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Biomedical subjects

M Scholz

Publications and source records attributed to M Scholz.

At least 91 records · Page 5Linked to original sources
PubMed2001

Direct evidence for the spatial correlation between individual particle traversals and localized CDKN1A (p21) response induced by high-LET radiation.

The spatial correlation between individual particle traversals and the nuclear CDKN1A (p21) response after high-LET irradiation of human fibroblasts was investigated. The experiments were based on a technique for the retrospective detection of particle traversals by means of nuclear track detectors, which were used as the cell substratum. This technique requires the precise repositioning of a sample at different steps of the experimental procedure and uses a computerized microscope stage control. The precision of the spatial correlation is further enhanced by means of reference marks in the track etch material that are produced by preirradiation of the plates with charged-particle beams at low fluences. The pattern of the CDKN1A foci that were induced by charged-particle traversals at 1 h postirradiation was found to coincide extremely well with the pattern of particle tracks. This represents direct evidence that CDKN1A foci are located at the sites of particle traversals and thus provides further evidence that the radiation-induced accumulation of the CDKN1A protein takes place at the sites of the primary damage.

Bystander Effect↗
PubMed2001

Intrapopulational relationships in ancient societies: a multidisciplinary study.

Kinship determination is one of the major challenges for the anthropologist studying graveyard populations. Traditional techniques based on morphological comparisons of bone remains are limited. However, recent methods which generate and characterise DNA sequences derived from bones bear the possibility for a more accurate analysis. Extraction and characterisation of authentic nucleic acids was performed on a number of individuals from the early Medieval graveyard of Neresheim, South Germany. From this cemetery a total of 38 skeletal remains of individuals buried between 450 and 700 AD were examined using PCR-based methods. Comparisons were made using four human-specific short tandem repeat loci and the X/Y-specific amelogenin sex test. Twenty-eight of the approximately 1,500-year-old individuals yielded alleles in at least one of the polymorphic nuclear loci HumCD4, HumFES, HumTH01, HumVWA, and the sex test. These along with a 96 bp DNA variant previously unknown in recent CD4 contexts, and supporting evidence from anthropology and archaeology were used for defining one parental and one filial generation in each of three multiple burials (Ne 2, Ne 9 and Ne 78) in the cemetery.

Anthropology↗
PubMed2001

Mathematical models of radiation-induced mitotic delay: time course analysis and statistics of lesions.

Detailed investigations of high and low LET radiation induced chromosome aberrations in various mammalian cell lines have shown that the registered yield of aberrations depends on cell cycle progression delays. The effect of radiation on the cell kinetics can be analyzed in terms of kinetic growth models. The method yields the number of aberrant cells and the number of aberrations as totals obtained after integration over given time-interval.

Animals↗
PubMed2000

Decreased neutrophil adhesion to human cytomegalovirus-infected retinal pigment epithelial cells is mediated by virus-induced up-regulation of Fas ligand independent of neutrophil apoptosis.

Human CMV (HCMV) retinitis frequently leads to blindness in iatrogenically immunosuppressed patients and in the end stage of AIDS. Despite the general proinflammatory potential of HCMV, virus infection is associated with a rather mild cellular inflammatory response in the retina. To investigate this phenomenon, the influence of HCMV (strains AD169 or Hi91) infection on C-X-C chemokine secretion, ICAM-1 expression, and neutrophil recruitment in cultured human retinal pigment epithelial (RPE) cells was studied. Supernatants from infected cultures contained enhanced levels of IL-8 and melanoma growth-stimulating activity/Gro alpha and induced neutrophil chemotaxis compared with supernatants from uninfected RPE cells. Despite HCMV-induced ICAM-1 expression on RPE cells, binding of activated neutrophils to HCMV-infected RPE cells and subsequent transepithelial penetration were significantly reduced. Reduced neutrophil adhesion to infected RPE cells correlated with HCMV-induced up-regulation of constitutive Fas ligand (FasL) expression. Functional blocking of FasL on RPE cells with the neutralizing mAbs NOK-1 and NOK-2 or of the Fas receptor on neutrophils with mAbB-D29 prevented the HCMV-induced impairment of neutrophil/RPE interactions. Fas-FasL-dependent impairment of neutrophil binding had occurred by 10 min after neutrophil/RPE coculture without apoptotic signs. Neutrophil apoptosis was first detected after 4 h. Treatment of neutrophils with a specific inhibitor of caspase-8 suppressed apoptosis, whereas it did not prevent impaired neutrophil binding to infected RPE. The current results suggest a novel role for FasL in the RPE regulation of neutrophil binding. This may be an important feature of virus escape mechanisms and for sustaining the immune-privileged character of the retina during HCMV ocular infection.

Adult↗
PubMed2000

Correction methods for three-dimensional reconstructions from confocal images: I. Tissue shrinking and axial scaling.

We show here, using locust wholemount ganglia as an example, that scaling artifacts in three-dimensional reconstructions from confocal microscopic images due to refractive index mismatch in the light path and tissue shrinking, can account for dramatic errors in measurements of morphometric values. Refractive index mismatch leads to considerable alteration of the axial dimension, and true dimensions must be restored by rescaling the Z-axis of the image stack. The appropriate scaling factor depends on the refractive indices of the media in the light path and the numerical aperture of the objective used and can be determined by numerical simulations, as we show here. In addition, different histochemical procedures were tested in regard to their effect on tissue dimensions. Reconstructions of scans at different stages of these protocols show that shrinking can be avoided prior to clearing when dehydrating ethanol series are carefully applied. Fixation and mismatching buffer osmolarity have no effect. We demonstrate procedures to reduce artifacts during mounting and clearing in methyl salicylate, such that only isometric shrinkage occurs, which can easily be corrected by rescaling the image dimensions. Glycerol-based clearing agents produced severe anisometric and nonlinear shrinkage and we could not find a way to overcome this.

Animals↗
PubMed2000

Genomic differentiation of Neanderthals and anatomically modern man allows a fossil-DNA-based classification of morphologically indistinguishable hominid bones.

Southern blot hybridizations of genomic DNA were introduced as a relatively simple fossil-DNA-based approach to classify remains of Neanderthals. When hybridized with genomic DNA of either human or Neanderthal origin, DNA extracted from two Neanderthal finds-the Os parietale, from Warendorf-Neuwarendorf, Germany, and a clavicula, from Krapina, Croatia-was shown to yield hybridization signals that differ by at least a factor of two compared to the signals obtained with the use of fossil DNA of an early Homo sapiens from the Vogelherd cave (Stetten I), Germany. When labeled chimpanzee DNA was used as a probe, Neanderthal and human DNA, however, revealed hybridization signals of similar intensity. Thus, the genome of Neanderthals is expected to differ significantly from the genome of anatomically modern man, because of the contrasting composition of repetitive DNA. These data support the hypothesis that Neanderthals were not ancestors of anatomically modern man.

Animals↗
PubMed2000

In vitro analysis of verapamil-induced immunosuppression: potent inhibition of T cell motility and lymphocytic transmigration through allogeneic endothelial cells.

BACKGROUND: Cyclosporine A (CsA) and tacrolimus prevent proliferation but not transendothelial migration of alloreactive lymphocytes into donor organs. As a result, serious adverse effects, such as nephrotoxicity and neurotoxicity, have been observed under CsA/tacrolimus therapy. The incorporation of new drugs with infiltration blocking properties might enhance the efficacy of the current immunosuppressive protocol, allowing lower CsA/tacrolimus dosage. Because Ca2+ plays a critical role in cell-cell interaction, the Ca2+-channel blocker verapamil might be a good cany. didate for supporting CsA/tacrolimus-based therapy. METHODS: A T-cell endothelial cell coculture model or immobilized immunoglobulin G globulin chimeras were employed to investigate how S- and R- verapamil interfere with the lymphocytic infiltration process. The expression and arrangement of membranous adhesion receptors and cytoskeletal F-actin filaments were analyzed by fluorometric method in the presence of. verapamil. RESULTS: Both verapamil enantiomers strongly inhibited lymphocyte infiltration. CD4+ and CD8+ T-cells were influenced to a similar extent with regard to horizontal locomotion (CD4+=CD8+), but to a different extent with regard to adhesion and penetration (CD4+ > CD8+). Moreover, penetration was blocked to a higher extent than was adhesion. ID50-values were 31 microM (CD4+-adhesion) and 11 microM (CD4+-penetration). Verapamil reduced P-selectin expression on endothelial cells and effectively down-regulated binding of T-cells to immobilized P-selectin immunoglobulin G globulins (ID50=4.4 microM; CD4+). A verapamil-induced reduction of intracellular F-actin in T-lymphocytes was proven to be mainly responsible for diminished cell locomotion. CONCLUSIONS: The prevention of CD4+ T-cell penetration by verapamil might argue for its use as an adjunct to CsA/tacrolimus-based immunosuppressive therapy.

Cell Movement↗
PubMed2000

A magnetoencephalographic study of brain activity related to recognition memory in healthy young human subjects.

Neural activity associated with recognition memory was investigated using magnetencephalography (MEG) in healthy young subjects. At sensor sites overlying frontal and temporoparietal cortices, magnetic evoked fields (MEFs) revealed a difference between studied and unstudied stimuli, which onset about 400 ms following stimulus onset and lasted about 600 ms. MEG yielded reliable source information revealing the activity of three independent dipoles, located in the right medial temporal lobe (MTL), the right inferior frontal and the left inferior parietal cortices. Our findings suggest that neural activity underlying recognition memory from both superficial and deep brain structures can be monitored by MEG.

Adult↗
PubMed2000

The antisense oligonucleotide ISIS 2922 prevents cytomegalovirus-induced upregulation of IL-8 and ICAM-1 in cultured human fibroblasts.

Human cytomegalovirus (HCMV) infection is associated with excessive proinflammatory immune responses such as cytokine/chemokine production or upregulation of adhesion molecules on the host cells. It is assumed that these features of HCMV-related immunopathology can not be treated effectively with currently available anti HCMV drugs. In the present study the efficacy of ganciclovir (GCV), foscarnet (PFA), cidofovir (HPMPC), and ISIS 2922, an antisense oligonucleotide complementary to HCMV immediate-early (IE) mRNA, was investigated on HCMV-induced secretion and functional activity of the C-X-C chemokine IL-8 and the expression of the intercellular adhesion molecule-1 (ICAM-1). As compared with mock-infected cells IL-8 production was increased up to 9-fold and ICAM-1 expression up to 4-fold in HCMV-infected fibroblasts. Treatment of infected cells with GCV (40 microM), PFA (200 microM) or HPMPC (2 microM) suppressed completely virus replication as demonstrated by quantification of late (L) antigen expression and infectious virus production. These drugs, however, failed to inhibit IE antigen expression and did not prevent HCMV-induced upregulation of IL-8 and ICAM-1. In contrast, ISIS 2922 (1 microM) suppressed both IE and L antigen expression by 99% and inhibited infectious virus production by 10(4)-fold. Moreover, ISIS 2922 significantly suppressed HCMV-induced upregulation of both IL-8 and ICAM-1 expression on the transcriptional and on the protein level. Our results indicate that ISIS 2922 but not inhibitors of HCMV DNA prevents HCMV-induced upregulation of IL-8 and ICAM-1, both hallmarks of inflammatory processes. Thus, inhibition of HCMV IE expression with ISIS 2922 may be an important strategy for the treatment of HCMV-related immunopathogenesis.

Antiviral Agents↗
PubMed2000

Voltage-induced release of nucleic acids from palaeontological samples.

Most of the protocols for the recovery of ancient DNA from palaeontological specimens are time-consuming and tend to yield inconsistent polymerase chain reaction (PCR) results. "Voltage-induced release" is a novel and rapid approach for the extraction of ancient DNA. Nucleic acids are directly electrophoresed out of powder derived from hard and soft tissues. This technique is much faster than other methods in which pulverized tissue conventionally undergoes time-consuming crude lysis steps. The total preparation time is 5-6 h. The reliability of the voltage-induced release method was validated by (i) measuring the ratio of D-to L-enantiomers of the amino acids aspartic acid, alanine, and leucine, and (ii) by specific PCR amplification of four single-copy markers of human chromosome 17 and 18. We compare voltage-induced release to a frequently used silica-based protocol. DNA extracted employing voltage-induced release was more effective in PCR amplifications, which may be attributed to the effective removal of PCR inhibitors.

DNA↗
PubMed2000

[Is the Bishop-Koop anastomosis in treatment of neonatal ileus still current?].

Fourty-three cases of ileus in newborns are presented. Twenty-seven newborns received a Bishop-Koop anastomosis. In 19 cases, the Bishop-Koop anastomosis was performed primarily and in 8 cases as a second intervention. We consider the Bishop-Koop anastomosis to be a safer procedure than primary end-to-end or end-to-side anastomosis. Only one anastomotic leak occurred in our patients. We prefer the Bishop-Koop anastomosis not only in cases of meconium ileus, but also in other types of intestinal atresia and stenosis, especially for the management of greatly different intestinal diameters. In our experience, this method is also suitable for re-anastomosing a double-barrel anastomosis. The Bishop-Koop procedure minimizes the risks of primary anastomosis without enterostoma, and later extraperitoneal closure of the stoma is easy and safe.

Anastomosis, Surgical↗
PubMed2000

Cytomegalovirus-infected neuroblastoma cells exhibit augmented invasiveness mediated by beta1alpha5 integrin (VLA-5).

Previously, experimental in vivo results showed that the productively and persistently human cytomegalovirus (HCMV)-infected neuroblastoma cell line UKF-NB-4AD169 exhibits a more malignant phenotype than the non-infected variant UKF-NB-4. To prove the assumption that enhanced malignancy may be due to enhanced invasive potential of the infected cells we studied interactions of both lines with monolayers of cultured endothelial cells. UKF-NB-4AD169 cells adhered to and transmigrated through endothelial monolayer to a significantly higher extent compared with UKF-NB4. Furthermore, the adhesion of UKF-NB-4AD169 but not of UKF-NB4 resulted in focal disruption of the monolayer integrity which facilitates tumor cell transmigration. Blocking antibodies directed against the beta1 integrin chain as well as beta1alpha5 on the tumor cells specifically inhibited adhesion in a concentration-dependent manner. When UKF-NB-4 were pretreated with a beta1 integrin activating antibody, focal disruption of the endothelial integrity also occurred. These findings lead us to suggest that HCMV infection activates beta1alpha5 in the host neuroblastoma cell which in turn enables these cells to tightly adhere to endothelial cells. In the presence of the protease inhibitor phenantroline, beta1alpha5-mediated adhesion was not impaired whereas UKF-NB4AD169-mediated endothelial monolayer permeabilization was dose dependently inhibited. We conclude that human cytomegalovirus infection contributes to augmented neuroblastoma invasiveness via adhesion of activated beta1alpha5 and subsequent matrix digestion by proteases.

Antibodies, Blocking↗
PubMed2000

[Promoting non-smoking behavior in 13-year-old students in primary schools and high schools. A prospective, randomized intervention study with 1,956 students].

1956 7th grade students of high schools and secondary modern schools in three cities with 110,000 to 180,000 inhabitants were asked about cigarette, alcohol and drug consumption using questionnaires. Subsequently 1080 of the students took part in a newly invented non-smoking curriculum which was held during 8 lessons within 4 weeks (intervention group (I)). The lessons were performed by non-smoking physicians who had passed a training programme before. 876 students served as control (C) group. 2 years later the questioning was repeated. The number of students who started smoking within the two years was significantly lower in the intervention group. In the high schools a significant effect was seen in boys (I: 13.0%, K: 22.4%; p < 0.01) and girls (I: 21.4%, K: 28.4%; p < 0.05) whereas in secondary modern schools a significant effect was seen only in boys (I: 17.4%, K: 25.2%; p < 0.05) not in girls (I: 18.0%, K: 22.0%; n.s.). First-time consumers of drugs like cannabis, marihuana and organic solvents were found less often in the intervention group among boys in high schools than in the control group (I: 14.9%; K: 23.6%; p < 0.05). No effects of the intervention were seen in girls of high schools and in students of secondary modern schools. No effects of the intervention were seen on alcohol consumption. Students who drank beer, wine or liquor several times a week were found at the same rate in the intervention and control groups. We conclude that a non-smoking intervention of 8 lessons in the 7th grade of high schools and secondary modern schools may lower the rate of first-time consumers of cigarettes but not of alcohol and drugs.

Adolescent↗
PubMed2000

High-LET-induced chromosome aberrations in V79 cells analysed in first and second post-irradiation metaphases.

PURPOSE: As an extension of previous studies, the time-course of high-LET-induced chromosomal damage was investigated in first- and second-cycle V79 Chinese hamster cells. MATERIALS AND METHODS: Cells were exposed in G1 to 10.4 MeV/u Ar ions (LET = 1226 keV/microm) and chromosomal damage was measured at 2h sampling intervals between 10 h and 34 h after irradiation. To distinguish between cells in different post-irradiation cycles, the fluorescence-plus-Giemsa technique was applied. RESULTS: For first- and second-generation cells, the number of aberrant metaphases and aberrations per metaphase were found to increase markedly with sampling time, demonstrating that cell cycle progression was delayed according to the number of lesions carried by the cell. To account for the time-dependent expression of chromosomal damage a mathematical approach was used based on the integrated flux of aberrant cells entering mitosis. Moreover, the analysis of Ar ion-induced chromosome lesions confirmed that high-LET radiation results in specific changes in the spectrum of aberration types. In particular, an increased rate of chromatid-type aberrations as well as a high frequency of chromosomal breaks was found, although the cells were exposed in G1. CONCLUSIONS: Due to the fact that cells collected at one sampling time are not representative of the entire population, the complete time-course of chromosomal damage has to be taken into account for the determination of a meaningful RBE value. Otherwise, the analysis of chromosomal damage can result in a pronounced over- or underestimation of the RBE depending on the subpopulation of cells entering mitosis at that particular sampling time.

Animals↗
PubMed2000

Treatment planning for heavy-ion radiotherapy: calculation and optimization of biologically effective dose.

We describe a novel approach to treatment planning for heavy-ion radiotherapy based on the local effect model (LEM) which allows us to calculate the biologically effective dose not only for the target region but also for the entire irradiation volume. LEM is ideally suited for use as an integral part of treatment planning code systems for active dose shaping devices like the GSI raster scan system. Thus it has been incorporated into our standard treatment planning system for ion therapy (TRiP). Single intensity modulated fields can be optimized with respect to a homogeneous biologically effective dose. The relative biological effectiveness (RBE) is calculated separately for each voxel of the patient CT. Our radiobiologically oriented code system has been used since 1995 for the planning of irradiation experiments with cell cultures and animals such as rats and minipigs. It has been in regular and successful use for patient treatment planning since 1997.

Animals↗