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C Rafferty

Publications and source records attributed to C Rafferty.

12 recordsLinked to original sources
PubMed1999

A signal recognition particle receptor gene from the early-diverging eukaryote, Giardia lamblia.

The molecular mechanisms for targeting and translocation of secreted proteins are highly conserved from bacteria to mammalian cells, although the machinery is more complex in higher eukaryotes. To investigate protein transport in the early-diverging eukaryote, Giardia lamblia, we cloned the gene encoding the alpha subunit (SRalpha) of the signal recognition particle (SRP) receptor. SRalpha is a small GTPase that functions in SRP-ribosome targeting to the ER. Sequence and phylogenetic analyses showed that SRalpha from G. lamblia is most homologous to SRalpha proteins from higher eukaryotes, although it lacks some conserved motifs. Specifically, giardial SRalpha has an N-terminal extension that enables SRalpha of higher eukaryotes to interact with a beta subunit that anchors it in the ER membrane. While the C-terminal regions are similar, giardial SRalpha lacks a prominent 13 amino acid regulatory loop that is characteristic of higher eukaryotic versions. Thus, giardial SRalpha resembles that of higher eukaryotes, but likely diverged before the advent of the regulatory loop. The 1.8 kb SRalpha transcript has extremely short untranslated regions (UTRs): a 1-2 nt 5'- and a 9 nt 3' UTR with the polyadenylation signal overlapping with the stop codon. RT-PCR, Northern and Western analyses showed that SRalpha is present at relatively constant levels during vegetative growth and encystation, even though there are extensive changes in endomembrane structures and secretory activity during encystation. Imnuno-EM showed that SRalpha localizes to ER-like structures, strengthening the observation of a typical ER in G. lamlia. Unexpectedly, SRalpha was also found in the lysosome-like peripheral vacuoles, suggesting unusual protein traffic in this early eukaryote. Our results indicate that the eukaryotic type of cotranslational transport appeared early in the evolution of the eukaryotic cell.

Amino Acid Sequence↗
PubMed1998

The genotoxic potential of electric and magnetic fields: an update.

We review 23 studies on the potential genotoxicity of electric and magnetic fields that have appeared in the published literature since our 1993 review of 55 published studies (McCann et al., Mutat. Res. 297 (1993) 61-95) and six additional studies published prior to 1993, which were not previously reviewed. As in our previous review, internal electric fields present in media (for in vitro experiments) and in the torso (for in vivo experiments) were estimated. Individual experiments are evaluated using basic data quality criteria. The potential for genotoxicity of electric and magnetic fields is discussed in light of the significant body of genotoxicity data that now exists. Three unsuccessful attempts to replicate previously reported positive results have appeared since our previous review. We conclude that, in spite of the 34 studies reviewed in this and our previous publication that report positive genotoxic effects, none satisfy all of three basic conditions: independent reproducibility, consistency with the scientific knowledge base, and completeness according to basic data quality criteria. As we discuss, these criteria are satisfied for several groups of negative studies in several exposure categories (ELF magnetic fields, 150 microT-5 mT, combined ELF electric and ELF magnetic fields, approx. 0.2 mT, 240 mV/m, and static magnetic fields, 1-3.7 T). The evidence reviewed here strengthens the conclusion of our previous review, that the preponderance of evidence suggests that ELF electric or magnetic fields do not have genotoxic potential. Nevertheless, a pool of positive results remains, which have not yet been tested by independent replication. Among the 12 studies reviewed here, which report statistically significant or suggestive positive results, we point particularly to results from five laboratories [J. Miyakoshi, N. Yamagishi, S. Ohtsu, K. Mohri, H. Takebe, Increase in hypoxanthine-guanine phosphoribosyl transferase gene mutations by exposure to high-density 50-Hz magnetic fields, Mutat. Res. 349 (1996) 109-114; J. Miyakoshi, K. Kitagawa, H. Takebe, Mutation induction by high-density, 50-Hz magnetic fields in human MeWo cells exposed in the DNA synthesis phase, Int. J. Radiat. Biol. 71 (1997) 75-79; H. Lai. N.P. Singh, Acute exposure to a 60-Hz magnetic field increases DNA strand breaks in rat brain cells, Bioelectromagnetics, 18 (1997) 156-165; H. Lai, N.P. Singh, Melatonin and N-tert-butyl-alpha-phenylnitrone block 60-Hz magnetic field-induced DNA single and double strand breaks in rat brain cells, J. Pineal Res. 22 (1997) 152-162; T. Koana, M. Ikehata, M. Nakagawa, Estimation of genetic effects of a static magnetic field by a somatic cell test using mutagen-sensitive mutants of Drosophila melanogaster, Bioelectrochem. Bioenergetics 36 (1995) 95-100; F.L. Tabrah, H.F. Mower, S. Batkin, P.B. Greenwood, Enhanced mutagenic effect of a 60-Hz time-varying magnetic field on numbers of azide-induced TA100 revertant colonies, Bioelectromagnetics 15 (1994) 85-93; S. Tofani, A. Ferrara, L. Anglesio, G. Gilli, Evidence for genotoxic effects of resonant ELF magnetic fields, Bioelectrochem. Bioenergetics, 36 (1995) 9-13], which satisfy most basic data quality criteria and may be of interest.

Animals↗
PubMed1996

A comparison of the forces exerted during laryngoscopy. The Macintosh versus the McCoy blade.

The forces exerted at laryngoscopy with the McCoy and Macintosh blades have been compared in 40 patients. The variables measured were the duration of laryngoscopy, the three maximally-applied forces and the mean force. The mean (SD) forces recorded were 18.9 (7.82) and 10.1 (5.33) N, respectively, with the Macintosh and the McCoy blades (p < 0.001) with a similar duration of laryngoscopy. There was a significant positive correlation between the mean force and patients' weight, height and body mass index for the Macintosh blade but only for weight and height for the McCoy blade. It is concluded that the use of the McCoy blade results in significantly less force being applied during laryngoscopy. This may be the reason for the reduction in the stress response reported previously with the use of the McCoy blade.

Adolescent↗
PubMed1995

General practice data retrieval: the Northern Ireland project.

OBJECTIVE: To develop an epidemiological database of morbidity in the community as presented to general practitioners and to support epidemiological research in general practice. DESIGN: The project is a sentinel network of 23 general practices in Northern Ireland that report the incidence of a list of selected diseases to a central unit for analysis. RESULTS: Results are presented for depression, diabetes, and myocardial infarction. The age--sex distributions of diabetes and myocardial infarction are comparable with other published data but the incidence of depression is under estimated. CONCLUSIONS: The importance of complete accuracy of data reported within sentinel networks depends on the purposes for which information is to be used. For some diagnoses, such as diabetes and acute myocardial infarction, the accuracy of the reported incidence is high while for other diseases, such as depression, where diagnostic behaviour varies more between doctors, the figures are much less reliable.

Adolescent↗
PubMed1994

Propofol sedation in severe head injury fails to control high ICP, but reduces brain metabolism.

We have compared the effects of an intravenous infusion of propofol with those of morphine and midazolam on global brain metabolism (AVDO2) and brain perfusion following severe head injury. Fifteen patients were sedated with either a continuous infusion of propofol (mean rate 232 mg/h, range 150-400 mg/h) or infusions of morphine (mean rate 2.3 mg/h, range 0-4 mg/h) and midazolam (mean rate 2.8 mg/h, range 0-5 mg/h). Both groups were well matched for sex, age and level of coma (Glasgow coma scale) prior to sedation. Continuous data collection of AVDO2, mean arterial blood pressure (MABP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) began at 12 hours post injury and continued for a mean period of 40 hours. Morphine and midazolam did not have a significant effect on any of the measured parameters. Propofol led to a fall in AVDO2 from 6.0 +/- 2.6 ml/dl to 3.0 +/- 0.6 ml/dl at 4 hours. However, there was no effect on MABP, ICP or CPP. Outcome was similar in the 2 groups.

Adolescent↗
PubMed1993

Continuous monitoring of jugular bulb oxygen saturation and the effect of drugs acting on cerebral metabolism.

The laser absorption spectrophotometric technique was used to continuously monitor jugular bulb oxygen saturation (SjO2), and thus to calculate arteriovenous oxygen differences (AVDO2), in three subgroups of intensively monitored, severely head injured patients. We have used this data to address two questions: 1. How do cerebral and systemic haemodynamic changes affect SjO2 and AVDO2; and 2. Can ADVO2 measurements be used to detect therapeutic changes in brain metabolism, in response to drugs. The major haemodynamic factor affecting SjO2 and AVDO2 was intracranial pressure (ICP). Increases in ICP were associated with concomitant increases in SjO2, and decreases in AVDO2, suggesting cerebral hyperaemia in response to ICP waves. Systemic changes were less frequent, but potent influences on SjO2. The short acting anaesthetic agent propofol produced a marked increase in SjO2 (decrease in AVDO2 to below the normal range) which became less marked with time. A new high affinity glutamate antagonist produced no change in SjO2. With rigorous attention to technical factors, and exclusion of extra and intracranial haemodynamic effects, SjO2 monitoring may be a useful "surrogate end point" for the effect of drugs acting on brain metabolism.

Adolescent↗
PubMed1993

A critical review of the genotoxic potential of electric and magnetic fields.

55 published articles were identified which reported results of tests of ELF (extremely low frequency) or static electric or magnetic fields for genotoxic effects. The biological assays used spanned a wide range, including microbial systems, plants, Drosophila, mammalian and human cells in vitro and in vivo. Experimental results were grouped into four exposure categories: ELF Electric; ELF Magnetic; Static Electric; and Static Magnetic. The internal electric fields present in media (for in vitro experiments) and in the torso and extremities (for in vivo experiments) were estimated, providing an index of comparison. All experiments were critically analyzed with respect to basic data quality criteria. Experiments within each exposure category were then compared to determine if results reinforced or contradicted one another. The preponderance of evidence suggests that neither ELF nor static electric or magnetic fields have a clearly demonstrated potential to cause genotoxic effects. However, there may be genotoxic activity from exposure under conditions where phenomena auxiliary to an electric field, such as spark discharges, electrical shocks, or corona can occur. In addition, two unconfirmed reports suggest the genotoxic potential of certain chemical mutagens or ionizing radiation may be affected by co-exposure to electric or magnetic fields. Certain exposure categories are not represented or are under-represented by tests in some genotoxicity test systems that are usually included in minimal test batteries as specified by EPA for chemicals. It is suggested that consideration be given to whether additional genotoxicity testing is warranted to fill these gaps.

Animals↗
PubMed1993

Neuroprotective doses of N-methyl-D-aspartate receptor antagonists profoundly reduce the minimum alveolar anesthetic concentration (MAC) for isoflurane in rats.

N-methyl-D-aspartate (NMDA) receptor antagonists, which block one of the glutamate receptors, have provided evidence of cerebral protection in animal models of focal cerebral ischemia. We examined the effect of neuroprotective doses of one noncompetitive (dizocilpine) and two competitive (D-CPP-ene, CGS 19755) NMDA antagonists on the minimum alveolar anesthetic concentration (MAC) of isoflurane in rats. A single bolus injection of any of the three NMDA antagonists produced a significant (P < 0.01) and sustained (> 3 h) decrease in the MAC of isoflurane. Dizocilpine decreased MAC by 33%-38% at a dose of 0.15 mg/kg and 48%-54% at a dose of 0.5 mg/kg. D-CPP-ene decreased MAC by 32%-37% at a dose of 1.5 mg/kg and 39%-45% at a dose of 4.5 mg/kg. CGS 19755 decreased MAC by 19%-24% at a dose of 3 mg/kg and 49%-58% at a dose of 10 mg/kg. Dizocilpine, but not the competitive antagonists, produced a small transient decrease in mean arterial blood pressure. The sustained anesthetic potency of neuroprotective doses of NMDA antagonists supports the idea that glutaminergic receptor activity is involved in determining the anesthetic state.

Anesthesia, Inhalation↗
PubMedDate not supplied

Caring without prejudice.

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Acquired Immunodeficiency Syndrome↗