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Biomedical subjects

M Blom

Publications and source records attributed to M Blom.

At least 19 recordsLinked to original sources

Priming of human eosinophils by platelet-activating factor enhances the number of cells able to bind and respond to opsonized particles.

Addition of platelet-activating factor (PAF) to human eosinophils leads to the modulation of eosinophil responses. Earlier work from our laboratory has shown that the respiratory burst and homotypic aggregation response in these cells induced by opsonized particles (serum-treated zymosan, STZ), is strongly enhanced after pretreatment (priming) with PAF. In the present study we have investigated the effect of PAF on the binding of fluorescent STZ particles to human eosinophils. Addition of STZ to eosinophils isolated from the peripheral blood of normal donors results in an interaction of the STZ particles with only 30 to 40% of the cells. Treatment of the eosinophils with PAF (1 microM) for 2 min strongly enhanced the rate of particle binding and also doubled the percentage of eosinophils binding STZ. The effect of PAF priming is most likely mediated by a change in CR3, because it is reversed by mAb B2.12 blocking the iC3b binding site of CR3 and unaffected by mAb IV.3 blocking Fc gamma RII. This change is not an increase in cell surface expression of CR3, and it requires an active cellular metabolism to be maintained. The functional consequences of the effect of PAF on STZ binding were investigated in the nitro-blue tetrazolium dye slide test. PAF priming strongly enhanced the percentage of eosinophils producing oxygen radicals after STZ stimulation. Our findings indicate that the priming phenomenon observed in human eosinophils consists, at least in part, of a recruitment of cells able to interact with and to respond to opsonized particles.

Adenosine Triphosphate

[Quality assurance of results of clinical chemical analyses in Danish hospital laboratories].

During the past 35 years, voluntary professional assessment of quality of the results of analyses in Danish hospital laboratories has been undertaken under the auspices of the Danish Society of Clinical Chemistry. The analytical quality of the laboratories is described by their "imprecision" and "accuracy" as expressed by "coefficient of variation" and "bias", respectively. The participation in these programmes was 90%. During the period between 1968 and 1987, inter-laboratory variation decreased markedly where all analyses were concerned. To ensure the necessary and adequate quality, establishment of specifications of quality based on clinical/biological goals of quality has proved necessary. The commonest reasons for large imprecision and bias from the target values are less specific methods of analysis, errors in calibration and sporadic "outliers". As the result of a stable organisation for ensuring quality, Denmark is well equipped for the introduction of the great demands in documentation of quality which may be anticipated from the Common Market during the immediate future.

Chemistry Techniques, Analytical

Release of platelet-activating factor is important for the respiratory burst induced in human eosinophils by opsonized particles.

The respiratory burst induced in human eosinophils by serum-treated zymosan (STZ) was found to be almost completely prevented by preincubation of the cells with WEB 2086, an antagonist of platelet-activating factor (PAF). When eosinophils were primed by the addition of 1 mumol/L PAF, subsequent addition of WEB 2086 had only a minor effect on the STZ-induced respiratory burst. These results suggest a role for PAF synthesis and PAF release in the activation of the respiratory burst by STZ. Indeed, supernatant of STZ-stimulated eosinophils was able to prime fresh eosinophils (as did PAF itself), and this effect was again inhibited by WEB 2086. This indicates that eosinophils synthesize and release PAF during STZ stimulation. Measurements of total PAF and PAF release showed that most of the PAF synthesized by eosinophils was released in the extracellular medium. This study shows that synthesis and release of PAF is important for respiratory burst activity induced in human eosinophils by STZ.

Azepines

The effect of acupuncture on salivary flow rates in patients with xerostomia.

Of 21 patients with severe xerostomia, 11 were treated with acupuncture and 10 patients received placebo acupuncture. Those patients who received acupuncture treatment showed increased salivary flow rates during and after the acupuncture treatment. The improved salivary values persisted during the observation year, whereas the patients who received placebo acupuncture showed some improvement of salivary flow rates only during the actual treatment. The results of the present study indicate that acupuncture may be a useful adjunct for the stimulation of salivary flow in some patients with xerostomia.

Acupuncture Points

Conditioning of drug-induced immunomodulation in human volunteers: a European collaborative study.

Although several studies on conditioning of the immune system in animals have been published, no comparable data on human research have been available in the past. The present paper presents results of conditioning studies in volunteers performed in two research centres, namely the University of Trier (Germany) and the University of Utrecht (The Netherlands). After administration of a neutral stimulus (conditioned stimulus: CS), subjects were injected with epinephrine (unconditioned stimulus) for three or four days (depending on study). Subcutaneous injection of epinephrine caused a rapid enhancement of the activity of natural killer cells (NKCA) in venous blood, which was chosen as the unconditioned response. On the test trial, when saline instead of epinephrine was injected, the Trier group found a conditional enhancement of NKCA. No changes in NKCA were found in the control subjects, who received saline injections on all days along with the CS. The Utrecht group tried to replicate these results using a slightly different design. After obtaining non-confirmative results, the Utrecht experimenters tried to parallel the experimental settings of the Trier group as closely as possible. However, once again they failed to replicate the results of the Trier group. Possible reasons for the different results obtained in the two research groups are discussed.

Adult

Characteristics of CR3-mediated aggregation in human eosinophils: effect of priming by platelet-activating factor.

We have used double-color fluorescence-activated cell sorter analysis to characterize the homotypic aggregation response of human eosinophils (EOs). With this method, we demonstrate for the first time that EOs are able to form stable aggregates. The aggregation response induced by the phorbol ester, phorbol myristate acetate (PMA), was low and was not primed by platelet-activating factor (PAF). In contrast, the aggregation response induced by opsonized particles was markedly enhanced after priming with PAF. Additional experiments with several blocking monoclonal antibodies indicate that the CR3 receptor present on human EOs mediates the homotypic aggregation induced by PMA and by small opsonized particles through a putative "cell-adhesion" site on CR3, which binds to its counter structure on the opposing cell. The signal that initiates this binding event is generated after PMA addition or activation of the iC3b-binding site and is not sensitive for priming by PAF. The priming by PAF of the aggregation response induced by opsonized particles is restricted to an action on the iC3b-binding site, possibly by enhancing the affinity for its ligand.

Antigens, CD

The effects of levodopa and haloperidol on flash and pattern ERGs and VEPs in normal humans.

We investigated the effects of single doses of the dopamine agonist levodopa and the dopamine antagonist haloperidol on pattern and flash electroretinograms (ERGs) and visual evoked potentials (VEPs) in normal subjects. A placebo and two treatment regimens were administered in a randomized double-masked design. No significant intertreatment differences in the pattern ERGs and VEPs were noted. Although not statistically significant, a clearly discernible tendency was found for increased flash ERG b-wave amplitudes after levodopa administration compared with placebo. In comparison with placebo and levodopa, haloperidol was associated with significantly prolonged flash ERG b-wave implicit times, including each oscillatory potential, which also showed increased duration, particularly in the O1-O3 interpeak implicit time. The failure of pattern ERGs and VEPs to show changes after haloperidol may have been related to the timing of the recordings, which took place during the presumed phase of rising blood levels and before the flash ERG and VEP recordings. Our findings further demonstrated the reliability of the flash ERG in revealing changes in dopaminergic status in the visual system and suggest that steady-state (flicker) ERGs, cone ERGs, and oscillatory potentials have particular use in this regard.

Adult

Effects of clobazam and clonazepam on saccadic eye movements and other parameters of psychomotor performance.

The effects of two benzodiazepine anticonvulsants clobazam (20 mg) and clonazepam (2 mg) in a variety of psychomotor performance tests were compared in a placebo controlled double-blind acute oral dose study in ten healthy volunteers. Assessments included critical flicker fusion (CFF) threshold, the Sternberg memory scanning and choice reaction time (CRT), peak saccadic velocity (PSV) and visual analogue scales, all previously shown to be sensitive to the effects of benzodiazepines. Clobazam did not significantly impair saccadic eye movements, CFF threshold, Sternberg memory scanning and CRT compared to placebo. Clonazepam significantly lowered PSV, reduced the CFF threshold, slowed the Sternberg CRT and decreased an alertness factor in the visual analogue scales compared to placebo. Clonazepam significantly increased memory scanning time compared to clobazam. Clobazam was remarkably free of cognitive and psychomotor side-effects.

Adult

Effects of single doses of diazepam, chlorpromazine, imipramine and trihexyphenidyl on visual-evoked potentials.

There is increasing evidence that the P 100 peak of the pattern-reversal visual-evoked potential (VEP-PR) is delayed by drug-induced dopamine antagonism and in Parkinson's disease. Recent studies have reported that components of the flash-VEP (VEP-F) are delayed by an anticholinergic which does not affect the VEP-PR. The present study found that a single dose of chlorpromazine increased the latencies of the VEP-PR and of the VEP-F and increased the VEP-F P2 amplitude. Trihexyphenidyl increased the VEP-PR amplitude but had only minor effects on the VEP-F. There was a tendency for imipramine to increase VEP-F latencies, especially the N3 peak, but had no effect on the VEP-PR. Both VEPs were unaffected by diazepam. These VEP findings add further support to the role of dopamine in the human visual system. Possible reasons are advanced for the failure of trihexyphenidyl to cause previously reported VEP changes associated with hyoscine hydrobromide. Several important issues need to be addressed by future research.

Adult

Effects on angina pectoris and exercise tests of a 2% nitroglycerin gel adhesive in patients on chronic beta-blockade. A placebo-controlled study.

Twenty patients on chronic beta-blockade for angina pectoris were included in a double-blind randomized cross-over placebo-controlled study on a 2% nitroglycerin gel administered transdermally by an adhesive. Topinitro. The dose, 2.5-10 mg/day, was individually titrated and each treatment period was 28 days. The effect was evaluated by exercise tests and diary cards for anginal attacks and nitroglycerin tablets consumed. Results. In the 17 patients who completed the trial, active treatment did not influence systolic and diastolic blood pressure or resting and maximal heart rate. Maximal performance increased insignificantly from 92 +/- 23 to 96 +/- 20 W. The level at which 1 mm of ST depression appeared increased from 62 +/- 26 to 73 +/- 28 W (p less than 0.05). The number of attacks decreased significantly, from 92 +/- 30 to 14 +/- 28/4 weeks. The reduction in the number of sublingual nitroglycerin tablets consumed was insignificant. Conclusion. Nitroglycerin adhesive, in individual dosages, may improve signs and symptoms of ischemia.

Administration, Topical

Simultaneous blank correction in a turbidimetric continuous flow system for immunochemical quantitation of plasma proteins.

By shortening the reaction time by polymer enhancement, it was possible to introduce a line for automatic blank correction in a turbidimetric continuous flow system. The turbidity resulting from the reaction was measured by a simply constructed photometer, the serum turbidity being subtracted by the reference photoelectric cell and the resulting net signal amplified by means of the recorder's stepwise electronic amplifier. Serum transferrin values obtained by this method correlated well with values obtained by estimating blank in separate runs, and with values given be electroimmune assays.

Autoanalysis

Whole salivary immunoglobulin levels in 60 healthy children: determined by a sensitive electroimmuno technique after prior carbamylation.

Immunoglobulins in whole saliva, collected unstimulated from 60 healthy children, 4 to 15 years of age, were determined by a modified electroimmuno technique using carbamylation of the samples prior to electrophoresis. This technique, which is generally used for measurement of immunoglobulins in serum, was found to be rapid, precise, and sensitive. The mean (median) for salivary IgA was 5.1 kIU/1, which was significantly higher than values obtained from stimulated or unstimulated parotid saliva by other investigators. The mean value for salivary IgG was 120 IU/1. IgM in saliva was only found in measurable amounts in 5 children.

Adolescent

Profile analysis of blood proteins with a centrifugal analyzer.

We describe a procedure for routine analysis of a profile composed of eight blood proteins with a GEMSAEC centrifugal analyzer. The end-point technique is used and four standards are included in each run in the immunochemical analysis of the individual proteins. Additional computer programs fit the absorbance readings from the samples to the (nonlinear) standard curve and store the results in a patient's file for a final printout, which also presents the patient's data and reference values. The proteins are analyzed in a given order, which allows common blank runs to be used. Antisera are used in suitably high concentrations, so that the "antigen in excess" problem only appears for analysis of IgA and IgM when sera contain high amounts of the M-components of these two classes. The capacity, accuracy, and precision of the method are satisfactory.

Antigen-Antibody Reactions

Immunochemical determination of serum albumin with a centrifugal analyzer.

The turbidity resulting from the reaction between albumin and specific anti-human serum was measured with a good precision by using a GEMSAEC centrifugal analyzer. The reaction was enhanced by polyethylene glycol to shorten the reaction time (5 min) and to displace the point of equivalence between antigen and antibody to an albumin concentration unlikely to occur in human sera (about 100 g/liter). An additional program for the computer was necessary to fit the absorbance readings of individual sera to the nonlinear standard curve. Serum albumin values obtained by the described method correlated well with values obtained by the electro-immuno-technique. About 100 samples could be analyzed per hour, 500 mul of 100-fold diluted antiserum being used per specimen.

Autoanalysis