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Biomedical subjects

J A Steele

Publications and source records attributed to J A Steele.

At least 19 recordsLinked to original sources
PubMed2000

Importance of phenylalanine 107 in agonist recognition by the 5-hydroxytryptamine(3A) receptor.

The 5-hydroxytryptamine (5-HT)(3) receptor is a member of the ligand-gated ion channel receptor family with significant homology to the nicotinic acetylcholine, gamma-aminobutyric acid(A), and glycine receptors. In this receptor class, the agonist binding site is formed by parts of the extracellular amino-terminal region. This study examines the effects of altering phenylalanine 107 (F107) of the 5-HT(3AL) subunit, obtained from NG108-15 cells, using site-directed mutagenesis. The wild-type (WT) and mutant receptors were expressed in HEK 293 cells and characterized using both whole-cell patch-clamp and radioligand binding. The tyrosine mutant F107Y exhibits a significantly lower affinity for the agonist 5-HT (K(i) = 203 versus 15.6 nM) and an increase of similar magnitude in the EC(50) value (10.6 versus 1.2 microM) compared with WT. The activation kinetics of the maximal currents generated by 5-HT with this mutant were markedly slower than those of the WT receptor, but application of supramaximal concentrations of the agonist markedly decreased the time to half-peak. The asparagine mutant F107N displayed a significantly higher affinity for 5-HT than the WT receptor (1.62 versus 15.6 nM), which was mirrored in direction and magnitude by changes in the EC(50) value for this agonist (0.2 versus 1.2 microM). In contrast to the WT receptor, the mutant F107N was activated by acetylcholine (EC(50) = 260 microM). The response to acetylcholine was blocked by the 5-HT(3) receptor antagonist renzapride with a similar IC(50) value as that determined against currents generated by 5-HT in the WT receptor. These data suggest that F107 is an important determinant of agonist recognition at the 5-HT(3) receptor.

Animals↗
PubMed1999

Plastic bullet injuries in Northern Ireland: experiences during a week of civil disturbance.

BACKGROUND: Plastic bullets were introduced to Northern Ireland for riot-control purposes in 1973. Their use has been controversial, with a number of fatalities. In the week beginning July 7, 1996, some 8,000 plastic bullets were fired during widespread rioting. METHODS: Details of injuries attributed to plastic bullets were obtained retrospectively from patient notes for the period July 8 to 14, 1996, in six hospitals. A total of 172 injuries in 155 patients were recorded. RESULTS: Nineteen percent of injuries were to the face/head/neck, 20% were to the chest or abdomen, and 61% were to the limbs. Abbreviated Injury Scale scores ranged from I to 3. Forty-two patients were admitted for hospitalization, three to intensive care units. No fatalities occurred. CONCLUSION: Plastic bullet impact to the abdomen or above may cause life-threatening injuries. Below this site, major trauma is unlikely.

Abbreviated Injury Scale↗
PubMed1996

The accident and emergency department as a single portal of entry for the reassessment of all trauma patients transferred to specialist units.

127 patients who were transferred to a regional referral centre for specialist treatment within 48 h of serious injury were reassessed on arrival in the receiving accident and emergency department by a trauma team. 80 transferred patients (63%) required intervention in the accident and emergency department to complete assessment or resuscitation. In view of the well recognised difficulties in managing patients with multiple trauma and the possibility that initially occult injuries may become clinically significant during transport, transferred trauma patients should be reassessed in the accident and emergency department of the receiving hospital by a trauma team consisting of senior medical staff experienced in all aspects of trauma care.

Emergency Medicine↗
PubMed1994

The effects of first aid training on public awareness of the management of a seriously injured patient.

Members of the public were questioned regarding previous first aid training and whether they believed that they would be able to manage a seriously injured person adequately. They were then assessed as to their awareness of basic principles of dealing with such a person. It was found that, whilst confidence as an independent variable was not associated with better knowledge, those who had some form of training were significantly more confident about their own abilities and also performed better in the assessment. However there remained a minority who would be unwilling to become involved in the initial treatment of a seriously injured person and training did not appear to reduce this tendency.

Educational Status↗
PubMed1993

Production of 15-HETE by cultured smooth muscle cells from cerebral artery.

Hydroperoxyeicosatetraenoic acids (HPETEs) are potent vasoconstrictors which have been implicated in the pathogenesis of the delayed cerebrovascular spasm which follows subarachnoid haemorrhage. We have previously shown that one of their stable breakdown products, 15-hydroxyeicosatetraenoic acid (15-HETE), is the major lipoxygenase product released from isolated cerebral arteries. To investigate the vascular cell type responsible for their production we have established the culture of smooth muscle cells from cerebral arteries and have measured their release of HETEs upon stimulation with arachidonic acid. The cultured cells isolated from bovine cerebral arteries expressed smooth muscle phenotype as they stained positively for smooth muscle alpha-actin and not factor VIII-related antigen. Furthermore, these cells possessed the calcium and potassium conductances characteristic of smooth muscle cells. Upon incubation with arachidonic acid, the major lipoxygenase product was 15-HETE; no leukotrienes were detected. The formation of 15-HETE was concentration-dependent and was attenuated by nordihydroguaiaretic acid, but not by indomethacin. Similar to intact cerebral artery, cultured cerebrovascular smooth muscle cells have lipoxygenase activity, the major product of which is 15-HETE. These results are consistent with a possible role of the HPETEs in the pathogenesis of cerebral vasospasm.

Animals↗
PubMed1991

Free radicals mediate actions of oxyhemoglobin on cerebrovascular smooth muscle cells.

Single smooth muscle cells were isolated from the basilar artery of the rat by enzymatic dispersion. The membrane properties of the cells were assessed using the patch-electrode voltage-clamp technique, and cell viability was monitored using fluorescein diacetate uptake. Exposure of the cells to oxyhemoglobin (5 microM) resulted in 1) contraction, 2) the appearance of membrane blebs, 3) an increase in the outward potassium currents, 4) a decrease in the membrane resistance, and 5) cell death. In contrast, no effect of oxyhemoglobin on cultured murine neuroblastoma cells was observed. Methemoglobin (100 microM) had no effects on the smooth muscle cells. Catalase (300 units/ml) or dimethyl sulfoxide (0.5%) protected against the effects of oxyhemoglobin; superoxide dismutase (100-1,000 units/ml) provided only partial protection. Exposure of the cells to superoxide anions generated by xanthine (1 mM) plus xanthine oxidase (10 units/l) or to hydrogen peroxide (500 microM) caused an increase in the outward potassium currents without affecting membrane resistance. Generation of hydroxyl radicals by metal ions plus hydrogen peroxide caused the same effects as oxyhemoglobin, that is, an increase in the potassium currents, followed by a decrease in the membrane resistance and cell death. In conclusion, it appears that oxyhemoglobin exerts its effects on vascular smooth muscle cells by the generation of free radicals, chiefly hydroxyl radicals.

Animals↗