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Biomedical subjects

G Laszlo

Publications and source records attributed to G Laszlo.

At least 19 recordsLinked to original sources
PubMed1992

Expression of variable exon A-, B-, and C-specific CD45 determinants on peripheral and thymic T cell populations.

A mAb (I/24) has been generated that is specific for a determinant on mouse CD45 molecules. Reactivity of this mAb with a panel of CD45 transfected cell lines demonstrated that the determinant recognized is dependent upon expression of one or more CD45 variable exons and that exon C is sufficient for its expression. The exon C-specific epitope detected by I/24 is expressed at high density on essentially all B lymphocytes and at an intermediate density on the vast majority of CD8+ splenic T cells. Two distinct subpopulations of CD4+ splenic T cells were detected, a minor subpopulation that expresses this exon determinant at high density and a major subpopulation that expresses it at a much lower density. This first identification of a CD45RC-specific reagent allowed a comparison of the expression of exon A-, exon B-, and exon C-specific determinants on peripheral and thymic lymphoid populations. When splenic lymphocytes were analyzed for expression of CD45RA (reactive with mAb 14.8), CD45RB (reactive with mAb 23G2 or mAb 16.A), and CD45RC (reactive with mAb I/24) determinants, it was found that each of these CD45 determinants had a distinct pattern of expression on CD4+ and CD8+ T cells and B cells. CD45RB and RC epitopes were also detected at high density on a small proportion (0.7 to 4.1%) of thymocytes. Both CD45RB and RC epitopes were found predominantly on CD4-CD8- and CD4-CD8+ thymocytes but were also found on small numbers of CD4+CD8+ and CD4+CD8- cells. The population of thymocytes that expressed CD45RB and CD45RC determinants displayed a novel TCR CD3 phenotype characterized by a level of expression that was intermediate between that seen in the larger CD3 bright and CD3 dull populations of thymocytes.

Animals↗
PubMed1991

Alterations of B lymphocyte Fc gamma R II expression and ligand binding capacity induced by various activators.

Murine B lymphocytes cultured with F(ab')2 anti-mouse mu or delta lost (85%) the capacity to bind antigen-IgG antibody complexes as assessed by flow microfluorometry. Anti-mu-induced loss of binding of complexes was concentration, time, and temperature dependent, reversible, and not due to decreased expression of the receptor because binding of monoclonal anti-Fc gamma R II to B lymphocytes cultured with anti-mu was unaffected. Activation of PKC and elevation of [Ca2+]i obtained by culturing B lymphocytes with the combination of PMA and Ca2+ ionophore induced a similar loss of binding of Cx. Since stimulation of B lymphocytes with anti-mu also activates PKC and elevates [Ca2+]i, these changes may be involved in the anti-mu-induced alterations in the binding of complexes to Fc gamma R II. In contrast to the effects of other activators, LPS caused increased expression (threefold) of B lymphocyte Fc gamma R II as measured by the binding of both complexes and monoclonal anti-Fc gamma R II. Thus, different B lymphocyte activators have distinct effects on Fc gamma R II expression or ligand binding capacity and can thereby affect Fc gamma R II-generated regulatory signals.

Animals↗
PubMed1991

Performance of Vitalograph wedge-bellows spirometer--comparison with a rolling seal spirometer.

The performance of a Vitalograph spirometer has been compared with a rolling seal spirometer (Ohio) to determine whether (i) spirometric measurements are normally distributed, (ii) fatigue occurs with repeated attempts, and (iii) how many tests are required. Twenty forced expiratory manoeuvres were performed on both spirometers at minute intervals, on ten normal subjects. To determine how many tests were required, the first five manoeuvres for each subject were analysed using eleven algorithms. The Vitalograph had a smaller volume, a shorter timing duration and a combined inertia and resistance greater than the European standards. The Ohio complied with the standards for volume and timing duration and had a much lower combined inertia and resistance. For each device, the spirometric indices were normally distributed, there were no fatigue effects, and no significant difference between any two algorithms. We conclude that (1) the performance of repeated forced expiratory manoeuvres using the Vitalograph spirometer does not result in fatigue, (2) spirometric indices are normally distributed, (3) estimation of forced expiratory flows between 25-50% of vital capacity from a Vitalograph may not be appropriate, and (4) the best of a number of technically satisfactory attempts, measured at one minute intervals, may be reported.

Algorithms↗
PubMed1991

Assessing lung function.

Breathing tests detect abnormalities of the structure and function of the lungs and respiratory system. They are used by physicians for diagnosing and monitoring disease, by clinical investigators wishing to elucidate the cause of disability and the effect of dysfunction, and by epidemiologists. They can be used to study the effects of genetic and environmental variation on respiratory health.

Airway Obstruction↗
PubMed1990

Regulation of Fc gamma R II expression and function by B lymphocyte activators.

B lymphocytes cultured with LPS show increased expression of Fc gamma R II and increased binding of Ag-IgG complexes (both greater than 200%). In contrast, B lymphocytes cultured with either IL-4 or anti-mu show a marked loss (85-90%) of binding of Ag-IgG complexes that is specific, time and temperature dependent, and reversible. Decreased binding of complexes was not due to decreased expression of the receptor and therefore appears to be due to some form of alteration of the receptor. Based on the observation that the loss of binding of complexes requires protein synthesis, we favor the view that the loss is due to association of Fc gamma R II with another membrane molecule whose expression is induced or increased by IL-4 or anti-mu. Anti-mu induced loss of Fc gamma R II ligand binding capacity does not require cross-linking of surface IgM because the effect can be generated with F(ab') anti-mu. Anti-mu induced loss of Fc gamma R II binding of complexes was substantially prevented by IFN-gamma, whereas IFN-gamma did not reduce the anti-mu caused increase in expression of MHC class II molecules. This result shows that increased expression of the latter molecules can be dissociated from loss of Fc gamma R II ligand binding capacity. A myeloid cell line was identified that constitutively expresses Fc gamma R II binds relatively few complexes. This cell line may be useful in identifying alterations of Fc gamma R II which lead to the loss of binding of complexes. These results indicate that various B lymphocyte activators have different effects on B lymphocyte expression and function, and can thereby affect Fc gamma R II generated regulatory signals.

Animals↗
PubMed1990

Detection of low numbers of lymphocyte surface membrane molecules using concentration immunofluorescence analysis (CIA).

Using viable lymphocytes in a concentration immunofluorescence assay (CIA), conditions were ascertained which allow detection of low numbers of surface membrane molecules. Utilizing 3 layer labeling [monoclonal antibody (MAb) specific for the membrane molecule, biotin-conjugated antibody specific for the MAb, and R-phycoerythrin-strepavidin], large numbers of lymphocytes in the assay wells, and the Pandex Fluorescence Concentration Analyzer, a fluorescence signal significantly above background was generated by as few as 8 x 10(7) molecules among 4 x 10(5) lymphocytes. Experiments using membrane molecules (Fc gamma R II, Ia antigens, Ly-39) which differ considerably in their level of expression indicated that comparable signals were generated by equivalent numbers of labeled molecules in a cell population irrespective of the number of molecules on an individual cell. Thus, CIA is theoretically capable of detecting membrane molecules whose expression is as low as 2 x 10(2) per cell. CIA should be useful in the assay of cytokine receptors and other lymphocyte membrane molecules expressed at low levels, and in the development of MAb specific for these molecules.

Animals↗
PubMed1990

CO transfer factor on exercise: age and sex differences.

The effects of age and sex on the single-breath transfer factor (TLCO) estimated during exercise have been investigated in 80 normal subjects (40 men) divided equally into four groups: 1) 20-29 yrs; 2) 30-39 yrs; 3) 40-49 yrs and 4) 50-59 yrs. Oxygen consumption (VO2), cardiac frequency (fc), TLCO and transfer coefficient (KCO) were estimated at rest and at 25 W increments up to 100 W in women and 150 W in men. Quadratic regression equations were obtained for the relationships of TLCO and KCO to VO2, fc and workload (WL). TLCO and KCO at any WL, VO2 or fc were greatest in group 1 and least in group 4. The rate of decline of TLCO and KCO in men and women at l.min-1 VO2 was 0.063 and 0.031 mmol.min-1.kPa-1.yr-1 and 0.006 and 0.007 mmol.min-1.kPa-1.l-1.yr-1, respectively. Within each sex the curvilinearity of the relationships was similar regardless of age. At any WL, TLCO was greater in men than in women, whilst KCO was greater in women than in men. Sex differences were not abolished by correcting TLCO and KCO for anthropometric indices. We conclude that age and sex have significant effects on TLCO and KCO on exercise.

Adult↗
PubMed1989

Single-breath breath-holding estimate of pulmonary blood flow in man: comparison with direct Fick cardiac output.

1. Resting pulmonary blood flow (Q), using the uptake of the soluble inert gas Freon-22 and an indirect estimate of lung tissue volume, has been estimated during breath-holding (Qc) and compared with direct Fick cardiac output (Qf) in 16 patients with various cardiac disorders. 2. The effect of breath-hold time was investigated by comparing Qc estimated using 6 and 10 s of breath-holding in 17 patients. Repeatability was assessed by duplicate measurements of Qc in the patients and in six normal subjects. 3. Qc tended to overestimate Qf, the bias and error being 0.09 l/min and 0.59, respectively. The coefficient of repeatability for Qc in the patients was 0.75 l/min and in the normal subjects was 0.66 l/min. For Qf it was 0.72 l/min. There was no significant difference in Qc measured at the two breath-hold times. 4. The technique is simple to perform, and provides a rapid estimate of Q, monitoring acute and chronic changes in cardiac output in normal subjects and patients with cardiac disease.

Adult↗
PubMed1988

IL-4 induces loss of B lymphocyte Fc gamma R II ligand binding capacity.

Murine B lymphocytes cultured for 24 h with rIL-4 lost (mean reduction of 88%, range 81 to 96%) the capacity to bind Ag-IgG antibody complexes to B lymphocytes as assessed by flow microfluorometry. This effect was specific in that it was not seen with IL-1, IL-2, or IFN-gamma; IL-4 did not have a similar effect on other B lymphocyte membrane molecules; and the effect was completely prevented by anti-IL-4 (mAb 11B11). More than 60% inhibition of the binding of complexes was seen with as little as 1 U/ml of IL-4 although maximal inhibition was seen with greater than or equal to 30 U/ml. IL-4-induced inhibition of the binding of complexes was time dependent (the effect was first seen after 8 h and was not maximal until 24 h), temperature dependent (it did not occur at 4 degrees C), and reversible (B lymphocytes that had lost the ability to bind complexes due to IL-4 regained this capacity when re-cultured for 24 h in the absence of IL-4). The effect could be partially prevented by IFN-gamma. The inability to bind complexes appeared to be mainly due to an alteration of Fc gamma R (Fc Receptors) II rather than down-regulation of receptor expression because IL-4 induced only a moderate reduction in the binding of two Fc gamma R II specific mAb (20% for 2.4G2 and 32% for K9.361). The IL-4-induced loss of binding of complexes to B lymphocyte Fc gamma R II appears to be a novel form of receptor regulation (function rather than expression), and likely plays a role in the up-regulation of B lymphocytes by IL-4 by preventing Fc gamma R II-mediated inhibition of B lymphocyte responses.

Animals↗
PubMed1988

Lung function and exercise performance in hyperthyroidism before and after treatment.

In order to investigate the mechanism of dyspnoea in hyperthyroidism measurements of spirometry, lung volume, transfer factor for carbon monoxide and its subdivisions, maximal respiratory pressures, methacholine challenge, arterial blood gases were made and exercise studies performed on 16 patients before treatment for hyperthyroidism. Methacholine challenge showed that only three of 14 patients increased airway reactivity, which was mild. Maximal pressures which could be generated by the respiratory muscles were reduced in some patients, as was functional residual capacity. Exercise ventilation and breathing frequency were increased and the respiratory exchange ratio was abnormally high. Anaerobic threshold was measured in nine of 15 subjects and was below normal in each case. All but two subjects stopped exercise because of dyspnoea, and the maximum oxygen uptake achieved by the group was 53 per cent (n = 15, range 26-66 per cent) of predicted maximum oxygen consumption. The maximum ventilation averaged only 43 per cent (n = 15, range 16-96 per cent) of the maximal breathing capacity predicted from spirometric tests. Nine patients were studied shortly after being rendered euthyroid by treatment. At rest, only maximal respiratory pressures increased significantly. On exercise, the maximal workload attained and the ventilation achieved increased significantly. Breathing patterns, maximal oxygen consumption, ventilation, anaerobic threshold and cardiac frequency remained unchanged. We conclude that: patients with hyperthyroidism do not generally have increased airway reactivity; when hyperthyroid, respiratory muscles are weak, and improve following treatment; exercise capacity is impaired in hyperthyroid patients probably because of a combination of an inefficiently rapid and shallow breathing pattern, an increase of anaerobic metabolism and discomfort associated with the act of breathing. Although exercise capacity increases and the sensation of dyspnoea may decrease after treatment the pattern of breathing does not immediately return to normal.

Adult↗
PubMed1987

Grading of dyspnoea and walking speed in cardiac disease and in chronic airflow obstruction.

A five-point dyspnoea scale (modified MRC questionnaire) and 12-minute walking test were used to compare the relationship between subjective assessment of dyspnoea and objective measurement of disability in patients with chronic airflow limitation, cardiac disease, and normal subjects. There was no overall difference in exercise performance between the cardiac and respiratory groups. There was a significant correlation between vital capacity and exercise performance, and the slope of the regression line was similar in the two groups. There was no correlation between vital capacity and exercise performance in the group of normal subjects. The five-point dyspnoea scale predicts similar levels of performance in the 12-minute walking test whether the dyspnoea is a result of cardiac or respiratory disease.

Adult↗
PubMed1986

Onset of right-to-left shunting through a foramen ovale in a 70-year-old woman: successful surgical treatment.

A 70-year-old woman presented with disabling breathlessness. She was found to have severe arterial hypoxaemia due to isolated right-to-left shunting through a patent foramen ovale. In the absence of pulmonary hypertension or evidence of right ventricular dysfunction this is attributed to reduced right atrial compliance. The phasic nature of the shunt, which occurred only during atrial filling, supports this view. Surgical closure of the foramen abolished the hypoxaemia and her symptoms.

Aged↗
PubMed1986

Domiciliary comparison of terbutaline treatment by metered dose inhaler with and without conical spacer in severe and moderately severe chronic asthma.

The bronchodilator response to cumulative doses of terbutaline administered by metered dose inhaler with and without a conical spacer device and by Acorn nebuliser has been compared in groups of patients with chronic severe and moderately severe asthma. After laboratory studies the patients undertook a randomised domiciliary crossover comparison of bronchodilator response to terbutaline given by metered dose inhaler with and without a spacer device, during which the severity of asthma was assessed by thrice daily recordings of peak expiratory flow (PEF) and symptom score. Improvement in FEV1 produced in the laboratory by the metered dose inhaler with spacer device was significantly greater than by metered dose inhaler alone (p less than 0.001) and similar to that from the nebuliser in both asthmatic groups throughout a range of terbutaline doses. In the domiciliary comparison mean midday and evening PEF rates were significantly higher with the use of the spacer device both in those with severe (p less than 0.01) and in those with moderately severe (p less than 0.05) asthma, and mean morning PEF was significantly higher in the severe group (p less than 0.05). The spacer device also produced a significant improvement in symptom score in both the severe and the moderately severe groups (p less than 0.05). Regular domiciliary use of the spacer device with the metered dose inhaler improves bronchodilator response, particularly in patients with chronic severe asthma, and may be a useful alternative to nebuliser treatment.

Administration, Inhalation↗
PubMed1986

Influence of knowledge of peak flow on self assessment of asthma: studies with a coded peak flow meter.

A portable peak flow meter based on a turbine transducer that can display results in code has been developed. Its performance compares well with the Wright peak flow meter. Records of subjective self assessment of asthma on a visual analogue scale and of peak flow (PEF) were compared in 12 subjects with asthma. PEF measurements were made with a coded meter for two weeks and an uncoded meter for two weeks in random order. The correlation between visual analogue scale score and PEF was invariably stronger when PEF was known. Changes in perception of asthma were measured by comparing the slopes and relative positions of the regressions of visual analogue on PEF. When PEF was uncoded awareness of asthma was significantly increased in five patients, predominantly those whose perception was poorest while they were using the coded meter, and decreased in only one patient. In two patients the results were unsuitable for this type of analysis. Knowledge of PEF therefore may influence subjective self assessment in patients with bronchial asthma. For objective studies of symptoms of asthma, PEF readings should be unknown to the patient. Perception of asthma may, however, be improved in patients with poor ability to detect changes in bronchial calibre by uncoded measurement of peak flow at home.

Adult↗