Virosomes can enter cells by non-phagocytic mechanisms.

Phagocytosis of fine particles (1 microm) by macrophages is a ligand-receptor-mediated, actin-based process, whereas the entering of smaller particles (< or = 0.2 microm) in macrophages occurs also by other mechanisms. Virosomes with a diameter of 0.

Drug targeting using OX7-immunoliposomes: correlation between Thy1.1 antigen expression and tissue distribution in the rat.

OX7 monoclonal antibody F((ab')2) fragments directed against Thy1.1 antigen can be used for drug targeting by coupling to the surface of drug-loaded liposomes. Such OX7-conjugated immunoliposomes (OX7-IL) were used recently for drug delivery to rat glomerular mesangial cells, which are characterized by a high level of Thy1.

Effects on hepatocellular carcinoma of doxorubicin-loaded immunoliposomes designed to target the VEGFR-2.

To maintain a tumour vasculature in proportion of the tumour growth, the endothelial cells proliferate and up-regulate the expression of the VEGF receptor 2 (VEGFR-2), whose expression is restricted to this cell type. This specificity implies that one therapeutically target the tumour endothelium. We investigated the use of immunoliposomes (IL), containing conjugated Fab' fragments of the monoclonal rat anti-VEGFR-2 antibody DC101 (DC101-IL) to cargo doxorubicin to the tumour endothelium.

Rapid endocytosis of copper-zinc superoxide dismutase into human endothelial cells: role for its vascular activity.

Cytosolic CuZn-SOD (SOD1) is a dimeric, carbohydrate-free enzyme with a molecular weight of about 32 kDa and also circulates in human blood plasma. Due to its molecular mass it has been believed that the enzyme cannot penetrate the cell membrane. Here we report that rapid endocytosis of FITC-CuZn-SOD into human endothelial cells occurs within 5 min.

Immunoliposome targeting to mesangial cells: a promising strategy for specific drug delivery to the kidney.

Mesangial cell-mediated nephropathies are a frequent cause of ESRD. Specific drug delivery to mesangial cells might be more effective and better tolerated than existing systemic treatments. Rat mesangial cells are characterized by Thy1.

Virosomes as new carrier system for cancer vaccines.

HER-2/neu, a tumor-associated antigen (TAAg), plays a critical role in oncogenesis of various tumor types, and its selective overexpression by malignant tumor cells makes it an ideal target for immunotherapy. A prerequisite for clinical vaccines is the construction of safe and highly immunogenic reagents able to generate efficient immune responses against TAAg. Previous protein vaccines, consisting of the extracellular domain of HER-2/neu (pNeuECD), were shown to elicit an immune response that did not provide protection from transplantable tumors expressing HER-2/neu.

Soluble IL-1 receptor type I binds to human dermal fibroblasts and induces calcium flux.

Soluble cytokine receptors appear to modify ligand concentrations by stabilizing ligands or by specifically inhibiting interactions of ligands with their membrane-bound receptors. Here we describe a new function of the soluble interleukin-1 receptor type I (IL-1sR I). This receptor induced a transient rise of intracellular free calcium concentration in human dermal fibroblasts in a dose-dependent fashion.

Delivery to cancer cells of antisense L-myc oligonucleotides incorporated in fusogenic, cationic-lipid-reconstituted influenza-virus envelopes (cationic virosomes).

Antisense oligodeoxy-nucleoside phosphorothioates (OPTs) of L-myc were encapsulated into reconstituted influenza-virus-A envelopes (virosomes). The envelopes of the virosomes consisted of a single positively charged (cationic) lipid bilayer. Binding of cationic virosomes to cellular receptors that are membrane glycoproteins or glycolipids containing terminal sialic acid is mediated by the hemagglutinin glycoprotein (HA) of the influenza virus.

Autologous versus allogeneic T cell-stimulated IL-6 production by dermal fibroblasts.

T cells adhere to human dermal fibroblasts (HDF). This cellular interaction leads to a pronounced secretion of the proinflammatory cytokines IL-6 and IL-8 via a juxtacrine stimulation induced by HDF-associated IL-1. Upon stimulation, fibroblasts express various surface proteins such as MCH-I molecules, which may interact with corresponding receptors on T cells.

Juxtacrine stimulation of cytokine production in cocultures of human dermal fibroblasts and T cells.

Adhesion of T cells to fibroblasts activates cells to produce cytokines, either by direct cell contact and/or soluble factors. A cell-associated form of IL-1 beta on fibroblasts might act through a cell contact mediated fashion. To test this hypothesis we analysed the activation of T cells and human dermal fibroblasts (HDF) in coculture experiments.

Proliferation and differentiation of cultured human follicular keratinocytes are not influenced by biotin.

In humans and in animals, biotin deficiency causes pathological changes in the skin and its appendages. High doses of biotin may also have beneficial effects on skin, hair and fingernails in humans and animals with normal biotin status. Therefore, we investigated the effects of low and high concentrations of biotin on proliferation and differentiation of cultured outer root sheath cells from human hair follicles as an in vitro model for skin.

Epstein-Barr virus subtype distribution in angioimmunoblastic lymphadenopathy.

The tissues of 16 patients bearing a T-cell lymphoma of angioimmunoblastic lymphadenopathy type (AILD-TCL) were investigated for the distribution of Epstein-Barr virus (EBV) subtypes 1 and 2. EBV-association had been proven in these cases by polymerase chain reaction (PCR) for EBV-DNA, in situ hybridization (ISH) for EBV-encoded small nuclear RNAs (EBER) and immunohistology for EBV-encoded latent membrane protein (LMP). PCR and EBER-ISH produced mostly identical results, but some cases were positive with only one of the 2 methods employed.

Association of the subtype 2 of the Epstein-Barr virus with T-cell non-Hodgkin's lymphoma of the midline granuloma type.

Lethal midline granuloma (LMG) is associated with Epstein-Barr virus (EBV). The latter has at least two subtypes with different biological properties. The subtypes can be identified by their genomic configuration.

Soluble factors from human hair papilla cells and dermal fibroblasts dramatically increase the clonal growth of outer root sheath cells.

Depending on environmental influences, follicular outer root sheath (ORS) cells in vivo can differentiate either towards interfollicular keratinocytes or, as demonstrated in the rat vibrissa, hair matrix cells. Crucial regulators of both their proliferation and differentiation are the mesenchymal cells of the respective tissues. The interactions of human ORS cells with human hair papilla cells (HPC) or human dermal fibroblasts (HDF) were studied using a two-chamber model separating the two cell types either by a microporous membrane or additionally by a medium layer.

Increased levels of inflammatory cytokines in human skin lymph derived from sodium lauryl sulphate-induced contact dermatitis.

A superficial peripheral lymph vessel draining the skin of the upper and medial part of the foot was cannulated on the lower leg of six healthy human volunteers. After 2 days an irritant contact dermatitis was induced by application of 10% sodium lauryl sulphate to the area of skin drained by the lymph vessel. Three days later the spontaneously regressing skin reaction was treated with clobetasol propionate.

Co-culture of human keratinocytes on post-mitotic human dermal fibroblast feeder cells: production of large amounts of interleukin 6.

A large synthesis of human IL-6 was demonstrated in co-cultures of human keratinocytes on post-mitotic human dermal fibroblast (HDF) feeder layers. Immunoreactive IL-1 beta could be detected in the co-cultures and the addition of rabbit anti-IL-1 beta antibodies to the co-cultures considerably reduced the IL-6 synthesis, suggesting that it was induced by endogenous IL-1 beta. Addition of saturating concentrations of IL-1 beta to HDF feeder layers as well as to subcultures of keratinocytes induced in both similar but moderate IL-6 production.

Immunocytochemical evidence of progesterone receptors in human meningiomas.

The presence of progesterone receptors in meningioma tissue is demonstrated by use of highly specific monoclonal antibodies against the rabbit progesterone receptors which cross-react with human progesterone receptors in breast cancer cells, thus giving evidence of the existence of genuine progesterone receptors in human meningiomas.

Endocrine manipulation of meningiomas with medroxyprogesterone acetate. Effect of MPA on growth of primary meningioma cells in monolayer tissue culture.

Intracranial meningiomas from patients treated with medroxyprogesterone acetate as well as from untreated patients were studied in monolayer tissue culture with trials of in vitro hormonal modulation with medroxyprogesterone acetate. The following conclusions were drawn from investigations which comprise 37 cell culture assays: (a) tissue cultures of meningiomas inherit the disadvantages of loss of the progesterone receptor and frequent transformation to cells resembling fibroblasts after three to four passages. For these reasons, drug testing as well as the establishment of cell cultures that exhibit the characteristics of meningioma are impeded; (b) the progesterone receptor-content of the solid tumors does not reflect the response to medroxyprogesterone acetate-therapy in vitro; (c) medroxyprogesterone acetate-pretreated meningiomas showed sufficient in vitro growth in 38%, and untreated meningiomas grew well in 56% of the cases; (d) medroxyprogesterone acetate-induced inhibition or delay of growth was observed in 35%.

Hormonotherapy of meningiomas with medroxyprogesterone acetate. Immunohistochemical demonstration of the effect of medroxyprogesterone acetate on growth fractions of meningioma cells using the monoclonal antibody Ki-67.

The effect of medroxyprogesterone acetate (MPA) on growth fractions of ex vivo meningiomas is demonstrated in using the Ki-67 monoclonal antibody in three cases of meningiomas operated on in two stages and in meningioma specimens from a group of eight patients operated on in one single stage after MPA therapy. Growth fractions in samples from five meningioma patients not treated with MPA were determined for comparison. In the three cases of two-stage operation of the tumors, the percentage of Ki-67-positive cells in meningioma tissue was lower by a factor of 6, 5, and 3, respectively, after MPA therapy.

Short-lasting accumulation in osteoid bone seams of radioactive iron injected as citrate into mice.

The possible role in vivo of osseous structures in binding radioactive iron injected as a low-molecular-weight complex was studied in mice, using combined autoradiography and histomorphometry on sections of undecalcified, plastic-embedded femur epiphyses/metaphyses. A single intraperitoneal injection of 10 microCi 59Fe (1.2 micrograms Fe) per animal as citrate within 3 hours led to a preferential accumulation of this metal in the osteoid mineralized tissue interphase (osteoid seams) of bone.

Endocrine manipulation of meningiomas with medroxyprogesterone acetate. Effect of MPA on receptor status of meningioma cytosols.

Fifteen patients with intracranial or spinal meningiomas have been treated with the semisynthetic progestational agent medroxyprogesterone acetate (MPA, Depo-Provera) prior to surgical removal of the tumors in order to investigate the influence of MPA on the progesterone receptor (PR) status of meningioma cytosols. MPA acted as a competitive binder to meningioma-PR: The mean PR values were 15.6 fmol/mg protein (range 0-69) and 338.

Estrogen and progestin receptors in acoustic and spinal neurilemmomas. Clinicopathologic correlations.

Estradiol and progestin receptors were studied in 20 patients with neuraxial Schwann cell tumors, and their presence was correlated to the clinicopathologic features and the amount of preoperative corticosteroid therapy. Based on an arbitrary cutoff value of 200 fmol per gram of tumor as indicative of a positive receptor value in breast cancer, 4 and 13 of the neurilemmoma tissue samples could be considered as positive for estrogen and progesterone receptors, respectively. Whereas there was no convincing correlation between the estrogen and progestin receptor activity and the age, sex, or menopausal status of the patients, overweight patients had significantly higher estrogen and progestin binding values.