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J Haensler

Publications and source records attributed to J Haensler.

13 recordsLinked to original sources
PubMed2005

Hepatic transit time: indicator of the therapeutic response to radiofrequency ablation of liver tumours.

The aim of this study was to evaluate changes of hepatic transit time (HTT) in patients treated by radiofrequency ablation (RFA). Five consecutive patients (2 females, 3 males; mean age 66 years) referred for treatment of liver neoplasm with percutaneous application of RFA were included in this study. The HTT of contrast agent (Sonovue(R); Bracco International B.V., Amsterdam, The Netherlands) was measured in patients with liver metastases on the basis of time intensity curve (TIC(R)) before and after RFA, respectively. Changes of HTT before vs after RFA were compared with therapeutic response based on three-phase dynamic CT or MRI. Before RFA HTT in all 5 patients was less than 10 s (mean 6.2+/-1.5 s). After RFA HTT in patients with complete therapeutic response was 11.3+/-1.2 s, whereas two patients with incomplete treatment showed unchanged HTT below 10 s (mean 6.3+/-1.8 s). Successful RFA leads to a normalization in HTT. HTT using ultrasound contrast agent appears to provide a new and alternative approach in assessing the therapeutic effect of RFA in liver metastases.

Aged↗
PubMed2001

Towards the rational design of Th1 adjuvants.

Finding adjuvants in order to enhance immune responses against target immunogens has been a major and recurrent issue for the vaccine industry. It is yet to be solved, most particularly in the context of a growing interest in designing new types of vaccines capable of eliciting Th1 immune responses. A review of synthetic adjuvants which have been (or are being) tested in clinical studies is presented. Importantly, recent advances in our understanding of the physiology of immune responses offer new avenues to design and test candidate adjuvants, based on either synthetic or natural molecules, with the aim to mimic and recapitulate pro-inflammatory signals initiating both innate and adaptative immune effector mechanisms. Thus, adjuvants of the future might be a mixture of molecules selected singularly for a capacity to attract, target or activate professional antigen presenting cells. Used as a combination, such molecules should facilitate antigen presentation by professional APCs and lead to a potent induction of T cell-mediated effector and immune memory mechanisms.

Adjuvants, Immunologic↗
PubMed2001

Design, characterization and preclinical efficacy of a cationic lipid adjuvant for influenza split vaccine.

We prepared a series of cationic lipid vesicles comprising a cationic cholesterol derivative, DC-Chol with or without a neutral phospholipid, DOPC or DOPE. The vesicles were tested for their ability to bind and adjuvant split inactivated influenza vaccines. We found that DC-Chol-containing liposomes are capable to strongly bind influenza vaccine antigens upon simple mixing with the vaccine. The resulting formulations induced robust anti-influenza immune responses both after s.c. and i.n. administration in BALB/c mice while neutral Cholesterol/DOPC liposomes displayed virtually no stable antigen binding and no adjuvant effect. The parenteral adjuvant effect of DC-Chol on trivalent split influenza vaccines was then confirmed in outbred mice and monkeys. Among the most potent formulations tested, a simple mixture of the vaccine with a microfluidized dispersion of DC-Chol in an aqueous buffer is being considered for further development to produce an improved influenza vaccine.

Adjuvants, Immunologic↗
PubMed2001

Formulations of single or multiple H. pylori antigens with DC Chol adjuvant induce protection by the systemic route in mice. Optimal prophylactic combinations are different from therapeutic ones.

The ability to induce a protective response against Helicobacter pylori infection has been investigated by systemic immunization of mice with urease formulated with the cationic lipid DC Chol. This compound acts both as a formulating agent and as an adjuvant and induces a balanced Th1/Th2 response shown to be more effective for protection in our previous studies. Urease-DC Chol induced a significant protection in prophylaxis but not in therapeutic immunization. The protection level was between 1.5 and 2 log reduction of bacterial density measured by quantitative culture compared to unimmunized-infected mice. In parallel, the protective efficacy of other H. pylori antigens formulated in a similar way and administered with DC Chol was tested. These antigens were tested alone or in combination in prophylactic and therapeutic regimens. Some combinations of antigens induced a better prophylactic or therapeutic activity than urease alone (0.5-1.5 log further reduction in prophylaxis and therapy respectively, P<0.05). The combinations that induced the best protection were different in prophylaxis and therapy. In conclusion, DC Chol provides a convenient and efficient method to formulate different antigens even when they are present in non-compatible buffers initially. Moreover, the results obtained in protection against H. pylori with such formulations should lead the way to future clinical trials.

Adjuvants, Immunologic↗
PubMed1999

Intradermal DNA immunization by using jet-injectors in mice and monkeys.

We have used spring powered jet injectors to deliver a solution of a naked DNA vaccine encoding the influenza hemagglutinin HA into the skin of mice and monkeys. We compared the immune responses induced by this needleless injection technique into the skin to the responses induced by a classical i.m. immunization. Both routes of immunization induced significant ELISA antibody titers and hemagglutination inhibition (HI) titers that were above the usual threshold values predictive of protection against influenza in mice and monkeys. In mice, both ways of immunization were equally efficient in inducing HA-specific CTL responses. Regarding antibody isotypes, the IgG1/IgG2a ratio was in favour of the IgG2a isotype for i.m. immunization and more balanced for i.d. immunization. The ability of the two injection techniques to induce immunity in mice did not correlate with transgene expression in the site of administration. In fact, local gene expression was 10-100 fold more important in the injected muscle as compared to the jet-injected skin when assessed by using the luciferase reporter system.

Animals↗
PubMed1998

Systemic immunization with urease protects mice against Helicobacter pylori infection.

The ability of systemic immunization to induce protection against Helicobacter pylori infection has been evaluated in a mouse model. It was observed that if appropriate formulations and adjuvants were used such immunization elicited in outbred Swiss mice levels of protection similar or better than those induced by the oral route in the presence of cholera toxin or Escherichia coli heat labile toxin. Recombinant urease mixed with adjuvants, which induced strong Th1 and Th2 responses elicited better protection than urease mixed with adjuvants which induced a predominant Th2 type response only. These experiments demonstrate the feasibility of parenteral immunization against H. pylori and suggest that an appropriate balance between Th1 and Th2 type responses is required to achieve complete protection.

Adjuvants, Immunologic↗
PubMed1991

Influence of the galactosyl ligand structure on the interaction of galactosylated liposomes with mouse peritoneal macrophages.

Liposomes bearing at their surface mono- and triantennary galactosyl ligands were prepared and their interaction with the galactose receptor of mouse peritoneal macrophages studied. Triantennary structures were synthesized by coupling derivatives of 1-thio-beta-D-galactose to the amino groups of lysyl-lysine dipeptide. Galactosylated liposomes were obtained either by synthesis of neo-galactolipids followed by their incorporation into the vesicles or by neo-galactosylation of performed liposomes by reaction between thiol-functionalized galactosyl ligands and vesicles bearing maleimido groups. The interaction of the galactosylated liposomes with the macrophage lectin was remarkably sensitive to the topology of the ligands, i.e., a spacer-arm length about 3 nm was necessary and, in contrast to results obtained with the galactose receptor of other cells, the triantennary structure did not provide additional binding. Related to the strategy of drug delivery with targeted liposomes, these results indicate that lectins from different cells might possibly be distinguished by using multiantennary ligands having optimal geometries.

Animals↗
PubMed1988

Preparation of neo-galactosylated liposomes and their interaction with mouse peritoneal macrophages.

In order to target liposomes to cells expressing at their surface a galactose-binding site we have prepared liposomes containing new synthetic galactolipids. Neo-galactosylated liposomes were prepared by covalently coupling beta-D-1-thiogalactopyranoside residues, substituted with a hydrophilic spacer-arm and functionalized with a sulfhydryl group, to preformed large unilamelar vesicles containing 4-(p-maleimidophenyl)butyryl phosphatidylethanolamine. The vesicles, having a galactose content above a threshold value of about 5 mol%, could be aggregated with Ricinus communis agglutinin. This aggregation was reversed by addition of excess free methyl beta-D-galactopyranoside, indicating that the surface glucidic moieties of these liposomes were accessible to the lectin. Compared to the control vesicles, the neo-galactosylated liposomes (containing 15 mol% galactose) presented in vitro an increased binding to cell possessing a beta-D-galactose specific receptor, i.e. resident mouse peritoneal macrophages. At 4 degrees C, the specific binding was about 2-fold, whereas at 37 degrees C it was increased to about 4-5-fold. This differential binding was largely unaffected by serum and, interestingly was much dependent on the degree of galactosylation of the liposomes, i.e. a threshold value of 5 mol% was needed to observe an increased binding of the targeted vesicles to the macrophages.

Animals↗
PubMedDate not supplied

Synthesis and characterization of a trigalactosylated bisacridine compound to target DNA to hepatocytes.

We have synthesized three bisacridine intercalators containing a galactose residue(s) to target DNA to cell surface receptors for use in gene-delivery systems. Each of the bisacridines could intercalate into DNA with micromolar dissociation constants. Bisacridines containing a single galactose on either a three- or six-carbon spacer from the secondary amine of spermidine-bisacridine could mediate binding of DNA to the soluble galactose receptor Ricinus communis lectin (RCA I), but not to the asialoglycoprotein receptor on primary hepatocytes. A trigalactosyl dilysyl bisacridine [(Gal-6)3Lys2-bA] compound could mediate the binding of DNA to both the ricin lectin and to primary hepatocytes. Binding of the (Gal-6)3Lys2-bA-DNA to the hepatocytes could be blocked by asialoorosomucoid. On the basis of luciferase expression, (Gal-6)3Lys2-bA did not induce transfection of the hepatocytes when attached to the pCLUC4 plasmid encoding the firefly luciferase gene.

Acridines↗
PubMedDate not supplied

Polyamidoamine cascade polymers mediate efficient transfection of cells in culture.

Cascade polymers also known as Starburst dendrimers are spheroidal polycations that can be synthesized with a well-defined diameter and a precise number of terminal amines per dendrimer. We show, using luciferase and beta-galactosidase containing plasmids, that dendrimers mediate high efficiency transfection of a variety of suspension and adherent cultured mammalian cells. Dendrimer-mediated transfection is a function both of the dendrimer/DNA ratio and the diameter of the dendrimer. Maximal transfection of luciferase are obtained using a diameter of 68 A and a dendrimer to DNA charge ratio of 6/1 (terminal amine to phosphate). Expression is unaffected by lysomotrophic agents such as chloroquine and only modestly affected (2-fold decrease) by the presence of 10% serum in the medium. Cell viability, as assessed by dye reduction assays, decreases by only 30% at 150 micrograms dendrimer/mL in the absence of DNA and about 75% in the presence of DNA. Under similar conditions polylysine causes a complete loss of viability. Gene expression decreased by 3 orders of magnitude when the charge ratio is reduced to 1:1. When GALA, a water soluble, membrane-destabilizing peptide, is covalently attached to the dendrimer via a disulfide linkage, transfection efficiency of the 1:1 complex is increased by 2-3 orders of magnitude. The high transfection efficiency of the dendrimers may not only be due to their diameter and shape but may also be caused by the pKa's (3.9 and 6.9) of the amines in the polymer. The low pKa's permit the dendrimer to buffer the pH change in the endosomal compartment. The characteristics of precise control of structure, favorable pKa's, and low toxicity make the dendrimers suitable for gene-transfer vehicles.

Animals↗
PubMedDate not supplied

Radiofrequency ablation of liver tumors: how to enlarge the necrotic zones?

In an attempt to increase necrotic zones in liver tissue by radiofrequency ablation fresh bovine liver was coagulated by means of a needle electrode continuously perfused with NaCl solution. Power output (60 W) and application time (15 min) were kept constant while the perfusion was varied in terms of saline concentration (0.9, 5.85 and 10%) and perfusion rate (40 or 80 ml/h). Our results showed that the use of higher osmolar saline solutions in radiofrequency ablation with perfused needle electrodes did not lead to significantly larger coagulation volumes. By contrast, increasing the perfusion rate produced significantly larger necrotic zones. Doubling the perfusion rate made it possible to reach higher temperatures (>60 degrees C) within significantly shorter time.

Animals↗