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Biomedical subjects

B Schwab

Publications and source records attributed to B Schwab.

At least 55 records · Page 3Linked to original sources
PubMed1992

Mechanisms of lipopolysaccharide-induced neutrophil retention. Relative contributions of adhesive and cellular mechanical properties.

Intravascular LPS rapidly induces neutrophil sequestration in pulmonary capillaries by mechanisms that, although currently unknown, must take into account the size difference between the neutrophil and capillary diameter. To determine whether LPS alters neutrophil stiffness, and hence the ability of neutrophils to traverse capillaries, neutrophil passage through pulmonary capillaries was modeled by passage through filters with 6.5-microns pores. LPS increased retention in the pores in a concentration-dependent fashion that required the presence of heat-inactivated platelet-poor plasma, and was evident as early as 10 min after stimulation. The effect of LPS on the structural properties of the neutrophil was then studied. LPS induced f-actin reorganization in neutrophils in the presence of plasma. Disruption of actin organization and assembly with cytochalasin D completely inhibited early LPS-induced retention and attenuated retention at later timepoints, indicating that LPS-stimulated retention depends on filament organization. LPS-induced actin assembly and retention were abrogated by an antibody directed against CD14, a putative LPS receptor. CD18-dependent adherence of neutrophils contributed significantly to retention only at later timepoints with no significant contribution to retention at 20 min as determined by inhibition of adherence with the mAb 60.3. Morphometric assessment of neutrophil accumulation in the lungs of rabbits given 1 microgram LPS showed a marked increase in apparent neutrophil number, which was unaltered by antibodies to CD18, suggesting that mechanisms other than adhesion may account for accumulation in vivo. Direct measurements showed that neutrophil stiffness increased with exposure to LPS in a fashion similar to LPS-induced retention and actin organization. Pretreatment of neutrophils with cytochalasin D attenuated the increased stiffness. These data suggest that reorganization of filamentous-actin induced by LPS leads to cell stiffening and retention in capillary-sized pores. Although the organization of f-actin continues to be important in retention at later time points, adherence of cells also contributes significantly to cell retention. The changes in mechanical properties of the neutrophil may be important in the sequestration of neutrophils in pulmonary capillaries noted in endotoxemia.

Actin Cytoskeleton↗
PubMed1991

Skin replica analysis of photodamaged skin after therapy with tretinoin emollient cream.

Computerized image analysis of silicone replicas, a reproducible, objective technique for measuring skin topography, was used in addition to clinical measures in two multicenter, double-blind, randomized, controlled studies of tretinoin emollient cream, a new formulation for treating photodamaged skin. Previously, the skin replica technique had been successfully used in a pilot study of tretinoin 0.05% cream by one investigator. In the present studies, subjects treated for 24 weeks with tretinoin emollient 0.05% cream consistently showed more improvement in skin topography than did vehicle-treated patients. A 0.01% concentration of tretinoin emollient cream also improved skin topography to a greater extent than the vehicle, while the lowest concentration tested (0.001%) showed little difference from vehicle. These results, reflecting a smoothening of the skin surface in tretinoin emollient cream-treated subjects, were consistent with clinical data showing greater improvement in fine wrinkling and roughness after tretinoin emollient cream therapy than after vehicle therapy. Findings from these multicenter studies confirm the value of the skin replica technique and help establish the efficacy of tretinoin emollient 0.05% cream for photodamaged skin.

Adult↗
PubMed1991

[Hormone dependence of juvenile nasopharyngeal fibroma].

Since Martin (1948) and Schiff (1959) first reported the use of sex hormones in JNF patients, many authors have described the various clinical effects and histological changes found after administration of androgens or estrogens. In 1980, Johns attempted unsuccessfully to detect estrogen receptors in the tissue of tumors from JNF patients. In 1987, however, Farag et al. succeeded in the demonstration of androgen receptors in homogenates of such tumor tissue.--In 1989, the authors were able to determine the uptake and receptor-binding of radioactively labelled dihydrotestosterone in cultured fibroblasts from a tumor from a 16-year-old JNF patient, and to confirm this result in two other cases. The maximum levels of hormone binding to the fibroblasts was much the same as is found with genital skin fibroblasts, included in the study as a control androgenic target-tissue with high receptor-density. At the same time it was demonstrated that it was possible to stimulate the tumor fibroblasts in vitro by adding testosterone to the culture medium. The attempt to block cell growth with the antiandrogen cyproterone acetate, was not successful, however. This can possibly be put down to the high progestogenic activity of this antiandrogen. Further in vitro studies with substances which are purely androgenic (e.g., flutamide) or with the acetate-free form of cyproterone (which has no progestogenic activity) will possibly be of help in the search for a substance capable of blocking tumor growth.

Adolescent↗
PubMed1991

[Silver nitrate burn after Credé's preventive treatment. A roentgen analytic and scanning electron microscopy study].

Following Credé's prophylaxis with silver-nitrate, the cornea of a newborn presented greyish-brown, lime-like plaques on the nasal part of the right eye. A paracentral ulcerating stromal opacification undermined these appositions, when the patient was admitted to the eye-clinic at Aachen. In the material taken in a lamellar keratectomy scanning electron microscopical examination was able to prove the existence of granules, previously described in light-microscopy. These granules measured 100 to 300 nm in diameter and were placed up to 110 microns deep into the corneal stroma of the specimen. An earlier chemical analysis of necrotic material showed no silver specific reaction. By means of EDX-Analysis these granules could be identified as silver-containing. This was once reassured by a newly developed modification of van-Kossa's-staining-method. The fact that the granular deposits contained mainly silver proves that the onset of a sodium-chloride-irrigation did not promote an intended therapeutic silver-chloride-precipitation and therefore had no effects on the silver-nitrate's penetration abilities. Injuries by silver-nitrate-solutions used for Credé's prophylaxis are seldom but still reported. The mechanism of injury in this case of a child, born by sectio remains unknown. Neither the use of an unusual silvernitrate solution, that was taken from a disposable ampoule (Mova-Nitrat) was reported, nor any corneal injury during sectio mentioned.(ABSTRACT TRUNCATED AT 250 WORDS)

Burns, Chemical↗
PubMed1991

Biophysical properties and microfilament assembly in neutrophils: modulation by cyclic AMP.

The microfilament lattice, composed primarily of filamentous (F)-actin, determines in large part the mechanical (deformability) properties of neutrophils, and thus may regulate the ability of neutrophils to transit a microvascular bed. Circulating factors may stimulate the neutrophil to become rigid and therefore be retained in the capillaries. We hypothesized that cell stiffening might be attenuated by an increase in intracellular cAMP. A combination of cell filtration and cell poking (mechanical indentation) was used to measure cell deformability. Neutrophils pretreated with dibutyryl cAMP (db-cAMP) or the combination of prostaglandin E2 (PGE2, a stimulator of adenylate cyclase) and isobutylmethylxanthine (IBMX, an inhibitor of phosphodiesterase) demonstrated significant inhibition of the n-formyl-methionyl-leucyl-phenylalanine (fMLP)-inducing stiffening. The inhibition of cell stiffening was associated with an increase in intracellular cAMP as measured by enzyme-linked immunoassay (EIA) and an increase in the activity of the cAMP-dependent kinase (A-kinase). Treatment with PGE2 and IBMX also resulted in a decrease in the F-actin content of stimulated neutrophils as assayed by NBD-phallacidin staining and flow cytometry or by changes in right angle light scattering. Direct addition of cAMP to electropermeabilized neutrophils resulted in attenuation of fMLP-induced actin assembly. Neutrophils stimulated with fMLP demonstrated a rapid redistribution of F-actin from a diffuse cortical location to a peripheral ring as assessed by conventional and scanning confocal fluorescence microscopy. Pretreatment of neutrophils with the combination of IBMX and PGE2 resulted in incomplete development and fragmentation of the cortical ring. We conclude that assembly and redistribution of F-actin may be responsible for cell stiffening after exposure to stimulants and that this response was attenuated by agents that increase intracellular cAMP, by altering the amount and spatial organization of the microfilament component of the cytoskeleton.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Retention of leukocytes in capillaries: role of cell size and deformability.

Leukocytes within the circulation are in dynamic equilibrium with a marginated pool, thought to reside mainly within the pulmonary capillaries. The size discrepancy between the mean diameter of circulating leukocytes (6-8 microns) and that of the pulmonary capillaries (approximately 5.5 microns) forces the cells to deform in order to transit the capillary bed. Consequently, we investigated the hypothesis that the biophysical properties of cell size and deformability determined differential leukocyte retention in the lung. Comparison of the filtration properties of human neutrophils, lymphocytes, monocytes, platelets, and erythrocytes through polycarbonate filters (5-micron pore diameter) revealed that the largest leukocytes (neutrophils and monocytes) were retained to the greatest extent and the smaller cells (lymphocytes and platelets) the least. Undifferentiated HL-60 cells, of greater diameter than their differentiated counterparts, were also retained to a greater extent, confirming that cell size was one important determinant of retention in these model capillaries. However, compared with neutrophils, which are of similar diameter, monocytes were retained to a greater extent, suggesting that monocytes might be less deformable than neutrophils. To test this hypothesis, deformability was measured directly using the cell poker. Monocytes were found to be the stiffest, neutrophils the softest, and lymphocytes intermediate. Glutaraldehyde treatment of neutrophils markedly increased their stiffness and decreased their ability to transit the pores of the filters in vitro and the pulmonary microvasculature of rabbits without changing their adhesive properties or size. These observations support the hypothesis that biophysical properties of leukocytes (size and deformability) determine in part their ability to transit the pulmonary capillaries and may determine the magnitude of their marginated pools.

Blood Platelets↗
PubMed1990

Activation of mechanical responses in leukocytes.

Different kinds of leukocytes undergo cytoskeleton-dependent mechanical responses associated with their specific physiological functions. We have investigated cellular stiffening of several types of leukocytes using a method which measures the force resisting cellular indentation. We have found that lymphocytes stiffen in response to crosslinking cell surface antigens in a process associated with the much studied capping and patching processes. Further studies of myosin-deficient mutants of the ameba Dictyostelium discoideum suggest that this stiffening process results from a myosin dependent contractile process. Rat basophilic leukemia cells and pancreatic islet cells stiffen when triggered to secrete. The function of these cytoskeleton dependent processes is now unknown, but, at least in the islet cells, may be related to a regulation of the rate of secretion. Primary neutrophils stiffen in response to the chemotactic agent, fMet-Leu-Phe. This stiffening may be responsible for retention of these cells in the pulmonary microcirculation during response to inflammation. These observations pose the challenge of determining the structural basis, mechanism, and physiological function of each of these cellular responses.

Animals↗
PubMed1990

Corneal silver deposits following Crede's prophylaxis an examination with electron dispersive x-ray analysis (EDX-analysis) and scanning electron microscope (SEM).

In a case of silver nitrate injury after Credé's prophylaxis, the cornea of a newborn presented yellow-brown, lime-like plaques on the nasal part of the right eye. A paracentral ulcerating stromal opacification undermined these appositions, when the patient was admitted to the eye-clinic at Aachen. In the material obtained by a lamellar keratectomy scanning electron microscopical examination was able to prove the existence of granules, previously described in light-microscopy. These granules measured 100 to 300 nm in diameter. An earlier chemical analysis of necrotic material showed no silver specific reaction. By means of EDX-analysis these granules could be identified as silver-containing. Injuries by silver nitrate solutions used for Credé's prophylaxis are seldom but still reported. The mechanism of injury in this case of a child, born by sectio remains unknown. Neither the use of an unusual silver nitrate solution, that was taken from a disposable ampoule (Mova-Nitrat R) was reported, nor any corneal injury during sectio mentioned. Nevertheless the method of EDX-analysis and SEM proved the diagnosis of corneal silver deposits, so that the origin of the granullar opacification of the cornea could be determined.

Cornea↗
PubMed1989

Mechanics of stimulated neutrophils: cell stiffening induces retention in capillaries.

The effect of peptide chemoattractants on neutrophil mechanical properties was studied to test the hypothesis that stimulated neutrophils (diameter, 8 micrometers) are retained in pulmonary capillaries (5.5 micrometers) as a result of a decreased ability of the cell to deform within the capillary in response to the hydrodynamic forces of the bloodstream. Increased neutrophil stiffness, actin assembly, and retention in both 5-micrometer pores and the pulmonary vasculature were seen in response to N-formyl-methionyl-leucyl-phenylalanine. These changes were abolished in cells that had been incubated with 2 micromolar cytochalasin D, an agent that disrupts cellular actin organization. A monoclonal antibody directed at the CD11-CD18 adhesive glycoprotein complex did not inhibit the increase in stiffness or retention in pores. These data suggest that neutrophil stiffening may be both necessary and sufficient for the retention that is observed. Hence, neutrophil sequestration in lung and other capillaries in the acute inflammatory process may be the result of increased stiffness stimulated by chemoattractants.

Actin Cytoskeleton↗
PubMed1989

Cell poking: quantitative analysis of indentation of thick viscoelastic layers.

A recently introduced device, the cell poker, measures the force required to indent the exposed surface of a cell adherent to a rigid substratum. The cell poker has provided phenomenological information about the viscoelastic properties of several different types of cells, about mechanical changes triggered by external stimuli, and about the role of the cytoskeleton in these mechanical functions. Except in special cases, however, it has not been possible to extract quantitative estimates of viscosity and elasticity moduli from cell poker measurements. This paper presents cell poker measurements of well characterized viscoelastic polymeric materials, polydimethylsiloxanes of different degrees of polymerization, in a simple shape, a flat, thick layer, which for our purposes can be treated as a half space. Analysis of the measurements in terms of a linear viscoelasticity theory yields viscosity values for three polymer samples in agreement with those determined by measurements on a macroscopic scale. Theoretical analysis further indicates that the measured limiting static elasticity of the layers may result from the tension generated at the interface between the polymer and water. This work demonstrates the possibility of obtaining quantitative viscoelastic material properties from cell poker measurements and represents the first step in extending these quantitative studies to more complicated structures including cells.

Cell Adhesion↗
PubMed1989

Actin polymerization induces a shape change in actin-containing vesicles.

We have encapsulated actin filaments in the presence and absence of various actin-binding proteins into lipid vesicles. These vesicles are approximately the same size as animal cells and can be characterized by the same optical microscopic and mechanical techniques used to study cells. We demonstrate that the initially spherical vesicles can be forced into asymmetric, irregular shapes by polymerization of the actin that they contain. Deformation of the vesicles requires that the actin filaments be on average at least approximately 0.5 micron long as shown by the effects of gelsolin, an actin filament-nucleating protein. Filamin, a filament-crosslinking protein, caused the surfaces of the vesicles to have a smoother appearance. Heterogeneous distribution of actin filaments within the vesicles is caused by interfilament interactions and modulated by gelsolin and filamin. The vesicles provide a model system to study control of cell shape and cytoskeletal organization, membrane-cytoskeleton interactions, and cytomechanics.

Actins↗
PubMed1988

Health care of the chronically mentally ill: the culture broker model.

The chronically mentally ill tend to receive inadequate medical care for nonpsychiatric illnesses and to have poor health care status. Their medical problems lead to excessive morbidity and mortality and adversely affect their adjustment to psychiatric illness. The authors argue that many of the barriers to medical care for these patients can be overcome by using case managers as "culture brokers"-persons who provide bridges between the worlds of the chronically mentally ill and medical providers. This paper presents the culture broker model and its roots in anthropology, and illustrates its application to the medical care of the chronically mentally ill with case examples.

Adult↗
PubMed1987

Microinjection of gelsolin into living cells.

Gelsolins are actin-binding proteins that cap, nucleate, and sever actin filaments. Microinjection of cytoplasmic or plasma gelsolin into living fibroblasts and macrophages did not affect the shape, actin distribution, deformability, or ruffling activity of the cells. Gelsolin requires calcium for activity, but the NH2-terminal half is active without calcium. Microinjection of this proteolytic fragment had marked effects: the cells rounded up, stopped ruffling, became soft, and stress fibers disappeared. These changes are similar to those seen with cytochalasin, which also caps barbed ends of actin filaments. Attempts to raise the cytoplasmic calcium concentration and thereby activate the injected gelsolin were unsuccessful, but the increases in calcium concentration were minimal or transient and may not have been sufficient. Our interpretation of these results is that at the low calcium concentrations normally found in cells, gelsolin does not express the activities observed in vitro at higher calcium concentrations. We presume that gelsolin may be active at certain times or places if the calcium concentration is elevated to a sufficient level, but we cannot exclude the existence of another molecule that inhibits gelsolin. Microinjection of a 1:1 gelsolin/actin complex had no effect on the cells. This complex is stable in the absence of calcium and has capping activity but no severing and less nucleation activity as compared with either gelsolin in calcium or the NH2-terminal fragment. The NH2-terminal fragment-actin complex also has capping and nucleating activity but no severing activity. On microinjection it had the same effects as the fragment alone. The basis for the difference between the two complexes is unknown. The native molecular weight of rabbit plasma gelsolin is 82,500, and the extinction coefficient at 280 nm is 1.68 cm2/mg. A new simple procedure for purification of plasma gelsolin is described.

Animals↗
PubMed1986

The influence of concentration and relaxation on the EEG power spectra during a CNV paradigm.

EEG segments of 1 sec duration, beginning 1 sec before the imperative stimulus were analysed by Fast Fourier Transformation in a CNV paradigm with interstimulus intervals (ISI) of different durations (1, 3, 5 sec) and with constant (K1, K3, K5) and randomized (R1, R3, R5) ISI presentation. In the alpha band, there were found differences in the power spectra between the constant and the longer randomized (R3, R5) ISI conditions, the latter having a slower center frequency, a smaller radius of gyration and a higher kurtosis. This describes a sharper alpha line of slower frequency in the R3 and the R5 ISI condition, due to pronounced synchronisation of alpha activity. It is discussed as an expression of increased relaxation and reduced concentration. In the theta band, differences appeared between the short ISI conditions (K1, R1) and the longer ones.

Adult↗
PubMed1984

Detection and quantitation of chloramphenicol by competitive enzyme-linked immunoassay.

A competitive enzyme-linked immunoassay for the detection and quantitation of chloramphenicol has been developed. The binding of specific rabbit antibody to solid-phase-bound chloramphenicol was competitively inhibited by free chloramphenicol in the sample to be assayed. Antibody not displaced was indicated by using a commercially available, enzyme-linked, anti-rabbit immunoglobulin preparation and reacted with added substrate. Enzyme activity, measured spectrophotometrically, was inversely proportional to the concentration of chloramphenicol in the sample. Quantitation of the antibiotic was linear to 100 ng/ml, with a lower limit of detection of 1 ng/ml (P less than 0.05). Specificity was demonstrated by the lack of inhibition by any of 31 selected antimicrobial agents or chemicals tested in the assay. Chloramphenicol sodium succinate and thiamphenicol, an experimental antibiotic similar in structure to chloramphenicol, were the only drugs found to produce cross-reactions. In addition to excellent sensitivity and specificity, the assay was shown to have good precision and economy and could be completed in approximately 24h.

Animals↗
PubMed1978

[Pigmented paravenous retino-choroidal atrophy (author's transl)].

A 22-year-old man presented a typical appearance of pigmented paravenous retino-choroidal atrophy. Fluorescein angiography demonstrated a profound loss of the choriocapillaris in the affected areas. The amplitude of the scotopic and photopic electroretinogramme response was reduced. The electro-oculographic light rise was normal.

Adult↗