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Biomedical subjects

W Philipp

Publications and source records attributed to W Philipp.

At least 19 recordsLinked to original sources
PubMed2001

A possible loophole in the theorem of Bell.

The celebrated inequalities of Bell are based on the assumption that local hidden parameters exist. When combined with conflicting experimental results, these inequalities appear to prove that local hidden parameters cannot exist. This contradiction suggests to many that only instantaneous action at a distance can explain the Einstein, Podolsky, and Rosen type of experiments. We show that, in addition to the assumption that hidden parameters exist, Bell tacitly makes a variety of other assumptions that contribute to his being able to obtain the desired contradiction. For instance, Bell assumes that the hidden parameters do not depend on time and are governed by a single probability measure independent of the analyzer settings. We argue that the exclusion of time has neither a physical nor a mathematical basis but is based on Bell's translation of the concept of Einstein locality into the language of probability theory. Our additional set of local hidden variables includes time-like correlated parameters and a generalized probability density. We prove that our extended space of local hidden variables does not permit Bell-type proofs to go forward.

Journal Article↗
PubMed2001

Bell's theorem and the problem of decidability between the views of Einstein and Bohr.

Einstein, Podolsky, and Rosen (EPR) have designed a gedanken experiment that suggested a theory that was more complete than quantum mechanics. The EPR design was later realized in various forms, with experimental results close to the quantum mechanical prediction. The experimental results by themselves have no bearing on the EPR claim that quantum mechanics must be incomplete nor on the existence of hidden parameters. However, the well known inequalities of Bell are based on the assumption that local hidden parameters exist and, when combined with conflicting experimental results, do appear to prove that local hidden parameters cannot exist. This fact leaves only instantaneous actions at a distance (called "spooky" by Einstein) to explain the experiments. The Bell inequalities are based on a mathematical model of the EPR experiments. They have no experimental confirmation, because they contradict the results of all EPR experiments. In addition to the assumption that hidden parameters exist, Bell tacitly makes a variety of other assumptions; for instance, he assumes that the hidden parameters are governed by a single probability measure independent of the analyzer settings. We argue that the mathematical model of Bell excludes a large set of local hidden variables and a large variety of probability densities. Our set of local hidden variables includes time-like correlated parameters and a generalized probability density. We prove that our extended space of local hidden variables does permit derivation of the quantum result and is consistent with all known experiments.

Journal Article↗
PubMed2000

Determination of the N-methyl-D-aspartate receptor NR2B subunit blocker Ro 63-1908 in rat, cynomolgus monkey and human plasma by high-performance liquid chromatography with column switching and fluorescence detection.

A HPLC method with automated column switching was developed and validated for the determination of Ro 63-1908 in rat and cynomolgus monkey plasma. Human plasma was used for calibration and was also included in the validation process. Ro 63-1908 belongs to a class of neuroprotective N-methyl-D-aspartate (NMDA) receptor blockers which were in development for the treatment of stroke and traumatic brain injury. The method involves deproteinisation of plasma samples with ethanol and direct injection of the supernatant (1.4 ml) into the HPLC column-switching system. To prevent a breakthrough of the analyte and the internal standard on the precolumn (Purospher RP-18, 75x4 mm) due to the high ethanol content, the injection solution was diluted, on-line, using an additional pump and a T-piece. 1% ammonium acetate-ethanol (100:2, v/v) was used as mobile phase for injection, as well as for on-line dilution, resulting in pre-concentration of the analyte and the internal standard on the precolumn. As Purospher RP-18 is a non-endcapped stationary phase with a special selectivity for amines, the analyte and the internal standard could then be selectively eluted with 30% acetonitrile (without any buffer in the mobile phase) and transferred to the analytical column [consisting of two coupled columns (125+250x4 mm) packed with Superspher 60 RP-select B], where they were separated by gradient elution and detected by fluorescence detection. Compared to the use of a 125 mm long precolumn and dilution of the supernatant with ammonium acetate prior to injection, the 75 mm precolumn and the on-line dilution procedure allowed about one third shorter run times (21 min) and, therefore, a higher sample throughput. The limit of quantification was 1 ng/ml using 0.4 ml plasma. The method was applied to more than 670 plasma samples from pharmacokinetic and toxicokinetic studies and is also suitable for other matrices and NMDA receptor blockers.

Animals↗
PubMed2000

The role of ferrioxamine E in pre-enrichment medium for determining Salmonella in environmental samples according to ISO method.

The effect of a siderophoric compound, ferrioxamine E, in the pre-enrichment broth on determining of Salmonella infantis in environmental samples was tested with combination of various pre-enrichment times and enrichment temperatures of 37 and 43 degrees C. Ferrioxamine E slightly improved the determination efficiency of this bacterium but the pre-enrichment time could not be reduced below 17 hours. The enrichment temperature of 43 degrees C was better than of 37 degrees C. The mixing ratios of 1:100 or 1:1000 for samples and pre-enrichment broth were more successful than the ratio of 1:10 as recommended by ISO.

Animals↗
PubMed2000

Expression of vascular endothelial growth factor and its receptors in inflamed and vascularized human corneas.

PURPOSE: To help further define the possible role of vascular endothelial growth factor (VEGF) in the pathogenesis of corneal neovascularization, the expression of VEGF and of its receptors Flt-1 and Flk-1 was investigated in various inflammatory corneal diseases. METHODS: Polyclonal antibodies to VEGF and its receptors were used for immunohistochemical staining of frozen sections of 38 human corneas with various degrees of neovascularization and inflammation. In addition, a panel of monoclonal antibodies was used to characterize the composition of the inflammatory infiltrates and to confirm the presence of neovascularization. Furthermore, VEGF concentrations were determined in vascularized corneas using a sensitive enzyme-linked immunosorbent assay. RESULTS: VEGF was expressed by epithelial cells, by corneal endothelial cells, by vascular endothelial cells of limbal vessels and of newly formed vessels in the stroma, and weakly by keratocytes. Furthermore, VEGF expression was often markedly increased in inflamed corneas on epithelial cells and on vascular endothelial cells, particularly in the vicinity of macrophage infiltrates, and on fibroblasts in scar tissue. Correspondingly, VEGF concentrations were significantly higher in vascularized corneas compared with normal control corneas (P < 0.001). Expression of both VEGF receptors, Flt-1 and Flk-1, was increased on endothelial cells of newly formed vessels in the stroma of inflamed corneas compared with limbal vessels of normal control corneas. In addition, Flt-1 was also expressed by corneal endothelial cells and by macrophages, whereas Flk-1 expression was lacking. CONCLUSIONS: These results demonstrate that VEGF, Flt-1, and Flk-1 are strongly expressed in inflamed and vascularized human corneas and, thus, may play an important role in corneal neovascularization.

Cornea↗
PubMed1999

The effect of streptozotocin-induced diabetes mellitus on substance P and calcitonin gene-related peptide expression in the rat trigeminal ganglion.

Substance P (SP) and calcitonin gene-related peptide (CGRP) constitute the main sensory peptides in the trigeminal ganglion (TG). The objective of this study was to characterize peptidergic changes in the streptozotocin-induced diabetes mellitus rat model both quantitatively and qualitatively. Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg) and the levels of SP and CGRP were measured by means of radioimmunoassay (RIA) in a time-dependent manner. Peptide immunoreactivities were characterized by high pressure liquid chromatography (HPLC). The expression of both neuropeptides was examined 5 weeks after streptozotocin injection using in situ hybridization with 35S-labelled oligonucleotides. Saline-injected rats served as controls. SP was significantly decreased in the diabetic rat TG, i.e. , a 44.6% (+/-10.9) decrease after 1 week, 40.2% (+/-11.8) after 3 weeks and 72.3% (+/-14.6) after 5 weeks. CGRP was decreased only after 5 weeks (19.6% decrease +/-3.9), whereas at later stages, both peptide levels returned to normal values. HPLC revealed one major peak coeluting with the synthetic peptides. By using in situ hybridization, a significantly increased signal of both peptide-encoding mRNAs was found (43.8%), which seems to act to restore a diabetes-associated depletion of neuropeptides in the diabetic rat TG. The decreased SP- and CGRP levels in the diabetic rat TG reflect a diabetes-associated deficit which may be clinically relevant. Diabetes mellitus is associated with a variety of ocular complications, even corneal complications, including decreased corneal sensitivity, which in many ways resemble those after interruption of the normal trophic innervation of the eye. Our results point to reduced availability of neuropeptides for corneal innervation and may thus support the idea of a partial loss of trophic influences from the trigeminal nerve in diabetics.

Animals↗
PubMed1999

['Microbial air pollutants'. Emission sources and preventive measures].

Already in the planning or monitoring phase, measures have to be realized for the reduction in emissions of bio-aerosols in biological waste treatment plants. For this purpose, operation-related measures (in open and partially closed plants) and technology-related measures (in closed plants with automatic ventilation) can be taken. A survey on the currently feasible measures for reduction is submitted. The realization has to be adapted to the individual site and type of plant. An enormous demand for examinations is envisaged in order to enable a qualified assessment of the emission behaviour of diverse waste air systems or process steps.

Air Microbiology↗
PubMed1999

[Microbial emissions in collection of residential garbage].

Two exemplary investigations with different questions were carried out in Munich and Stuttgart by sampling bio-aerosols due to and during the collection and emptying of different types of waste bins. The emissions were regarded qualitatively and quantitatively, in order to answer the question, whether and to which amount differences of bio-aerosol emissions occurred due to the kind of wastes collected. The lowest emissions of airborne microorganisms were found during the collection of the paper waste fraction. In comparison, the amounts of them during the collection of unseparated household wastes as well as source separated bio-wastes and the remaining residual waste fraction were higher. Between the three latter, no significant differences could be found, only a tendency of higher values for the thermotolerant mould A. fumigatus during the collection of bio- and residual wastes was observed. Maybe this was caused by special features of the different sampling locations, but it could also be due to the longer collection intervals (bio- and residual wastes were partially collected every two weeks, unseparated wastes every week).

Air Microbiology↗
PubMed1998

Determination of several N-methyl-D-aspartate receptor blockers in plasma and brain by a selective high-performance liquid chromatographic method with column switching.

A general procedure is presented for the determination of several N-methyl-D-aspartate (NMDA) receptor open-channel and subtype-selective blockers, which have been evaluated and developed as neuroprotective drugs for the treatment of brain stroke and trauma. The method involves deproteination of plasma with ethanol, or homogenization of brain samples in ethanol, dilution of the supernatant with ammonium acetate and direct injection into an HPLC column-switching system. Although the investigated NMDA receptor blockers are all tertiary amines, they have quite different structures. However, they are all concentrated on the first column (Purospher RP-18, 125 x 4 mm), whereas polar interfering compounds are washed out with 1% ammonium acetate-acetic acid-acetonitrile (100:1:5, v/v/v). Due to the special selectivity of the Purospher RP-18 material, the analytes and the internal standard are then selectively eluted with 25% acetonitrile (without any buffer in the mobile phase) and transferred to the analytical column (Superspher 60 RP-select B, 250 x 4 mm), where they are separated by gradient elution and detected by UV or fluorescence detection. The low degree of interference allowed the development of sensitive methods with quantification limits of 5 ng/ml for animal plasma (0.4 ml used), 0.5 ng/ml for human plasma (1 ml used) and 50 ng/g for brain tissue (200 mg used).

Animals↗
PubMed1995

Characterization of the Mycobacterium tuberculosis erp gene encoding a potential cell surface protein with repetitive structures.

Using the phoA gene fusion methodology adapted to mycobacteria, several Mycobacterium tuberculosis DNA fragments encoding exported proteins were recently identified. In this paper, the molecular cloning, genomic positioning, nucleotide sequence determination and transcriptional start site mapping of a new M. tuberculosis gene, identified by this methodology, are reported. This gene was called erp (for exported repetitive protein) and has a sequence similar to that of the Mycobacterium leprae 28 kDa antigen irg gene M. tuberculosis erp gene contains a putative iron box close to the mapped transcriptional start site. The predicted Erp protein displays a typical N-terminal signal sequence, a hydrophobic domain at the C-terminus and harbours repeated amino acid motifs. These structural features are reminiscent of cell-wall-associated surface proteins from Gram-positive bacteria. We found that these repeats are conserved among M. tuberculosis isolates, and are absent from the published M. leprae irg gene sequence. In addition to being present in M. leprae, erp sequences were found in other members of the M. tuberculosis complex, but not in other mycobacteria tested. These results suggest that erp might encode a cell surface component shared by major pathogenic mycobacteria.

Amino Acid Sequence↗
PubMed1995

Mycobacterium tuberculosis is a natural mutant with an inactivated oxidative-stress regulatory gene: implications for sensitivity to isoniazid.

The systems participating in detoxification of reactive oxygen intermediates in Mycobacterium tuberculosis are believed to play a dual role in the biology of this highly adapted human pathogen: (i) they may contribute to the survival of this bacterium in the host; and (ii) alterations in the gene encoding catalase/peroxidase have been linked to this organism's resistance to the front-line antituberculosis drug isoniazid. These relationships prompted us to extend investigations of the oxidative-stress-response systems in M. tuberculosis by analysing the alkyl hydroperoxide reductase gene ahpC and its putative regulator oxyR. Surprisingly, the oxyR gene was found to be inactivated by multiple lesions in M. tuberculosis H37Rv. These alterations were observed in all M. tuberculosis strains tested, and in members of the M. tuberculosis complex: Mycobacterium bovis BCG, Mycobacterium africanum, and Mycobacterium microti. The corresponding region carrying these genes in Mycobacterium leprae, an organism not sensitive to isoniazid, has a complete oxyR gene divergently transcribed from ahpC. An increase in minimal inhibitory concentration for isoniazid was observed upon transformation of M. tuberculosis H37Rv with cosmids carrying the oxyR-ahpC region of M. leprae. In keeping with the observed inactivation of oxyR, transcriptional activity of the corresponding region in M. tuberculosis was an order of magnitude lower than that of the oxyR gene from M. leprae. While the loss of this putative regulator of oxidative-stress response in M. tuberculosis is paradoxical considering the fact that survival in host macrophages is regarded as a critical feature of this pathogen, it offers a partial explanation for the exquisite sensitivity of M. tuberculosis to isoniazid.

Amino Acid Sequence↗
PubMed1994

Leukocyte adhesion molecules in rejected corneal allografts.

Leukocyte adhesion molecules are believed to play a key role in the selective recruitment of different leukocyte populations to inflammatory sites. In this study, we investigated the presence and distribution of intercellular adhesion molecule-1 (ICAM-1), E-selectin (endothelial leukocyte adhesion molecule-1) and vascular cell adhesion molecule-1 (VCAM-1) in 12 rejected corneal allografts and compared the presence of these adhesion molecules with the composition of the associated inflammatory infiltrates. ICAM-1 was focally expressed on corneal epithelial cells and its expression was increased on keratocytes, corneal and vascular endothelial cells particularly at the site of dense infiltration with mononuclear leukocytes. E-selectin was present on endothelial cells of vessels in the stroma of rejected corneal allografts which were characterized by dense infiltration with T cells and macrophages. VCAM-1 was predominantly expressed on inflammatory cells of the macrophage/monocyte lineage, but only sporadically on vascular endothelial cells in the stroma of vascularized rejected corneal allografts. Our results suggest that ICAM-1, E-selectin and VCAM-1 may all be involved in the pathogenesis of corneal allograft rejection, particularly in the generation of the inflammatory infiltrates.

Cell Adhesion Molecules↗
PubMed1994

Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations.

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis has resulted in increased interest in the fluoroquinolones (FQs) as antituberculosis agents. To investigate the frequency and mechanisms of FQ resistance in M. tuberculosis, we cloned and sequenced the wild-type gyrA and gyrB genes, which encode the A and B subunits of the DNA gyrase, respectively; DNA gyrase is the main target of the FQs. On the basis of the sequence information, we performed DNA amplification for sequencing and single-strand conformation polymorphism analysis to examine the presumed quinolone resistance regions of gyrA and gyrB from reference strains (n = 4) and clinical isolates (n = 55). Mutations in codons of gyrA analogous to those described in other FQ-resistant bacteria were identified in all isolates (n = 14) for which the ciprofloxacin MIC was > 2 micrograms/ml. In addition, we selected ciprofloxacin-resistant mutants of Mycobacterium bovis BCG and M. tuberculosis Erdman and H37ra. Spontaneously resistant mutants developed at a frequency of 1 in 10(7) to 10(8) at ciprofloxacin concentrations of 2 micrograms/ml, but no primary resistant colonies were selected at higher ciprofloxacin concentrations. Replating of those first-step mutants selected for mutants with high levels of resistance which harbored gyrA mutations similar to those found among clinical FQ-resistant isolates. The gyrA and gyrB sequence information will facilitate analysis of the mechanisms of resistance to drugs which target the gyrase and the implementation of rapid strategies for the estimation of FQ susceptibility in clinical M. tuberculosis isolates.

Anti-Infective Agents↗
PubMed1993

Retinal phakomata associated with cerebral astrocytoma. An incomplete form of Bourneville-Pringle disease?

We report on a 21-year-old, male patient with unilateral retinal phakomata associated with histologically proved cerebral astrocytoma. The patient had presented with bilateral loss of vision and a left-sided hemiparesis. Ophthalmoscopy showed bilateral optic nerve atrophy, multiple punched-out areas of depigmentation and astrocytic hamartomata in the right eye. Despite the absence of classic signs of Bourneville-Pringle disease such as adenoma sebaceum, epilepsy and mental retardation, a strongly presumptive diagnosis of tuberous sclerosis could be made. This unusual case demonstrates that retinal phakomata can be the solely visible manifestation of Bourneville-Pringle disease.

Adult↗
PubMed1993

[Leukocyte adhesion molecules in chronic inflammatory diseases of the cornea].

Using immunohistochemical techniques, we investigated the expression of leukocyte adhesion molecules-intercellular adhesion molecule-1 (ICAM-1), E-selectin (endothelial leukocyte adhesion molecule-1), and vascular cell adhesion molecule-1 (VCAM-1)--in various chronic inflammatory corneal diseases of different etiology. ICAM-1 was focally expressed on epithelial cells and showed an increased expression, on keratocytes, corneal endothelial cells, and vascular endothelial cells. E-selectin was present on vascular endothelial cells of several corneas, while VCAM-1 was found particularly on macrophages and only sporadically on vascular endothelial cells. Our results suggest that ICAM-1, E-selectin, and VCAM-1 may be involved in the pathogenesis of various chronic inflammatory corneal diseases, particularly in the selective recruitment of different leukocyte populations.

Adult↗
PubMed1993

Leukocyte adhesion molecules in diseased corneas.

PURPOSE: To help define the possible role of leukocyte adhesion molecules in the pathogenesis of corneal inflammation, we investigated the presence and distribution of intercellular adhesion molecule-1 (ICAM-1), E-selectin (endothelial leukocyte adhesion molecule-1 [ELAM-1]), and vascular cell adhesion molecule-1 (VCAM-1) in various corneal diseases. METHODS: Monoclonal antibodies (mAbs) to ICAM-1, E-selectin, and VCAM-1 were used for immunohistochemical staining of frozen sections of 55 human corneas with various inflammatory and degenerative diseases. In addition, we used a panel of mAbs to characterize the composition and density of the inflammatory infiltrates in the diseased corneas. RESULTS: ICAM-1 was focally expressed on epithelial cells in corneas with chronic allograft rejection, herpetic stromal keratitis, zoster keratitis, chemical burns, atopic keratitis, fungal keratitis, and bacterial keratitis. Furthermore, the expression of ICAM-1 was focally increased on keratocytes, corneal endothelial cells, and vascular endothelial cells (particularly at the site of lymphoid infiltration) in these corneas. E-selectin was present on vascular endothelial cells of limbal vessels in corneas with bacterial keratitis and also on endothelial cells of vessels in the stroma of several corneas with chronic inflammatory diseases. VCAM-1 was focally expressed on endothelial cells of vessels in the stroma of some corneas with chronic allograft rejection, herpetic stromal keratitis, chemical burns, and atopic keratitis. Interestingly, VCAM-1 was also found on inflammatory cells of the macrophage-monocyte lineage in inflamed corneas. CONCLUSIONS: Our results demonstrate that ICAM-1, E-selectin, and VCAM-1 are expressed in diseased corneas, often in areas of inflammation.

Adult↗