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Biomedical subjects

J S Gibson

Publications and source records attributed to J S Gibson.

At least 55 records · Page 3Linked to original sources
PubMed1993

Volume-sensitive KCl co-transport and taurine fluxes in horse red blood cells.

Potassium (using 86Rb+ as a tracer), amino acid and taurine fluxes were measured in horse red blood cells (RBCs). No volume-sensitive component of alanine and glycine transport was observed, and although volume-sensitive taurine fluxes were observed in most animals, their absolute magnitudes were small. K+ fluxes, however, were shown to be particularly volume sensitive; they were stimulated by cell swelling and inhibited by cell shrinkage. Sizeable fluxes were present at normal cell volumes. The volume-sensitive K+ flux was Cl- dependent and was abolished by Cl- replacement with methylsulphate. The Cl(-)-dependent K+ fluxes in horse red blood cells were stimulated by lowering in external pH to 6.9 and by treatment with the sulphydryl-reacting agent, N-ethylmaleimide. They were inhibited by the potent K(+)-Cl- co-transport inhibitor, DIOA, ([(dihydroindenyl)oxy]alkanoic acid) but were insensitive to the Na(+)-K(+)-Cl- co-transport inhibitors, frusemide and bumetanide. A Cl- channel inhibitor, 5-nitro-2-(phenylpropyl-amino)-benzoate (NPPB), produced partial inhibition. These results suggest that regulatory volume decrease in horse red blood cells is achieved predominantly by volume-sensitive K+ efflux mediated via a K(+)-Cl- co-transport system with similar properties to those observed in the red blood cells of other species. The significance of these findings and their rheological consequences are discussed.

Animals↗
PubMed1992

Chromatin structure changes suggest a compensatory response to c-myc gene amplification in malignant fibrous histiocytoma.

Changes in chromatin structure as determined from DNAse I hypersensitive site analysis are associated with c-myc amplification and increased transcript/protein levels in malignant fibrous histiocytoma (MFH) cell lines. A DNAse I hypersensitive site near the PO promoter region was observed in one MFH cell line (UR HCL 1), and in normal fibroblasts (HFF), but not in an MFH cell line with an amplified c-myc gene (P3C). A DNAse I hypersensitive site exclusive to P3C amplified c-myc was identified slightly 3' of exon one. No alterations in c-myc DNAse I hypersensitive site patterns were observed in HFF fibroblasts following serum release, when peak levels of c-myc transcript were induced. DNAse I hypersensitive site patterns associated with gene amplification may reflect a compensatory response by P3C cells to an abundance of c-myc transcript. Furthermore, elevated levels of protein in P3C cells provide additional evidence that amplified c-myc is an oncogene in MFHs.

Chromatin↗
PubMed1992

Pathogenesis of equine herpesvirus-1 in specific pathogen-free foals: primary and secondary infections and reactivation.

Six specific pathogen-free foals shown to be free of equine herpesvirus-1 and 4 (EHV-1 and -4) and lacking in maternally-derived antibodies were used to investigate the pathogenesis of EHV-1 in horses. Following primary intranasal inoculation with EHV-1 all foals showed signs of a mild, self-limiting upper respiratory tract infection. A leucopenia was observed, comprising both a lymphopenia and neutropenia. Virus was isolated from nasal mucus and buffy coat cells over several days during the clinical episode and after the animals became clinically normal. Notwithstanding the mildness of the clinical disease, virus was not eliminated completely and intravenous administration of dexamethasone resulted in reactivation of latent EHV-1 in animals which had received only a single dose of the virus. In a second infection given to four foals, 61 days after the primary inoculation, no clinical signs were observed, haematological changes were minimal and viraemia was absent.

Animals↗
PubMed1992

The pathogenicity of Ab4p, the sequenced strain of equine herpesvirus-1, in specific pathogen-free foals.

The sequencing of the genome of equine herpesvirus-1 (EHV-1) is reported in Elizabeth A. R. Telford, Moira S. Watson, Kathryn McBride, and Andrew J. Davison, 1992, Virology, 189, 304-316. The sequence was derived using a plaque-purified clone of EHV-1 strain Ab4 (designated Ab4p). To ensure that Ab4p shares the pathogenic characteristics of parental Ab4 (hereafter Ab4), both were inoculated intranasally into foals, specifically free from EHV-1 and EHV-4. Clinical signs, including rectal temperature, were similar for both viruses. In addition, nasal shedding of virus was observed over a 1- to 2-week period postinfection, and viremia was established with both Ab4 and Ab4p. Isolation of virus from one foal following intravenous administration of steroids indicates that Ab4p can establish latency and undergo reactivation. Finally, retinal lesions were observed and these were similar to those seen with Ab4. In conclusion, several pathogenic characteristics of Ab4 are retained in the plaque-purified clone, Ab4p.

Animals↗
PubMed1992

The activity of (S)-1-[(3-hydroxy-2-phosphonyl methoxy) propyl] cytosine (HPMPC) against equine herpesvirus-1 (EHV-1) in cell cultures, mice and horses.

The activity of the nucleotide analogue, (S)-1-[(3-hydroxy-2-phosphonyl methoxy) propyl] cytosine (HPMPC), against equine herpesvirus-1 (EHV-1) was tested in cell culture, mice and foals. The ED50 for plaque reduction was found to be 0.07 and 0.03 microgram/ml in RK-13 and EEL cells respectively. In mice, a single administration of HPMPC (20 mg/kg, s.c.) was very effective at reducing clinical signs and virus replication if given on the day before intranasal inoculation with EHV-1. Treatment on the day of infection or day 1 p.i. was less effective, but still significantly reduced clinical signs and virus titres in the target organs (lungs and nasal tissue). Furthermore, HPMPC was found to protect mice partially from an intracerebral inoculation with EHV-1. Experiments in the horse suggested that HPMPC was also very active against EHV-1 in the natural host. Thus a single administration of HPMPC at 20 mg/kg, s.c., on the day of infection, markedly reduced clinical signs and nasal excretion of virus following intranasal inoculation with EHV-1. HPMPC given as a divided dose of 1 mg/kg on day 0 and day 3 p.i. had no effect on clinical signs but did reduce nasal excretion of virus. The significance of these results is discussed.

Administration, Intranasal↗
PubMed1992

Serological responses of specific pathogen-free foals to equine herpesvirus-1: primary and secondary infection, and reactivation.

Serum antibody (virus neutralisation, complement fixation, IgM and IgG) responses to equine herpesvirus-1 (EHV-1) infection were measured in six foals which were initially free from EHV-1 and EHV-4 infection and maternally-derived antibodies. Following primary infection, high titres of virus neutralisation and complement fixation antibodies were detectable against EHV-1, however, corresponding antibody levels against EHV-4 were low or inapparent, although the two viruses share a number of cross-reactive epitopes. In addition, following the primary infection with EHV-1, IgM levels increased before those of IgG, virus neutralisation and complement fixation antibodies, peaked sooner and thereafter declined. Stimulation of IgM levels was observed on secondary infection with EHV-1 given 61 days later. In contrast, IgG, virus neutralisation and complement fixation antibodies following primary infection were more sustained and no increase in their levels was observed on secondary infection. No consistent changes in IgM or IgG levels were seen after administration of dexamethasone to reactivate latent virus.

Animals↗
PubMed1992

Gastroduodenal dysfunction as a cause of gastric bacterial overgrowth in patients undergoing mechanical ventilation of the lungs.

We have studied 15 patients undergoing mechanical ventilation of the lungs for evidence of a relationship between gastroduodenal dysfunction and gastric bacterial overgrowth. Duodenal reflux was detected by quantitative measurement of conjugated bilirubin in gastric aspirate specimens. The pH and bacterial content of these specimens were analysed. A minority of specimens with pH less than 3.5 contained measurable numbers of viable bacteria. The total bacterial count and the count of Gram negative bacteria correlated significantly with specimen pH in both cases (P less than 0.001, in both). In the 72 specimens of gastric aspirate with pH greater than 3.5, the presence of Gram negative bacteria was associated significantly with detectable bilirubin (P less than 0.001). The total bacterial count was greater also in specimens containing bilirubin (P = 0.009). These results suggest that gastroduodenal dysfunction may promote gastric bacterial overgrowth, contributing to the development of ventilator-associated pneumonia.

Adult↗
PubMed1991

A murine model for studying EHV-1-induced abortion.

Balb/c mice were infected with two abortigenic strains of equine herpesvirus-1 (EHV-1) by intranasal inoculation. The inoculation of one strain produced subclinical disease while the other produced a disease characterised by weight loss, constitutional signs, and death in the most severely affected animals. When pregnant mice were infected by the same method of inoculation, one strain of virus produced premature parturition; both strains produced fetal abnormalities. In some cases, virus could be detected in the aborted fetuses by means of virus isolation and immunofluorescent staining.

Abortion, Veterinary↗
PubMed1991

Amantadine and sparteine inhibit ATP-regulated K-currents in the insulin-secreting beta-cell line, HIT-T15.

1. The effects of pharmacological agents that potentiate insulin release were studied on ATP-regulated K-currents (K-ATP currents) in the insulin-secreting beta-cell line HIT-T15 by use of patch-clamp methods. 2. The tricyclic drug, 1-adamantanamine (amantadine), reversibly inhibited both whole-cell currents (with a Ki of 120 microM) and single channel currents in inside-out patches. This effect was principally due to an increase in a long closed state which reduced the channel open probability. The related compound, 1-adamantanol, in which the amino group is substituted by a hydroxyl one, did not inhibit K-ATP currents substantially. 3. The alkaloid, sparteine, reversibly inhibited both whole-cell K-ATP currents (Ki = 171 microM) and single channel currents in inside-out patches. 4. The results suggest that sparteine and amantadine can block the K-ATP channel from either side of the membrane and support the idea that at least part of the stimulatory effect of these agents on insulin secretion results from inhibition of this channel.

Adenosine Triphosphate↗
PubMed1989

The ATP- and tolbutamide-sensitivity of the ATP-sensitive K-channel from human pancreatic B cells.

The ATP- and sulphonylurea-sensitivity of the ATP-sensitive K-channel was measured in human pancreatic B cells. In inside-out patches, half-maximal inhibition of channel activity was produced by 10 mumol/l ATP (with 2 mM Mg2+) and ATP-inhibition was partially antagonised by ADP. A significantly lower sensitivity to ATP was found in whole-cell recordings. Tolbutamide inhibited whole-cell ATP-sensitive K-currents half-maximally at 18 mumol/l; the sensitivity to tolbutamide was somewhat less in the inside-out patch. Ca-activated K-channels were unaffected by tolbutamide (10 mmol/l). These results resemble those found for rodent B cells and suggest that sulphonylureas exert their therapeutic effects in Type 2 (non-insulin dependent) diabetes by inhibition of the ATP-sensitive K-channel.

Adenosine Triphosphate↗
PubMed1986

Effect of high-dose dexamethasone on outcome from severe head injury.

The conflicting evidence concerning the influence of high-dose steroids on intracranial pressure (ICP) and outcome following severe head injury has led to the institution of the prospective double-blind controlled trial reported here. Severely head-injured patients admitted to intensive care during a 3-year period were randomly allocated to a dexamethasone- or placebo-treated group. Adults in the steroid group received dexamethasone, 50 mg intravenously, as a bolus on admission to the neurosurgical unit, then 100 mg on Days 1, 2, and 3, 50 mg on Day 4, and 25 mg on Day 5 on continuous intravenous infusion. Children received proportionate intravenous dosages calculated on a weight basis. Severity of head injury was assessed from admission Glasgow Coma Scale (GCS) scores and the appearance of the admission computerized tomography scan. Intracranial pressure (ICP) was monitored in all patients from the surface subarachnoid space. Outcome at 6 months was assessed using the Glasgow Outcome Scale. Steroid and placebo groups were similar in terms of admission GCS score, intracranial pathology, incidence of associated injuries, and time interval from injury to admission to intensive care. The ICP generally increased during the first 48 hours of intensive therapy; there was no difference in this trend between the steroid and placebo groups. A poorer outcome was observed in patients with elevated ICP who received steroids. No increase in the incidence of pulmonary, gastrointestinal, or other extracranial complications was seen in the steroid group. The 6-month outcome did not differ between the steroid and placebo groups. No advantage of high-dose dexamethasone on ICP trends or clinical outcome in the treatment of severe head injury has emerged from this study.

Adolescent↗
PubMed1985

Electrically evoked activity in the human external anal sphincter.

Following electrical stimulation of perianal skin, short latency evoked electromyographic (EMG) responses from the external and sphincter have been interpreted as the electrophysiological correlate of the anal reflex. Delayed responses in patients with idiopathic faecal incontinence have been interpreted as evidence for denervation of the external anal sphincter. Electrically evoked responses were studied in normal subjects, either before and during spinal anaesthesia (n = 8), or before and during competitive neuromuscular blockade (n = 4), instituted for operative purposes. Short latency responses persisted unchanged in either latency or duration during spinal anaesthesia whereas long latency responses were completely abolished. Both short and long latency responses were abolished during competitive neuromuscular blockade. Short latency responses are not spinal reflex in nature, but due to stimulus activation of alpha-motoneuronal terminal branches. Delayed responses in incontinent patients cannot be interpreted as evidence for pudendal neuropathy. Long latency (i.e. greater than 40 ms) responses demand a functional sacral spinal cord and represent the true anal reflex. Their wide range of latency in normal subjects suggests this measurement will be of little use in confirming the presence or absence of pudendal neuropathy, and that other measures of neuropathy may be more appropriate.

Adolescent↗
PubMed1984

Effect of amphotericin B and gestational age on sodium transport across the rat visceral yolk sac placenta in vitro.

The transport properties of the rat visceral yolk sac placenta from Days 14.5 to 18.5 of gestation were studied in vitro. All tissues had a positive potential difference, fetal side relative to maternal side, and showed net Na transport towards the fetus. Basal short-circuit current and net Na flux increased rapidly with gestational age over the period studied. Amphotericin B applied to the maternal surface of the yolk sac stimulated current and net Na flux, indicating that the apical membrane Na permeability limited transport and revealing a reserve capacity for transport. Contrary to their basal values, current and Na flux following treatment with amphotericin were independent of gestational age.

Amphotericin B↗
PubMed1984

Effects of intravenous delivery systems on infused red blood cells.

The effects of various intravenous delivery systems on the integrity of infused red blood cells (RBCs) were studied. Using a factorial design, whole blood and packed RBCs were infused through i.v. delivery systems employing various combinations of i.v. tubing diameter and length, needle gauge, infusion rate (5 and 50 ml/hr), type of infusion pump (piston, diaphragm, or peristaltic operation), and type of blood product. The age and temperature of the blood filter used were held constant. A 5-ml sample of the blood product obtained during each experimental run was analyzed for plasma free-hemoglobin to assess the degree of hemolysis. Osmotic fragility of the RBCs was evaluated by measuring the percentage of hemolysis in the blood products in various concentrations of sodium chloride solution. Type of blood product and i.v. pump were the only variables significantly influencing RBC hemolysis. In both blood products, a greater degree of hemolysis occurred with the peristaltic-type pump than with the other types of pumps. In packed RBCs, the diaphragm-type pump produced greater hemolysis than the piston-type pump, but hemolysis was similar in whole-blood samples. Regardless of the type of pump, more hemolysis occurred in whole blood at the 5-ml/hr infusion rate than at the 50-ml/hr rate, but the converse was true in packed RBCs. Samples of both blood products were less osmotically fragile than their respective controls at sodium chloride concentrations ranging from 0.30 to 0.50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Transfusion↗
PubMed1983

Intensive management of severe head injuries. A scheme of intensive management of severe head injuries.

Seventy-six severely head-injured patients, 67% of whom had Glasgow Coma scores of five or less on admission, were managed according to an intensive treatment regime which included controlled hyperventilation (under full muscular paralysis), high-dose steroids, dehydrating agents, diuretics and hypnotics (Althesin and thiopentone). Intracranial pressure (ICP) was measured throughout the period of controlled ventilation. Treatment was directed to keeping the mean ICP below 25-30 mmHg and to the prevention of increases in ICP during chest physiotherapy and other noxious stimulation. Six months after injury 46% of patients had died and 4% were vegetative survivors, whilst 43% had made a good recovery or were only moderately disabled. Features associated with worse than average prognosis were: low coma score, pupillary abnormalities, respiratory dysrhythmia and ICP greater than 30 mmHg. Spontaneous hyperventilation was a relatively good initial feature. These results support the employment of intensive care in severely head-injured patients, particularly those with diffuse brain injury.

Adolescent↗