derived DNA adduct formed in vitro and in vivo did not co-migrate on HPLC and large TLC plates with (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti BPDE)-, B[b]F-,B[j]F-,B[k]F-or chrysene-DNA adduct standards. By co-chromatography DNA adducts formed by chrysene from both in vitro and in vivo samples were identified. Nissan diesel extract containing higher PAH concentrations than Volkswagen automobile extract formed skin DNA adducts that co-migrated with chrysene- and anti BPDE- DNA-derived adducts. We conclude that the use of a highly sensitive 32P-postlabeling method combined with HPLC improves the identification of PAH adducts formed by complex mixtures such as diesel exhaust extracts.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1994

Formation of DNA adducts in rat lung following chronic inhalation of diesel emissions, carbon black and titanium dioxide particles.

Exposure of rats to diesel emissions results in the development of lung tumors. The objective of this study was to determine whether the polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs or other polycyclic organic matter adsorbed to diesel particles induces the formation of DNA adducts in the lung when compared to particles with little or no adsorbed organic matter. Rats were exposed to diesel emissions containing particles with over 30% solvent-extractable adsorbed organic matter and to particles with < 0.1% adsorbed organic matter (carbon black particles and TiO2). Wistar rats were exposed to diesel emissions (7.5 mg/m3) for 2 months, 6 months and 2 years and for 2 years to carbon black (11.3 mg/m3) and TiO2 particles (10.4 mg/m3) to compare tumorigenic response and DNA adduct formation in the lung. Two versions of the 32P-postlabeling assay for the detection of DNA adducts were used to tentatively identify nitrated-amine or arylamine adducts formed relative to other nitro PAH based on the demonstrated sensitivity of these adducts to nuclease P1 treatment. Total adduct levels were determined for peripheral lung tissue DNA as detected in a diagonal radioactive zone. One major adduct which migrated outside this region (adduct 1) and a nuclease P1-sensitive adduct (adduct 2) were quantitated separately. Adduct 1 increased significantly over time in the filtered air exposed animals but decreased markedly at the 2 year time points regardless of particle type, presumably as a result of adduct dilution through de novo cell synthesis or cell proliferation invoked in response to particle loading and/or effect on the endogenous synthesis or degradation of DNA reactive moieties. The nuclease sensitive adduct (adduct 2), possibly resulting from exposure to nitro-PAHs, was detected in diesel-exposed rats but was not detected in the rats exposed to TiO2 and carbon black. No significant elevation in PAH-derived adducts, relative to the filtered air controls, was observed in the rodents exposed to diesel emission. Our data suggest that long-term contact with these particles may result in a cell proliferative response, enhanced degradation of I-compounds not related to cell proliferation, and/or synthesis of I-compounds, irrespective of the differences in organic content associated with the three particle types. This response may be an important factor in explaining the reported similarity in tumorigenic response in rodents exposed to diesel emissions, carbon black and TiO2 particles.

Administration, Inhalation↗
PubMed1992

Gene-dose-dependent expression of soluble mammalian cytochrome b5 in Escherichia coli.

A synthetic structural gene encoding a mammalian cytochrome b5, carrying an optimised ribosomal binding sequence, was tandemly polymerised ranging from one (n = 1) to six (n = 6) gene copies. The gene, placed in p lambda-ncyt under the control of the lambda PL promoter, transcribed mono- to hexahomocistronic mRNA, expressing one to six copies of cytochrome b5. The expressed levels of cytochrome b5 in Escherichia coli p lambda-ncyt corresponded linearly with the gene dose when up to five copies were present; saturating build-up of the recombinant protein was reached at six gene copies. Cells bearing p lambda-6cyt produced 75 micrograms cytochrome b5/ml of unit optical density at 600 nm culture, constituting 55% of the soluble bacterial protein. The recombinant protein accumulated predominantly in a haem-deficient, apoform, together with lesser amounts of the holocytochrome b5. Whereas the overall expressed protein (apo and holo forms) was gene dose dependent, there was an inverse relationship between holocytochrome b5 production and gene dose. Incubation of the thermally induced bacterial lysates with exogenous haem a converted all of the soluble apocytochrome b5 into holocytochrome b5 that was spectrally indistinguishable with its native counterpart. Culture supplementation with the likely metabolic precursors of haem synthesis, 5-aminolevulinic acid, glycine/succinate or glutamate, significantly alleviated the protoporphyrin deficiency during hyperproduction of cytochrome b5 in E. coli.

Aminolevulinic Acid↗
PubMed1992

A pink bacterium as a reporter system signaling expression of a recombinant protein.

We describe a set of expression vectors, pEX-PINK/0-3, for high-level production of (un)fused target proteins. The vectors incorporate a 'pink' reporter element, which signals in vivo the expression status of a target gene. A target sequence is cloned between the lambda PL promoter and the downstream mammalian cytochrome b5 gene. Thermo-induction drives transcription of a dicistronic mRNA from which the target protein and cytochrome b5 are independently and concurrently synthesized. Positive expression is indicated by visual transformation of bacteria from a grey/translucent to a bright pink color derived from tandemly expressed holocytochrome b5. The signal can be monitored in vivo spectrophotometrically.

Base Sequence↗
PubMed1992

Spinal fusion for back pain: a clinical and radiological review.

Eighty-one patients who had spinal fusions performed for back pain over a 7-year period were reviewed; 74% were satisfied with the outcome of their surgery, mainly because of the degree of pain relief obtained. Based on lateral radiographs of the fusion area in flexion and extension, there was a 34% pseudarthrosis rate in first-time fusions. However, there was no clear relationship between the integrity of fusion and clinical success, indicating that many factors other than bony fusion influence the eventual outcome of the operation.

Adult↗
PubMed1992

Comparison of nurses' and family members' perceived needs during postanesthesia care unit visits.

Today, more PACUs are opening their doors to visiting family members. This change can be exciting and challenging for the PACU nurse. The expertise involved when caring for the patient must be also extended to the family. Literature shows that families have identifiable needs. By attending to those needs, the nurse may help decrease stress for the family during the patient's hospitalization and enable everyone to cope more effectively. Limited published research is available regarding the needs of family members of PACU patients. This descriptive study explores and compares needs identified by family members when visiting PACU patients with needs of these family members perceived by PACU nurses. Analysis of data using the Mann Whitney-U Test indicates a significant difference between the groups. PACU nurses believed that family members' most important need was information. Family members stated that the need to see the family member was more important than was perceived by the nurses. Both groups agreed that education was an important need. Further studies using a larger sample are needed to validate findings of this study.

Adaptation, Psychological↗
PubMed1991

Studies on N-acetylglucosaminidase activity produced by Streptomyces hygroscopicus.

Following growth on chitin-containing media the actinomycete, Streptomyces hygroscopicus produces N-acetylglucosaminidase. When the organism was grown in submerged culture on chitin-containing media, at 30 degrees C, production of the N-acetylglucosaminidase activity has been shown to increase to a maximum at around day 18. Following electrophoretic analysis of culture filtrates and subsequent zymogram staining with fluorescent substrate analogues, at least three general pools of N-acetylglucosaminidase activity were detected. These were named NA1, NA2 and NA3. In addition, a potential chitinase was also identified. The N-acetylglucosaminidases, referred to above as NA1 and NA2, were separated and their enzymatic properties were investigated.

Acetylglucosaminidase↗
PubMed1991

Structural requirements for the action of parathyroid hormone-related protein (PTHrP) on bone resorption by isolated osteoclasts.

Parathyroid hormone-related protein (PTHrP) plays a major role in the syndrome of humoral hypercalcemia of malignancy (HHM) by its actions on bone and kidney. In this study an isolated osteoclast bone resorption assay was used to investigate the actions of this peptide and the structure-activity relationships for its resorption effect. As with PTH, neither synthetic nor recombinant PTHrP preparations stimulated resorption within highly purified osteoclast populations. Resorption was stimulated only in the presence of contaminating osteoblasts or in cocultures with the osteoblast-like cell line UMR-106. In the presence of osteoblasts PTHrP-(1-34) and PTHrP-(1-84) stimulated bone resorption in a dose-dependent manner with a potency comparable to that of PTH-(1-34) on a molar basis. The biologic activity of the PTHrP was shown to reside in the first 34 amino acids, and within that region the structural requirements for promotion of osteoclastic resorption resembled closely those for promotion of cyclic AMP formation in osteoblast-like cells. Using emulsion autoradiography with iodinated PTHrP-(1-34) and PTHrP-(1-84) on mixed bone cell preparations from neonatal rats, specific binding was demonstrated only to osteoblasts, not to osteoclasts. These results clearly demonstrate that PTHrP is a potent stimulator of bone resorption and that these effects are, like those of PTH, mediated by initial actions upon cells of the osteoblast lineage.

Animals↗
PubMed1991

Supportive care for viral infections in cancer patients.

Viral infections are more frequent and more severe in patients with cancer. As treatments for malignancy become ever more aggressive, the supportive care must also advance or the gains from innovative antineoplastic treatments will be lost to morbidity and mortality from secondary immune suppression and opportunistic infections. While empiric antibacterial and antifungal therapies for neutropenic leukemia patients were improving patients' survival, viral infections in cancer patients were often relegated to a clinical footnote in review articles since little could be done about them. Recently, however, acyclovir, ganciclovir, immunoglobulins, and ribavirin have given new opportunities for successful management of severe viral opportunistic infections in patients with leukemia and in bone marrow and other transplant patients.

Herpes Simplex↗
PubMed1991

An introduction to research: a primer for the nurse anesthetist.

The goals of this article are to provide an overview of the research process and highlight some of the most important aspects. In the process, the definition of research and some general terminology will be reviewed. Discussions of how to define a problem, reviewing the literature, types of study designs, sampling, types of measurement, reliability and validity, limitations and assumptions, data analysis, ethical concerns with human subjects, and time management are included, as are examples of published research.

Data Collection↗
PubMed1990

Cross-sectional study of platinum salts sensitization among precious metals refinery workers.

A cross-sectional medical evaluation was conducted to determine respiratory and dermatological effects of platinum salts sensitization among workers in a secondary refinery of precious metals. Fifteen of 107 current employees and eight (28%) of 29 former employees, who had been terminated from employment on average for 5 years because of respiratory symptoms, had positive skin reactivity to platinum salts. Platinum salts skin reactivity was significantly associated with average air concentrations of platinum salts in employees' present work area. Workers with positive platinum salts skin tests had significantly higher prevalences of reported rhinitis, asthma, and dermatitis than negative skin test workers. They also had increased bronchial response to cold air challenge and elevated levels of total serum IgE. Platinum salts sensitization was not associated with atopic tendency as measured by sensitivity to common aeroallergens, but was strongly associated with cigarette smoking status. The findings indicate that cigarette smoking may be a risk factor for the development of platinum salts allergy. The persistence of platinum salts sensitization and high prevalence of adverse health outcomes among former workers demonstrate the importance of regular medical monitoring so that sensitized workers can be removed from exposure before they develop long-term health problems.

Animals↗
PubMed1990

Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases.

Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to increased serum concentration of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This disorder is associated with a G to A mutation in exon 26 of the apolipoprotein B (apo B) gene which creates a substitution of glutamine for arginine in the codon for amino acid 3500. We have searched for this mutation in 374 unrelated individuals with hyperlipidaemia from the United Kingdom, and in 371 unrelated individuals with a primary clinical diagnosis of atherosclerosis from the United Kingdom and Scandinavia. Ten individuals, 9 from the U.K. and 1 from Denmark, were identified. The frequency of the mutation was 3% in individuals classified clinically as having familial hypercholesterolaemia (FH) and 3% in individuals with type IIa hyperlipidaemia without FH, and was not found in patients with types IIb and III hyperlipidaemia. The mutation was rare in individuals with a primary clinical diagnosis of atherosclerosis. Plasma lipid levels and clinical characteristics of the ten patients identified in the present study are similar to those reported for heterozygous FH. Thus, in our study, FDB is associated with moderate to severe hypercholesterolaemia, and appears to be a serious disorder causing premature cardiovascular disease. Individuals with this mutation can be identified unambiguously using routine molecular screening techniques.

Adult↗
PubMed1990

Changes in ovine erythrocyte morphology due to sphingomyelin degradation by Corynebacterium pseudotuberculosis phospholipase D.

Corynebacterium pseudotuberculosis produces a sphingomyelin-specific phospholipase D exotoxin that is a major determinant in the pathogenesis of caseous lymphadenitis. We assessed the changes induced in the morphology and sphingomyelin concentration of ovine erythrocytes after incubation with broth culture filtrates or purified exotoxin. Sphingomyelin was hydrolysed nearly in parallel with shape change. Morphologically, spherostomatocytes were seen initially, and later these contained numerous vacuoles at the periphery. Vacuoles seen in thin sections with transmission electron microscopy appeared as pits with scanning electron microscopy. Pitting became progressively worse with time, leading to extensive scalloping of the membrane surface. Chemically, significant decreases (P less than or equal to 0.05) in erythrocyte membrane sphingomyelin content and significant increases (P less than or equal to 0.05) in the content of glycerophospholipids (i.e. phosphatidylglycerol) were observed in erythrocytes incubated with broth culture filtrates or purified exotoxin. These alterations may contribute to the pathophysiology of acute infections induced by C. pseudotuberculosis.

Animals↗
PubMed1990

Cold air challenge and platinum skin reactivity in platinum refinery workers. Bronchial reactivity precedes skin prick response.

An investigation of a platinum refinery operation consisted of an administered questionnaire, spirometry, skin prick testing with platinum salts and common aeroallergens, serum total IgE, radioallergosorbent test for platinum salts, and measurement of nonspecific airway hyperresponsiveness by cold air challenge testing. Among 136 employees examined, there were 107 current and 29 medically terminated workers; 23 (17 percent) subjects had a positive platinum salts prick skin test and 19 (14 percent) displayed a positive cold air challenge. RAST binding for platinum salts IgE antibodies showed a high level of agreement with platinum skin prick test results. A proportion (63 percent) of the population (74 current and 12 terminated workers) underwent repeat platinum skin testing one year later. Among current workers, there was conversion of the platinum skin test from negative to a positive test in five employees, with three conversions occurring in workers who showed only a positive cold air challenge test the year before. Platinum skin sensitivity, asthma symptoms, and nonspecific airway hyperresponsiveness persisted for years after termination of exposure in some medically terminated workers presumably because of a delay in removal from work of employees who became sensitized to platinum salts. It is suggested that proper surveillance for occupational asthma involves the use of several testing procedures. Prompt removal from work of individuals found to become sensitized to platinum salts is important in this industry.

Adult↗
PubMed1990

Evaluation of occupational asthma from airborne egg protein exposure in multiple settings.

We previously reported IgE-mediated occupational asthma among workers exposed to airborne egg protein at a plant that produces liquid and dried powdered egg products. To demonstrate that our original observations are generalizable to other facilities that process eggs, and to estimate the prevalence of IgE-mediated occupational asthma among egg-exposed workers, we conducted surveys at two additional plants. We administered a questionnaire to 188 employees to identify workers with symptoms suggestive of occupational asthma. We further evaluated 88 workers with and without symptoms by a clinical examination by a physician blinded to results of other tests, serial peak expiratory flow rate (PEFR) determinations every three hours while awake for one week, and skin prick tests and serum specific IgE levels to extracts of factory egg products, commercial egg test reagents, and egg white protein fractions. Fourteen workers had work-related asthmalike symptoms by questionnaire, a physician diagnosis of occupational asthma, and evidence of IgE-mediated sensitization to one or more egg proteins. Workers exposed exclusively to liquid egg aerosol, as well as workers exposed primarily to dried airborne egg protein, developed occupational asthma. This study replicated our original observations and demonstrated that workers in all areas of liquid and powdered egg production are at risk of developing occupational asthma from exposure to airborne egg proteins.

Air Pollutants, Occupational↗
PubMed1990

Complex mixtures of urban air pollutants: identification and comparative assessment of mutagenic and tumorigenic chemicals and emission sources.

Current research on the cancer risks of complex mixtures of urban air pollutants addresses the identification and comparative assessment of mutagenic and carcinogenic chemicals and emission sources. To identify genotoxic compounds in urban air, micromutagenesis methods are coupled to analytical fractionation and new chemical characterization methods. Among polar mutagenic compounds, many appeared to be nitrated and or oxygenated aromatic compounds. Source apportionment of the mutagenic activity observed in urban air shows that vehicles and residential heating are major contributors to the ambient mutagenicity of the aerosol fraction. Comparative tumorigenesis and DNA adduct dosimetry studies are also being conducted with these same combustion emission sources and urban aerosols. The potential hazard and sources of the gaseous emissions have not been determined, but appear to be significantly increased by atmospheric transformation by ozone and nitrogen oxides.

Air Pollutants↗