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Biomedical subjects

Christian Beck

Publications and source records attributed to Christian Beck.

14 recordsLinked to original sources
PubMed2007

Importance of comparison of current and prior mammograms in breast cancer screening.

PURPOSE: To retrospectively determine the influence of comparing current mammograms with prior mammograms on breast cancer detection in screening and to investigate a protocol in which prior mammograms are viewed only when necessary. MATERIALS AND METHODS: Institutional review board approval was not required. Participants gave written informed consent. Twelve experienced screening radiologists read 160 soft-copy screening mammograms twice, once with and once without prior mammograms. Eighty mammograms were obtained in women in whom breast cancer was diagnosed later; the other 80 mammograms had been reported as normal or benign. All cancers were visible in retrospect. Readers located potential abnormalities, estimated likelihood of malignancy for each finding, and indicated whether prior mammograms were considered necessary. The effect of prior mammograms on detection was determined by computing the mean lesion localized fraction in a range of low fractions of nonlesion locations corresponding to operating points in screening. Scores for both reading sessions were combined to assess the effect of making prior mammograms available only when requested. Data were analyzed by comparing the number of localized lesions between the two reading conditions with a paired two-tailed Student t test and applying a linear mixed model to test differences in average mean lesion localized fraction between reading conditions. P values less than .05 indicated statistical significance. RESULTS: Without prior mammograms, significantly more annotations were made. When only positive cases were considered, no difference was observed. Reading performance was significantly better when prior screening mammograms were available. At fixed lesion localized fraction, nonlesion localized fraction was reduced by 44% (P<.001) on average when prior mammograms were read. Performance was also increased for combined reading mode (ie, when prior mammograms were available on request only). However, this increase was smaller than that when prior mammograms were always available. Prior mammograms were requested in 24%-33% of all cases and were requested more often in positive cases. CONCLUSION: Comparison with prior mammograms significantly improves overall performance and can reduce referrals due to nonlesion locations. Limiting the availability of prior mammograms to cases selected by the reader reduces the beneficial effect of prior mammograms.

Aged↗
PubMed2006

Scaling behavior of nonhyperbolic coupled map lattices.

Coupled map lattices of nonhyperbolic local maps arise naturally in many physical situations described by discretized reaction diffusion equations or discretized scalar field theories. As a prototype for these types of lattice dynamical systems we study diffusively coupled Tchebyscheff maps of Nth order which exhibit strongest possible chaotic behavior for small coupling constants a. We prove that the expectations of arbitrary observables scale with sqrt of a in the low-coupling limit, contrasting the hyperbolic case which is known to scale with a . Moreover we prove that there are log-periodic oscillations of period ln N2 modulating the sqrt of a dependence of a given expectation value. We develop a general 1st order perturbation theory to analytically calculate the invariant one-point density, show that the density exhibits log-periodic oscillations in phase space, and obtain excellent agreement with numerical results.

Journal Article↗
PubMed2006

Structural determinants of M-type KCNQ (Kv7) K+ channel assembly.

The ability of KCNQ (Kv7) channels to form hetero-oligomers is of high physiological importance, because heteromers of KCNQ3 with KCNQ2 or KCNQ5 underlie the neuronal M-current, which modulates neuronal excitability. In KCNQ channels, we recently identified a C-terminal subunit interaction (si) domain that determines their subunit-specific assembly. Within this si domain, there are two motifs that comprise approximately 30 amino acid residues each and that exhibit a high probability for coiled-coil formation. Transfer of the first or the second coiled-coil (TCC) domain from KCNQ3 into the KCNQ1 scaffold resulted in chimeras KCNQ1(TCC1)Q3 and KCNQ1(TCC2)Q3, both of which coimmunoprecipitated with KCNQ2. However, only KCNQ1(TCC2)Q3 enhanced KCNQ2 currents and surface expression or exerted a strong dominant-negative effect on KCNQ2. Deletion of TCC2 within KCNQ2 yielded functional homomeric channels but prevented the current augmentation measured after coexpression of KCNQ2 and KCNQ3. In contrast, deleting TCC1 within KCNQ2 did not give functional homomeric KCNQ2 or heteromeric KCNQ2/KCNQ3 channels. Mutations that disrupted the predicted coiled-coil structure of TCC1 in KCNQ2 or KCNQ3 abolished channel activity after expressing these constructs singly or in combination, whereas helix-breaking mutations in TCC2 of KCNQ2 gave functional homomeric channels but prevented the heteromerization with KCNQ3. In contrast, KCNQ3 carrying a coiled-coil disrupting mutation in TCC2 hetero-oligomerized with KCNQ2. Our data suggest that the TCC1 domains of KCNQ2 and KCNQ3 are required to form functional homomeric as well as heteromeric channels, whereas both TCC2 domains facilitate an efficient transport of heteromeric KCNQ2/KCNQ3 channels to the plasma membrane.

Amino Acid Sequence↗
PubMed2006

Cutting edge: a novel nonoxidative phagosomal mechanism exerted by cathepsin-D controls Listeria monocytogenes intracellular growth.

Deciphering how Listeria monocytogenes exploits the host cell machinery to invade mammalian cells is a key issue in understanding the pathogenesis of this food-borne pathogen, which can cause diseases ranging from gastroenteritis to meningitis and abortion. In this study, we show that the lysosomal aspartyl-protease cathepsin-D (Ctsd) is of considerable importance for nonoxidative listericidal defense mechanisms. We observed enhanced susceptibility to L. monocytogenes infection of fibroblasts and bone-marrow macrophages and increased intraphagosomal viability of bacteria in fibroblasts isolated from Ctsd-deficient mice compared with wild type. These findings are further supported by prolonged survival of L. monocytogenes in Ctsd-deficient mice after infection. Transient transfection of Ctsd in wild-type cells was sufficient to revert these wild-type phagosomes back to microbicidal compartments. Based on infection experiments with mutant bacteria, in vitro degradation, and immunoprecipitation experiments, we suggest that a major target of cathepsin D is the main virulence factor listeriolysin O.

Animals↗
PubMed2006

Nasal RANTES and eotaxin production pattern in response to rhinovirus infection.

Tissue eosinophilia is a hallmark of nasal polyposis and its pathogenesis is an area of high interest. RANTES and eotaxin are both known to recruit eosinophils, however, the mechanisms triggering their induction are still uncertain, and viral infections have been suggested to be involved in this process. Therefore, we investigated whether rhinovirus infection is a stimulus for RANTES and eotaxin expression and production. Fibroblasts were cultured from healthy nasal mucosa obtained during endonasal surgery. Cultured cells were infected with human rhinovirus-16 for one to 72 hours. Following total RNA isolation and reverse transcription, RANTES- and eotaxin-mRNA levels were analyzed. In addition, RANTES and eotaxin secretion was measured in culture supernatants by means of an ELISA. Rhinovirus infection induces RANTES-mRNA expression as early as one hour after infection, persisting for up to 72 hours. Eotaxin-mRNA profiles did not alter significantly from control. Protein production was confirmatory for both chemokines, indicating distinct translational latency. Our data suggest that RANTES functions as a host defence mechanism responding to rhinovirus infection, thus supporting a linkage between rhinovirus infections and the pathogenesis of nasal polyposis.

Cells, Cultured↗
PubMed2005

Defensin and chemokine expression patterns in the palatine tonsil: a model of their local interaction.

Defensins and chemokines are an essential part of the immune response mechanisms in the head and neck mucosa. This work investigates their correlation and their expression pattern in tonsillar disease. Forty-four tonsil tissue samples were obtained from patients who underwent tonsillectomy between 1998 and 1999 for chronic tonsillitis with (n =9) and without (n =25) inflammatory infiltrates and hyperplasia of the tonsil (n =10). Defensin (hBD-1, hBD-2, HNP-1 and HNP-4) and chemokine (RANTES, eotaxin, eotaxin-2, MCP-3, MCP-4 and IL-8) mRNA expressions were analyzed by SQRT-PCR. HNP-4 and eotaxin-2 expressions were positively correlated (P <0.05) in the acute tonsillitis group. HBD-2 and MCP-3 expressions were positively correlated in the hyperplastic tonsils group. Within all groups together, HNP-4 and RANTES expressions were highly positively correlated (P <0.01), and HNP-1 and hBD-2 were positively correlated with IL-8 expressions. Immunohistochemistry demonstrated eotaxin-1 as well as IL-8 production to be predominantly located within the lymphoid follicles and submucosa. RANTES production was shown in the epithelial lining and perivascular tissue. The expression of hBD-1 and hBD-2 was limited to the epithelial lining. Our data support an association between the innate and acquired immune systems on the defensin-chemokine level. The finding of positively correlated hBD-2 and IL-8 expression is biologically relevant because of the proximity of hBD-2 (epithelium) and IL-8 (submucosa) release, as well as the synergistic support of the Th1 system. In addition, our data suggest RANTES as a first-line mediator of perivascular leukocyte recruitment.

Chemokine CCL11↗
PubMed2005

From time series to superstatistics.

Complex nonequilibrium systems are often effectively described by a "statistics of a statistics", in short, a "superstatistics". We describe how to proceed from a given experimental time series to a superstatistical description. We argue that many experimental data fall into three different universality classes: Chi2 superstatistics (Tsallis statistics), Chi2 inverse superstatistics, and log-normal superstatistics. We discuss how to extract the two relevant well separated superstatistical time scales tau and T, the probability density of the superstatistical parameter beta, and the correlation function for beta from the experimental data. We illustrate our approach by applying it to velocity time series measured in turbulent Taylor-Couette flow, which is well described by log-normal superstatistics and exhibits clear time scale separation.

Journal Article↗
PubMed2005

Asymptotics of superstatistics.

Superstatistics are superpositions of different statistics relevant for driven nonequilibrium systems with spatiotemporal inhomogeneities of an intensive variable (e.g., the inverse temperature). They contain Tsallis statistics as a special case. We develop here a technique that allows us to analyze the large energy asymptotics of the stationary distributions of general superstatistics. A saddle-point approximation is developed which relates this problem to a variational principle. Several examples are worked out in detail.

Journal Article↗
PubMed2005

Establishment and optimization of a flow cytometric method for evaluation of viability of CD34+ cells after cryopreservation and comparison with trypan blue exclusion staining.

BACKGROUND: Trypan blue exclusion staining is probably the most frequently applied method (Method I) for assessment of viability in peripheral blood progenitor cell grafts after cryopreservation. Alternatively, a flow cytometry-based method (Method II) was established and optimized. STUDY DESIGN AND METHODS: In a first series of 22 autologous apheresis products, the influence of duration of antibody staining and red cell (RBC) lysis on viability was investigated. In a second series of 21 autologous and 1 allogeneic apheresis products, the effect of omitting the RBC lysis was evaluated. On the basis of the results of the first two series, 155 autologous and 57 allogeneic apheresis products were analyzed with Method I and the now optimized Method II. RESULTS: Halving the incubation times did not influence the viability of CD45+ or CD34+ cells. Omission of RBC lysis resulted in a significantly (p = 0.022) increased median viability of CD45+ cells (75.8% vs. 71.0%) without any influence on CD34+ cells. In the third series, the median viability of CD34+ cells (96.9%) was significantly (p < 0.0001) higher compared with the viability of CD45+ cells (76.2%) and the viability determined by Method I (86.5%). CONCLUSION: The viability of CD34+ cells was significantly higher compared with the viability of all white blood cells. The presented cytometry-based method is superior to the standard trypan blue method regarding the number of analyzable cells and documentation, regarding observer independence and standardization; it allows the analysis of the cells of interest for transplantation after minimal sample manipulation.

Antigens, CD34↗
PubMed2004

A novel method for simultaneous analysis of specific platelet antibodies: SASPA.

Glycoprotein (GP)-specific platelet antibodies can cause allo-immune and auto-immune thrombocytopenia. The specific detection of relevant antibodies is a prerequisite for diagnosis and treatment. Here, we describe an improved method based on simultaneous detection of various platelet-specific immunoglobulin G (IgG) and IgM antibodies. Bead populations with distinct fluorescence intensities, coated with monoclonal antibodies specific for mouse heavy chain isotypes, were used for the simultaneous immobilization of platelet-GP [IIb/IIIa, Ib/IX, human leucocyte antigen (HLA) class I, or Ia/IIa, CD32, GPIV or CD109, Ib/IX, HLA class I]. In order to detect human IgG and IgM antibodies simultaneously, phycoerythrin- and fluorescein isotiocyanate-conjugated goat anti-human IgG and IgM were added. On this basis, the abundance of six distinct antibodies (three anti-GP, each with subclasses IgG and IgM) were simultaneously analysed without cross-reaction by flow cytometry. For evaluation, sera and platelets from 169 patients with platelet-binding and/or platelet-associated antibodies were investigated. The monoclonal antibody-specific immobilization of platelet antigen (MAIPA) assay was performed in parallel as reference test. The simultaneous analysis of platelet-specific antibodies (SASPA) assay was able to detect all platelet-specific IgG and IgM that were also recognized by MAIPA with a comparable sensitivity. SASPA proved to be a rapid and reliable assay that required less platelets than other methods. This method has the potential to pave the way for new investigations of platelet-specific antibodies.

Antibodies↗
PubMed2003

C-kit+ FcR+ myelocytes are increased in cancer and prevent the proliferation of fully cytolytic T cells in the presence of immune serum.

Immunogenic cancers induce both IgG antibodies and CD8(+) cytotoxic T lymphocytes (CTL). Rejection of almost all immunogenic tumors depends ultimately on CTL. When tumors grow progressively, IgG continues to be produced but CTL may no longer be demonstrable. Using syngeneic mixed lymphocyte tumor cell cultures, we found that proliferation of fully activated proliferating CTL is prevented by a small subpopulation of immature myeloid c-kit(+) FcR(+) cells, for convenience referred to as "barrier cells". Both, FcR on barrier cells and IgG linked to TGF-beta (IgG-TGF-beta) present in immune serum, are obligatory for barrier cells to prevent proliferation of CTL, suggesting that IgG-TGF-beta binds FcR to activate suppression. Growing tumors increase barrier cells in the spleen. Interfering with the cells or molecules essential for barrier cells to prevent proliferation of CTL may enhance tumor and other CD8(+) CTL-mediated immunity.

Animals↗
PubMed2003

Engraftment capacity of umbilical cord blood cells processed by either whole blood preparation or filtration.

Umbilical cord blood (UCB) preparation needs to be optimized in order to develop more simplified procedures for volume reduction, as well as to reduce the amount of contaminating cells within the final stem cell transplant. We evaluated a novel filter device (StemQuick((TM))E) and compared it with our routine buffy coat (BC) preparation procedure for the enrichment of hematopoietic progenitor cells (HPCs). Two groups of single or pooled UCB units were filtered (each n = 6), or equally divided in two halves and processed by filtration and BC preparation in parallel (n = 10). The engraftment capacity of UCB samples processed by whole blood (WB) preparation was compared with paired samples processed by filtration in the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse animal model. Filtration of UCB units in the two groups with a mean volume of 87.8 and 120.7 ml, respectively, and nucleated cell (NC) content of 9.7 and 23.8 x 10(8) resulted in a sufficient mean cell recovery for mononucleated cells ([MNCs] 74.2%-77.5%), CD34(+) cells (76.3%-79.0%), and colony-forming cells (64.1%-86.3%). Moreover, we detected a relevant depletion of the transplants for RBCs (89.2%-90.0%) and platelets ([PLTs] 77.5%-86.1%). In contrast, the mean depletion rate using BC processing proved to be significantly different for PLTs (10%, p = 0.03) and RBCs (39.6%, p < 0.01). The NC composition showed a highly significant increase in MNCs and a decrease in granulocytes after filtration (p < 0.01), compared with a less significant MNC increase in the BC group (p < 0.05). For mice transplanted with WB-derived progenitors, we observed a mean of 15.3% +/- 15.5% of human CD45(+) cells within the BM compared with 19.9% +/- 16.8% for mice transplanted with filter samples (p = 0.03). The mean percentage of human CD34(+) cells was 4.2% +/- 3.1% for WB samples and 4.5% +/- 3.2% for filter samples (p = 0.68). As the data of NOD/SCID mice transplantation demonstrated a significant engraftment capacity of HPCs processed by filtration, no negative effect on the engraftment potential of filtered UCB cells versus non-volume-reduced cells from WB transplants was found. The StemQuick((TM))E filter devices proved to be a useful tool for Good Manufacturing Practices conform enrichment of HPCs and MNCs out of UCB. Filtration enables a quick and standardized preparation of a volume-reduced UCB transplant, including a partial depletion of granulocytes, RBCs, and PLTs without the need for centrifugation. Therefore, it seems very probable that filter-processed UCB transplants will also result in sufficient hematopoietic reconstitution in humans.

Animals↗
PubMed2002

Nonobese diabetic-severe combined immunodeficient mice transplantation of volume-reduced and thawed umbilical cord blood transplants following closed-system immunomagnetic cell selection.

BACKGROUND: Protocols for the expansion of human umbilical cord blood (UCB) progenitors begin with the selection of CD34+ cells from stored frozen and thawed units. Use of an immunomagnetic selection procedure within a closed blood bag system for volume-reduced UCB transplants was evaluated, and the influence of CD34 cell selection on in vivo engraftment potential was studied. STUDY DESIGN AND METHODS: Eleven thawed buffy coat-processed UCB units were processed within a standard blood bag with a washing solution. In six independent experiments, the same dosage of 2 x 104 CD34+ cells from paired selected and nonselected samples was transplanted into NOD-SCID mice. In two experiments, cells from the negative fraction were also transplanted. RESULTS: The purity of CD34+ cells after selection was correlated with the removal of supernatant after the first washing step and therefore with adequate removal of damaged or dead cells (r=0.86, p < 0.01). Mice transplanted with unselected UCB cells had more human cells within their marrow than animals transplanted with selected cells (8.6 +/- 5.9% selected group vs. 19.8 +/- 14.2% unselected group; p=0.04), whereas no engraftment could be observed transplanting cells from the two negative fractions. A higher percentage of human CD45+ cells in the unselected group were found to be positive for CD38, CD14, CD33, and CD19, indicating a higher potential for these unselected progenitors to differentiate into myeloid cells and B cells. CONCLUSIONS: Processing of volume-reduced and thawed UCB transplants within a closed-bag system before immunomagnetic CD34+ cell selection allows for the preparation of CD34+ cells of significant purity at technically useful cell recoveries. However, these experiments indicate a potential impairment of engraftment capacity for the CD34+ cell-enriched fraction.

Animals↗