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Biomedical subjects

J R Dawson

Publications and source records attributed to J R Dawson.

At least 73 records · Page 4Linked to original sources
PubMed1984

Activity of antibodies recovered from immune complexes of ovarian cancer patients.

Ascites fluids from ovarian cancer patients contain immune complexes (IC). Attempts were made to characterize those antigens to which the patient is reacting using antibody recovered from these complexes. Polyethylene glycol (PEG) precipitation and protein A Sepharose 4B affinity chromatography were used to isolate IC. Dissociation of the IC was achieved by G-150 gel filtration in 0.1 M acetic acid, 0.15 M NaCl. Activity of antibody preparations was measured using a binding assay with 125I-labeled staphylococcal protein A. Confluent monolayers of various cell lines (including human ovarian and cervical carcinoma lines, human lymphoblastoid cell lines, human and chick embryo fibroblasts) were used. Six of nine antibody preparations isolated from ovarian cancer patient IC contained at least some reactivity against all cell types. Specificity was further defined using cell adsorption assays and polyacrylamide gel electrophoresis. These results indicate what appears to be autoreactivity directed against a normal component(s) of many cells. No evidence for an ovarian cancer-restricted response was shown. Immunoprecipitation analyses showed several polypeptide bands on autoradiograms (49K, 46K, 33K, 25K), which deviated distinctly from the pattern obtained for whole cell extracts.

Adenocarcinoma↗
PubMed1984

The effectiveness of N-acetylcysteine in isolated hepatocytes, against the toxicity of paracetamol, acrolein, and paraquat.

The protective effect of N-acetylcysteine against the toxicity of paracetamol, acrolein, and paraquat was investigated using isolated hepatocytes as the experimental system. N-acetylcysteine protects against paracetamol toxicity by acting as a precursor for intracellular glutathione. N-acetylcysteine protects against acrolein toxicity by providing a source of sulfhydryl groups, and is effective without prior conversion. Paraquat toxicity can be decreased by coincubating the cells with N-acetylcysteine, but the mechanism for the protective effect is not as clear in this instance. It is probable that N-acetylcysteine protects against paraquat toxicity by helping to maintain intracellular glutathione levels.

Acetaminophen↗
PubMed1984

Incoordinate left ventricular wall motion after acute myocardial infarction. Serial echocardiographic assessment.

Serial simultaneous M mode echocardiograms, phonocardiograms, and apexcardiograms were recorded and digitised in 20 patients with a first myocardial infarction immediately after and two, three, seven, and 56 days after hospital admission. Left ventricular maximum and minimum dimensions, normalised maximum rate of change of dimension during systole and diastole, and three previously defined indices of the coordination of left ventricular wall motion were measured. Incoordinate left ventricular wall motion was detected in all patients but was more pronounced in those with an anterior infarction (15) than in those with an inferior infarction (5). Although on the first three days after admission patients with heart failure (7) were indistinguishable echocardiographically from those without (13), differences became apparent later with an increase in left ventricular dimension and more pronounced evidence of incoordination in those with heart failure. In the first two days after admission patients with full thickness infarcts (14) were indistinguishable echocardiographically from those with partial thickness infarcts (6) despite the former being of much larger size as judged by the measurement of cardiac enzyme activity. Abnormal indices of coordination reverted to normal with time in patients with partial thickness infarctions, whereas only partial reversion of these indices occurred in those with full thickness infarctions. The use of digitised M mode echocardiograms is a sensitive means of detecting and following the evolution of incoordinate left ventricular wall motion in patients with an acute myocardial infarction whatever the position, type, or size of the infarct. Incoordination so detected is, however, quantitatively unrelated to infarct type or size or to the clinical state of the patient.

Adult↗
PubMed1984

The role of the lysosome in natural killing: inhibition by lysosomotropic vital dyes.

Recent evidence has indicated the importance of lysosomes in natural killing (NK). The lysosomotropic dye neutral red, at concentrations greater than 2 X 10(-5) M, inhibits NK activity of large granular lymphocytes (LGL). Inhibition is at the level of effector cell activity rather than target cell susceptibility. Neutral red inhibits NK activity without affecting the viability of the effector cell population or the response of lymphocytes to the mitogen, phytohaemagglutinin (PHA). While the mechanism of this inhibition is unknown, neutral red-treated peripheral blood lymphocytes (PBL) do not suppress untreated effector cell populations. Furthermore, neutral red does not influence the binding of effector cells to target cells. Since natural killing by neutral red-treated PBL recovers slowly upon incubation of the cells at 37 degrees, inhibition is not due to selective toxocity. Trypan blue, another frequently used lysosomotropic vital stain, has no effect when effector cells are pretreated with 10(-3) M dye for 30 min or less. However, effector cells first treated with neutral red lose red granular staining following treatment with trypan blue for as little as 10 min at room temperature. Natural killing by neutral red pretreated PBL also recovers more quickly following brief incubation with trypan blue. Treatment of effector cells with trypan blue and neutral red simultaneously prevents accumulation of neutral red in cytoplasmic granules and subsequent inhibition of NK.

Cytoplasmic Granules↗
PubMed1983

The effectiveness of different sulfate precursors in supporting extrahepatic sulfate conjugation.

The effectiveness of different sulfur-containing compounds in supplying inorganic sulfate for sulfate conjugation was studied in isolated cells from rat small intestine, kidney and lung. With cells isolated from the small intestine and kidney, inorganic sulfate was by far the most effective source for intracellular active sulfate as judged by the ability to support sulfate conjugation of 7-hydroxycoumarin. Kidney cells could also use cysteine, N-acetylcysteine and glutathione as a sulfate source, whereas isolated small intestinal cells did not seem to break down and use these sulfur-containing compounds. With isolated lung cells cysteine was the most efficient sulfate precursor. Of the other precursors N-acetylcysteine and inorganic sulfate were used for sulfate conjugation to some extent.

Animals↗
PubMed1983

Human natural killing against ovarian carcinoma.

Natural killing (NK) by lymphocytes from normal individuals against primary and established ovarian carcinoma cell lines was tested in short-term chromium release assays. Two established cell lines and 5/6 primary cell lines tested showed significant susceptibility to NK. Primary cell lines are, in general, less sensitive to NK than long-term cultured target cells. A common NK recognition determinant on ovarian carcinoma cells and on the erythroleukaemic K562 cells was demonstrated by cold target inhibition assays. The recognition structure was also present on an ovarian cell line resistant to NK but not on the insensitive leukaemic cell line, SB. The activity against ovarian carcinoma cells was associated with the presence of large granular lymphocytes (LGL) previously shown to be the major effector cells against K562 targets. In fractions obtained by Percoll gradient centrifugation of lymphocytes, only fractions with a high content of LGL demonstrated good NK activity. LGL mediated NK against both non-adherent K562 and the adherent ovarian carcinoma target cells independent of monocytes.

Cell Line↗
PubMed1983

Symptoms, haemodynamics, and exercise capacity during long term treatment of chronic heart failure. Experience with pirbuterol.

An open study of long term treatment with an oral beta 2 agonist (pirbuterol 20 mg three times daily) was undertaken in 63 patients with severe chronic heart failure. During three months of treatment 20 (32%) patients died, of whom 16 were taking the drug at the time of death. Mortality was related to initial functional class (New York Heart Association classification: 23% in grade III and 75% in grade IV). Concomitant treatment with digoxin did not affect mortality. The drug was well tolerated by most patients but unwanted side effects necessitated withdrawal of the drug in six (10%). Thirty-five patients were continuing to take the drug after three months, of whom 22 reported symptomatic improvement and only four deterioration. There was a relation between symptomatic improvement and increase in exercise capacity. At initial haemodynamic assessment a single dose of pirbuterol increased the cardiac index by 34% and the stroke index by 21%. Left ventricular filling pressure fell by 23% and systemic vascular resistance by 22%. Haemodynamic reassessment after three months of continuous treatment in 29 patients showed maintained improvement in the group as a whole, although individual variation was considerable. There was no apparent relation between haemodynamic improvement and improvement in exercise duration and symptoms. Severe heart failure has a poor prognosis. Identification of those patients who may derive benefit from treatment with a particular drug is not yet possible.

Adrenergic beta-Agonists↗
PubMed1982

The isolation of rat lung cells for the purpose of studying drug metabolism.

A method was developed for the isolation of viable cells from rat lungs. The cells were a heterogeneous population, which maintained a high percentage viability for up to 3 hr on incubation at 37 degrees. Reduced cofactor levels (NADH, NADPH) decreased on incubation, but ATP remained constant. The cells were active in the metabolism of the two xenobiotics studied. A model compound, 7-ethoxycoumarin, was O-deethylated and subsequently conjugated with glucuronic acid and sulphate, whilst a pharmaceutical agent, N-acetylcysteine, was de-acetylated.

Adenosine Triphosphate↗
PubMed1982

Regulation of human natural killing by levamisole.

The effect of levamisole on human natural killing (NK) has been studied. In short-term chromium release assays, levamisole at a concentration of 10(-3) M was inhibitory to NK when present in the assays. Pretreatment of NK effector cells and K562 target cells with levamisole separately indicated that the effect was on effector cell activity and was not due to any change in target cell susceptibility. Inactivation of the effector cells required greater than 4 h pretreatment with levamisole if NK activity was subsequently tested in the absence of the drug. Pretreatment with levamisole for up to 19 h had no effect on the lymphocyte proliferative response to phytohemagglutinin (PHA). NK activity of drug-inactivated effector cells recovered after further incubation in levamisole-free medium. Levamisole at 10(-4) M or less had no effect on NK either by pretreatment or by its presence in the NK assays.

Cell Line↗
PubMed1981

Treatment of chronic heart failure with pirbuterol: acute haemodynamic responses.

Fifty-nine patients with severe chronic heart failure were given pirbuterol, a beta agonist with vasodilator and positive inotropic properties. The acute haemodynamic responses to both single (20 patients) and incremental doses (39 patients) were measured. Pirbuterol increased cardiac index and reduced left ventricular filling pressure and systemic vascular resistance with only small changes in heart rate and blood pressure. Maximal effects were observed at an average of 170 minutes after a single oral dose of pirbuterol. In the incremental dose studies the plasma pirbuterol concentration was found to increase with increasing doses and was related to the magnitude of the haemodynamic response. Pirbuterol was well tolerated, and no drug-related side effects were recorded. Oral pirbuterol clearly improved pump performance in these patients, the haemodynamic changes being consistent with vasodilatation as the dominant mechanism rather than a direct inotropic effect.

Administration, Oral↗
PubMed1981

The mechanism of entry of viruses into plant protoplasts.

Plant protoplasts may be efficiently infected with viruses. Attachment to the plasmalemma is a critical step in infection; positively charged viruses readily adhere and infect but negatively charged viruses require the presence of a polycation (e.g. poly-L-ornithine) before infection can occur. The role of the polycation appears to be twofold: to modify the charge of the virus and to damage the surface of the protoplast. Virus probably enters the protoplast during repair of damaged regions of the plasmalemma. Pinocytosis does not appear to play a significant part in inoculation.

Adhesiveness↗
PubMed1981

Calcium antagonist drugs in chronic stable angina. Comparison of verapamil and nifedipine.

The relative efficacy of two calcium antagonist drugs, verapamil, 120 mg three times a day and nifedipine, 20 mg three times a day, was examined in a double-blind randomised trial. Patients were assessed at the end of four week periods by a maximal treadmill exercise test, the frequency of anginal attacks, glyceryl trinitrate consumption, and side effects. Sixteen point praecordial maps were recorded at rest, immediately after exercise, and at minute intervals for 10 minutes. Total ST segment depression (epsilon ST) was used as a measure of myocardial ischaemia. Both verapamil and nifedipine increased maximal work capacity but epsilon ST at the termination of the test remained constant. Both drugs reduced the frequency of anginal attacks and glyceryl trinitrate consumption. Systolic blood pressure at rest and on exercise was reduced by both drugs. Verapamil and nifedipine were equally effective in treating angina, but side effects were more common with nifedipine.

Adult↗