Search PubMed⌕ Search

Biomedical subjects

B Jansen

Publications and source records attributed to B Jansen.

At least 19 recordsLinked to original sources
PubMed2005

Modern strategies in the prevention of implant-associated infections.

The application of medical devices either for temporary or permanent use has become an indispensible part of almost all fields of medicine. However, foreign bodies are associated with a substantial risk of bacterial and fungal infections. Implant-associated infections significantly contribute to the still increasing problem of nosocomial infections. To reduce the incidence of such infections, specific guidelines providing evidence-based recommendations and comprising both technological and nontechnological strategies for prevention have been established. Strict adherence to hygienic rules during insertion or implantation of the device are aspects of particular importance. Besides such basic and indispensable aspects, the development of new materials which could withstand microbial adherence and colonization has become a major topic in recent years. Modification of surface by primarily physico-chemical methods may lead to a change in specific and unspecific interactions with microorganisms and, thus, to a reduction in microbial adherence. Medical devices made out of a material that would be ideally antiadhesive or at least colonization-resistant would be the most suitable candidates to avoid colonization and subsequent infection. However, it appears impossible to create a surface with an absolute 'zero'-adherence due to thermodynamical reasons and due to the fact that a modified material surface is in vivo rapidly covered by plasma and connective tissue proteins. Therefore, another concept for the prevention of implant-associated infections involves the impregnation of devices with various antimicrobial substances such as antibiotics, antiseptics, and/or metals. In fact, already commercially available materials for clinical use such as antimicrobial catheters have been introduced, in part with considerable impact on subsequent infections. However, future studies are warranted to translate the knowledge on the pathogenesis of device-associated infections into applicable prevention strategies.

Anti-Bacterial Agents↗
PubMed2004

ENDOR-assisted study of the stable EPR spectrum of X-irradiated alpha-L-sorbose single crystals: MLCFA and simulation decomposition analyses.

After X irradiation of single crystals of alpha-L-sorbose at 295 K, previous electron paramagnetic resonance (EPR), electron nuclear double resonance (ENDOR), and ENDOR-induced EPR (EI-EPR) results have indicated the formation of at least 10 different free radicals, and also that conceivably each carbon in the pyranose ring is a possible radical center. The radicals appear to be formed mostly by net H-abstraction reactions followed by standard elimination (e.g. beta-OH elimination) reactions or proton shifts, in turn leading to ring opening and fragmentation. In the present work, EPR spectra were recorded at room temperature with the external magnetic field along each of the three crystallographic axes subsequent to careful annealing at different temperatures using a high-temperature cavity. Each of the three sets of spectra was subjected to a maximum likelihood common factor analysis (MLCFA) that contributed to a better understanding of the spectral decays. Furthermore, the most stable spectra were simulated by optimization of previous ENDOR and EI-EPR results. The optimized EPR parameters resulted in excellent simulations of the experimental stable sorbose spectra and hence provided an improved insight of their spectral compositions.

Crystallization↗
PubMed2003

Bcl-x(L) antisense oligonucleotides radiosensitise colon cancer cells.

Advanced colon cancer is a malignancy with poor response to various treatment modalities including ionising radiation (IR) and chemotherapy. Both IR and chemotherapeutic agents have been shown to act by inducing apoptosis, a type of cell death antagonised by the Bcl-x(L) gene product. Since approximately 60% of human colon cancers express Bcl-x(L), it was the aim of this study to explore the potential of Bcl-x(L) antisense oligonucleotides as a novel radiosensitisation strategy. Caco-2 colon cancer cells were treated with Bcl-x(L) antisense oligonucleotides in combination with IR or cisplatin, and Bcl-x(L) protein expression, apoptosis, cell viability and clonogenic survival were examined. Bcl-x(L) antisense oligonucleotide specifically reduced the Bcl-x(L) protein level by almost 50% in Caco-2 cells. The decreased threshold for the induction of apoptosis resulted in a 300% increase of apoptosis after IR or cisplatin treatment and led to a 60% reduction of cell proliferation beyond response rates achieved with IR. These data suggest that Bcl-x(L) is an important factor contributing to the treatment resistance of human colon cancer. Specific reduction of Bcl-x(L) protein levels by antisense oligonucleotides qualifies as a promising therapeutic strategy for colon cancer that may help overcome resistance and improve clinical outcome in this malignancy.

Antineoplastic Agents↗
PubMed2003

Efficacy of NaOCl/H2O2 irrigation and GaAlAs laser in decontamination of root canals in vitro.

BACKGROUND AND OBJECTIVES: To investigate the bactericidal effect of an 809 nm semiconductor laser alone, and in combination with NaOCl/H(2)O(2) irrigation in root canals in vitro. STUDY DESIGN/MATERIALS AND METHODS: A total of 72 human single-rooted teeth extracted for periodontal reasons were included. The crowns were removed, the roots shortened to a length of 12 mm, and the canals enlarged up to an apical size of #50 file. The specimens were autoclaved and incubated with a suspension of Streptococcus sanguinis (ATCC 10556). Laser irradiation was performed on a PC-controlled XY translation stage. A 200 micron optic fiber was used. Twelve specimens were irradiated at a power output of 1.5, 3.0, and 4.5 W in the cw-mode. The total irradiation time was 60 seconds per canal. Twelve specimens were rinsed with NaOCl and H(2)O(2) only, 12 were rinsed and laser treated, and 12 served as untreated controls. After laser treatment, the specimens were sonicated and the bacterial growth was examined by counting colony forming units on blood agar plates. Temperature changes at the outer root surface during irradiation were registered by means of thermocouples. Treated and control specimens were investigated by means of scanning electron microscopy. RESULTS: Mean bacterial reductions of 0.35 log steps at a power output of 1.5 W, 1.44 at 3.0 W, and 2.84 at 4.5 W were calculated. Bacterial reduction by the NaOCl/H(2)O(2) solution alone was 1.48 and comparable to that achieved by irradiation at 3.0 W. With a log kill 2.85, the combination of rinsing and laser irradiation at 3.0 W resulted in a further significant bacterial reduction as compared to rinsing alone (P = 0.004). Irradiation did not result in excessive heat generation at the root surface. Carbonization of the root canal wall was observed in single teeth at 3.0 and 4.5 W and no controlled sealing of the dentinal tubules could be achieved in the root canal. CONCLUSIONS: The application of the diode laser might be an adjunct to conventional endodontic treatment when used in combination with a NaOCl/H(2)O(2) solution.

Colony Count, Microbial↗
PubMed2003

Rifampin-impregnated silicone catheters: a potential tool for prevention and treatment of CSF shunt infections.

BACKGROUND: Infection continues to be one of the major complications of cerebro-spinal fluid shunting procedures. Recent insights in the pathophysiological mechanism of these foreign body infections have elucidated the difficulty of achieving successful treatment without device removal. The development of a rifampin-impregnated silicone catheter yielded excellent results in infection prevention and treatment in vitro as well as in an animal model. PATIENTS AND METHODS: Here, we describe the application of this device in two patients with a complicated course of shunt infection. RESULTS: In one patient the rifampin-impregnated shunt system was implanted after external drainage to prevent further infection. The shunt infection of the second patient was treated by replacement of the infected shunt system with a rifampin-impregnated device. Both patients recovered immediately without any signs of adverse effects and the two shunt systems have now been working properly for more than 36 and 21 months, respectively. CONCLUSION: These results suggest that rifampin-impregnated silicone catheters could become a valuable tool in the treatment and prevention of shunt infections.

Anti-Bacterial Agents↗
PubMed2003

Effect of glutathione depletion and hydrophilic bile acids on hepatic acute phase reaction in rats with extrahepatic cholestasis.

BACKGROUND: Extrahepatic cholestasis by biliary obstruction induces an acute phase reaction in the liver. It is a complex process involving cytokines, hormones and growth factors. To determine whether the regulation of acute phase proteins (APP) in cholestasis depends on glutathione (GSH), the effect of buthionine sulfoximine-induced (BSO-induced) GSH depletion on the expression of various APP was studied. In addition, we determined the influence of hepatoprotective bile acids on hepatic APP and underlying cytokine events. METHODS: Liver samples of bile-duct-ligated or sham-operated rats were examined. mRNA expression was quantified by densitometric analysis of Northern blots. RESULTS: Expression of APP increased 2-5-fold in bile-duct-ligated rats as compared to sham-operated controls. This acute phase reaction remained similar independently of whether cholestasis occurred for 5 days or 3 weeks. In contrast to alpha2-macroglobulin and tissue inhibitor of metalloproteinases-1 (TIMP-1), mRNA levels of both beta-fibrinogen and haptoglobin were significantly up-regulated after GSH depletion by BSO in cholestasis. Feeding of ursodeoxycholic and iso-ursodeoxycholic acid markedly down-regulated alpha2-macroglobulin and TIMP-1 expression in cholestasis but did not affect overexpression of beta-fibrinogen and haptoglobin. Cholestasis leads to an increased APP expression accompanied by an increased expression of inflammatory cytokines (IL-6, TNF-alpha). After feeding of hydrophilic bile acids, increases in inflammatory cytokines were abrogated. CONCLUSIONS: We show that GSH is involved in the acute phase reaction during obstructive cholestasis. In addition, bile acids might selectively ameliorate the acute phase response by reducing expression of the APP not affected by GSH depletion (alpha2-macroglobulin and TIMP-1).

Acute-Phase Proteins↗
PubMed2003

Equine melanoma in a population of 296 grey Lipizzaner horses.

REASONS FOR PERFORMING STUDY: Equine melanomas occur most commonly in grey horses at age 5 years or more. Generally, benign and malignant melanomas are distinguished by microscopy, but a more distinct classification would be helpful. OBJECTIVES: The objectives of this study were to gain further evidence concerning the occurrence of melanotic tumours, and to evaluate the impact of heredity on melanoma development. METHODS: A clinical study was conducted on a defined population of 296 grey horses of Lipizzaner breed. Individuals were classified according to their stage of disease using a 0-5 scale. Heritability was estimated on a sample of 296 grey horses with pedigrees traced back as far as 32 generations. RESULTS: Of the 296 horses, dermal melanomas were present in 148 horses (50%), 68 of which were more than age 15 years; 51 of these were melanoma-bearing. In 75.6% of cases, melanotic tumours were detected underneath the tail. Although melanoma-bearing grey horses were encountered up to stage 4, none of the affected individuals suffered any severe clinical effect or was handicapped in performance. Statistical analysis revealed highly significant effects of stud and age (P < 0.0001), explaining 28% of the total variability. CONCLUSIONS: In contrast to melanomas in solid-coloured horses characterised by early metastases, melanomas in grey horses showed less malignancy. Affected individuals often had encapsulated nodules or structures similar to human blue nevi. Grey horse-specific genetic factors inhibiting metastatic processes may be responsible for this phenomenon. POTENTIAL CLINICAL RELEVANCE: Although the obtained heritability estimate of 0.36 with a standard error of 0.11 indicates a strong genetic impact on the development of melanoma in ageing grey horses, a possible influence of the genes with large effects was also suggested. Therefore, further analysis is required of melanoma development in the ageing grey horse.

Age Distribution↗
PubMed2002

Effect of blackcurrant-, cranberry- and plum juice consumption on risk factors associated with kidney stone formation.

OBJECTIVE: To evaluate the influence of plum-, cranberry- and blackcurrant juice on urinary stone risk factors. DESIGN: Investigations were carried out in 12 healthy male subjects aged 18-38 y. All subjects received a standardized diet formulated according to the dietary recommendations of the German Society of Nutrition. The subjects provided 24 h urine collections in a control, three loading phases. In each loading phase a neutral mineral water was substituted for 330 ml of the particular juice. RESULTS: Cranberry juice decreased the urinary pH, whereas the excretion of oxalic acid and the relative supersaturation for uric acid were increased. Blackcurrant juice increased the urinary pH and the excretion of citric acid. The excretion of oxalic acid was increased too. All changes were statistically significant. The plum juice had no significant effect on the urinary composition. CONCLUSION: It is concluded that blackcurrant juice could support the treatment and metaphylaxis of uric acid stone disease because of its alkalizing effect. Since cranberry juice acidifies urine it could be useful in the treatment of brushite and struvite stones as well as urinary tract infection. SPONSORSHIP: Funded by our own Division respectively the University.

Adolescent↗
PubMed2002

Protein kinase C isoforms in normal and transformed cells of the melanocytic lineage.

Enzymes belonging to the protein kinase C (PKC) family represent one of the major mediators of signal transduction in melanocytes. To identify PKC isoforms that may be associated with the process of malignant transformation and metastasis, we investigated the expression pattern of 11 different PKC isoforms (alpha, beta I, beta II, gamma, delta, epsilon, eta, theta, zeta, lambda, and iota) in melanoma lymph node metastases, in cell lines established from these metastases, in primary cell cultures from normal melanocytes, and in permanent cell lines established from spontaneously transformed melanocytes. PKC alpha, beta I, beta II, delta, epsilon, eta, zeta, lambda and iota were found to be expressed in total lysates from melanoma metastases. In permanent cell lines established from these metastases, the expression levels of PKC beta I, beta II, delta, epsilon, and eta were lower or undetectable when compared with initial expression in tumour lysates. In normal primary melanocyte cultures, the PKC isoforms beta II, delta, epsilon, eta and iota were undetectable. PKC gamma and theta isoforms were undetectable in all melanocytic cell types examined. PKC iota was the only isoform exclusively detected in tumour lysates, in spontaneously transformed melanoma cells and melanoma cell lines, but not in normal melanocytes, and may therefore be associated with the transformed phenotype in human melanoma in vitro and in vivo.

3T3 Cells↗
PubMed2001

Penetration of dacarbazine and its active metabolite 5-aminoimidazole-4-carboxamide into cutaneous metastases of human malignant melanoma.

BACKGROUND: Dacarbazine has been on the market for approximately 3 decades but remains the most effective single agent available for the therapy of metastatic malignant melanoma (MMM). Most MMMs, however, respond poorly to dacarbazine therapy. Apart from tumor resistance at a molecular level, several studies support the notion that therapeutic failure in tumor therapy also might be attributed to an impaired transcapillary drug transfer. METHODS: On the basis of this hypothesis, the authors measured intratumor transcapillary transfer rates of dacarbazine and its active metabolite 5-aminoimidazole-4-carboxamide (AIC) by in vivo microdialysis after intravenous administration of dacarbazine at doses of 200 mg/m(2) to 1000 mg/m(2) (n = 7) in patients suffering from MMM. RESULTS: For all doses, area under the concentration curve (AUC) values for dacarbazine and AIC were not significantly different between plasma and tumor interstitium with AUC(tumor)/AUC(plasma) ratios of 0.97 +/- 0.08 (mean +/- standard error of the mean) for dacarbazine and 0.76 +/- 0.22 for AIC. AUC(0-240) values for dacarbazine and AIC measured in plasma correlated closely with corresponding AUC(0-240)values measured in the interstitium of MMMs with values of r(s) = 0.82 (P = 0.042) and r(s) = 0.90 (P = 0.037), respectively. CONCLUSIONS: The results of this study indicate favorable tumor penetration characteristics of dacarbazine and its active metabolite AIC. The relative lack of response to antineoplastic therapy with dacarbazine, thus might be explained by resistance of melanoma cells at a molecular level rather than by an inability of dacarbazine and AIC to penetrate into the interstitium of MMM.

Aged↗
PubMed2001

Comparison of diffusive gradients in thin films and equilibrium dialysis for the determination of Al, Fe(III) and Zn complexed with dissolved organic matter.

The distinction between 'free' metals and organically complexed metals in aqueous solutions is important for research involving the mobility or bioavailability of metals in the environment. In this study, the applicability of equilibrium dialysis (molecular weight cut-off = 1000 Da) and diffusive gradients in thin films (DGT) to determine 'free' Al, Fe(III) and Zn in four forest soil solutions was compared. The 'free' metals as measured by both methods, consist of hydrated metal cations and soluble inorganic metal complexes. In addition, dialysis measures any organic complexes < 1000 Da and DGT measures a portion of smaller labile organic complexes. The four soil solutions were prepared by water extraction of an organic soil horizon (H) from a Fimic Anthrosol, and contained either 20 or 75 mg C/l dissolved organic matter at pH 4.0 and pH 7.0. To test the performance of both methods and optimize experimental volume and time, experiments using metal nitrate solutions were carried out. In the solutions at pH 4.0, no significant differences in average 'free' metal contents were found for Al, Fe(III) or Zn. This makes DGT a viable alternative for equilibrium dialysis for the study of the complexation of all three metals in acidic soils. At pH 7.0, again no significant difference between both methods were found for Al and Fe(III), but the DGT results for Zn were significantly higher. This was likely caused by labile organic complexes that were only detected by DGT.

Aluminum↗
PubMed2001

Bioanalysis and preliminary pharmacokinetics of the acridonecarboxamide derivative GF120918 in plasma of mice and humans by ion-pairing reversed-phase high-performance liquid chromatography with fluorescence detection.

We have developed and validated a sensitive and selective method for the determination of the P-glycoprotein modulator GF120918 in murine and human plasma. Chlorpromazine is used as internal standard. Sample pretreatment involves liquid-liquid extraction with tert-butyl methyl ether. Chromatographic separation is achieved by reversed-phase high-performance liquid chromatography using a Symmetry C18 column and detection was accomplished with a fluorescence detector set at excitation and emission wavelengths of 260 and 460 nm, respectively. The mobile phase consists of acetonitrile-50 mM ammonium acetate buffer, pH 4.2 (35:65, v/v). To achieve good separation from endogenous compounds and to improve the peak shape the counter-ion 1-octane sulfonic acid (final concentration 0.005 M) was added to the mobile phase. The lower limit of quantitation was 5.7 ng/ml using 200 microl of human plasma and 23 ng/ml using 50 microl of murine plasma. Within the dynamic range of the calibration curve (5.7-571 ng/ml) the accuracy was close to 100% and within-day and between-day precision were within the generally accepted 15% range. The stability of GF120918 was tested in plasma and blood from mice and humans incubated at 4 degrees C, room temperature, and 37 degrees C for up to 4 h. No losses were observed under these conditions. This method was applied to study the pharmacokinetics of orally administered GF120918 in humans and mice. The sensitivity of the assay was sufficient to determine the concentration in plasma samples obtained up to 24 h after drug administration.

Acridines↗
PubMed2001

Bcl-2 antisense oligonucleotides chemosensitize human gastric cancer in a SCID mouse xenotransplantation model.

We used Bcl-2 antisense oligonucleotides (G3139) to chemosensitize human gastric cancer by downregulation of Bcl-2 expression in vivo. Oligonucleotides and cisplatin were administered systemically in a human gastric cancer SCID mouse model, and Bcl-2 expression, apoptosis, tumor size, and survival were assessed. Used alone, G3139 treatment led to downregulation of Bcl-2 and moderate tumor reduction compared to saline control. G3139 combined with cisplatin treatment markedly enhanced the antitumor effect of cisplatin (70% tumor size reduction vs. cisplatin alone), associated with increased apoptosis measured in tumor biopsy specimens. Combined treatment with G3139 and cisplatin prolonged survival of the tumor-bearing SCID mice by more than 50% without adding significant drug-related toxicity. Treatment with Bcl-2 antisense oligonucleotides is thus a promising novel approach to enhance antitumor activity of cisplatin or other drugs used in gastric cancer therapy and warrants further evaluation in clinical trials.

Animals↗
PubMed2001

Perilesional injection of r-GM-CSF in patients with cutaneous melanoma metastases.

Based on evidence that granulocyte-macrophage colony stimulating factor (GM-CSF) induces a potent systemic antitumor immunity, we tested recombinant GM-CSF in advanced melanoma. Seven patients with histologically confirmed cutaneous melanoma metastases were treated with perilesional intracutaneous injections of recombinant GM-CSF and observed for a follow-up time of 5 y. All but two patients had a decrease in the total number of metastases. At the end of the 5 y follow-up three of the seven patients are still alive with only one patient receiving other than surgical therapy, and one patient died tumor free at the age of 93. The remaining three patients died from progressive melanoma. Perilesional intradermal GM-CSF therapy resulted in a mean survival time of 33 mo. The treatment was well tolerated and no side-effects other than local erythema at the injection sites and mild drowsiness were seen. Immunohistochemical analysis with staining for CD14 and GM-CSF receptor demonstrated an increased infiltration of monocytes into both injected and noninjected cutaneous melanoma metastases compared with lesions excised prior to the initiation of therapy. The same was true for CD4- and CD8-positive lymphocytes. This phenomenon, together with GM-CSF-induced leukocyte counts of more than 20,000 during therapy, support the possible impact of a systemic over a locally induced reaction by GM-CSF. To our knowledge this is the first report that intracutaneously injected GM-CSF results in long-lasting reduction of melanoma metastases.

Aged↗
PubMed2001

Differential expression levels of Par-4 in melanoma.

The pro-apoptotic prostate apoptosis response-4 gene product Par-4 sensitizes prostate cells to the induction of programmed cell death. In this study we examined Par-4 expression in human melanoma cell lines and melanoma metastases. The heterogeneous expression detected prompted us to investigate the biological relevance of Par-4 in a human melanoma xenotransplantation model. Overexpression of Par-4 by transfection decreased tumour development in xenotransplanted A375-C6 melanoma cells in SCID mice and correlated to an increase in tumour cell apoptosis. These data suggest that high expression of the pro-apoptotic protein Par-4 could qualify as a prognostic marker in human melanoma.

Animals↗
PubMed2001

Elevated procaspase levels in human melanoma.

In this study procaspase expression levels were investigated by Western blotting in a panel of established melanoma cell lines, transformed melanocytic cell lines and normal primary melanocytes. Upstream caspases such as procaspase-8 that contain a death effector domain were found to be overexpressed in transformed melanocytes and melanoma cell lines compared with melanocytes. Heterogeneous levels of procaspase-8 were seen in melanoma cells, including one cell line that completely lacked procaspase-8 expression. Procaspase-10 is generally overexpressed in transformed melanocytes and melanoma cell lines. Expression of the downstream procaspases-3 and -7 was increased in melanoma cells compared with normal melanocytes. Procaspases containing caspase recruitment domains such as procaspase-2 were expressed at similar levels in nearly all the cell lines investigated. Reduced levels of procaspase-1 compared with normal melanocytes were detected in transformed melanocytes and melanoma cell lines. These data indicate that procaspase levels in general increase during the malignant transformation of melanocytic cells.

Blotting, Western↗