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Biomedical subjects

A Scott

Publications and source records attributed to A Scott.

At least 145 records · Page 8Linked to original sources
PubMed1996

Single channel properties and calcium conductance of the cloned expressed ryanodine receptor/calcium-release channel.

The calcium-release channel/ryanodine receptor of the sarcoplasmic reticulum is a 2.3 million-D structure required for intracellular calcium release during excitation-contraction coupling in skeletal muscle. This structure is the largest ion channel characterized to date and is composed of four 565,000-D ryanodine receptors plus four molecules of FKBP12. In the present study we describe the single channel properties of the cloned expressed ryanodine receptor, with and without FKBP12, reconstituted into planar lipid bilayers with Ca as the charge carrier. The conductance for Ca (luminal, 53 mM/cytoplasmic, 10 microM) was 103 pS for the cloned expressed RyR and for the native channel from rabbit skeletal muscle. Conductance through the channel was Ca dependent: A decrease in the Ca gradient to luminal 10.6/cytoplasmic 10 microM reduced conductance to 68 pS for both the cloned and native RyR. The recombinant ryanodine receptor consistently behaved like the native skeletal muscle channel in terms of activation by caffeine, calcium, and ATP; inhibition by ruthenium red; and modulation by ryanodine. In the absence of FKBP12, the cloned expressed RyR exhibited multiple subconductance states and addition of FKBP12 reduced the frequency of subconductance states. These results show that with Ca as the charge carrier, the single channel properties of the cloned expressed RyR plus FKBP12 are essentially the same as those of the native channel.

Animals↗
PubMed1996

Breast feeding and antibiotics.

At all times the necessity of prescribing to breast feeding mothers should be questioned. The advantages and disadvantages should be carefully assessed for both mother and baby. Whenever possible the long-acting form of the drug should be avoided. The use of drugs with short half lives minimises the risk of accumulation, e.g. Cefotaxime 1.1 hours, Ceftriaxone 7.25 hours. Aim to avoid breast feeding when milk drug concentrations are at their peak. In general, this occurs 1-2 hours following oral medication. As a general principle, advising the administration of medication immediately following a breast feed is the safest option for the baby but this is not true for all drugs. Where information is available, choose the drug which appears in the least concentration in breast milk. All infants should be monitored for uncharacteristic symptoms and signs. If it is essential that a drug with known potential serious toxicity to the infant has to be prescribed to the mother, then breast feeding should be discontinued. As the infant's metabolic and excretory capacities rapidly improve during the first months of life, the risk of toxicity to the infant will decrease with increasing age of the infant.

Anti-Bacterial Agents↗
PubMed1995

Purification of a 12,020-dalton protein that enhances the activation of mitogen-activated protein (MAP) kinase by MAP kinase kinase.

We have purified 3500-fold from rabbit skeletal muscle a 12,020-Da mitogen-activated protein kinase kinase (MEK)-enhancing factor (MEF) that stimulates both mitogen-activated protein kinase (MAPK) autophosphorylation and the rate (24-fold) at which the enzyme is phosphorylated by MEK in vitro. This was manifest by the finding that in the presence of MEF, molar equivalents of MEK to MAPK were sufficient to produce fully phosphorylated (2.1 +/- 0.4 mol/mol; S.D., n = 3) and activated MAPK. This contrasted with the 40:1 molar excess ratio of MEK to MAPK required to produce fully phosphorylated and activated MAPK in the absence of MEF. Phosphoamino acid analysis revealed that in the presence of MEF, phosphorylation of MAPK by MEK was ordered, with Tyr-185 phosphorylation preceding Thr-183 phosphorylation. However, the rate at which Thr-183 was phosphorylated relative to Tyr-185 was greatly increased. The finding that MEF stimulated MAPK autophosphorylation and increased its ability to be phosphorylated by MEK suggests a mechanism of action in which MEF interacts with MAPK to alter its conformation.

Amino Acid Sequence↗
PubMed1995

Lactation is disrupted by alpha-lactalbumin deficiency and can be restored by human alpha-lactalbumin gene replacement in mice.

Mice carrying either a deletion of the murine alpha-lactalbumin (alpha-lac) gene (null allele) or its replacement by the human alpha-lac gene (humanized allele) have been generated by gene targeting. Homozygous null females are alpha-lac-deficient, produce reduced amounts of thickened milk containing little or no lactose, and cannot sustain their offspring. This provides definitive evidence that alpha-lac is required for lactose synthesis and that lactose is important for milk production. Females homozygous for the humanized allele lactate normally, indicating that human alpha-lac can replace murine alpha-lac. Mouse and human alpha-lac expression was compared in mice heterozygous for the humanized allele. The human gene expressed approximately 15-fold greater mRNA and approximately 14-fold greater protein than the mouse, indicating that the major determinants of human alpha-lac expression are close to, or within, the human gene and that the mouse locus does not exert a negative influence on alpha-lac expression. Variations in alpha-lac expression levels in nondeficient mice did not affect milk lactose concentration, but the volume of milk increased slightly in mice homozygous for the humanized allele. These variations demonstrated that alpha-lac expression in mice is gene dosage dependent.

Alleles↗
PubMed1995

Evaluating the effects of GP remuneration: problems and prospects.

General practice reform is occurring in a number of countries. Little is known, however, of the effects of remunerating general practitioners on the costs and outcomes of care. Valuable lessons can be learned for the scope and design of future research, however, from the existing literature on the effects of general practioner (GP) remuneration. The objectives of this paper are to highlight some of the problems and pitfalls that should be avoided in any further research on the effects of GP remuneration and to identify the main issues for future research. Eighteen studies of the effects of GP remuneration have been reviewed, with a focus on the methods used. Eight studies addressed the effect of changes in the level of remuneration, three evaluated the effect of special payments and bonuses and seven assessed the effects of different remuneration systems. Although there are often practical constraints on the choice of study design, crude 'before and after' analyses and the use of aggregate data should be avoided in favour of prospective evaluations using consultation-based data. The studies reviewed did not evaluate the effects of remuneration on patient welfare and were characterised by the omission of major confounding variables and an inability to generalise to other settings. These issues present a considerable challenge to researchers, GPs and policy makers.

Australia↗
PubMed1995

Carotid surgery in northern Tasmania: a retrospective review.

A retrospective survey of 138 carotid endarterectomies performed in Northern Tasmania over a 6 year period was conducted to identify risk factors for postoperative neurological complications. A total of 80% of patients were operated on for transient ischaemic attacks (TIA) referable to stenosis of the ipsilateral internal carotid artery (ICA). A total of 77% of patients who were operated on had angiographic evidence of severe (over 80%) stenosis of the affected ICA. A combined postoperative permanent neurological deficit and mortality rate of 5.8% was achieved. Severe stenosis of the contralateral internal carotid artery and pre-operative symptomatic instability were associated with the development of postoperative neurological complications.

Adult↗
PubMed1995

Heart and arterial disease risk factor levels in the Scottish workforce: cross-sectional study of risk factor levels. The SHARP Committee. Scottish Heart and Arterial Disease Risk Prevention.

Between 1991-93 a specially trained team of nurses screened 19,435 subjects from various workforces in different regions of Scotland to identify cardiovascular disease risk factor levels in the Scottish working population. The regions visited provided a wide geographical spread. Name, age, occupation, social class, personal and family history of cardiovascular disease were recorded along with consumption of tobacco, alcohol and salt. Height and weight were measured and Body Mass Index (BMI) calculated; systolic (SBP) and diastolic (DBP) blood pressure, blood glucose and blood cholesterol were also measured. The proportion of social class I-IV in men studied was 49, 22, 22, and 7% respectively and in women 28, 29, 39 and 5%. Fifty two per cent of men and 61% of women had never smoked and 24% of men and 17% of women had previously stopped smoking. Twenty one per cent of both sexes were still smoking. Eighteen per cent of men drank more than 21 units of alcohol per week and 3.4% of women drank more than 14 units per week. Mean values of SBP and DBP increased with age and the percentage with hypertension (> or = 148/90 mm Hg) in men and women was 5% and 24% respectively. Mean BMI was slightly higher in men than women (25.3 & 24.5 respectively) and there was a significant (p < 0.01) rise in BMI with age in both sexes. Forty six per cent of men and 32% of women were classified as overweight (BMI > 25) while 9% of men and 9% of women were classified as obese (BMI > 30).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Private costs associated with abdominal aortic aneurysm screening: the importance of private travel and time costs.

OBJECTIVES: To assess the importance of the private costs incurred by patients when making a judgment on the economics of screening for abdominal aortic aneurysm (AAA), and to explore the variation in such costs depending on screening location. SETTING: A district general hospital and general practitioner surgeries. METHODS: Four hundred and ninety nine consecutive subjects attending for AAA screening completed a questionnaire asking about travel arrangements for the journey to and from the clinic, the distance travelled, the time taken, the mode of transport, and any out-of-pocket expenses incurred. In addition, at the clinic each subject was asked what activities they had forgone in attending the clinic. Time was valued differently depending on whether work or leisure activities were forgone. The total private cost for each attender was calculated and comparison was made between attenders at hospital and at general practice. RESULTS: A significantly greater proportion of subjects were accompanied when attending hospital than when attending general practitioner (GP) surgeries. Most attenders travelled by car, but the journey time was significantly longer for those visiting hospital. The expected total private cost associated with attendance for AAA screening was 5.47 pounds. Attendance at GP surgeries had a lower private cost (4.21 pounds) than attendance at hospital (6.87 pounds). Only 7.3% of all men surveyed, and 6.5% of all companions, would have been taking part in some form of paid occupation if they had not attended for screening. CONCLUSION: Despite the fact that most attenders for AAA screening will be retired, the associated private costs are appreciable and should be considered in assessing the economics of such screening programmes. The level of private costs varied depending on the location of screening; clinics held at GP practices had lower private costs than those held at hospital.

Aged↗
PubMed1995

Improving patient moving and handling skills.

Training in manual handling should incorporate a problem-solving approach. The handling and moving of patients is a learned skill that needs regular revision. Assessment of patient capabilities is essential, as is the provision of a safe, ergonomically satisfactory environment. There is no single technique that works in all situations.

Back Pain↗
PubMed1994

Stabilization of calcium release channel (ryanodine receptor) function by FK506-binding protein.

FK506-binding protein (FKBP12) was originally identified as the cytosolic receptor for the immunosuppressant drugs FK506 and rapamycin. The cellular function of FKBP12, a ubiquitously expressed 12,000-dalton proline isomerase, has been unknown. FKBP12 copurifies with the 565,000-dalton ryanodine receptor (RyR), four of which form intracellular Ca2+ release channels of the sarcoplasmic and endoplasmic reticula. By coexpressing the RyR and FKBP12 in insect cells, we have demonstrated that FKBP12 modulates channel gating by increasing channels with full conductance levels (by > 400%), decreasing open probability after caffeine activation (from 0.63 +/- 0.09 to 0.04 +/- 0.02), and increasing mean open time (from 4.4 +/- 0.6 ms to 75 +/- 41 ms). FK506 or rapamycin, inhibitors of FKBP12 isomerase activity, reverse these stabilizing effects. These results provide the first natural cellular function for FKBP12, and establish that the functional Ca2+ release channel complex includes FKBP12.

Animals↗
PubMed1994

Diffuse astrocytic swelling and increased second messenger activity following acute Haemophilus influenzae meningitis--evidence from a rat model.

Despite numerous epidemiological analyses of bacterial meningitis there is very little pathological data concerning the acute glial and neuronal responses to the disease. We have developed a safe, easily used rat model for Haemophilus influenzae type b meningitis. We measured cerebral blood flow, glucose utilisation and second messenger activity in this model, and carried out parallel light and ultrastructural analysis of glial and neuronal responses. Only protein kinase C activity was changed from control values. We obtained evidence for massive astrocytic swelling and neuronal degeneration. We posit that cytotoxic mechanisms may contribute to the pathology of meningitis.

Adenylyl Cyclases↗
PubMed1994

Tracer imaging in lung cancer.

Lung cancer is the leading cause of death from cancer in males. Adequate staging is essential if proper treatment is to be administered. Current morphological imaging modalities are confronted with problems in the staging of lung cancer, in the evaluation of treatment response, and in establishing whether a residual mass is due to fibrosis, residual tumors or local recurrence. Nuclear medicine imaging techniques have advanced from planar gallium-67 citrate scans in the 1970s to multihead-detector single-photon emission tomography for 67Ga, Thallium-201 chloride, technetium-99m SestaMIBI, monoclonal antibodies, and octreotide compounds. Results of positron emission tomography (PET) with fluorine-18 deoxyglucose or carbon-11 methionine are very promising. PET units are now employed in centers all over the world and the recently introduced whole-body PET units will be ideal for the correct staging of malignant diseases. The current status of various nuclear medicine imaging procedures is reviewed. The problems and advantages of each scintigraphic procedure are discussed. It appears that many of the problems that confront morphological imaging will be solved by nuclear medicine techniques in the future.

Aged↗