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Biomedical subjects

J Lasch

Publications and source records attributed to J Lasch.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Apoptosis and cell proliferation in HHV-6 infections. Regulatory mechanisms of p53/bcl-2/ras interactions].

HHV-6 infected immature T (HSB2) and Hodgkin (HDLM2) cells and biopsy tissues from lymph nodes of patients with Hodgkin's disease (HD) and Kikuchi lymphadenitis (KL) were studied immunohistologically for virus antigen expression and for the oncogene/anti-oncogene products ras, bcl-2 and p53. Cell proliferation and cell death were tentatively monitored in tissue culture by PCNA staining, by viability testing and in situ end labeling of fragmented DNA. PCNA was also used in biopsy samples. KL is characterized by high incidences of focal cell death (i.e. histiocytic necrotizing lymphadenitis), while HD is apparently more a proliferative disease. The techniques used revealed no significant differences in the cellular expression of viral DNA or antigens among cell lines, HD or KL. The HDLM2 cell line with the superior survival after HHV-6 infection showed a significantly lower expression of p53 and PCNA than HSB2 cells. Biopsy samples from patients with KL did not express p53, and ras and PCNA were observed in fewer cells than in HD. Bcl-2, however, was significantly more frequently seen than in HD. The interpretation of the data is difficult; they suggest that there are additional regulatory influences in control of cell proliferation and cell death, such as cytokines and growth factors, which are altered after viral infection. Also, virus-induced cell death probably includes other mechanisms besides apoptosis, such as cell damage caused by oxygen radicals.

Apoptosis↗
PubMed1994

Release of GPI-anchored membrane aminopeptidase P by enzymes and detergents has some peculiarities.

The enzyme aminopeptidase P (APP) of rat small intestine is an integral membrane protein. It is not released from the membrane by proteinases and is also resistant to bacterial inositol-specific phospholipases C (PI-PLC's). We show that this resistance is due to a hindered accessibility of the bond split by PI-PLC and not to a modified glycosylphosphatidyl inositol (GPI)-anchor.

Aminopeptidases↗
PubMed1994

Alteration of structural order of human erythrocyte ghost membrane by glucocorticoids and the influence of the glucocorticoid receptor antagonist RU 486.

High-dose pulse glucocorticoid therapy has been used successfully in the clinic in severe pathological conditions for about 20 years. The mode of glucocorticoid action after administration of such megadoses is inexplicable up to now. It is supposed that some effects may be due to membrane alterations. In the present in-vitro experiments the effect of dexamethasone, of further glucocorticoids, and of the glucocorticoid receptor antagonist RU 486, on structural order of human erythrocyte ghost membranes was investigated by determining the steady-state fluorescence anisotropy of diphenylhexatriene (DPH). Dexamethasone was found to induce a significant decrease in membrane structural order at concentrations of about 10(-6) M in a concentration-dependent manner. We found a correlation between the uptake of dexamethasone by the ghost membranes and the decrease in the structural order. The other glucocorticoids tested, methylprednisolone and corticosterone, were also effective at concentrations of 10(-5) M or greater. We observed no change in membrane structural order with RU 486 up to a concentration of 10(-4) M. However, simultaneous incubation of RU 486 with dexamethasone caused a distinct interference of RU 486 with dexamethasone. Thus, the glucocorticoid-induced membrane perturbation, the possibility to inhibit it by RU 486, and the inactivity of the structurally related progesterone, refer to relatively specific binding sites for the glucocorticoids in the membrane of erythrocyte ghosts.

Diphenylhexatriene↗
PubMed1993

Destabilization of egg lecithin liposomes on the skin after topical application measured by perturbed gamma gamma angular correlation spectroscopy (PAC) with 111In.

Unilamellar and oligolamellar liposomes were topically applied to the skin of porcine ears. Perturbed angular correlation spectroscopy of 111In-DTPA, initially entrapped into the liposomes, was used to study the release kinetics of the hydrophilic probe. After drying of the liposomal suspensions, a decrease of the time-integrated perturbation factor within 30 min indicated destabilization of the liposomes and total marker release in the upper epidermal layers.

Animals↗
PubMed1991

Carboxyacyl derivatives of cardiolipin as four-tailed hydrophobic anchors for the covalent coupling of hydrophilic proteins to liposomes.

Two carboxyacyl derivatives of cardiolipin, O-succinyl- and O-glutarylcardiolipin, were synthesized with the aim of using them as artificial membrane anchors for the immobilization of hydrophilic proteins to liposomes. Four adjacent fatty acid residues can be introduced into a protein with only one single amino group being blocked, by reacting the cardiolipin derivatives with the protein amino groups after carbodiimide activation. alpha-Chymotrypsin, used as a model protein, and modified with on average two molecules of O-succinylcardiolipin was incorporated into liposomes, which had been prepared by different methods, with very high yield. If incorporated in preformed liposomes, the carboxyacyl cardiolipin anchors were also efficient in binding proteins to liposomal surfaces. Up to 350 micrograms chymotrypsin/mumol lipid were coupled to small unilamellar vesicles, preserving reactivity of the enzyme towards specific macromolecular inhibitors. Human IgG could also be bound to anchor-containing liposomes with high protein to lipid coupling ratio as well as high coupling yield.

Acylation↗
PubMed1991

The use of macromolecular protease inhibitors to study liposome-cell interactions.

A method is introduced that quantitates the release of a high molecular weight compound from small unilamellar vesicles. The technique is based on the liposomal encapsulation of trypsin inhibitor from bovine lung. Because liposomes are impermeable to all components of the test system (inhibitor, enzyme, macromolecular substrate), only the free inhibitor released from disturbed liposomes is measured. Using this technique, the exit of the macromolecular solute from liposomes induced by erythrocyte ghosts was studied. The results were compared with the leakage of a low molecular weight fluorescent marker. They indicate that, especially during the first hours of incubation, ghost-induced release of solutes is dependent on their size.

Animals↗
PubMed1990

Interaction of Triton X-100 and octyl glucoside with liposomal membranes at sublytic and lytic concentrations. Spectroscopic studies.

The molecular mechanism of the solubilisation of phospholipid bilayers by nonionic detergents was studied by turbidity changes, carboxyfluorescein fluorescence dequenching, steady-state and time-resolved fluorescence anisotropy of DPH, lifetime measurements, ANS binding and 31P-NMR. Particular attention has been paid to the effective detergent-to-lipid ratio in the lipid phase. The disturbance of the bilayer arrangement varies considerably for various detergents depending on the hydrophilic and lipophilic parts of the molecule. Small amounts of detergents with low CMC (e.g. Triton X-100) can even induce an optimisation of packing of the lipid molecules.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Interactions of liposomes with human erythrocyte ghosts.

Interactions between human erythrocyte ghosts and small unilamellar vesicles consisting of various lipids and containing high intravesicular concentrations of calcein were studied. The entrapped marker leaked out under the influence of erythrocyte ghost in dependence on ghost and vesicle concentration, phospholipid composition as well as cholesterol content of the liposomes. Small unilamellar vesicles composed of sphingomyelin/cholesterol mixtures at a molar ratio of 1:1 are less permeable than those prepared from other phospholipids in the presence of erythrocyte ghosts. The amount of ghost associated liposomal lipid was measured by addition of cholesteryl [14C]oleate. It was shown to be minimal compared to the transfer of [14C]cholesterol between liposomes and ghosts. The half-time of the transfer process was also increased by incorporation of sphingomyelin into the liposomes, the retarding effect being apparent at levels of 5 mol% sphingomyelin.

Adsorption↗
PubMed1989

Covalent coupling of sugars to liposomes.

A procedure is described for the covalent coupling of p-aminophenyl-alpha-D-mannopyranoside, in the presence of carbodiimide, to a derivative of phosphatidylethanolamine (N-glutarylphosphatidylethanolamine) incorporated into the bilayers of multilamellar liposomes prepared by the dehydration-rehydration method. It appears that much of the phospholipid derivative exposed on the surface of the outer liposomal bilayer interacts with the aminosugar. The procedure is simple, does not destabilize liposomes and could be applied to other receptor-specific aminosugars.

Binding Sites↗
PubMed1989

The effect of liposomal incorporation of topically applied hydrocortisone on its serum concentration and urinary excretion.

We demonstrated previously, that hydrocortisone incorporated in the phospholipid bilayer of liposomes (liposomal hydrocortisone) shows an improved concentration-time profile in the different skin layers after external application when compared with a conventional ointment. In the present work, it was investigated under in vivo conditions, whether or not the liposomal formulation also enhances the percutaneous absorption rate. The results obtained in guinea pigs clearly demonstrate a decrease in serum concentration and urinary excretion. Thus, hydrocortisone-loaded liposomes, when applied topically, act as a selective drug delivery system or "drug localizer" increasing the therapeutic efficacy and, simultaneously, decreasing adverse systemic effects. The significance of liposomal attenuative and potent glucocorticoids in topical treatment is discussed.

Administration, Topical↗
PubMed1989

[Skin permeation of liposomal incorporated hydrocortisone].

With the liposomal incorporated hydrocortisone a very much improved concentration-time profile was obtained in the different layers of human skin after topical application when compared with conventional hydrocortisone in the ointment. The increased hydrocortisone penetration into human skin correspond with the degree of blanching results by vasoconstriction test. Under in vivo conditions the influence of liposomal hydrocortisone on percutaneous resorption was investigated. In guinea pigs a decreased serum concentration and urinary excretion of hydrocortisone could be demonstrated. Thus, hydrocortisone-loaded liposomes, when applied topically, act as a selective drug delivery system, it can be provide increased therapeutic efficacy and, simultaneously, decreased unwanted systemic effects. The significance of liposomal incorporated attenuative and higher potent glucocorticoids in external therapy is discussed.

Animals↗
PubMed1989

[Interactions of detergents with phospholipid bilayers at sublytic concentrations--partition or binding?].

Using the bubble pressure method the interaction of liposomes with detergents at sublytic concentrations was studied. The results are discussed in terms of a partition or binding model. The findings support an equilibrium partition of the surfactant between the aquous and lipid phase. For some detergents, however, concentration dependent partition coefficients were found.

Chemical Phenomena↗
PubMed1988

Enzymic properties of intestinal aminopeptidase P: a new continuous assay.

A continuous photometric assay of aminopeptidase P activity was developed which is based on a coupled enzymic assay with the substrate Gly-Pro-Pro-pNA and DPP IV as auxiliary enzyme. This assay was used to evaluate the kinetic parameters and inhibitory profile of intestinal brush border aminopeptidase P.

Amino Acid Sequence↗
PubMed1987

Thiolation of preformed liposomes with iminothiolane.

Preformed phosphatidylethanolamine-containing liposomes were thiolated with 2-iminothiolane (Traut's reagent) and subsequently activated by mixed disulfide formation with 5,5'-dithiobis(2-nitrobenzoic acid). Up to 65% of amino groups of the outer liposomal lamella, corresponding to 230 SH-groups per vesicle, were modified. Covalent attachment of thiolated alpha-chymotrypsin to these thiol-liposomes via S-S bridges yielded a protein/lipid ratio of 3.6 X 10(-4) mol enzyme/mol lipid.

Chymotrypsin↗