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Biomedical subjects

J Gallagher

Publications and source records attributed to J Gallagher.

At least 73 records · Page 4Linked to original sources

Sulphated proteoglycan is required for collecting duct growth and branching but not nephron formation during kidney development.

Kidney epithelia have separate origins; collecting ducts develop by ureteric bud growth and arborisation, nephrons by induced mesenchyme-epithelium transition. Both express sulphated glycosaminoglycans (GAGs) which are strikingly upregulated during nephron differentiation. However, sodium chlorate, an inhibitor of GAG sulphation, and the GAG-degrading enzymes heparitinase plus chondroitinase, did not prevent nephron development. In contrast, ureteric bud growth and branching were reversibly inhibited by the above reagents, the inhibition correlating quantitatively with sulphated GAG deprivation caused by a range of chlorate concentrations. Growth and branching could be independently restored during GAG deprivation by hepatocyte growth factor and phorbol-12-myristate acetate (PMA) respectively. Together these signalling effectors stimulated both branch initiation and growth. Thus growth and morphogenesis of ureteric bud involve distinct signalling pathways both regulated by GAGs.

Animals↗

Cancer biomarkers in human atherosclerotic lesions: detection of DNA adducts.

Since somatic mutations are suspected to contribute to the pathogenesis not only of cancer but also of atherosclerotic plaques, we measured DNA adducts in the smooth muscle layer of atherosclerotic lesions in abdominal aorta specimens taken at surgery from seven patients. DNA adducts were evaluated in three laboratories by means of different molecular dosimetry methods, including: (a) HPLC/fluorescence, which specifically identifies the DNA adducts of the anti-benzo(a)pyrene (BPDE) isomer; (b) two- and three-dimensional synchronous fluorescence spectrophotometries, which detect DNA adducts of BPDE and other reactive metabolites of polycyclic aromatic hydrocarbons; and (c) 32P postlabeling, which reveals the presence of a variety of types of DNA adducts. The HPLC/fluorescence method provided for the first time evidence for the presence of BPDE-DNA specific adducts in three of six specimens tested. Synchronous fluorescence spectrophotometry displayed broad areas of fluorescence in all seven specimens, thereby suggesting the occurrence not only of BDPE-DNA but also of other DNA adducts with similar fluorescence characteristics. All specimens were also positive at 32P postlabeling, which revealed multiple spots detectable following enrichment either with nuclease P1 or butanol, indicative of the presence of different aromatic DNA adducts. Thus, the data obtained by applying typical cancer biomarkers provide further support to the hypothesis that there may be similarities between the carcinogenic and the atherogenic processes, and in particular that genetic alterations caused by DNA-binding agents in the artery wall may be detected in atherosclerotic lesions.

Aged↗

Who should give lifestyle advice in general practice and what factors influence attendance at health promotion clinics? Survey of patients' views.

BACKGROUND: Health promotion activity in general practice has increased greatly since 1990. A large proportion of this work is undertaken by practice nurses. Little is known about patients' views about the providers of health promotion or their views about general practice health promotion clinics. AIM: A study was carried out in 1992 to determine patients' views about the provision of health promotion advice by general practitioners and practice nurses and their views about attending health promotion clinics. METHOD: A postal questionnaire was sent to a random sample of 1750 patients aged 16 years and over from five general practices in south Tyneside. The questionnaire explored patients' preferences regarding health promotion advice from the general practitioner or practice nurse in relation to four areas of lifestyle advice and factors that might encourage patients to attend a health promotion clinic. RESULTS: A response rate of 75% was obtained from 1639 eligible patients. Receiving health promotion advice from either the general practitioner or the practice nurse was the most commonly preferred option expressed by patients overall. The ability of health promotion clinic staff to deal with patients' concerns about their illness and short waiting times were more likely to influence patients' attendance at health promotion clinics than the presence of a general practitioner or practice nurse. CONCLUSION: In the present study, many patients found health advice received from practice nurses and general practitioners equally acceptable. However, it was the ability of health professionals to respond to patients' health concerns in the health promotion clinic rather than the type of health professional running the clinic that was important for patients.

Adolescent↗

Outcome of out-of-hospital cardiac arrest in New York City. The Pre-Hospital Arrest Survival Evaluation (PHASE) Study.

OBJECTIVE: To determine survival from out-of-hospital cardiac arrest in New York City and to compare this with other urban, suburban, and rural areas. DESIGN: Observational cohort study. SETTING: New York City. PARTICIPANTS: Consecutive out-of-hospital cardiac arrests occurring between October 1, 1990, and April 1, 1991. INTERVENTION: Trained paramedics performed immediate postarrest interviews with care providers, using a standardized questionnaire. MAIN OUTCOME MEASURES: Entry criteria, elapsed time intervals, and nodal events conformed to Utstein recommendations. The single target end point was death or discharge home. RESULTS: Of 3243 consecutive cardiac arrests on which resuscitation was attempted, 2329 (72%) met entry criteria as primary cardiac events. Overall survival was 1.4% (99% confidence interval [CI], 0.9% to 2.3%). No patients were lost to follow-up. Survival from witnessed ventricular fibrillation was 5.3% (99% CI, 2.9% to 8.8%). Using survival from witnessed ventricular fibrillation for intersystem comparison, our survival rate was similar to that of Chicago, Ill (4.0%; 99% CI, 1.9% to 7.5%; P = .41), the only other large city on which data were available. However, it was significantly lower than that reported from midsized urban/suburban areas (33.0%; 99% CI, 30.4% to 35.6%; P < .0001) and suburban/rural areas (12.6%; 99% CI, 8.9% to 16.3%; P < .0001). Survival rate among arrests occurring after arrival of emergency medical services personnel (8.5%; 99% CI, 4.7% to 14.0%) was comparable with Chicago (6.6%; 99% CI, 3.3% to 11.5%; P = .41) but markedly lower than King County, Washington (36%; 99% CI, 28.6% to 43.8%; P < .0001). CONCLUSIONS: Survival from out-of-hospital cardiac arrest in New York City was poor. This was partly attributable to lengthy elapsed time intervals at every step in the chain of survival. However, examination of survival among arrests occurring after emergency medical services arrival suggests that other features may predispose residents of large cities to higher cardiac arrest mortality than individuals living in more suburban or rural settings. Since half the US population resides in large metropolitan areas, this represents a public health problem of considerable magnitude.

Aged↗

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↗

Choosing the correct pain relief for extracorporeal lithotripsy.

OBJECTIVES: To determine the best choice of analgesic for patients undergoing lithotripsy, and to attempt to identify factors which might predict which patients are most likely to find the procedure painful. PATIENTS AND METHODS: Sixty patients with stones in the pelvicalyceal system of the kidney were randomized prospectively to undergo lithotripsy with the Dornier MPL9000 lithotripter (Dormier Medical Systems, Marietta, GA, USA) after receiving either diclofenac 100 mg per rectum (n = 30) or pethidine 50 mg intravenously (n = 30) for analgesia. The patients completed a detailed questionnaire prior to treatment, and the level of pain perceived during lithotripsy was monitored using visual analogue scales (VASs). Arterial oxygen saturation (SaO2) was monitored before analgesia was given, throughout the treatment and for 30 min after cessation of treatment. RESULTS: The VASs were available for 56 patients and the results of pulse oximetry for 51 patients. Although a higher kilovoltage was recorded in the group who received pethidine this difference was not significant. Patients who received diclofenac or pethidine alone, showed a non-significant fall of SaO2 30 minutes after the end of treatment, although the largest fall in SaO2 observed with pethidine was 10%. Patients who received diclofenac and pethidine similarly showed a non-significant fall in SaO2. Four patients received intravenous benzodiazepines in addition to pethidine, and in this group there was a dramatic fall in SaO2 which persisted more than 30 min after the end of treatment (P < 0.0027). Diclofenac provided effective analgesia for most of the patients who underwent lithotripsy. Overall 11 patients (18%) required additional analgesia. Diclofenac or pethidine alone, in the doses used in this study, did not cause a significant drop in SaO2 during ESWL. The only response found to be of value in predicting a painful experience was fear of the dentist. CONCLUSIONS: This study shows that modern lithotripsy, in addition to being safe and effective, can be performed as an out-patient procedure using simple non-opiate analgesics. The need for stronger analgesia and/or sedation should be tailored to the needs of the individual patient, although it remains difficult to predict which patients will require such measures.

Adult↗

Assay of the c-erbB-2 oncogene encoded protein by ELISA and immunocytochemistry in human breast cancer.

The c-erbB-2 gene is amplified in a wide variety of different adenocarcinomas. Generally, gene amplification correlates with increased expression of the c-erbB-2 oncoprotein. Previous assays for the c-erbB-2 oncoprotein have been qualitative or semi-quantitative. In this investigation using human breast cancers, c-erbB-2 oncoprotein levels as measured by enzyme-linked immunosorbent assay (ELISA) correlated significantly with semi-quantitation by immunocytochemistry (r = 0.843, P < 0.0001, n = 97). The cut-off point for the ELISA which gave the strongest agreement with immunocytochemistry was 15 units/micrograms protein. It is concluded that detection of c-erbB-2 oncoprotein by ELISA is quantitative and objective.

Biomarkers, Tumor↗

The ethics of health communication.

The scope of application of ethical principles in health communication is discussed with particular reference to the influence of the mass media on people's perceptions of benefit and risk in the field of health care.

Biomedical Research↗

Detection and comparison of DNA adducts after in vitro and in vivo diesel emission exposures.

Development of methods to evaluate certain classes of polycyclic aromatic compounds (PAC) detected in complex mixtures to which humans are exposed would greatly improve the diagnostic potential of 32P-postlabeling analysis. Identification of DNA adduct patterns or specific exposure-related marker adducts would strengthen associations between observed DNA adducts and exposures to different environmental pollutants (e.g., kerosene, cigarette smoke, coke oven, and diesel). We have compared diesel-modified DNA adduct patterns in various in vitro and in vivo rodent model systems and compared them to DNA reactive oxidative and reductive metabolites of 1-nitropyrene. The formation of nitrated polycyclic aromatic hydrocarbon (nitrated PAH) DNA adducts, derived from the metabolism of diesel extract constituents, was enhanced relative to other PAH-derived DNA adducts via xanthine oxidase-catalyzed nitroreduction. These adducts were detectable only by the butanol extraction version of the postlabeling analysis. Five major DNA adducts were detected in human lymphocytes treated in vitro with diesel extract. A major adduct detected in human lymphocytes treated in vitro with diesel extract comigrated with a major adduct detected in lymphocyte DNA treated with benzo[a]pyrene (BaP) alone. Other adducts that co-migrated with the major BaP-derived adducts were detected in skin and lung DNA isolated from rodents topically treated with (50 mg) diesel extract and the major adduct detected in calf thymus DNA treated with rat liver S9 and diesel particle extract. Postlabeling of lung DNA isolated from rodents exposed via lung inhalation for 24 months to diesel combustion emissions resulted in the formation of a major nuclease-P1-sensitive DNA adduct that did not co-migrate with the major BaP-diol epoxide adduct.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

DNA adduct profiles and levels in placenta, blood and lung in relation to cigarette smoking and smoky coal emissions.

Tobacco smoking and indoor smoky coal combustion emissions lead to exposures to complex environmental mixtures that have been associated with increased lung cancer mortality rates in the USA and Xuan Wei County, China, respectively. Human exposures to benzo[a[pyrene (BaP) present in smoky coal emissions are 20-200 times greater than exposure to BaP from smoking 1-2 packs of cigarettes per day. We compared DNA adducts resulting from cigarette smoking and coal smoke exposures in blood cells, placental syncytial nuclei, whole placental tissue homogenates and lung cells. Postlabelling analysis of DNA isolated from placental tissue of smokers revealed multiple adducts as a diagonal radioactive zone. DNA adduct levels for both white blood cells (WBC) and lymphocyte DNA were approximately 2.5-fold higher in smokers than in non-smokers. One smoking-related adduct was detected in both WBC and lymphocyte DNA, but no exposure-related adducts were detected in either WBC DNA or placental tissue DNA isolated from coal smoke-exposed individuals, despite higher exposure to BaP and aromatic organics. In contrast, discrete adducts unrelated to smoking status were detected, by 32P-postlabelling analysis, in DNA from syncytial nuclei isolated from placental villus samples from smokers and non-smokers. One major placental syncytial adduct co-migrated with a major BaP-derived DNA adduct. DNA adduct levels were approximately four-fold higher in bronchoalveolar lavage (BAL) cells from coal smoke-exposed individuals compared to unexposed individuals and suggest that DNA-reactive intermediates concentrate in the respiratory tract and may not be detectable in whole WBC or placental tissue homogenates. Our findings also suggest that the distribution and concentration of placental DNA adducts may be dependent on the site at which the placenta is sampled.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

Trends in managed care contracting.

This article describes trends in managed care contracting and offers physicians practical guidance for evaluating managed care plans and negotiating and dealing with problems in managed care contracts.

Contract Services↗