A Single-Center Prospective Cohort Study on Postsplenectomy Sepsis and its Prevention.

Background: This study evaluated the impact of a dedicated outpatient service on vaccination uptake after splenectomy and on the incidence of postsplenectomy sepsis.

Methods: From 2009 to 2016 at the University Hospital Freiburg (Germany), asplenic patients were referred to a dedicated outpatient service, provided with comprehensive preventive care including vaccinations, and enrolled in a prospective cohort study. The impact of the service on vaccination uptake and the occurrence of severe sepsis/septic shock was compared between patients who had splenectomy (or were asplenic) within 3 months of study entry ("early study entry") and those who had splenectomy (or were asplenic) >3 months before study entry ("delayed study entry").

Nine months to progression using fourth-line liposomally encapsulated paclitaxel against hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths. Difficulties to diagnose HCC at early stages remain the major obstacle to curative (surgical) therapy. Therapy in advanced stages has to be considered palliative.

Morphology and transfection study of human microvascular endothelial cell angiogenesis: an in vitro three-dimensional model.

Microvascular endothelial cells from human neonatal foreskin were grown in vitro until a three-dimensional network of capillary-like structures was formed. All stages of the angiogenic cascade could be observed in this in vitro model, including the formation of an internal lumen. The microscopy focused on morphology, formation of an internal lumen, role of the extracellular matrix, polarity of the cells, and the time-course of the angiogenic cascade.

Endostatin cDNA/cationic liposome complexes as a promising therapy to prevent lung metastases in osteosarcoma: study in a human-like rat orthotopic tumor.

Antiangiogenesis or destruction of tumor neovessels is an effective strategy to prevent tumor growth. Endostatin, one of the many inhibitors of angiogenesis that have been discovered, has shown conflicting results in preclinical assays. We studied the therapeutic potential of lipid/DNA complexes consisting of cationic liposomes and an endostatin-coding plasmid (Endo cDNA/CLP) in an orthotopic osteosarcoma model in rats.

Protamine enhances uptake of cationic liposomes in angiogenic microvessels.

Introduction: Cationic liposomes have been shown to target angiogenic endothelial cells of solid tumours. Supposing a charge-related mechanism might be responsible for liposome-endothelial interaction, we investigated the effect of intravenous pre-injection of the charged molecules protamine, a polycationic protein, and fucoidan, a polyanionic polysaccharide on the accumulation of cationic liposomes within the blood vessels of a solid tumour.

Materials And Methods: Experiments were performed using the amelanotic hamster melanoma A-Mel-3 growing in a dorsal skinfold chamber of hamsters.

Targeting diphtheria toxin A-chain transcription to activated endothelial cells using an E-selectin promoter.

Targeting the transcription of a toxin gene to activated endothelial cells might be used for inhibiting angiogenesis in solid tumors. As a model, we transiently transfected human endothelial cells (HUVEC) in culture with expression plasmids for the toxic A-chain of diphtheria toxin (DT-A), using electroporation (achieving approximately 70% transfection efficiency). Protein synthesis in HUVEC was highly sensitive to DT-A expression from constitutive viral promoters.

Neovascular targeting therapy: paclitaxel encapsulated in cationic liposomes improves antitumoral efficacy.

Purpose: Cationic liposomes have been shown to selectively target tumor endothelial cells. Therefore, the encapsulation of antineoplastic drugs into cationic liposomes is a promising tool to improve selective drug delivery by targeting tumor vasculature. It was the aim of our study to evaluate tumor selectivity and antitumoral efficacy of paclitaxel encapsulated in cationic liposomes in comparison with the free drug paclitaxel (Taxol(R)) in vivo.

Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels.

Recently, cationic liposomes have been shown to preferentially target the angiogenic endothelium of tumors. It was the aim of our study to investigate the influence of liposomal surface charge on the uptake and kinetics of liposomes into solid tumors and tumor vasculature. Experiments were performed in the amelanotic hamster melanoma A-Mel-3 growing in the dorsal skinfold chamber preparation of male Syrian golden hamsters.

Paclitaxel encapsulated in cationic liposomes diminishes tumor angiogenesis and melanoma growth in a "humanized" SCID mouse model.

Paclitaxel is an alkaloid that inhibits endothelial cell proliferation, motility, and tube formation at nanomolar concentrations. Cationic liposome preparations have been shown to target blood vessels. We wished to explore the possibility that paclitaxel encapsulated in cationic liposomes carries paclitaxel to blood vessels and thereby provides an antiangiogenic effect.

[Induction of antitumor immune response in the mouse model after vaccination with B7.1 expressing tumor cells].

The aim of the study was the induction of an antitumor immune response by genetic modification of tumor cells. This was done by transfecting the costimulatory molecule B7.1 into a murine tumor cell line SCCVII/SF in order to increase T cell recognition and to install an immunologic memory.

Gene therapy--phase I trial for primary untreated head and neck squamous cell cancer (HNSCC) UICC stage II-IV with a single intratumoral injection of hIL-2 plasmids formulated in DOTMA/Chol.

Recombinant IL-2 protein has shown many immunostimulatory effects in a variety of human tumors. However, the clinical use of rIL-2 is limited by common and serious side effects after systemic administration. IL-2 expression plasmids may circumvent these drawbacks, producing high local IL-2 concentrations that cause limited or no systemic side effects.

Lipofection of cultured mouse muscle cells: a direct comparison of Lipofectamine and DOSPER.

Cationic lipid-DNA complexes (lipoplexes) have been widely used as gene transfer vectors which avoid the adverse immunogenicity and potential for viraemia of viral vectors. With the long-term aim of gene transfer into skeletal muscle in vivo, we describe a direct in vitro comparison of two commercially available cationic lipid formulations, Lipofectamine and DOSPER. Optimisation of transfection was performed in the C2C12 mouse muscle cell line, before further studies in primary mouse myoblasts and C2C12 myotubes.

Regional, developmental and interspecies expression of the four NMDAR2 subunits, examined using monoclonal antibodies.

Mouse monoclonal antibodies were raised against bacterially expressed protein sequences of the NR2A, NR2B, NR2C and NR2D subunits of the rat NMDA receptor. From immunoblots of rat brain proteins, the apparent molecular weights of these subunits were 165, 170, 135 and 145 kDa, respectively. Proteins of similar masses were observed on immunoblots of specifically transfected HEK293 cells.

Evidence for safety and efficacy of DOTAP cationic liposome mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis.

In cystic fibrosis (CF), mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene results in defective transepithelial ion transport, leading to life shortening inflammatory lung disease. Before lung studies, we tested the safety and efficacy of gene delivery to the nasal epithelium of CF patients using pCMV-CFTR-DOTAP cationic liposome complex. A single dose of 400 micrograms pCMV-CFTR:2.

Laboratory and clinical studies in support of cystic fibrosis gene therapy using pCMV-CFTR-DOTAP.

The first phase I study of cystic fibrosis gene therapy using cationic liposomes to deliver the cystic fibrosis conductance regulator gene to the nose reported partial and transient correction of the nasal transepithelial ion transport defect, While encouraging, further improvements will be required if this form of treatment is to be of therapeutic value. We tested a new formulation, pCMV-CFTR-DOTAP. The complex is stable for 10 days and effective at correcting the electrophysiological deficit in the trachea of CF mutant mice at 8 or 9 days after intratracheal instillation.

[Somatic gene therapy in squamous epithelial carcinomas of the head-neck area].

Gene therapy is an important new approach to the treatment and prevention of human diseases. Somatic gene therapy involves the introduction of novel genetic material into somatic cells to express therapeutic gene products. Two main strategies in somatic gene therapy of cancer are applied: the genetic correction of the defect, or the elimination of cancer cells by cytotoxic drugs or the immuno system.

Characterization of mono- and polyclonal antibodies against highly purified choline acetyltransferase: a monoclonal antibody shows reactivity in human brain.

Choline acetyltransferase (ChAT) from porcine brain was purified by immunoaffinity chromatography, and the highly purified enzyme was subsequently used for immunization of mice and rabbits. After fusion of mouse spleen cells, 32 cultures producing monoclonal antibodies directed against ChAT were detected by an enzyme-linked immunosorbent assay (ELISA) with immunoaffinity-purified ChAT. Of these original 32, the most active 11 cultures were cloned and used for ascites production.

A monoclonal antibody that specifically inhibits human salivary alpha-amylase.

Our monoclonal antibody 88E8 specifically binds to and inhibits human salivary alpha-amylase (EC 3.2.1.

Specific immunoassay of alpha-amylase isoenzymes in human serum.

A monoclonal antibody (66C7) was prepared that specifically binds human salivary amylase (EC 3.2.1.

Nerve growth factor-mediated enzyme induction in primary cultures of bovine adrenal chromaffin cells: specificity and level of regulation.

Primary cultures of bovine adrenal chromaffin cells provide large quantities of a homogeneous population of target cells for nerve growth factor (NGF) and, thus, are a suitable system for studying the molecular mechanism of action of NGF. In this study, we have shown that NGF mediates the specific induction of the key enzymes in catecholamine biosynthesis, tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT). Acetylcholinesterase (AChE), an enzyme which catalyzes the breakdown of acetylcholine, is also induced by NGF.