Search PubMed⌕ Search

Biomedical subjects

S Fletcher

Publications and source records attributed to S Fletcher.

At least 73 records · Page 4Linked to original sources
PubMed1996

Onboard acoustic recording from diving northern elephant seals.

This study was the first phase in a long-term investigation of the importance of low-frequency sound in the aquatic life of northern elephant seals, Mirounga angustirostris. By attaching acoustic recording packages to the backs of six translocated juveniles, the aim was to determine the predominant frequencies and sound levels impinging on them, and whether they actively vocalize underwater on their return to their rookery at Ano Nuevo, California, from deep water in Monterey Bay. All packages contained a Sony digital audio tape recorder encased in an aluminum housing with an external hydrophone. Flow noise was minimized by potting the hydrophone in resin to the housing and orienting it posteriorly. The diving pattern of four seals was recorded with a separate time-depth recorder or a time-depth-velocity recorder. Good acoustic records were obtained from three seals. Flow noise was positively correlated with swim speed, but not so high as to mask most low-frequency sounds in the environment. Dominant frequencies of noise impinging on the seals were in the range 20-200 Hz. Transient signals recorded from the seals included snapping shrimp, cetacean vocalizations. boat noise, small explosive charges, and seal swim strokes, but no seal vocalizations were detected. During quiet intervals at the surface between dives, the acoustic record was dominated by respiration and signals that appeared to be heartbeats. This study demonstrates the feasibility of recording sounds from instruments attached to free-ranging seals, and in doing so, studying their behavioral and physiological response to fluctuations in ambient sounds.

Acoustics↗
PubMed1996

Mutation segregation and rapid carrier detection of X-linked muscular dystrophy in dogs.

OBJECTIVES: To use exon 7-specific genomic polymerase chain reaction (PCR) products to identify the genotypes of normal, affected, and carrier female dogs in pedigrees segregating Golden Retriever muscular dystrophy (GRMD), and to confirm the concordant segregation of the mutation in all carrier and affected dogs presently available. DESIGN: The GRMD mutation is found in the consensus splice acceptor site in intron 6 of the canine dystrophin gene. PCR cycle-sequencing and restriction fragment length polymorphism/PCR were used for determination of the pattern of segregation of the point mutation which causes GRMD. ANIMALS: Normal, clinically affected, and obligate carrier dogs in pedigrees of GRMD. PROCEDURE: DNA from blood was amplified, using PCR and primers that bracket all of exon 7 of the canine dystrophin gene as well as 100 base pairs of intron on either side. PCR products were either cycle-sequenced directly or submitted to a second round of PCR, using 1 of the original primers coupled with a mutagenic restriction fragment length polymorphism-primer, which thus creates an artificial restriction site. Digestion with Stu I detected the normal allele. To detect the affected allele, Sau96 I was used to digest the 310-base pair exon 7 genomic fragment directly. CONCLUSIONS: Simple, clear diagnosis of carrier status was possible using these methods. This mutation is passed through all carrier and affected dogs in both United States GRMD colonies and the colony in Australia. CLINICAL RELEVANCE: Rapid, accurate diagnosis of carrier and affected dogs will enhance study of this homologue of Duchenne muscular dystrophy.

Alleles↗
PubMed1995

Neuropeptides modulate immune deviation induced via the anterior chamber of the eye.

Ag presentation via the anterior chamber of the eye results in a form of immune deviation termed anterior chamber-associated immune deviation (ACAID). The hallmarks of this response are the suppression of delayed-type hypersensitivity with simultaneous induction of Ab production. In this study, we examined the role of the neuropeptides vasoactive intestinal peptide (VIP) and substance P (SP) and found that the levels of these two peptides are controlled by neurogenic stimulation of the eye by light, and that these molecules determine the outcome of Ag presentation in the eye. Mice reared under diurnal conditions had VIP in the iris and ciliary body (not free in aqueous humor) and low levels of SP. Mice that were reared in the dark (or dark-adapted) did not contain detectable levels of VIP but had high levels of SP. The adaptation of diurnal mice to the dark eliminated VIP and increased SP, while adapting dark-reared mice to the diurnal cycle increased VIP and reduced SP. We then tested the hypothesis that immune reactions resulting from Ag presentation in the eye were linked to SP and VIP. We found that a VIP receptor antagonist, when injected into the eye with Ag, reversed ACAID in diurnal mice, while a SP receptor antagonist restored ACAID to dark-adapted mice. We further determined that injection of Ag or TNF-alpha induced VIP release, while SP was liberated into the aqueous humor following reexposure of dark-reared mice to light. Our results demonstrate a close linkage of intraocular immune reactions to neuropeptide levels in the eye.

Animals↗
PubMed1995

Comparative pharmacology of epibatidine: a potent agonist for neuronal nicotinic acetylcholine receptors.

Pharmacological properties of the (+)- and (-)-isomers of synthetic epibatidine, exo-2-(6-chloro-3-pyridyl)-7-azabicyclo-[2.2.1]heptane, were compared with nicotine and acetylcholine on several subtypes of chicken and human nicotinic acetylcholine receptors (AChRs). Both isomers of epibatidine behaved as extremely potent full agonists on chicken (alpha 3 beta 2, alpha 3 beta 4, alpha 4 beta 2, alpha 7, and alpha 8) and human (alpha 3 beta 2, alpha 3 beta 4, and alpha 7) neuronal AChRs expressed in Xenopus oocytes. Currents induced by epibatidine were effectively blocked by the nicotinic antagonists hexamethonium and mecamylamine. Apparent affinity was 100 to 1000-fold higher for epibatidine than for nicotine or acetylcholine. EC50 values ranged from 1 nM (for homomeric chicken alpha 8) to 2 microM (for homomeric chicken alpha 7). Epibatidine showed comparatively lower affinity for muscle-type AChRs from Torpedo and humans (EC50 values, 1.6 and 16 microM respectively). In binding assays, epibatidine was used on AChR subtypes immunoisolated from chicken brain and retina (alpha 4 beta 2, alpha 7, and alpha 8), the human neuronal cell line SH-SY5Y (alpha 3 and alpha 7), Torpedo electric organ (alpha 1 beta 1 gamma delta), or the human rhabdomyosarcoma cell line TE671 (alpha 1 beta 1 gamma delta). Both isomers of epibatidine exhibited extremely high affinity for all neuronal AChRs tested, with KI values ranging from 0.6 pM (human alpha 3 AChRs) to 0.6 microM (chicken alpha 7 AChRs). In contrast, epibatidine had lower affinity for Torpedo muscle-type AChRs (KI approximately 5 microM). Racemic [3H]epibatidine was an effective labeling reagent for human alpha 3 beta 2 AChRs, exhibiting a KD (0.14 nM) similar to the KI values observed for unlabeled (+)-epibatidine (0.23 nM) or (-)-epibatidine (0.16 nM).

Animals↗
PubMed1994

Long-term outcome after intravenous magnesium sulphate in suspected acute myocardial infarction: the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2)

The second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) examined the effect of an intravenous regimen of magnesium sulphate in 2316 patients with suspected acute myocardial infarction. Treatment, according to a double-blind randomised protocol, was started with a loading injection, before any thrombolytic therapy, and continued with a maintenance infusion for a further 24 h. Cause-specific mortality of randomised patients has now been examined over 1.0-5.5 (mean 2.7) years of follow-up. Mortality rate from ischaemic heart disease was reduced by 21% (95% CI 5-35%, p = 0.01) and all-cause mortality rate reduced by 16% (2-29%, p = 0.03) in magnesium-treated patients. Magnesium protects the contractile function of the myocardium from reperfusion injury ("stunning") in experimental models; this observation accords with the 25% (7-39%, p = 0.009) reduction in early left ventricular failure in the magnesium group of LIMIT-2. For such protection to occur, magnesium must be raised by the time of reperfusion since the injury is immediate. In the clinical context the timing of magnesium treatment in relation to thrombolytic therapy or spontaneous reperfusion is likely to be critical. The early benefits of this simple and safe intervention are reflected in improved long-term survival.

Double-Blind Method↗
PubMed1994

Photomutagenicity assays in bacteria: factors affecting assay design and assessment of photomutagenic potential of para-aminobenzoic acid.

Photomutagenicity assays are required for regulatory submissions of some chemicals. As yet there are no well-validated protocols available for these assays. Critical factors which may contribute to the ability of a bacterial assay to detect photomutagens (e.g. dose of UV and test chemical, exposure conditions, light source, bacterial strains) were investigated using two known photomutagens, chlorpromazine and 8-methoxypsoralen. Salmonella typhimurium strains TA98, TA102 and TA1537 and Escherichia coli strains WP2 and WP2(pKM101) were used and differences in the responsiveness of these strains were observed with these substances. Both chemicals were detected using either UV exposure in suspension or on the agar plates. On the basis of these observations and on other results reported in the literature, recommendations are made on protocol aspects for assessing photomutagenic potential in routine screening tests. Using these recommendations the sunscreen para-aminobenzoic acid was tested in S.typhimurium strains TA98, TA100, TA1535, TA1537 and E. coli strains WP2 and WP2 (pKM101), using both plate irradiation and suspension exposure conditions. No evidence of mutagenic potential was detected.

4-Aminobenzoic Acid↗
PubMed1994

Investigation of the effects of intravenous magnesium sulphate on cardiac rhythm in acute myocardial infarction.

OBJECTIVE: To examine the effect of doubling serum magnesium concentration on the incidence of arrhythmias in patients with suspected acute myocardial infarction. DESIGN: Randomised double blind clinical trial. SETTING: Coronary care unit of a teaching hospital. PATIENTS: Clinical data were collected on 2316 randomised patients with suspected acute myocardial infarction. Holter monitoring was performed in a subgroup of 70 patients and analysed in 48 patients in whom acute myocardial infarction was confirmed. INTERVENTIONS: By random allocation, patients received either an intravenous loading dose of 8 mmol magnesium sulphate over five minutes plus 65 mmol over the next 24 hours, or equal volumes of saline. MAIN OUTCOME MEASURES: (a) Clinically documented arrhythmias; (b) use of antiarrhythmic treatments, cardioversion, and insertion of a pacemaker; (c) incidence of all abnormal rhythms during Holter monitoring. RESULTS: In the main trial the incidence of rhythm disturbance while in the coronary care unit (expressed as the odds ratio (OR) for magnesium: placebo and its 95% confidence interval) was not significantly different between treatment groups for ventricular fibrillation (OR 0.74; 0.46 to 1.20), ventricular tachycardia (OR 0.87; 0.63 to 1.20), supraventricular tachycardia (OR 0.69; 0.38 to 1.26), atrial fibrillation (OR 0.92; 0.69 to 1.23), or heart block of any degree (OR 1.17; 0.83 to 1.65). Sinus bradycardia was significantly more common in the magnesium group (OR 1.38; 1.03 to 1.85; p = 0.02). These findings were corroborated by the use of treatments for rhythm disturbance and the data from Holter monitoring. CONCLUSION: The regimen of intravenous magnesium sulphate used here had no significant effect on arrhythmia in acute myocardial infarction. The reduction in mortality that has been shown with this form of treatment is not attributable to suppression of life threatening rhythm disturbances.

Aged↗