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Biomedical subjects

B Feuerstein

Publications and source records attributed to B Feuerstein.

14 recordsLinked to original sources

Coincident fragment detection in strong field photoionization and dissociation of H2.

Electron-ion momentum spectroscopy is used to investigate the correlated electronic and nuclear motion in fragmentation of H2 in 4 x 10(14) W/cm(2), 25 fs laser pulses at 795 nm. Reaction channel dependent photoelectron spectra indicate that besides the main, stepwise H2 ionization H2(+) dissociation mechanism resulting in the products H(1s) + H(+) + e(-) a second new mechanism has to be assumed. The momentum distribution of H(+) ions in the dissociation channels H(1s) + H(+) + e(-) and 2H(+) + 2e(-) is found to be independent of the kinetic energy of the photoelectrons.

Journal Article↗

Separation of recollision mechanisms in nonsequential strong field double ionization of Ar: the role of excitation tunneling.

Vector momentum distributions of two electrons created in double ionization of Ar by 25 fs, 0.25 PW/cm(2) laser pulses at 795 nm have been measured using a "reaction microscope." At this intensity, where nonsequential ionization dominates, distinct correlation patterns are observed in the two-electron momentum distributions. A kinematical analysis of these spectra within the classical "recollision model" revealed an (e,2e)-like process and excitation with subsequent tunneling of the second electron as two different ionization mechanisms. This allows a qualitative separation of the two mechanisms demonstrating that excitation-tunneling is the dominant contribution to the total double ionization yield.

Journal Article↗

Collection of MNCs with two cell separators for adoptive immunotherapy in patients with stage IV melanoma.

BACKGROUND: MNCs for adoptive immunotherapy may be collected by leukocytapheresis with a cell separator. STUDY DESIGN AND METHODS: Six healthy cytapheresis donors donated two MNC concentrates on a cell separator (AS.TEC 204, Fresenius): one on the standard MNC program and one on a modified MNC program with reduced centrifuge velocity that leads to a lower platelet contamination. Seventeen patients with malignant melanoma donated 26 MNC concentrates: 5 on the AS.TEC 204 MNC program, 9 on the modified AS.TEC 204 MNC program, and 12 on another modified MNC program (Spectra, COBE). RESULTS: In the course of cultivation of MNCs to dendritic cells (DCs), the donor MNC concentrates with the lower platelet contamination (475 +/- 85 x 10(9)/L) had a significantly higher relative DC yield (low platelet contamination: 3.9 +/- 1.6% of the plated cells; high platelet contamination: 2.5 +/- 1.8% of the plated cells; p = 0.019) than the concentrates with the higher platelet contamination (2364 +/- 448 x 10(9)/L). No significant difference was found in the yields of MNCs and CD14+ cells in the three protocols used for the collection of MNCs from patients with melanoma. The components obtained by the standard AS.TEC 204 MNC program had a significantly higher platelet contamination (1768 +/- 994 x 10(9)/L) than the components obtained by the modified AS.TEC MNC program (360 +/- 98 x 10(9)/L; p<0.05) and the modified Spectra MNC program (636 +/- 266 x 10(9)/L); p<0.05). Because of the low number of investigated components, no significant difference in the DC yield of the three protocols could be detected (mean DC yield after cultivation: 746 +/- 429 x 10(6)). CONCLUSION: A high platelet contamination of MNC concentrates intended for adoptive immunotherapy can lead to a significant impairment of the DC yield after cultivation. Both the modified AS.TEC 204 and the modified Spectra MNC programs are well suited for collecting MNC concentrates with high MNC yields and low platelet contamination from patients with malignant melanoma.

Adult↗

A method for the production of cryopreserved aliquots of antigen-preloaded, mature dendritic cells ready for clinical use.

Dendritic cells (DC) are increasingly used as a vaccine. Unfortunately, a satisfactory cryopreservation of DC in the absence of FCS is not yet available, so that laborious repeated generation of DC from fresh blood or frozen peripheral blood mononuclear cells for each vaccination has been required to date. We now aimed at developing an effective cryopreservation method, and by testing several variables found that it was crucial to combine the most advantageous maturation stimulus with an improved freezing procedure. We generated monocyte-derived DC from leukapheresis products by using GM-CSF and IL-4 and showed that amongst several known maturation stimuli the cocktail consisting of TNF-alpha+IL-1 beta+IL-6+PGE(2) achieved the highest survival of mature DC. We then systematically explored cryopreservation conditions, and found that freezing matured DC at 1 degrees C/min in pure autologous serum+10% DMSO+5% glucose at a cell density of 10x10(6) DC/ml gave the best results. Using this approach 85-100% of the frozen DC could be recovered in a viable state after thawing (Table 1). The morphology, phenotype, survival as well as functional properties (allogeneic mixed leukocyte reaction, induction of influenza matrix or melan A peptide-specific cytotoxic T cells) of these thawed DC were equivalent to freshly prepared ones. The addition of CD40L or TRANCE/RANKL further improved DC survival. Importantly, we demonstrate that DC can effectively be loaded with antigens (such as Tetanus Toxoid, influenza matrix and melan A peptides) before cryopreservation so that it is now possible to generate antigen-preloaded, frozen DC aliquots that after thawing can be used right away. This is an important advance as both the generation of a standardized DC vaccine under GMP conditions and the carrying out of clinical trials are greatly facilitated.

Antigens↗

Electron correlations observed through intensity interferometry

Intensity interferometry was applied to study electron correlations in doubly ionizing ion-atom collisions. In this method, the probability to find two electrons emitted in the same double ionization event with a certain momentum difference is compared to the corresponding probability for two uncorrelated electrons from two independent events. The ratio of both probabilities, the so-called correlation function, is found to sensitively reveal electron correlation effects, but it is rather insensitive to the collision dynamics.

Journal Article↗

Momentum distributions of ne(n+) ions created by an intense ultrashort laser pulse

Vector momentum distributions of Ne(n+) (n = 1,2,3) ions created by 30 fs, approximately 1 PW/cm(2) laser pulses at 795 nm have been measured using recoil-ion momentum spectroscopy. Distinct maxima along the light polarization axis are observed at 4.0 and 7.5 a.u. for Ne2+ and Ne3+ production, respectively. Hence, mechanisms based on an instantaneous release of two (or more) electrons can be ruled out as a dominant contribution to nonsequential strong-field multiple ionization. The positions of the maxima are in accord with kinematical constraints set by the classical "rescattering model."

Journal Article↗

[Cowpox and catpox infection. 2 Clinical case reports].

In patients with painful, possibly hemorrhagic vesicles or black crusts, especially on hands/fingers or face/neck with typical history (contact to cows or feral/cats) the possibility of a cowpox/catpox infection has to be considered. The clinical diagnosis can be confirmed with the electron microscopy; cytoplasmic inclusions may be detected histologically. Further useful diagnostic tools are the identification of the cowpox/catpox virus by PCR or in cell culture as well as serological tests to detect virus specific antibodies. We report the development of typical skin lesions of a cowpox/catpox infection in two female patients who had contact with cows or cats. Recent diagnostic and therapeutic approaches are also discussed.

Adult↗

Heterotypic cell-cell adhesion of human mast cells to fibroblasts.

Skin mast cells are typically located in the perivascular or perineural connective tissue. We observed that HMC-1 mast cells growing in suspension adhered efficiently to (> 90% of cells) and spread on top of fibroblast monolayers and to a lesser degree on purified extracellular matrix proteins. Since adhesive interactions determine cell migration and tissue localization we studied the mechanism. It was found that HMC-1 cells attach to collagen I and fibronectin, laminin, collagen IV and vitronectin, but not to collagens III and VI or hyaluronic acid. Adhesion to fibronectin, collagen I and laminin was completely inhibited by mAbs blocking beta 1-integrins, whereas adhesion of HMC-1 cells to vitronectin was inhibited by anti-alpha v-chain mAbs. However, attachment of HMC-1 cells to fibroblasts was not influenced by mAbs blocking beta 1- or alpha v-chain function, by RGD peptides or by mAbs interfering with other receptors, most notably c-kit. Identical results were obtained with normal mast cells isolated from human foreskin. These results indicate that human mast cells attach to fibroblasts independently of beta 1- or alpha v-integrins as well as of c-kit receptor-mediated mechanisms. The functional characteristics observed (i.e. only partial sensitivity to trypsin and EDTA, no increase in trypsin sensitivity by pretreatment with EDTA) suggest that cadherin receptors were not involved, and it is likely that the adhesion process observed involved not-yet-defined heterotypic cell-cell adhesion receptors.

Antibodies, Monoclonal↗

Scrapie prions alter receptor-mediated calcium responses in cultured cells.

The molecular basis of neurologic dysfunction in prion diseases is unknown. Spongiform degeneration of neurons is the most characteristic neuropathologic change which raises the possibility of abnormal ion channel function. Here we examined the regulation of Ca2+ fluxes in two cell lines chronically infected with scrapie prions, designated ScN2a (scrapie-infected mouse neuroblatoma) and ScHaB (scrapie-infected hamster brain) cells. In uninfected HaB cells, bradykinin caused increases in intracellular Ca2+ concentration ([Ca2+]i) by release of Ca2+ from internal stores and influx of extracellular Ca2+ whereas, in N2a cells, bradykinin increased [Ca2+]i exclusively from internal stores. Prion infection of both cell lines markedly reduced or eliminated bradykinin-activated increases in [Ca2+]i, whether driven by internal or extracellular sources. Stressing the cells with high extracellular [Ca2+], 8 to 20 mM, led to cytopathologic changes in ScHaB but not in ScN2a cells. Cytopathology was not preceded by an increase in [Ca2+]i. These findings indicate that scrapie infection induces abnormalities in receptor-mediated Ca2+ responses and raise the possibility that nerve cell dysfunction and degeneration in prion diseases is related to ion channel aberrations.

Animals↗

A selective effect of methylglyoxal-bis(guanylhydrazone) on the synthesis of mitochondrial DNA of cultured L1210 leukemia cells.

Methylglyoxal-bis(guanylhydrazone) (MGBG) is a polycationic drug which is useful in the chemotherapy of lymphoid and myeloid proliferative disorders. The drug has recently been shown to produce selective ultrastructural damage to the mitochondria of proliferating cell populations. It is important to understand the molecular basis for this action, since it may be related to the known ability of MGBG to block polyamine biosynthesis. Accordingly, the effect of MGBG treatment on the incorporation of [3H]thymidine into both mitochondrial and nuclear DNA has been examined. Exponentially growing L1210 leukemia cells were prelabeled with [14C]thymidine, treated with MGBG for 1.5 to 16 hr, and then pulse labeled with [3H]-thymidine. Incorporation of [3H]thymidine into mitochondrial DNA was selectively inhibited at 5 hr with concentrations of 1 to 10 microM MGBG. Nuclear DNA, however, was not similarly affected until 8 to 11 hr of drug treatment. Dye-CsCl gradients of mitochondrial DNA indicated that the inhibition of synthesis occurred in replicative forms of circular DNA. Uptake studies excluded the possibility of drug interference with cellular uptake of thymidine. Ultrastructural studies revealed a very close correlation between the dose-response curve for mitochondrial damage and that for MGBG inhibition of mitochondrial DNA synthesis. This correlation suggests a direct cause-and-effect relationship between inhibition of mitochondrial DNA synthesis and ultrastructural damage, but the possibility of both phenomena being related to another action by the drug, such as inhibition of polyamine biosynthesis, or a drug effect on mitochondrial function, must also be considered.

Animals↗

Laparoscopic cholecystectomy during pregnancy: three case reports.

OBJECTIVE: The purpose of this presentation is to investigate the effects and feasibility of laparoscopic cholecystectomy during pregnancy. METHODS AND PROCEDURES: We present three pregnant patients who underwent a laparoscopic cholecystectomy for biliary colic during the early second and early third trimester of pregnancy. We also reviewed the literature regarding this topic. RESULTS: All three pregnant patients had uneventful hospital courses after their procedures and delivered full-term babies without complications. Laparoscopic cholecystectomy during the first trimester of pregnancy is contraindicated due to the ongoing fetal organogenesis and during the third trimester is not technically feasible due to the large uterine size. CONCLUSIONS: We conclude that laparoscopic cholecystectomy during the second and very early third trimester of pregnancy is safe and feasible.

Adult↗