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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 487 records · Page 27Linked to original sources
PubMed1990

Pulmonary diffusing capacities for nitric oxide and carbon monoxide determined by rebreathing in dogs.

Pulmonary diffusing capacities (DL) of NO and CO were determined simultaneously from rebreathing equilibration kinetics in anesthetized paralyzed supine dogs (mean body wt 20 kg) after denitrogenation (replacement of N2 by Ar). During rebreathing the dogs were ventilated in closed circuit with a gas mixture containing 0.06% NO, 0.06% 13C18O, and 1% He in Ar for 15 s, with tidal volume of 0.5 liter and frequency of 60/min. The partial pressures of NO, 13C18O, 16O18O, N2, Ar, CO2, and He in the trachea were continuously analyzed by mass spectrometry. Measurements were performed at various O2 levels characterized by the mean end-expired PO2 during rebreathing (PE'O2). In control conditions ("normoxia," PE'O2 = 67 +/- 8 Torr) the following mean +/- SD values were obtained (in ml.min-1.Torr-1): DLNO = 52.4 +/- 11.0 and DLCO = 15.4 +/- 2.9. In hypoxia (PE'O2 = 24 +/- 7 Torr) DLNO increased by 11 +/- 8% and DLCO by 19 +/- 10%, and in hyperoxia (PE'O2 = 390 +/- 26 Torr) DLNO decreased to 87 +/- 3% and DLCO to 56 +/- 8% with respect to values in normoxia. DLNO/DLCO of 3.24 +/- 0.06 (hypoxia), 3.38 +/- 0.31 (normoxia), and 5.54 +/- 1.04 (hyperoxia) were significantly higher than the NO/CO Krogh diffusion constant ratio (1.92) predicted for simple diffusion through aqueous layers. With increasing O2 uptake elicited by 2,4-dinitrophenol, DLNO and DLCO increased and DLNO/DLCO remained close to unchanged. The results suggest that the combined effects of diffusion and chemical reaction with hemoglobin limit alveolar-capillary transport of CO. If it is assumed that reaction kinetics of NO with hemoglobin (known to be extremely fast) are not rate limiting for NO uptake, the contribution of the slow chemical reaction with hemoglobin to the total CO uptake resistance (= 1/DLCO) was estimated to be 38% in hypoxia, 41% in normoxia, and 64% in hyperoxia. The various factors expected to restrict the validity of this analysis are discussed, in particular the effects of functional inhomogeneity.

2,4-Dinitrophenol↗
PubMed1990

Alveolar slope and dead space of He and SF6 in dogs: comparison of airway and venous loading.

Series (Fowler) dead space (VD) and slope of the alveolar plateau of two inert gases (He and SF6) with similar blood-gas partition coefficients (approximately 0.01) but different diffusivities were analyzed in 10 anesthetized paralyzed mechanically ventilated dogs (mean body wt 20 kg). Single-breath constant-flow expirograms were simultaneously recorded in two conditions: 1) after equilibration of lung gas with the inert gases at tracer concentrations [airway loading (AL)] and 2) during steady-state elimination of the inert gases continuously introduced into venous blood by a membrane oxygenator and partial arteriovenous bypass [venous loading (VL)]. VD was consistently larger for SF6 than for He, but there was no difference between AL and VL. The relative alveolar slope, defined as increment of partial pressure per increment of expired volume and normalized to mixed expired-inspired partial pressure difference, was larger by a factor of two in VL than in AL for both He and SF6. The He-to-SF6 ratio of relative alveolar slope was generally smaller than unity in both VL and AL. Whereas unequal ventilation-volume distribution combined with sequential emptying of parallel lung regions appears to be responsible for the sloping alveolar plateau during AL, the steeper slope during VL is attributed to the combined effects of continuing gas exchange and ventilation-perfusion inequality coupled with sequential emptying. The differences between He and SF6 point at the contributing role of diffusion-dependent mechanisms in intrapulmonary gas mixing.

Administration, Inhalation↗
PubMed1990

Cardiogenic oscillations in He and SF6 expirograms during airway and venous loading.

Cardiogenic oscillations in the expired partial pressure profiles of two inert gases (He and SF6) were monitored in seven anesthetized paralyzed mechanically ventilated dogs. He and SF6 were administered either intravenously by a membrane oxygenator and partial arteriovenous bypass [venous loading (VL)] or by washin into lung gas [airway loading (AL)]. The single-breath expirograms obtained during constant-flow expiration after inspiration of test gas-free air displayed distinct and regular cardiogenic oscillations. The relative oscillation amplitude (ROA), calculated as oscillation amplitude divided by mixed expired-inspired partial pressure difference, was in the range of 1-8%. The ROA for both He and SF6 was approximately 4.2 times higher in VL than in AL, which indicated that among lung units that emptied sequentially in the cardiac cycle, the effects of alveolar ventilation-perfusion (VA/Q) inequality were more pronounced than those of alveolar ventilation-alveolar volume (VA/VA) inequality. In AL, He and SF6 oscillations were 180 degrees out of phase compared with CO2 and O2 oscillations and with He and SF6 oscillations in VL, which suggests that regions with low VA/VA had high VA/Q and very low Q/VA. The ROA was practically unaffected by breath holding in both AL and VL, which indicates that there was little diffusive or convective (cardiogenic) mixing between the lung units that were responsible for cardiogenic oscillations. The ROA was consistently higher for He than for SF6, and the He-to-SF6 ratio was independent of route of test gas loading, averaging 1.6 in both AL and VL. This result may be explained by laminar Taylor dispersion, whereby oscillations generated in peripheral lung regions are dissipated in inverse proportion to diffusion coefficient during transit through the proximal (larger) airways.

Administration, Inhalation↗
PubMed1990

[Importance of the interaction of surface receptors with the cytoskeleton for platelet function].

Two Triton-X-100-insoluble cytoskeletal fractions were prepared from washed human blood platelets by centrifugation: a low speed sediment (TP) and a fraction recovered as ultracentrifugation pellet (UP). Glycoproteins associated with both fractions prior to and after different times of thrombin activation were analyzed by electrophoretic techniques. In the TP fraction of unstimulated platelet the major membrane glycoproteins (GP) Ib and Ia were detected. After thrombin stimulation there is a rapid increase of GPs Ia, Ib, IIIb and a Mr 250,000-GP and a slower appearance of GPs IIb and IIIa in this fraction. The UP fraction contains mainly GPs Ib, Ia, IIb, IIIa and a Mr 250,000-GP. Thrombin activation does not cause any significant changes in the glycopeptide pattern of this fraction.

Blood Platelets↗
PubMed1990

[Acquired dysfibrinogenemia in a child in the course of a liver disease].

This report documents the results of coagulation studies in a 15-year old boy with hepatic disease of possibly autoimmune origin. Thrombin- and reptilase clotting times were prolonged. The results of fibrinogen determinations with different methods (heat precipitation, kinetic assay according to Clauss) lead to the assumption of a qualitative anomaly of fibrinogen (dysfibrinogenaemia). Investigations with purified fibrinogens from the patient and a healthy control confirmed this assumption. The thrombin clotting time of purified fibrinogen from the patient was clearly prolonged in comparison to the purified fibrinogen from a healthy control. The fibrin monomers of the patient exhibited impaired polymerization. No structural abnormalities were detected by electrophoretic techniques, particularly the thrombin-induced release of fibrinopeptides was found to be normal. The coagulation abnormalities resolved after glucocorticoid administration.

Adolescent↗
PubMed1990

[Gastritis: immunohistochemical detection of specific and nonspecific immune response to Helicobacter pylori].

Granulocyte infiltration was studied in 88 biopsies of antrum mucosa from patients with B-gastritis. Evidence of IgA-, IgG- and IgM-antibodies as well as of lysozyme in the mucosa was demonstrated by immunohistochemical methods. Helicobacter pylori (Hp) is coated by antibodies and a significant correlation between extent of opsonisation and number of plasma cells in the connective tissue of the lamina propria could be stated. Thus, the infiltration of plasma cells is a specific immune response against Hp. In the depths of gastric pits the antibody-coating of bacteria is faint. Instead, lysozyme and lactoferrin are produced there. By means of a Cross-sectional study a model is developed which characterizes B-gastritis as a dynamic process. Lagging behind, the inflammation follows the motile bacteria resulting in a patchy distribution of inflamed areas in the mucosa. At the peak of these local inflammation-waves the production of antibodies and lysozyme is intensified. Coating the bacteria with IgG and IgM results in complement activation liberating chemotaxin C5a. Consequently, there is a massive granulocyte infiltration leading to local reduction or eradication of Hp.

Antibodies, Bacterial↗
PubMed1989

Palmitylation of the glycoprotein IIb-IIIa complex in human blood platelets.

The presence of covalently bound palmitic acid in fibrinogen receptors, glycoproteins (GP) IIb and IIIa, has been explored in human blood platelets. Membrane fractions were isolated from fresh blood platelets labeled with [9,10-3H]palmitic acid and then analyzed for radioactive proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Protein bands were visualized by staining with Coomassie Brilliant Blue, excised, and counted in a liquid scintillation counter. The results indicate that membrane proteins with electrophoretic mobility corresponding to glycoproteins IIb and IIIa incorporate [9,10-3H]palmitic acid. The palmitylated glycoproteins IIb and IIIa were immunoprecipitated by specific anti-GP IIb and GP IIIa antisera. It is interesting to note that the palmitylation of these glycoproteins occurred rapidly in platelets activated with 0.5 unit of thrombin or 30 microM ADP. At the concentration used (100 micrograms/ml), cycloheximide did not inhibit incorporation of [3H]palmitate into the glycoproteins showing that this process is not dependent upon protein synthesis. The acyl moiety was resistant to denaturating detergents, delipidation with organic solvents, and hydrolyzable with hydroxylamine. In the case of membrane protein with the electrophoretic mobility of GP IIb, the radioactive label was significantly decreased after reduction with 2-mercaptoethanol. Final identification of GP IIIa as an acylated product in human platelets incubated with [9,10-3H]palmitic acid was provided by two-dimensional polyacrylamide gel electrophoresis. In contrast to GP IIb alpha, GP IIIa isolated by this method showed the presence of attached radioactive palmitic acid residues. Analysis by high performance liquid chromatography after methanolysis of the [3H]palmitate-labeled glycoproteins confirmed the fatty acid nature of the label. Palmitylation is a newly identified post-translational modification of the fibrinogen receptor which may play an important role in its interaction with the membrane and/or its biological function.

Adult↗
PubMed1989

The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells.

Antibodies that enhance human immunodeficiency virus (HIV) infectivity have been found in the blood of infected individuals and in infected or immunized animals. These findings raise serious concern for the development of a safe vaccine against acquired immunodeficiency syndrome. To address the in vivo relevance and mechanism of this phenomenon, antibody-dependent enhancement of HIV infectivity in peripheral blood macrophages, lymphocytes, and human fibroblastoid cells was studied. Neither Leu3a, a monoclonal antibody directed against the CD4 receptor, nor soluble recombinant CD4 even at high concentrations prevented this enhancement. The addition of monoclonal antibody to the Fc receptor III (anti-FcRIII), but not of antibodies that react with FcRI or FcRII, inhibited HIV type 1 and HIV type 2 enhancement in peripheral blood macrophages. Although enhancement of HIV infection in CD4+ lymphocytes could not be blocked by anti-FcRIII, it was inhibited by the addition of human immunoglobulin G aggregates. The results indicate that the FcRIII receptor on human macrophages and possibly another Fc receptor on human CD4+ lymphocytes mediate antibody-dependent enhancement of HIV infectivity and that this phenomenon proceeds through a mechanism independent of the CD4 protein.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Mutant proteins of human interleukin 2. Renaturation yield, proliferative activity and receptor binding.

Muteins, i.e. proteins altered by mutation of their genes, of interleukin 2 (Il2) were generated by oligonucleotide-directed mutagenesis in vitro. All acidic and basic residues conserved between man and mouse were exchanged as well as four lipophilic residues contained within four hydrophobic segments of the protein. The muteins were produced in Escherichia coli and submitted to a renaturation and purification protocol, before bioactivity and receptor binding of each of them was determined. All muteins besides two (K44/T125 and Q110/T125) could be renatured and purified. One mutein (K94/T125) exhibited a more than tenfold-improved renaturation yield. One amino exchange (Asp-20 to Asn) resulted in an about 20-fold reduction in proliferative activity and high-affinity receptor binding. The binding to the low-affinity Il2-binding protein (Tac antigen) was unimpaired. A second exchange (Arg-38 to Gln) had no effect on proliferative activity. The binding to both the high- and the low-affinity receptor, however, was reduced about 20-fold. Preliminary trials on the stability of these muteins by guanidinium hydrochloride denaturation studies detected no differences between wild-type interleukin 2 and muteins. It is suggested that Asp-20 forms part of the binding site for the large receptor subunit whereas Arg-38 is involved in the contact site to the small subunit.

Animals↗
PubMed1989

[Megakaryocytic myelosis--clinical aspects, morphology and platelet function].

The study reviews 22 patients, aged between 19 to 73 years, with megakaryocytic myelosis. In the course of the disease 11 patients presented haemorrhagic manifestations, 12 patients thrombotic complications, and 6 patients the association of haemorrhage and thrombosis. The maximum platelet counts ranged from 524 to 2700 x 10(9)/l. The bone marrow showed a conspicuous megakaryocytic proliferation with polyploidy of the nuclei, giant forms and clusters. Marked alterations of erythro- and granulopoiesis were excluded. There was no evidence for a reactive thrombocytosis in any case. Patients with thrombocythaemia due to megakaryocytic myelosis (n = 14), with secondary thrombocytosis of various origin (n = 16), and a control group of healthy donors (n = 20) were investigated with respect to the aggregation behaviour and the total calcium content of blood platelets. In 9 of 14 patients with megakaryocytic myelosis platelet rich plasma did not respond to epinephrine (15 mumol/l), a concentration which induced at least weak aggregation in 14 of 16 patients with secondary thrombocytosis and also in healthy subjects. In patients with megakaryocytic myelosis the mean extent of aggregation induced by epinephrine, collagen or adenosine diphosphate was significant lower as compared to controls whereas in patients with secondary thrombocytosis in most cases this parameter did not differ significantly from that of controls. The total calcium content of platelets was significantly lower in both groups of patients as compared to controls. In 14 patients with megakaryocytic myelosis the concentration of the glycoprotein (GP) IIb-IIIa complex was estimated by crossed- and rocket-immunoelectrophoresis and found to be decreased in 8 of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Spatial and temporal variability of blood flow in stimulated dog gastrocnemius muscle.

The distribution of blood flow in skeletal muscle stimulated to rhythmic isotonic contractions was studied by injections of radioactive microspheres into the arterial supply of gastrocnemius muscles (mean weight 88 g) subsequently cut into 0.5 g pieces for determination of radioactivity. The coefficient of variation (CV = SD/mean) of the ratio of simultaneously injected 10 microns and 15 microns microspheres, 0.12, was taken as the inherent scatter of the method. The average spatial distribution inequality of 10-15 microns microspheres corresponded to a CV of 0.45 and the specific local blood flow inhomogeneity to a CV = 0.43 (= square root of 0.45(2) - 0.12(2)), but there were marked differences between muscles. The temporal variability of blood flow in individual muscle pieces was obtained from the comparison of fractional trapping of 4 to 5 differently labeled microspheres injected at intervals of 2 minutes into steadily stimulated muscles. The mean CV for the variations in time was 0.23 and that corrected for methodological scatter, 0.19. There were large differences between muscle pieces within a muscle and between muscles. The presence of considerable spatial and temporal variations of blood flow in exercising muscle during apparent steady state may be important in limiting and/or modulating tissue O2 supply.

Animals↗