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Biomedical subjects

H Janssen

Publications and source records attributed to H Janssen.

At least 19 recordsLinked to original sources
PubMed2007

Postmortem determination of concentrations of stress hormones in various body fluids--is there a dependency between adrenaline/noradrenaline quotient, cause of death and agony time?

To find out whether a certain cause of death or a certain length of an agonal period shows specific adrenaline or noradrenaline profiles, heart blood, femoral vein blood, liquor, urine and vitreous humour were taken from corpses (n = 98) at the Medical School Hannover, and noradrenaline and adrenaline were determined using high-performance liquid chromatography (HPLC). Corpses were classified according to the following five categories: short agony, long agony, state after hanging, state after asphyxiation and state after CPR with documented administration of epinephrine. Once results were collected the adrenaline/noradrenaline quotient was determined. It became clear that there were no significant differences regarding the concentration of adrenaline and noradrenaline in the various body fluids in relation to the above-mentioned categories. The means adrenaline/noradrenaline quotients in femoral vein blood were 0.21 +/- 0.29 for hanged persons, 0.38 +/- 0.47 for asphyxiated persons, 0.17 +/- 0.19 for those with short agony and 0.42 +/- 0.43 for those with long agony, significantly below 1 (p < 0.001; p = 0.001; p = 0.003). For condition after CPR we found an adrenaline/noradrenaline quotient of 2.81 +/- 5.8. In liquor the adrenaline/noradrenaline quotients for short agony was 0.17 +/- 0.17, for hanged persons 0.18 +/- 0.19 and for asphyxiated ones 0.30 +/- 0.38, significantly lower than 1 (p < 0.001). In urine the adrenaline/noradrenaline quotients for all categories are lower than 1 (p < 0.001); short agony (0.13 +/- 0.09), long agony (0.21 +/- 0.16), hanged (0.15 +/- 0.16), asphyxiated (0.14 +/- 0.08) and CPR (0.14 +/- 0.06). In vitreous humour the quotients for short agony (0.14 +/- 0.28), long agony (0.13 +/- 0.12), hanged (0.07 +/- 0.09) and asphyxiated (0.09 +/- 0.11) are lower than 1 (p < 0.001). The spread of data for the adrenaline/noradrenaline quotient did not allow for any conclusions about cause of death and length of agony in individual cases.

Asphyxia↗
PubMed2006

Activity standardization and nuclear decay data of 109Cd.

The activity of a (109)Cd solution has been accurately determined without using (109)Cd nuclear decay data such as emission probabilities. An ampoule containing this calibrated (109)Cd solution was sent to the Bureau International des Poids et Mesures to include the activity result in the database of the International Reference System (SIR). The emission rate of conversion electrons was measured by means of pressurized proportional counters as well as by a liquid scintillation spectrometer. The combination of the results with the photon emission rate measured with the aid of gamma-ray spectrometers yields the activity concentration. The measurement results were also used to deduce emission probabilities with high accuracy. For the 88 keV transition, a photon emission probability of p(gamma)=0.03663(33) and a total internal conversion coefficient of alpha(t)=26.30(25) were determined.

Journal Article↗
PubMed2006

A modified method for the characterisation and activity determination of large area sources.

Large area sources emitting alpha and beta radiations, respectively, are often used for calibrations of surface contamination monitors and meters. It is well known, however, that their properties are strongly influenced by their construction and by their active layer preparation. Non-uniformity of activity distributions over the active surface and the thickness of absorption and backscattering layers cause changes not only in the ratio of particle emission rate and activity but also in emitted particle spectra distributions. Consequently, different sources need to be characterised by one or more parameters related to their emitted particle spectra and used for their activity determination. A modified method based on simple particle absorption spectrometry has been developed. The correlation between a source characteristic parameter and its radiation detection efficiency is utilised for its activity estimation.

Calibration↗
PubMed2006

Standardization and nuclear decay data of 65Zn.

Standardization by means of 4pibeta-gamma coincidence counting was applied to calibrate a 65Zn solution within the scope of EUROMET project no. 721. The activity result was combined with gamma-ray spectrometry measurements to investigate the photon emission probabilities. The half-life of 65Zn was measured with improved accuracy by means of 4pi ionization chamber measuring systems that were also used for secondary activity determination. In addition, we tested a new secondary standardization procedure by means of liquid scintillation counting.

Algorithms↗
PubMed2002

Causative factors, surgical treatment and outcome of incisional hernia after liver transplantation.

BACKGROUND: Little is known about the incidence and causes of herniation, and the results of hernia repair in patients undergoing liver transplantation. Likewise, nothing is known about the best surgical approach for hernia repair. METHODS: A retrospective analysis was conducted of the occurrence of incisional hernia in 290 patients who had liver transplantation between 1990 and 2000, and survived more than 6 months. Follow-up data were obtained from medical records and the outpatient service. Patients were evaluated for various clinical and surgical factors. Hernias were analysed with respect to localization, type of surgical repair and recurrence rate. RESULTS: Some 17 per cent of the transplanted patients experienced an incisional hernia. Risk factors were acute rejection with affiliated steroid bolus therapy (P = 0.025), a low platelet count after transplantation (P = 0.048), and a transverse abdominal incision with upper midline approach (P = 0.04). Hernias were mainly located at the junction of the transverse and midline incision (P < 0.001) and the recurrence rate was highest here (P = 0.007). Prosthetic hernia repair achieved the lowest rate of recurrence and did not increase the incidence of infectious complications. CONCLUSION: Improved immunosuppression should avoid early steroid bolus therapy after transplantation. A low platelet count promotes herniation. Transverse abdominal incision seems to be the best approach for liver transplantation. Prosthetic hernia repair does not increase the complication rate.

Adult↗
PubMed2001

The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors.

Many intracellular compartments, including MHC class II-containing lysosomes, melanosomes, and phagosomes, move along microtubules in a bidirectional manner and in a stop-and-go fashion due to the alternating activities of a plus-end directed kinesin motor and a minus-end directed dynein-dynactin motor. It is largely unclear how motor proteins are targeted specifically to different compartments. Rab GTPases recruit and/or activate several proteins involved in membrane fusion and vesicular transport. They associate with specific compartments after activation, which makes Rab GTPases ideal candidates for controlling motor protein binding to specific membranes. We and others [7] have identified a protein, called RILP (for Rab7-interacting lysosomal protein), that interacts with active Rab7 on late endosomes and lysosomes. Here we show that RILP prevents further cycling of Rab7. RILP expression induces the recruitment of functional dynein-dynactin motor complexes to Rab7-containing late endosomes and lysosomes. Consequently, these compartments are transported by these motors toward the minus end of microtubules, effectively inhibiting their transport toward the cell periphery. This signaling cascade may be responsible for timed and selective dynein motor recruitment onto late endosomes and lysosomes.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Gap junction protein connexin-43 interacts directly with microtubules.

Gap junctions are specialized cell-cell junctions that mediate intercellular communication. They are composed of connexin proteins, which form transmembrane channels for small molecules [1, 2]. The C-terminal tail of connexin-43 (Cx43), the most widely expressed connexin member, has been implicated in the regulation of Cx43 channel gating by growth factors [3-5]. The Cx43 tail contains various protein interaction sites, but little is known about binding partners. To identify Cx43-interacting proteins, we performed pull-down experiments using the C-terminal tail of Cx43 fused to glutathione-S-transferase. We find that the Cx43 tail binds directly to tubulin and, like full-length Cx43, sediments with microtubules. Tubulin binding to Cx43 is specific in that it is not observed with three other connexins. We established that a 35-amino acid juxtamembrane region in the Cx43 tail, which contains a presumptive tubulin binding motif, is necessary and sufficient for microtubule binding. Immunofluorescence and immunoelectron microscopy studies reveal that microtubules extend to Cx43-based gap junctions in contacted cells. However, intact microtubules are dispensable for the regulation of Cx43 gap-junctional communication. Our findings suggest that, in addition to its well-established role as a channel-forming protein, Cx43 can anchor microtubule distal ends to gap junctions and thereby might influence the properties of microtubules in contacted cells.

Amino Acid Sequence↗
PubMed2001

Regulation of MHC class II antigen presentation by sorting of recycling HLA-DM/DO and class II within the multivesicular body.

MHC class II molecules bind antigenic peptides in the late endosomal/lysosomal MHC class II compartments (MIIC) before cell surface presentation. The class II modulatory molecules HLA-DM and HLA-DO mainly localize to the MIICs. Here we show that DM/DO complexes continuously recycle between the plasma membrane and the lysosomal MIICs. Like DMbeta and the class II-associated invariant chain, the DObeta cytoplasmic tail contains potential lysosomal targeting signals. The DObeta signals, however, are not essential for internalization of the DM/DO complex from the plasma membrane or targeting to the MIICs. Instead, the DObeta tail determines the distribution of both DM/DO and class II within the multivesicular MIIC by preferentially localizing them to the limiting membrane and, in lesser amounts, to the internal membranes. This distribution augments the efficiency of class II antigenic peptide loading by affecting the efficacy of lateral interaction between DM/DO and class II molecules. Sorting of DM/DO and class II molecules to specific localizations within the MIIC represents a novel way of regulating MHC class II Ag presentation.

Amino Acid Motifs↗
PubMed2001

Serum bile acids in liver transplantation--early indicator for acute rejection and monitor for antirejection therapy.

We studied the course of serum bile acids to investigate its reliability in the diagnosis of acute rejection after liver transplantation in relation to pathohistological findings. Serum bile acid concentration, bilirubin and transaminases were measured in 41 patients who underwent liver transplantation. Their course was correlated to liver biopsy. Group I (n = 19) patients were without acute rejection, whereas group II (n = 22) patients showed acute rejection. Bile acid concentrations in group II showed a statistically highly significant (P < or = 0.001) threefold increase 3 days prior to biopsy. Successful antirejection treatment was correlated with a statistically significant (P = 0.008) decrease of serum bile acid 1 day after initiation of therapy. Patients without acute rejection showed a baseline bile acid concentration at the time of biopsy. Bilirubin and transaminases did not show any statistically significant correlation to acute rejection. Infection did not lead to a significant bile acid increase. Our study shows that serum bile acids monitored after liver transplantation can easily be used to detect acute rejection and at the same time they reflect the success of antirejection therapy.

Acute Disease↗
PubMed2001

Strategic information management plans: the basis for systematic information management in hospitals.

Information management in hospitals is a complex task. In order to reduce complexity, we distinguish strategic, tactical, and operational information management. This is essential, because each of these information management levels views hospital information systems from different perspectives, and therefore uses other methods and tools. Since all these management activities deal only in part with computers, but mainly with human beings and their social behavior, we define a hospital information system as a sociotechnical subsystem of a hospital. Without proper strategic planning it would be a matter of chance, if a hospital information system would fulfil the information strategies goals. In order to support strategic planning and to reduce efforts for creating strategic plans, we propose a practicable structure.

Hospital Information Systems↗
PubMed2001

Hypoxia and perfusion measurements in human tumors--initial experience with pimonidazole and IUdR.

We describe our preliminary studies on the development of methods to measure hypoxia in standard paraffin sections of human tumors. Three parameters were investigated. First, image analysis of tumor vascularity yielded the parameter diffusion limited fraction (DLF), which is the amount of tumor tissue greater than a fixed distance from the nearest blood vessel. Secondly, the amount of tumor tissue stained with antibodies against bound reduced products of the bioreductive marker pimonidazole was assessed. Finally, the fraction of blood vessels showing no surrounding tumor tissue labeled with lUdR, a cell kinetic marker, was measured. DLF and pimonidazole monitor primarily chronic hypoxia, while it is hypothesized that the IUdR-negative fraction monitors acute hypoxia. Feasibility was demonstrated in a series of 10 esophageal and 10 rectal tumors (no drug administration), 10 cervix tumors (pimonidazole) and 14 head and neck tumors (pimonidazole and lUdR). Significant differences between tumors were found for all parameters. DLF correlated significantly with the pimonidazole fraction when all images of all tumors were included, although mean values per tumor showed no correlation. The IUdR-negative fraction did not correlate with either of the other two parameters. We conclude that it is feasible to measure hypoxia-related, and possibly perfusion-related, parameters on paraffin sections for predictive purposes, although each method needs further validation. Each parameter will be correlated with outcome in a larger study on head and neck tumors treated with surgery with or without postoperative radiotherapy.

Antibodies↗
PubMed2000

The tetraspan molecule CD151, a novel constituent of hemidesmosomes, associates with the integrin alpha6beta4 and may regulate the spatial organization of hemidesmosomes.

CD151 is a cell surface protein that belongs to the tetraspan superfamily. It associates with other tetraspan molecules and certain integrins to form large complexes at the cell surface. CD151 is expressed by a variety of epithelia and mesenchymal cells. We demonstrate here that in human skin CD151 is codistributed with alpha3beta1 and alpha6beta4 at the basolateral surface of basal keratinocytes. Immunoelectron microscopy showed that CD151 is concentrated in hemidesmosomes. By immunoprecipitation from transfected K562 cells, we established that CD151 associates with alpha3beta1 and alpha6beta4. In beta4-deficient pyloric atresia associated with junctional epidermolysis bullosa (PA-JEB) keratinocytes, CD151 and alpha3beta1 are clustered together at the basal cell surface in association with patches of laminin-5. Focal adhesions are present at the periphery of these clusters, connected with actin filaments, and they contain both CD151 and alpha3beta1. Transient transfection studies of PA-JEB cells with beta4 revealed that the integrin alpha6beta4 becomes incorporated into the alpha3beta1-CD151 clusters where it induces the formation of hemidesmosomes. As a result, the amount of alpha3beta1 in the clusters diminishes and the protein becomes restricted to the peripheral focal adhesions. Furthermore, CD151 becomes predominantly associated with alpha6beta4 in hemidesmosomes, whereas its codistribution with alpha3beta1 in focal adhesions becomes partial. The localization of alpha6beta4 in the pre-hemidesmosomal clusters is accompanied by a strong upregulation of CD151, which is at least partly due to increased cell surface expression. Using beta4 chimeras containing the extracellular and transmembrane domain of the IL-2 receptor and the cytoplasmic domain of beta4, we found that for recruitment of CD151 into hemidesmosomes, the beta4 subunit must be associated with alpha6, confirming that integrins associate with tetraspans via their alpha subunits. CD151 is the only tetraspan identified in hemidesmosomal structures. Others, such as CD9 and CD81, remain diffusely distributed at the cell surface. In conclusion, we show that CD151 is a major component of (pre)-hemidesmosomal structures and that its recruitment into hemidesmosomes is regulated by the integrin alpha6beta4. We suggest that CD151 plays a role in the formation and stability of hemidesmosomes by providing a framework for the spatial organization of the different hemidesmosomal components.

Antigens, CD↗
PubMed2000

On the determination of activity profiles in wide-area reference sources

A method is described for determining the depth distribution of the radioactive substance of alpha-emitting nuclides in a wide-area reference source. The method combines measurements and calculations. In the experimental part, the energy spectrum of the source is measured by means of an alpha spectrometer. The energy spectrum is then modelled by the Monte Carlo method, taking into account energy loss of alpha particles in the source matrix, energy-loss straggling and the parameters of the spectrometer. Additional parameters for the characterization of reference sources are derived from the integral of the depth distribution. The investigations prove that the production process of commercial sources can be controlled in such a way that more than 90% of the radioactive material is implanted in the top layer of 5 microm thickness of an aluminum foil.

Journal Article↗
PubMed2000

Calculation of emission probabilities of X-rays and Auger electrons emitted in radioactive disintegration processes

A complete set of data for the decay scheme of a radionuclide requires knowledge of the emission probabilities of X-rays and Auger electrons. If adopted sets of transition probabilities for the transitions of the decay scheme and atomic shell data (such as fluorescence yields and relative emission probabilities) are available, the emission probabilities of the X-rays and Auger electrons can be calculated from these data. Only data calculated in this way are consistent with the adopted input data and can be compared with measured data. Conclusions can be drawn with respect to the internal consistency of the data sets by comparing the measured and calculated data. Hence, the EMISSION program has been developed and tested to calculate X-ray and Auger electron emission probabilities along with their error propagation.

Journal Article↗
PubMed2000

The bactericidal/permeability-increasing protein (BPI) is membrane-associated in azurophil granules of human neutrophils, and relocation occurs upon cellular activation.

Neutrophilic granulocytes contain the 55 kDa bactericidal/permeability-increasing protein (BPI). BPI binds to lipopolysaccharides (LPS), and exerts bacteriostatic and bactericidal effects against a wide variety of Gram-negative bacterial species. We have investigated the subcellular location of BPI in immature and mature neutrophils using cryotechnique for immunoelectron microscopy. BPI was found to colocate with myeloperoxidase (MPO), a marker for azurophil granules, and it also showed the same pattern of distribution as CD63, a transmembrane-anchored protein. This suggests that BPI is membrane-associated in the azurophil granules in neutrophils. Its presence in azurophil granules was further confirmed by the finding of BPI in the azurophil granules of neutrophil promyelocytes of the bone marrow. Induction of selective release of azurophilic granules by the Na-ionophore monensin resulted in fusion of endosomes with azurophil granules, leading to the formation of large vacuoles containing MPO, CD63, and BPI. After phagocytosis of serum-treated zymosan (STZ), BPI was detected in phagosomes, both in association with membranes as well as in the lumen, suggesting the release of BPI into activated compartments. The results show that BPI is present in azurophil granules, is probably primarily membrane-associated, and is relocated after activation, following the same route as MPO and CD63.

Anti-Infective Agents↗