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Biomedical subjects

B Jansen

Publications and source records attributed to B Jansen.

At least 19 recordsLinked to original sources
PubMed1992

Successful treatment of human acute T-cell leukemia in SCID mice using the anti-CD7-deglycosylated ricin A-chain immunotoxin DA7.

The study of new therapeutic approaches for refractory human leukemia has been hampered by the lack of relevant in vivo models with disseminated disease, particularly T acute lymphoblastic leukemia (T-ALL). In the present study we evaluated methods for establishing and therapy of a human T-ALL cell line (MT-ALL) in 73 SCID mice. MT-ALL is a T-cell receptor alpha/beta +, CD3+, and CD7+ leukemia cell line, derived from a patient with refractory disease and early death. Injection of 5 x 10(7) MT-ALL cells i.v. caused disseminated human leukemia in hematopoietic and nonhematopoietic organs in 100% of SCID mice (n = 9) leading to death or terminal disease at 65 to 70 days after a uniform clinical course. To study possible therapeutic approaches for disseminated leukemia we utilized an immunotoxin, DA7, constructed by chemically linking the mouse IgG2b anti-CD7(3A1E) monoclonal antibody which recognizes a pan-T-cell marker expressed on almost all T-cell leukemias to deglycosylated ricin A-chain, a catalytic plant toxin and inhibitor of protein synthesis. Administration of DA7 led to greater than 5 log kill of clonogenic MT-ALL cells in vitro and selectively inhibited protein synthesis. DA7 was administered to mice at a dose of 10 micrograms/mouse/day for 5 consecutive days starting 8 days after i.v. inoculation of leukemia. The immunotoxin therapy resulted in significant long term survival over 348 days compared to untreated or control mice treated with anti-CD7 antibody and deglycosylated ricin A-chain which were all dead by day 70 (P less than 0.001). Even after more than 11 months there was no evidence of disease in 82% of the DA7 treated animals. SCID mice given i.p. injections (n = 9) developed an i.p. tumor mass but demonstrated metastasis outside the peritoneum with disseminated leukemia in hematopoietic and nonhematopoietic organs, a finding different from most conventional nude mouse models. The leukemia was fatal in 100% and killed the animals at 68-95 days. SCID mice given i.p. injections of MT-ALL completely responded to therapy with DA7, resulting in survival of 100% of the animals (n = 10) at 216 days (P less than 0.001 compared to untreated animals). Anti-CD7 antibody, deglycosylated ricin A-chain, and a control anti-melanoma immunotoxin (IND1-RTA) showed no therapeutic effect. We conclude that DA7 is an effective in vivo therapeutic agent against human MT-ALL in the SCID mouse system, suggesting potential usefulness for therapy of humans with poor prognosis T-cell leukemia.

Animals↗
PubMed1992

Establishment of a human t(4;11) leukemia in severe combined immunodeficient mice and successful treatment using anti-CD19 (B43)-pokeweed antiviral protein immunotoxin.

Human acute leukemia, with a chromosomal translocation involving chromosomes 4 and 11, t(4;11)(q21;q23), is the most common form of leukemia in infants and responds very poorly to conventional therapy. A human CD19+ mixed-lineage leukemia cell line with a t(4;11)(q21;q23) translocation, RS4;11, disseminated and proliferated in the hematopoietic tissues and other organs of mice with severe combined immunodeficiency in a manner similar to that observed in humans and killed 100% of the animals. The anti-CD19(B43)-pokeweed antiviral protein immunotoxin selectively inhibited clonogenic RS4;11 cells in vitro, markedly reduced the burden of disseminated leukemia of severe combined immunodeficient mice, and, most importantly, resulted in the long-term survival of treated animals. This severe combined immunodeficient mouse model should be useful for the design of more effective treatment strategies for refractory human leukemias.

Animals↗
PubMed1992

In-vitro efficacy of a central venous catheter ('Hydrocath') loaded with teicoplanin to prevent bacterial colonization.

A technique is described by which a central venous catheter ('Hydrocath') is loaded with the glycopeptide teicoplanin for the prevention of catheter infection. Catheters are immersed in teicoplanin solution and, due to the hydrophilic surface coating of the 'Hydrocath' catheter, teicoplanin is absorbed by the surface layer. The catheter loading is influenced by the experimental conditions and is assessed by measuring teicoplanin elution from the catheter using a bioassay. Increasing the antibiotic concentration, incubation time and temperature leads to the binding of higher amounts of teicoplanin to the catheter, resulting in a higher teicoplanin release from the catheter. Experiments on in-vitro bacterial adherence to teicoplanin-loaded and unloaded catheters reveal that the initial bacterial adhesion is not prevented. However, in the case of the teicoplanin-loaded catheter initially adherent bacteria are eliminated from the catheter surface, thus preventing catheter colonization by bacteria for at least 48 h. Such loaded catheters could be suitable for inhibiting early-onset, catheter-related infections.

Bacterial Adhesion↗
PubMed1992

Adhesion of fimbriated and non-fimbriated Klebsiella strains to synthetic polymers.

Adherence of three fimbriated and non-fimbriated Klebsiella strains to polyetherurethane was investigated in order to assess the possible role of fimbriae in the adhesion of Klebsiella to synthetic polymers. Fimbriated strains with type 1 and type 1.3 fimbriae adhere significantly stronger to polyurethane than the same strains lacking fimbriae, whereas a strain with type 3 fimbriae shows no different adherence compared with the non-fimbriated variant. Analysis of adhesion kinetics and isotherms reveals that adherence of fimbriated Klebsiella strains is proceeded by the formation of multicellular bacterial layers on the polymer surface. Measurements of the relative hydrophobicity of the strains and adherence experiments under exclusion of unspecific interactions point out that fimbriae obviously play a more important role in adhesion than relative hydrophobicity. The demonstration of reduction of bacterial adherence to polyetherurethane by blocking fimbrial action with fimbriae-specific sugars supports this further.

Bacterial Adhesion↗
PubMed1992

In-vitro efficacy of a central venous catheter complexed with iodine to prevent bacterial colonization.

Infections of central venous lines are still a problem in daily medicine. Despite adequate antibiotic therapy, removal of an infected catheter often becomes necessary. A simple procedure has been developed by which a special hydrophilic central venous catheter (Secalon-Hydrocath) can be loaded with iodine. Iodine is complexed in the hydrophilic polyvinylpyrrolidone surface coating of the Hydrocath catheter and is released during contact with an aqueous medium. The amount of complexed iodine depends on the incubation time in Lugol's solution. Antimicrobial activity of the loaded catheters was assessed with Staphylococcus epidermidis, showing complete inhibition of bacterial adherence to the catheters for the duration of iodine release. Depending on the experimental conditions, iodine released from the catheter is also active on bacteria in the surrounding medium.

Bacterial Adhesion↗
PubMed1992

[New strategies for the prevention of foreign body infections].

Foreign body infections continue to present a challenge to modern medicine. New aspects for the prevention of such infections are presented on the basis of modifying medical devices or implant materials (synthetic polymers). Physicochemical treatment of polymer surfaces is a possible tool to create anti-adhesive and thus anti-infective surfaces. Coupling or incorporation of antimicrobial substances to or into polymers is another way to prevent bacterial colonization and subsequently the development of polymer-associated infections.

Bacterial Adhesion↗
PubMed1991

Differentiation in mature T lymphoid leukemia cells is unstable and reversible to myeloid cells, without the involvement of a common stem cell.

Mechanisms for the unstable and reversible differentiation of a mature CD3+ CD7+TCR-alpha/beta+ T lymphoid leukemia into the myeloid lineage were investigated. Inasmuch as productive rearrangement of the TCR-alpha is a late determinant of T cell differentiation, the TCR-alpha rearrangement was sequenced to determine the state of differentiation of the leukemic multipotent cell. An identical productive rearrangement of J alpha C to a novel V alpha region was found in the myeloid and T lymphoid leukemic cells. Thus, a "terminally" differentiated T lymphoid leukemic cell after productively rearranging TCR-alpha and -beta continues to display potential for multilineage differentiation. Therefore, multilineage potential is due to an unstable and reversible differentiation in a mature T lymphocyte as opposed to differentiation of an uncommitted common T and myeloid precursor cell.

Amino Acid Sequence↗
PubMed1991

Modern strategies in the prevention of polymer-associated infections.

Foreign body infections continue to present a challenge to modern medicine. New aspects for the prevention of such infections are presented on the basis of modifying medical devices or implant materials (synthetic polymers). Physicochemical treatment of polymer surfaces is a possible tool to create anti-adhesive and thus anti-infective surfaces. Coupling or incorporation of antimicrobial substances to or into polymers is another way to prevent bacterial colonization and subsequently the development of polymer-associated infections.

Anti-Bacterial Agents↗
PubMed1991

Evidence for degradation of synthetic polyurethanes by Staphylococcus epidermidis.

The survival of Staphylococcus epidermidis strain KH 11 in the presence of synthetic high molecular polyurethanes was prolonged in comparison to control experiments performed in the absence of any nutrients. Investigations of the bacteria after contact with the polymers revealed changes in their surface properties and metabolism, in particular a marked induction of urease activity. ESCA (Electron Spectroscopy for Chemical Analysis) measurements detected a decrease in elementary nitrogen in the polyurethane surfaces after incubation with the bacteria. The alterations observed indicate an urease-induced degradation of synthetic polymers by Staphylococcus epidermidis KH 11.

Absorption↗
PubMed1991

Late onset endophthalmitis associated with intraocular lens: a case of molecularly proved S. epidermidis aetiology.

A case of severe endophthalmitis after cataract extraction followed by posterior chamber lens implantation is reported. Microbiological cultures from a tap of the patient's aqueous humour prior to lens explantation as well as from the explanted lens and aqueous and vitreous humour during operation yielded Staphylococcus epidermidis sensu stricto. Scanning electron microscopy showed massive colonisation of the lens loop by staphylococci. Clonal identity of all isolates was demonstrated by plasmid DNA analysis and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of extra-cellular products. This is strongly suggestive of the aetiological role of S. epidermidis in this case of late onset endophthalmitis.

Aged↗
PubMed1991

Antimicrobial activity of polymers coated with iodine-complexed polyvinylpyrrolidone.

Polymer-associated infection is a problem of increasing importance in modern medicine. In a new approach to prevent such infections we have modified polyvinylfluoride (TEDLAR) films by graft copolymerization with N-vinylpyrrolidone to which iodine can be complexed. Grafting reaction was performed by the preirradiation technique using an electron accelerator. Grafted films were then treated in Lugol's solution for at least 24 h. Release of free iodine from the films was determined either by titration or using the agar disc diffusion test, showing an iodine release for up to 4-5 days. The antimicrobial activity of the films was tested in bacterial adhesion measurements. Bacterial and fungal cells in the range of 10(3) to 10(6) cfu/cm2 polymer were found on control samples without iodine, whereas on iodine-complexed films no viable cells could be detected at least for 5 days or even longer. Thus, microbial adhesion and growth can be inhibited by iodine-containing polymers.

Animals↗
PubMed1991

[Problems of infection in polymer implants].

Infections associated with indwelling devices have become a major problem in modern medicine. Coagulase-negative staphylococci and to a lesser extent Staphylococcus aureus, enterobacteriaceae und fungi are the predominant causative organisms in the etiology of these infections. The general features of the pathogenesis of foreign body infections are discussed, as are the clinical picture and therapy. Special emphasis is given to the occurrence of polymer-associated infections in urological devices such as penile prostheses and to their prevention and therapy.

Enterobacteriaceae↗
PubMed1990

Ultrastructure of neutrophilic granulopoiesis in the bone marrow of patients with chronic myeloid leukemia (CML). A morphometric study with special emphasis on azurophil (primary) and specific (secondary) granules.

In seven patients with chronic myeloid leukemia (CML) and ultrastructural and morphometric study was performed on neutrophilic granulopoiesis in bone marrow trephine biopsies. Bone marrow specimens from five patients without hematological abnormalities served as controls. In stable phases of CML, abnormalities of the maturing granulocytic lineage were most conspicuously expressed by an infrequently occurring nuclear disfiguration (blebs and disturbed bridging of segments). Morphometric evaluation included the numbers of azurphil (primary) and specific (secondary) granules, the cisternal length of the endoplasmic reticulum and the area of the mitochondrial profiles. These variables could be determined in early and late myeloblasts, promyelocytes, metamyelocytes, band cells and mature polymorphonuclear granulocytes. Statistical analysis with regard to control specimens demonstrated no significant differences in the total amount of neutrophil granules or of the other cell organelles.

Bone Marrow↗
PubMed1990

New concepts in the prevention of polymer-associated foreign body infections.

Polymer-associated foreign body infections, especially those caused by coagulase negative staphylococci, have become a problem of increasing importance in modern medicine. Therapy of such infections is often difficult and requires in many cases the removal of a catheter or an implant. On the basis of polymer material modification alternative strategies for the prevention of foreign body infections are presented. By use of high energy radiation or glow discharge techniques polymers can be modified so that new chemical groups with potential antiadhesive or antimicrobial activities can be introduced to the polymer (surface). Another approach is the coupling or incorporation of antimicrobial agents (e.g. antibiotics) to or into polymers. Such polymer-antibiotic systems are obviously not able to prevent initial bacterial adhesion to the polymer material but can effectively eliminate already adherent bacteria from the polymer surface.

Anti-Bacterial Agents↗
PubMed1990

Evidence for lectin-mediated adherence of S. saprophyticus and P. aeruginosa to polymers.

By hemagglutination tests surface lectins on S. saprophyticus strain S 1 with N-acetylgalactosamine (GalNac) and N-acetylglucosamine (GlcNac) specificity and on P. aeruginosa ATCC strain 27853 with N-acetylneuraminic acid (NANA) specificity could be demonstrated. To elucidate the role of bacterial surface lectins for the specific adhesion, polyether urethane discs were preincubated for 15 h at 4 degrees C in human serum or urine. Adhesion studies with S. saprophyticus S1 and P. aeruginosa ATCC 27853 onto precoated polymers revealed that microbial lectins may play a role in the colonization of prosthetic devices since lectin-blocking with competitive glycoconjugates significantly decreased bacterial adherence to the coated surfaces. Non-specific carbohydrates did not inhibit the adherence demonstrating specificity of this process.

Bacterial Adhesion↗