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Biomedical subjects

J D Johnston

Publications and source records attributed to J D Johnston.

At least 19 recordsLinked to original sources

Regulation of GABA(A) receptor alpha1 protein is a sensitive indicator of benzodiazepine agonist efficacy.

The effect of benzodiazepine agonists of varying efficacy on gamma-aminobutyric acidA receptor alpha1 subunit protein expression was determined in primary cultured cerebellar granule cells. After 48 h exposure to 1 microM drug concentrations, flunitrazepam, diazepam, and the partial agonists Ro 19-8022 and bretazenil, but not the partial agonists Ro 42-8773, Ro 41-7812 or imidazenil, decreased alpha1 subunit protein expression. The grading of effect of the benzodiazepine partial agonists on alpha1 subunit protein expression is consistent with their agonist efficacies. This model, therefore, appears to act as a sensitive indicator of benzodiazepine agonist efficacy with the ability to differentiate between partial agonists.

Animals

Flunitrazepam rapidly reduces GABA(A) receptor subunit protein expression via a protein kinase C-dependent mechanism.

Acute flunitrazepam (1 microM) exposure for 1 h reduced GABA(A) receptor alpha1 (22+/-4%, mean+/-s.e.mean) and beta2/3 (21+/-4%) subunit protein levels in cultured rat cerebellar granule cells. This rapid decrease in subunit proteins was completely prevented by bisindolymaleimide 1 (1 microM), an inhibitor of protein kinase C, but not by N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H-89, 4.8 microM), an inhibitor of protein kinases A and G. These results suggest the existence of a benzodiazepine-induced mechanism to rapidly alter GABA(A) receptor protein expression, that appears to be dependent on protein kinase C activity.

Animals

Cardiopathia fantastica exposed by rapid sequential serum creatine kinase analysis.

Rapid, sequential serum creatine kinase measurements may be used to exclude acute myocardial infarction in patients presenting with acute chest pain. Two cases of cardiopathia fantastica (the cardiac variant of Munchausen's syndrome) are described. Both patients presented with symptoms of acute myocardial infarction and had electrocardiographic changes consistent with this diagnosis. Both patients also had a raised serum creatine kinase level at the time of presentation but were unable to mimic the rise in serum creatine kinase associated with acute myocardial infarction. Munchausen's syndrome was suspected when both patients responded poorly to news that their enzyme results excluded acute myocardial infarction.

Adult

Serum total antioxidant activity after myocardial infarction.

Serum total antioxidant activity (TAA), albumin and uric acid were measured on admission, and for the next 2 days in 56 patients suffering myocardial infarction, 20 of whom received streptokinase. The 'antioxidant gap', the difference between the serum TAA and the sum of the serum albumin and uric acid activity, was calculated. No significant changes in serum total antioxidant activity were observed in either group of patients between admission, day 1 and day 2. However, a decline in the 'antioxidant gap' after myocardial infarction was associated with a significantly higher mortality.

Adult

Gastrointestinal permeability and absorptive capacity in sepsis.

OBJECTIVE: To assess gastrointestinal permeability and functional absorptive capacity in patients with sepsis. DESIGN: Case control study to analyze gastrointestinal permeability and functional absorptive capacity of septic patients by differential saccharide absorption (from an oral test solution) and excretion. SETTING: The intensive Therapy Unit of St. Thomas' Hospital, London, UK. PATIENTS: Twenty patients with a mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 18.4 who were admitted to the intensive care unit with a diagnosis of sepsis. All patients were on enteral feeding. Patients with abdominal pathology were excluded. INTERVENTIONS: An oral test solution containing 5 g of lactulose, 1 g of L-rhamnose, 0.5 g of D-xylose, and 0.2 g of 3-O-methyl-D-glucose dissolved in water to a final volume of 100 mL was administered to patients and controls. Urine was collected for 5 hrs starting immediately after administration of the test solution and the saccharide content of the urine was estimated and expressed as a percentage recovery of the oral test solution. MEASUREMENTS AND MAIN RESULTS: Septic patients had increased lactulose/L-rhamnose urine excretion ratios (0.23 +/- 0.19) compared with control subjects (0.03 +/- 0.01, p < .001), consistent with increased gastrointestinal permeability in sepsis. Septic patients had decreased L-rhamnose/3-O-methyl-D-glucose urine excretion ratios (0.14 +/- 0.07) compared with normal controls (0.28 +/- 0.08, p < .001), consistent with decreased gastrointestinal functional absorptive capacity in sepsis. CONCLUSIONS: Patients with acute sepsis exhibit increased gastrointestinal permeability and decreased gastrointestinal functional absorptive capacity in comparison with healthy control subjects. These abnormalities may contribute to the pathophysiology of sepsis.

3-O-Methylglucose

Serial measurements of serum creatine kinase are of most use in the exclusion of acute myocardial infarction in patients with a history of heart disease.

Rapid sequential measurements of serum CK were assessed in the diagnosis and exclusion of acute myocardial infarction (MI) in 94 patients presenting to St Thomas' Hospital, London, with acute chest pain of less than 12 h duration. A blood sample was taken from patients on admission to hospital and then a second sample was taken within 12 h of admission. Serum CK activity was assayed on both samples and delta log10 (serum CK) per hour calculated to distinguish infarct from non-infarct using a discriminant value of 0.015. Ninety-six per cent of patients with acute MI were diagnosed on the basis of clinical history and electrocardiographic evidence alone, and did not require biochemical confirmation. Serial estimation of serum CK contributed positively towards the exclusion of acute MI in 77% of patients who presented with chest pain and who had a previous history of heart disease, but towards only 11% of cases in the absence of a history of heart disease.

Adult

Smokers have less dense bones and fewer teeth.

Women and men who smoke are more slender than their non-smoking counterparts and have a bone density appropriate to their degree of slenderness. As a result, they are more likely to sustain a fracture than their non-smoking counterparts. The lower bone density found in smokers may arise because of less stress and strain imposed on the skeleton by a slim physique. Smokers have poorer oral hygiene and less teeth than their non-smoking counterparts. The relationship between smoking and tooth pathology remains unclear: smoking may either act via a direct mechanism based on the toxicity of tobacco smoke or indirectly through body weight (ie the effect on teeth is part of a wider effect on bone structure).

Adult

Bone-derived serum enzymes and bone density in perimenopausal Caucasian women.

Serum levels of bone-origin alkaline phosphatase and of tartrate-resistant acid phosphatase were measured in Caucasian women aged 41-69 years who had volunteered for bone densitometry. Bone alkaline phosphatase and tartrate-resistant acid phosphatase were inversely correlated with vertebral bone density and with femoral neck bone density. Bone alkaline phosphatase and acid phosphatase were also significantly correlated, consistent with the concept of 'coupling' between osteoblast and osteoclast activity.

Acid Phosphatase