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Biomedical subjects

H Johnston

Publications and source records attributed to H Johnston.

At least 19 recordsLinked to original sources
PubMed1992

Effects of oral contraceptives containing oestrogen combined with norethisterone or levonorgestrel on erythrocyte cation transport in normal women.

1. Studies were undertaken in pre-menopausal women to examine the effects of treatment with standard oestrogen-progestogen and progestogen-ony oral contraceptives on erythrocyte Na+,K+ co-transport and Na(+)-Na+ countertransport over 3- and 6-month periods. Concurrent observations were made on other erythrocyte cation transport components, plasma lipid concentrations, plasma renin activity, plasma aldosterone concentration and blood pressure. 2. Na+,K+ co-transport, measured as the ouabain-resistant, frusemide-sensitive component of 86Rb+ influx, and Na(+)-Na+ countertransport, measured as the ouabain-resistant, phloretin-sensitive component of 22Na+ influx, were both increased in women taking, on days 1-21 of their cycle, ethinyloestradiol (30-50 micrograms) combined with norethisterone (1000 micrograms or 500-1000 micrograms) for 3 or 6 months. Neither of these fluxes was increased in a control group of women, or in women treated for the same time periods with ethinyloestradiol combined with levonorgestrel. 3. In a separate study of erythrocyte cation transport (excluding Na(+)-Na+ countertransport), in which women undertook treatment with norethisterone only (350 micrograms/day) for 6 months starting 6 weeks post partum, no changes in Na+,K+ co-transport were observed at 3 or 6 months; there were no changes in cation transport in a corresponding control group. 4. The results of these studies confirm that certain oral contraceptive compounds can alter erythrocyte cation transport, and indicate that norethisterone in higher dose preparations is the component predominantly responsible. The alterations observed could not be explained by a direct link with concurrent changes in plasma triacylglycerol concentrations or in the renin-aldosterone axis and were not closely associated with elevation of blood pressure.

Adolescent↗
PubMed1992

Increase in serum total angiotensin-converting enzyme activity with enalapril therapy in humans: a controlled trial.

1. In a controlled, randomized double-blind trial, 15 patients with essential hypertension were treated with enalapril 5-20 mg/day, or doxazosin 1-8 mg/day, during a 7 week dose titration phase. This was followed by 7 weeks of combined treatment with doxazosin and enalapril. 2. Blood was taken after a 2 week placebo run-in phase, and at 3 and 7 weeks in the single-agent and combined treatment phases, for measurement of plasma renin activity (PRA), plasma angiotensin II (AII), plasma aldosterone and serum free and total angiotensin-converting enzyme (ACE) activities. 3. Doxazosin had no effect on serum free or total ACE activities. 4. Enalapril reduced serum free ACE activity and increased serum total ACE activity, which at 7 weeks was significantly greater than in patients receiving doxazosin. 5. In those patients who received enalapril, 10 mg/day for 3 weeks and then 20 mg/day for 4 weeks (n = 12), with or without doxazosin, mean serum total ACE activity increased by 51%. PRA was also increased in this group, but there were no changes in plasma AII or aldosterone concentrations.

Double-Blind Method↗
PubMed1992

An Na, K ATPase inhibitor from ultrafiltrate obtained by hemodialysis of patients with uremia.

Ultrafiltrate obtained by hemodialysis of patients with uremia who were not taking cardiac glycosides was used as a source of Na, K adenosine triphosphatase inhibitor for purification and further study. Inhibitory activity was measured by a linked-enzyme assay and by effect on rubidium 86 uptake in guinea pig aortic strips. Two approaches were used in purification: dialysis with a 500 dalton membrane followed by gel filtration with Sephadex G-25, and removal of protein by acidification and boiling followed by Sephadex G-10. The first procedure failed to separate the inhibitor from the salt fraction, whereas the second separated the inhibitor from the salt peak but resulted in partial coelution of the inhibitor with endogenous pyruvate, which interferes with the linked-enzyme assay. Pooled, concentrated G-10 elution fractions from the early part of the inhibitor peak, which were free of pyruvate, produced a dose-response relationship by enzymatic assay that was close to parallel with that for ouabain. Like ouabain, these fractions also inhibited 86Rb uptake in guinea pig aorta. Despite these properties, our previous work has demonstrated that the inhibitor, unlike some other ouabain-like or digitalis-like substances obtained from blood or urine, has no apparent role in body fluid homeostasis.

Animals↗
PubMed1992

The relationship between long-term glycaemic control and diabetic nephropathy.

Urine albumin excretion was studied by two widely accepted methods in 210 patients with insulin-dependent diabetes mellitus and related to the mean of serial glycosylated haemoglobin (HbA1) measurements made every 3 months during the previous 6 years. Microalbuminuria (albumin excretion rate > 20 micrograms/min) was present in 9.5 per cent of patients when defined by a 24-hour collection and 8.1 per cent of patients when defined by a timed overnight urine sample. Those with microalbuminuria, as estimated from a timed overnight urine sample, had a longer duration of diabetes but otherwise did not differ in age, duration of diabetes or arterial blood pressure from patients whose albumin excretion rate was 20 micrograms/min or less irrespective of the method of urine collection. The mean and the most recent HbA1 levels differed significantly between the normal and the microalbuminuric groups when defined by the 24-hour albumin excretion rate (p < 0.001, p < 0.01), but no significant difference between these groups was found when albumin excretion rates were calculated from the timed overnight urine sample. Albumin excretion rate, examined in relation to mean HbA1, increased significantly with worsening glycaemic control whether measured over 24 hours or overnight (p < 0.05, p < 0.01). These findings support an association between glycaemic control and microalbuminuria, but the correlation is weak, dependent on the method of urine collection and is just as good for a relatively short-term as for a long-term measure of average blood glucose.

Adolescent↗
PubMed1992

Models for the in vitro assessment of neurotoxicity in the nervous system in relation to xenobiotic and neurotrophic factor-mediated events.

We have been investigating the use of three culture types for both screening and mechanistic neurotoxicology in vitro. These are the neuroblastoma cell lines (IMR32 - human; C-1300 - mouse), primary mixed monolayer cultures of the rat and chick embryonic midbrain ('micromass' systems) and organotypic whole rat brain reaggregate cultures. The performance of these models for neurotoxicity resting has been investigated with ethylcholine mustard aziridinium (ECMA), vincristine, aluminium, glutamate receptor antagonists, MPTP, and 'hypothyroidism'. From a 'screening' viewpoint, in vitro exposure through a tiered testing system (ranging from simple cytotoxicological parameters in the neural cell lines to neurotransmitter measurements in the organotypic cultures) may permit detection of CNS neurotoxicity and delineation of possible mechanisms. The type of developmental neurotoxicological information gained is highlighted in the cases of aluminum and the glutamate receptor antagonists. High concentrations of aluminum caused significant neural cell death in differentiated neuroblastoma cell lines after approximately two weeks exposure in vitro. In contrast, cell death was detected in the developing midbrain cultures as early as 24 - 48 hr. Studies in whole brain reaggregates suggest that cholinotoxicity may occur in a similar time-frame and is consistent with some of aluminium's effects in vivo. Preliminary experiments have shown that exposure of immature developing midbrain rat primary cultured neurones to the glutamate receptor antagonists, AP3 and MK-801 induces neural cell death which may relate to control of NGF by glutamate cells. Developing neural culture systems may prove useful for testing agents which cause neurotoxicity through disturbances of neurotrophic function.

Aluminum↗
PubMed1990

Effect of dialysis on circulating Na,K ATPase inhibitor in uremic patients.

Deproteinized plasma from patients with renal failure had an inhibitory effect on Na,K ATPase activity measured in vitro by a linked-enzyme assay. No inhibitory effect was observed with plasma from normal subjects or from patients undergoing chronic ambulatory peritoneal dialysis. The inhibition of Na,K ATPase whether measured by the linked-enzyme assay or by 86Rb uptake in guinea pig aortic strips was decreased acutely by a single hemodialysis treatment, but was unaffected during a time-control study or ultrafiltration. Changes in Na,K ATPase activity and in Rb uptake were correlated, indicating that the presence of the enzyme inhibitor in uremic plasma was associated with depressed Na pump activity. Change in inhibition of Na,K ATPase activity did not correlate with change in body weight. Dialysis in vitro against a membrane of molecular weight 3,500 cut-off decreased the inhibitory effect of uremic plasma on Na,K ATPase. It was concluded that a dialyzable, low-molecular-weight Na,K ATPase inhibitor circulates in uremia but has no demonstrable role in volume homeostasis.

Adult↗
PubMed1990

Breast Cancer Screening Project in Northeast Florida.

The American Cancer Society--Duval Unit, in June, 1987, helped organize a community demonstration screening project involving all hospitals and institutions with mammography units in the area. A Northeast Florida Cooperative Breast Cancer Screening Group was formed comprised of physicians and administrators from each institution. A total of 1,200 women agreed to participate in the project and each underwent complete screening including education, instruction in self-examination, physical examination by a physician and mammography as indicated according to ACS guidelines. Of the study group, 1,032 women were eligible for mammography at a participating center, and 628 (61%) underwent a mammogram at no cost to them as instructed. Twenty four (4%) had definite abnormalities which led to biopsy and seven (1%) of them had malignant lesions. The medical community organized to provide breast cancer screening and follow-up with low-cost mammography.

Adult↗
PubMed1989

Changing spectrum of hemoptysis. Underlying causes in 148 patients undergoing diagnostic flexible fiberoptic bronchoscopy.

A retrospective study to examine the underlying causes of hemoptysis in patients undergoing diagnostic bronchoscopy was conducted. We found hemoptysis to be caused by bronchitis in 55 (37%) of 148, bronchogenic carcinoma in 28 (19%) of 148, tuberculosis in 10 (7%) of 148, and bronchiectasis in 1 (1%) of 148 patients. Compared with previous studies, it appears that hemoptysis is less likely to be caused by bronchiectasis or tuberculosis while hemoptysis caused by bronchitis has increased proportionately. The rate of occurrence of hemoptysis caused by bronchogenic carcinoma has not changed significantly. All patients with underlying bronchogenic carcinoma had a positive smoking history and abnormal chest roentgenogram. The rate of hemoptysis was not a good indicator of the underlying disease.

Adult↗
PubMed1989

Calcium homeostasis and exercise.

Calcium homeostasis is altered by strenuous physical exercise. The mechanism is unclear. Our study was designed to investigate this relationship, particularly any associated changes in the calcium regulating hormones. Six subjects carried out a strenuous exercise programme for 10 min on a bicycle ergometer. Blood samples were analysed for ionized calcium, total calcium, calcitonin and pH. Plasma parathormone was assayed using a new and very sensitive N-terminal assay. Serum ionized calcium was significantly elevated by exercise at 50% of maximum aerobic capacity (VO2 max). The rise persisted until the late recovery phase, when it fell significantly below resting levels. Plasma parathormone levels were initially depressed by moderate exercise (50% VO2 max.) but were significantly elevated during and immediately after severe exercise. Our results suggest that exercise stimulates the hormonal, osteolytic influences acting on the skeleton, with increases in plasma parathormone and mobilisation of calcium stores. These changes may provide a supply of raw material allowing the osteogenic mechanical forces initiated by exercise to produce a positive skeletal balance. In view of the possible relevance of these findings to the understanding and management of osteoporosis we feel that this area merits further study.

Adult↗
PubMed1989

Obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder complain of anxiety-producing intrusive thoughts and/or perform repetitive, anxiety-reducing rituals. A combination of behavior therapy and drug therapy is generally beneficial in this relatively common disorder. Behavior therapy consists of exposing patients to anxiety-provoking situations and helping them avoid ritualistic responses. Drug therapy appears to work by blocking serotonin reuptake in the brain.

Adult↗
PubMed1987

Bone marrow transplantation in a patient with myelodysplasia associated with diffuse eosinophilic fasciitis.

A 34-year-old man with diffuse eosinophilic fasciitis and a hypocellular myelodysplastic syndrome underwent marrow transplantation from an HLA-identical brother. Prompt hematopoietic reconstitution was observed, strongly suggesting that the marrow hypocellularity was caused by neither a serum inhibitory factor nor a microenvironmental disorder. The patient died of disseminated cytomegalovirus infection too early to evaluate the impact of hematopoietic reconstitution on the eosinophilic fasciitis. Nevertheless, marrow transplantation may offer a therapeutic option for those patients with this disorder who develop severe hematopoietic dysfunction and who have a suitable marrow donor.

Adult↗
PubMed1987

Involvement of cyclic nucleotides in prejunctional modulation of noradrenaline release in mouse atria.

1 In mouse isolated atria previously incubated with [3H]-noradrenaline, 8-bromo-cyclic AMP (3-270 microM) produced a concentration-dependent increase in the fractional stimulation-induced outflow of radioactivity. 8-Bromo-cyclic GMP induced a lesser increase in the stimulation-induced outflow. 2 The phosphodiesterase inhibitors: M&B 22948 (90 microM); ICI 63197 (30 and 90 microM) and 3-isobutyl-1-methylxanthine (90 microM) increased the fractional stimulation-induced outflow. Together these results indicate that cyclic AMP may have a modulatory effect on noradrenaline release. 3 The inhibition of the stimulation-induced outflow produced by clonidine (0.03 microM) and its facilitation produced by phentolamine (1 microM) were unaltered in the presence of 8-bromo-cyclic AMP (90 microM). However, in the presence of 8-bromo-cyclic AMP (270 microM), the facilitatory effect of phentolamine was enhanced, but the inhibitory effect of clonidine (0.03 microM) was unaltered. In the presence of ICI 63197 (30 microM) the inhibitory effect of clonidine (0.03 microM) was unaltered, but the facilitatory effect of phentolamine (1 microM) was slightly enhanced. 4 Isoprenaline (0.003-0.1 microM) enhanced the fractional stimulation-induced outflow, an effect blocked by propranolol (0.1 microM). In the presence of 8-bromo-cyclic AMP (90 microM), the facilitatory effect of isoprenaline (0.01 microM) was blocked. In the presence of ICI 63197 (30 microM) the facilitatory effect of isoprenaline (0.003 microM) was potentiated. 5 These results suggest that whereas beta-adrenoceptor-mediated enhancement of noradrenaline release is linked to the stimulation of adenylate cyclase and enhanced formation of cyclic AMP, alpha-adrenoceptor-mediated inhibition of noradrenaline release is not linked to inhibition of adenylate cyclase activity.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Antipicornavirus activity of substituted phenoxybenzenes and phenoxypyridines.

Phenoxybenzenes and phenoxypyridines were prepared and tested for the effect of substituents on antipicornavirus activity. The most active compound, 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (8), demonstrated broad-spectrum antipicornavirus activity. Compound 8 and several analogues each given orally prior to and during infection protected mice against an otherwise lethal challenge with coxsackievirus A21.

Animals↗
PubMed1986

Prejunctional beta-adrenoceptors in rabbit pulmonary artery and mouse atria: effect of alpha-adrenoceptor blockade and phosphodiesterase inhibition.

In rabbit isolated pulmonary artery previously incubated with [3H]-noradrenaline, isoprenaline (0.3 microM) had no effect on the stimulation-induced outflow of radioactivity. However, if the phosphodiesterase inhibitor ICI 63,197 (30 microM) or the alpha-adrenoceptor blocker phentolamine (1 microM) was present, then isoprenaline significantly enhanced the stimulation-induced outflow, an effect blocked by propranolol (0.1 microM). ICI 63,197 (30 microM) but not phentolamine significantly enhanced the stimulation-induced outflow of radioactivity. In mouse isolated atria previously incubated with [3H]-noradrenaline and stimulated at a frequency of 10 Hz, isoprenaline had no effect on the stimulation-induced outflow of radioactivity; this is in contrast to its release-enhancing effects at stimulation frequencies of 4 Hz and 2 Hz. The facilitation of stimulation-induced outflow by isoprenaline at 4 Hz was blocked by propranolol (0.08 microM) which, by itself, had no effect on the stimulation-induced outflow. At a stimulation frequency of 2 Hz in mouse atria the facilitatory effect of isoprenaline (0.01 microM) was significantly greater in the presence of ICI 63,197 (30 microM) which, by itself, had no effect on the stimulation-induced outflow. Similarly, the facilitatory effect of isoprenaline was significantly greater in the presence of phentolamine (1 microM) but, in this case, phentolamine significantly enhanced the stimulation-induced outflow. These results suggest that facilitatory prejunctional beta-adrenoceptors are present in both rabbit pulmonary artery and mouse atria. The effects of the phosphodiesterase inhibitor ICI 63,197 suggest that they are linked to adenylate cyclase in both tissues and we propose that the ability of phentolamine to facilitate the release and enhance the effect of isoprenaline may be due to the blockade of alpha-adrenoceptor inhibition of adenylate cyclase. This latter proposition needs further investigation.

Adenylyl Cyclases↗
PubMed1979

Eosinophilic granuloma mimicking a pituitary tumor.

The authors present the case report of a patient in whom hypopituitarism, diplopia, and visual field defects were due to eosinophilic granuloma. Radiographic studies were suggestive of a pituitary tumor and subsequent histological evaluation showed replacement of the anterior pituitary by histiocytic cells. Eosinophilic granuloma should be included in the differential diagnosis of an intrasellar mass.

Adult↗