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Biomedical subjects

C Johnston

Publications and source records attributed to C Johnston.

At least 253 records · Page 14Linked to original sources
PubMed1986

Effect of diclofenac sodium, tolfenamic acid and indomethacin on the production of superoxide induced by N-formyl-methionyl-leucyl-phenylalanine in normal human polymorphonuclear leukocytes.

The effect of three non-steroidal anti-inflammatory drugs, diclofenac, indomethacin and tolfenamic acid, on the production of superoxide (O2-), by normal human polymorphonuclear leukocytes (PMNL) was studied, in vitro. The cells were activated with N-formyl-methionyl-leucyl-phenylalanine (FMLP) and O2- production was measured as superoxide dismutase inhibitable cytochrome c reduction. Cell viability was checked with assays of liberated LDH. Concentrations of the drugs considerably higher than those of therapeutic plasma were required to inhibit O2- production. The drug concentrations producing a 50% inhibition (IC50) of total O2- production were: diclofenac 2.7 X 10(-4) M, indomethacin 4.0 X 10(-4) M and tolfenamic acid 4.2 X 10(-4) M. At drug concentrations causing a significant suppression of O2- generation, diclofenac showed a slight and tolfenamic acid a marked inhibition of [3H]FMLP binding to its cellular receptor; indomethacin has earlier been shown to inhibit FMLP-binding slightly. No dismutating activity of the drugs could be demonstrated. It is concluded that the inhibition of O2- production is due to a combined effect on FMLP binding and on cellular O2- metabolism. Because of the high drug concentrations required to inhibit O2- production, this phenomenon is obviously of little significance for the anti-inflammatory effect obtained with therapeutic doses of the drugs studied.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1986

Pulmonary disease in Behçet's syndrome.

Five patients with Behçet's syndrome presenting with haemoptysis and recurrent radiographic opacities are reported, with a review of 23 similar cases. All 28 cases conformed to a definite clinical pattern with haemoptysis, usually accompanied by pyrexia, chest pain and dyspnoea, being the major feature. Typically pulmonary disease was associated with active disease at other sites, although the patients often only complained of haemoptysis. Patients with Behçet's syndrome and haemoptysis, compared to those without haemoptysis, showed a marked male predominance, with thrombophlebitis and deep vein thrombosis being more common. Rarely pulmonary disease occurred in the absence of one or other of the so called 'major' criteria on which the diagnosis of Behçet's syndrome is usually made, as was so for four of our patients who did not have ocular disease. Immunopathological evidence suggests that the underlying pathogenesis is a pulmonary vasculitis which may result in arterial and venous thromboses, pulmonary infarction, pulmonary haemorrhage and pulmonary arterial aneurysm formation. A role for immune complexes in the pathogenesis of pulmonary disease in Behçet's syndrome is suggested by the finding of circulating immune complexes in association with active pulmonary disease. Corticosteroids were initially helpful in treating active disease in the lungs, and at other sites, in most of the patients in whom they were tried, including our five patients, but serious haemoptysis occasionally recurred, despite further treatment. Four of our patients were initially treated with anticoagulants for a presumed diagnosis of pulmonary embolism, but continued to have haemoptysis. One of these patients subsequently died following massive haemoptysis, despite good anticoagulant control. The haemoptysis in most of the 28 cases was notable for its severity, and in at least 11 (39.3 per cent), pulmonary haemorrhage was the probable cause of death. All deaths due to haemoptysis occurred within six years of the first episode. Whilst pulmonary disease with haemoptysis is infrequent, it carries a very serious prognosis and for this reason correct diagnosis and appropriate treatment is imperative. Pulmonary disease with haemoptysis should be included as one of the so called 'minor' criteria in the diagnosis of Behçet's syndrome.

Adult↗
PubMed1985

Peer relationships in ADDH and normal children: a developmental analysis of peer and teacher ratings.

Peer and teacher perceptions of younger and older ADDH and normal children were compared. Peer nominations on the Pupil Evaluation Inventory revealed that ADDH children received more nominations on the Aggression factor and fewer on the Likability factor. ADDH boys received more nominations on the Withdrawal factor. Generally, older children received fewer nominations, but age did not interact with diagnosis; that is, younger and older ADDH children were perceived by peers as equally deviant. Discriminant analyses showed that peer ratings were useful in discriminating between ADDH and normal boys, but not between ADDH and normal girls. Teacher ratings of peer behavior suggested that older ADDH girls were perceived as less disturbed than younger girls. However, teacher ratings of boys revealed no age by diagnosis interactions. Low to moderate correlations were found between peer and teacher ratings of ADDH boys, and the pattern of relationship varied with age.

Age Factors↗
PubMed1985

Adriamycin cardiomyopathy in the rabbit: an animal model of low output cardiac failure with activation of vasoconstrictor mechanisms.

Chronic administration of intravenous adriamycin (1 mg . kg-1 twice weekly for 8 weeks) to rabbits resulted in a cardiomyopathy which was similar to that occurring in patients with adriamycin cardiotoxicity. We studied systemic and renal haemodynamics and the activation of vasoconstrictor mechanisms reflected by changes in plasma renin activity (PRA), noradrenaline (NA) and vasopressin (AVP) levels during the development of heart failure in this animal model. By 8 weeks cardiac failure was clearly established. At postmortem all animals had dilated hearts, pleural and pericardial effusions, ascites and hepatic congestion. Heart weights were increased (8.1 +/- 0.7 g in treated animals n = 9 vs 6.0 +/- 0.2 g in controls n = 9 p less than 0.05). Cardiac output (measured by thermodilution) fell at 8 weeks from 799 +/- 61 ml . min-1 to 624 +/- 44 ml . min-1 (n = 6 p less than 0.05) with a parallel fall in mean blood pressure from 85 +/- 2 mmHg to 75 +/- 4 mmHg. Total peripheral resistance rose in four of the six rabbits. Renal blood flow fell from 108 +/- 4 ml . min-1 to 61 +/- 6 ml . min-1 (p less than 0.05) by 8 weeks. Renal vascular resistance increased in all animals. PRA increased from 5.1 +/- 0.5 ng AI . ml-1 . h-1 to 11.6 +/- 2.6 ng AI . ml-1 . h-1 by 4 weeks (p less than 0.05) and remained elevated thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Reduced insulin sensitivity in nondiabetic, HLA-identical siblings of insulin-dependent diabetic subjects.

Nondiabetic, HLA-identical siblings of insulin-dependent diabetic subjects have an increased risk of developing diabetes. Since insulin resistance is present in newly diagnosed diabetic subjects, we studied 12 HLA-identical siblings to determine whether they have impaired insulin sensitivity. Each sibling was carefully matched for age, sex, and body weight to a control from a nondiabetic family. The insulin sensitivity index (SI) was determined after an intravenous glucose tolerance test (IVGTT) using the minimal model of insulin kinetics. The insulin sensitivity index was significantly lower in the HLA-identical siblings compared with their matched controls.

Adolescent↗
PubMed1984

Pathogenesis of insulin-dependent diabetes: a role for activated T lymphocytes.

Expression of HLA DR antigens on T lymphocytes indicates that these cells are actively involved in an immune response. Raised levels of activated T lymphocytes were found in 14 of 15 recently diagnosed but in only 7 of 28 long-standing insulin-dependent diabetics. 9 of the recently diagnosed patients retested 6 months later still had high levels of activated T lymphocytes. Even long-standing insulin-dependent diabetics had significantly higher levels of activated T lymphocytes than non-insulin-dependent diabetics and healthy controls. 5 of 7 unaffected co-twins of recently diagnosed insulin-dependent diabetics had high levels of activated T cells; this increase persisted in 2 retested 6 months later, when mildly impaired glucose tolerance had developed. These results confirm that there is an active cellular immune reaction in newly diagnosed insulin-dependent diabetics which may precede the disease and persist for at least 6 months after its appearance.

Adolescent↗
PubMed1984

Prostacyclin and thromboxane in non-insulin dependent diabetes: the chlorpropamide alcohol flush reaction revisited.

Levels of immunoreactive 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) and thromboxane B2 (TXB2) were measured in peripheral venous plasma in a group of volunteers and non-insulin dependent diabetic patients (NIDDS). Levels of these eicosanoids were close to the limit of sensitivity of the radioimmunoassays and consequently data are reported as maximal values. Basal plasma levels of 6-oxo-PGF1 alpha did not exceed 5 pg/ml in either group and maximal levels of immunoreactive TXB2 were 125 +/- 14 and 128 +/- 8 pg/ml for volunteers and NIDDS respectively. Attempts to elicit peripheral vascular prostacyclin biosynthesis in volunteers by using forearm ischaemia produced no increase in plasma 6-oxo-PGF1 alpha levels. Measurement of the combined plasma levels of 6-oxo-PGF1 alpha, 13,14-dihydro-6-oxo-PGF1 alpha, 13,14-dihydro-6,15-dioxo-PGF1 alpha and 6-oxo-PGE1 indicated that these were also low (less than 5 pg/ml) and that failure to demonstrate increased 6-oxo-PGF1 alpha levels was unlikely to have arisen from metabolism of prostacyclin to one or more of these metabolites. Measurement of 6-oxo-PGF1 alpha and TXB2 in peripheral venous plasma before and during chloropropamide alcohol flushing (CPAF) did not provide evidence for a role for these eicosanoids in the etiology of this phenomenon. These findings point to the need for a reappraisal of studies that have described altered plasma levels of 6-oxo-PGF1 alpha and TXB2 in CPAF and other pathophysiological conditions in man.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

The role of endogenous opioids in the chlorpropamide alcohol flush.

The response of plasma immunoreactive met-enkephalin (IR-met-enkephalin) to ethanol (8 g by mouth) after chlorpropamide (250 mg daily for 14 d) was studied in three groups of non-insulin dependent diabetics (a) six diabetics who showed chlorpropamide alcohol flush (CPAF) and in whom the reaction could be blocked by indomethacin, (b) five diabetics who showed CPAF but in whom the flush could not be blocked by indomethacin and (c) five diabetics who did not show CPAF. A rise in plasma IR-met-enkephalin was observed in all three groups. When the two groups of flushers were re-tested with the addition of an infusion of naloxone a rise in plasma IR-met-enkephalin was still demonstrated in both groups regardless of whether the flush was blocked by naloxone. Naloxone blocked the flush only in those six subjects whose flush could be blocked by indomethacin. In five subjects, all flushers, CPAF was tested using intravenous and oral ethanol in doses producing similar plasma ethanol levels. A facial flush was induced by both intravenous and oral ethanol. In three flushers, plasma IR-met-enkephalin levels were measured during CPAF testing with both intravenous and oral ethanol. None showed a rise in plasma IR-met-enkephalin after intravenous ethanol, despite the appearance of a facial flush, whereas all showed a rise after oral ethanol. We therefore conclude that CPAF is unlikely to be caused by a rise in plasma IR-met-enkephalin.

Administration, Oral↗
PubMed1984

Prediction of reading disability in twin boys.

Thirty-six twin boys aged between nine and 13 were assessed for intelligence and reading disability. Records of their birth status, early language development and social demographic characteristics were also available. 72 per cent of the sample had an accuracy reading age below their chronological age, and 59 per cent had a comprehension reading age below their chronological age, despite above-normal IQ. The best predictor of reading disability was preschool language status, accounting for 33 per cent of the variance in accuracy reading age discrepancy, and 23 per cent in comprehension reading age discrepancy in regression equations. This study shows that male twins are at very high risk for reading disability, and also offers support for the claim that language disability is basic to the development of reading problems.

Achievement↗
PubMed1984

Technique-related variation in results of FANA tests.

We compared the reliability and reproducibility of three tests for fluorescent antinuclear antibodies (FANA) that are routinely performed in our laboratory. Sera from 72 patients, selected according to diagnosis (SLE in 28, RA in 12, and other connective-tissue diseases in 33), and from 32 healthy controls were tested with all three assays. There were wide variations between the results obtained with these tests. The variations did not reflect sensitivity or degree of standardisation (reproducibility on retesting was greater than 95%) and appeared to be inherent in the techniques. Clinicians should be aware of the technique-related differences in FANA assays.

Antibodies, Antinuclear↗
PubMed1984

Increased responsiveness of the hypothalamic-pituitary axis after neurotoxin-induced hypothalamic denervation.

Neonatal treatment with monosodium glutamate (MSG) induces severe neuronal damage in selected brain areas, which in turn results in a number of neuroendocrine abnormalities during adult life. The present study was designed to determine what effects this partial and selective denervation of the hypothalamic-pituitary axis may have on the sensitivity of two key components of that axis, the median eminence (ME) and the anterior pituitary (AP). In order to test any changes in response that may occur after MSG treatment, the release of several peptide hormones from either the ME or the AP was evaluated in vitro, employing specific or general secretagogues. Male newborn pups of the Holtzman strain were injected with MSG every other day for 5 days, starting on day 2 of life; littermate controls received an injection of 10% NaCl. All animals were used when adult, at about 5-7 months of age. After decapitation, ME and AP tissues from control and MSG-treated rats were dissected out and incubated in vitro. Release of LHRH, SRIF, arginine vasopressin, and oxytocin from the ME was measured by direct RIA, under basal conditions and after stimulation with high K+ medium (28 mM). The results clearly indicate a marked hyperresponse of the release of each of the four neuropeptides by ME fragments from MSG-lesioned animals. The altered release was not attributable to changes in ME peptide content. In the case of the AP, the release of ACTH, LH, PRL, and GH in response to high K+ or, in some cases, to specific releasing factors, was evaluated in a dispersed cell preparation. The release of all four protein hormones was increased by high K+, and again the MSG-lesioned rats showed a pronounced hyperresponse. Corticotropin-releasing factor, at concentrations of 10(-9) and 10(-8) M enhanced ACTH release from control and MSG-lesioned rats, but the latter presented a marked hyperresponse. A similar observation on LH release was seen after stimulation with LHRH (10(-9) M). The results indicate that the neuronal damage induced by neonatal MSG treatment results in a generalized hyperresponsiveness in vitro to either specific or general secretagogues by ME or AP tissues, which may suggest the development of a denervation-type supersensitivity in the hypothalamic-pituitary axis. Since the release of these peptide hormones is sluggish in MSG-lesioned rats under in vivo conditions, it seems plausible to conclude that the major defect after the neurotoxin damage may reside in the loss of neurotransmitter systems normally innervating and regulating the activity of the peptidergic neurons.

Adrenocorticotropic Hormone↗
PubMed1983

Low serum C4 concentrations: an inherited predisposition to insulin dependent diabetes?

Twenty two out of 86 insulin dependent diabetics had serum C4 concentrations below the normal range. None of 41 non-insulin dependent diabetics tested had low concentrations. Low C4 values were seen in insulin dependent diabetes irrespective of the duration of the disease and did not appear to correlate with complement activation. There was a close correlation in C4 values between identical cotwins, even when only one was diabetic. These results suggest that a low serum C4 concentration is an inherited phenomenon and may predispose towards the development of insulin dependent diabetes.

Adolescent↗
PubMed1983

HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs.

A total of 106 pairs of identical twins, of whom 56 were concordant and 50 discordant for insulin-dependent diabetes, were typed for HLA-DR. In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. This was therefore the first demonstration of a genetic difference between concordant and discordant identical twin pairs. These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone.

Adolescent↗