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C Bittner

Publications and source records attributed to C Bittner.

18 recordsLinked to original sources
PubMed2006

Cytogenetic characteristics of a murine in vitro model for the human anaplastic large cell lymphoma (ALCL).

Anaplastic large cell lymphoma (ALCL) is an entity of non-Hodgkin lymphomas (NHL) that often occurs in young children and adolescents. In the majority of cases, ALCL are of T-cell origin and contain the t(2;5)(p23;q35) leading to an NPM-ALK fusion or variant ALK translocations. In addition, there is an ALK-negative subtype of ALCL. The anaplastic lymphoid cell line TS1G6 established by interleukin (IL)-9 transfection of T-helper cells represents a murine model of this subtype. Here, we describe the cytogenetic features of this cell line using spectral karyotyping (SKY) and single-color fluorescence in situ hybridization (FISH). We show that TS1G6 cells exhibit a hypotetraploid karyotype with complex structural alterations. Several unbalanced translocations involved the chromosomal region 14E5, and different translocation partners, i.e. X?A6, 3A3 and 8A1. FISH analysis using a BAC clone containing c-myc confirmed the presence of six copies, but also demonstrated that two loci were irregularly located, indicating that additional intrachromosomal rearrangements had occurred. Moreover, a duplication of the region XF2 approximately 3 was identified. Furthermore, six chromosomes 15 were found, representing a trisomy 15 in a tetraploid chromosome complement, indicating an altered gene dosage of the oncogene c-myc located in region 15D3.

Animals↗
PubMed2001

Facial-selective allylation of methyl ketones for the asymmetric synthesis of alpha-substituted tertiary homoallylic ethers.

The asymmetric synthesis of enantiomerically pure a-substituted tertiary homoallylic ethers 4a, 11 and 12a-c by the allylation of ethyl methyl ketone (la) with gamma-substituted allylsilanes 9a-h is described. The allylsilanes were obtained by a nickel-catalysed Grignard cross-coupling reaction of (E)- and (Z)-(3-iodoallyl)trimethylsilane with various Grignard reagents. The reaction of the allylsilanes with la in the presence of the trimethylsilyl ether of N-trifluoroacetylnorpseudoephedrine (3), and catalytic amounts of a mixture of trimethylsilyl triflate and trifluoromethanesulfonic acid led to the homoallylic ethers 4a, 11 and 12a-c with two new stereogenic centres, with a selectivity of 1:9 to >20:1 for the homoallylic and of 1:99 to >60:1 for the allylic centre. The facial selectivity does not depend on the configuration of the allylsilane, and in all reactions the anti product is preferentially formed. Interestingly, a pronounced switch of facial selectivity takes place with increasing length of the alkyl group of the allylsilane.

Journal Article↗
PubMed2001

Synthesis of enantiopure homoallylic ethers by reagent controlled facial selective allylation of chiral ketones.

The stereoselective allylation of chiral methyl ketones to give tertiary homoallylic ethers, which can easily be transformed into homoallylic alcohols, is described. Reaction of the enantiopure ketones 8a-d and the racemic ketones 26a-d with the norpseudoephedrine derivative 2 or ent-2 and allylsilane in the presence of a catalytic amount of trifluoromethanesulfonic acid, led to a series of homoallylic ethers with good to excellent diastereoselectivity (85:15 to > 97:3). The allylation is reagent controlled and nearly independent from the stereogenic centers in the substrates. A partial kinetic resolution was observed using the racemic ketones 26a-d. In the reaction of the chiral ketones 8a-d with the achiral reagents ethoxytrimethylsilane and allylsilane only a low diastereoselectivity was observed.

Journal Article↗
PubMed2001

A preclinical model for experimental chemotherapy of human head and neck cancer.

We developed a mouse model in a representative human derived head and neck cancer cell line for preclinical studies to evaluate antitumor response, tumor-free survival and host toxicity of alkylating agents, antimetabolites, platinum analogs and taxanes alone or in combination. Ninety athymic NMRI mice were inoculated with human derived oral squamous cell carcinoma cells growing on the hind paw to an average volume of 180 +/- 80 mm3. Animals were stratified according to tumor volume into 10 groups (n=6-10) and treated with ifosfamide (65 mg/kg b.w.), docetaxel (24 mg/kg b.w.), cisplatin (2 mg/kg b.w.), carboplatin (6 or 10 mg/kg b.w.), methotrexate (1 mg/kg b.w.), and fluorouracil (15 mg/kg b.w.) intravenously in single agent or combination (ifosfamide plus docetaxel or ifosfamide plus carboplatin) treatment schedules or controls. Tumor volume was measured 3 times per week for 60 days. The average tumor volume, the overall survival time and the response rates (CR, PR) of the treated animals were compared with the data obtained from untreated controls and statistically evaluated. Untreated tumors showed rapid and exponential tumor growth. Single agent therapies with ifosfamide, cisplatinum, and docetaxel lead to significant tumor regression and improved overall survival. Low dose carboplatin monotherapy induced significant tumor growth delay, but not significant tumor regression. Most impressive tumor-free survival was achieved by combination treatment with ifosfamide and docetaxel. This preclinical study demonstrates an animal model capable of differentiating various chemotherapy regimens.

Animals↗
PubMed2000

An animal model for anaplastic large cell lymphoma in the immunocompetent syngeneic C57Bl/6 mouse.

We report on the analysis of a murine anaplastic lymphoid cell line TS1G6, established recently by interleukin (IL)-9 transfection. TS1G6 revealed a highly characteristic pattern of large anaplastic cells with mononuclear, binuclear, or multinuclear cells resembling Hodgkin (H) or Sternberg-Reed (SR) cells. This cell line is tumorigenous after injection of as few as 10(4) lymphoma cells into nude or immunocompetent C57Bl/6 mice and leads to death from progressive disease of all treated animals within a few weeks. The histological analysis of these tumors revealed a diffuse large cell malignant lymphoma that is morphologically almost identical to human anaplastic large cell lymphoma (ALCL). The lymphoma cells did not show overexpression of the anaplastic lymphoma kinase (ALK) gene, which is found in about 50% of the cases of human ALCL. Thus, this model may be an animal model for an important subset of human ALCL. The cytokine profile, which is of the T helper 2 type, showed strong parallels to the human lymphoma counterpart. Mice suffering from such lymphomas could not be cured with a regimen using high dose cyclophosphamide similar to many ALCL patients. Such an animal model for ALCL has not yet been recognized, but may provide the basis for investigating new antitumor immunotherapies in a fully immunocompetent host.

Anaplastic Lymphoma Kinase↗
PubMed2000

[New immunotherapeutic approaches for the treatment of anaplastic large cell lymphoma in a mouse model].

As there is still a high mortality of the large cell anaplastic non Hodgkin lymphoma (ALCL) (between 40-70%, depending on prognostic factors) there is a need for new therapeutic approaches. Therefore, we studied different strategies for cancer immunotherapy in an immunogenic ALCL tumor model system: A murine IL-9 dependent T cell line was transfected with IL-9 cDNA, resulting in an autonomous growing T cell line designated G6BB, which had a high tumor incidence after injecting of as few as 10(4) cells subcutaneously into syngeneic C57Bl/6 mice. Tumor growth, dissemination, histology, and immunohistochemistry were similar to human ALCL. This mouse model provides an immunogenic in vivo system to investigate antitumor immunotherapies. In order to increase antigen recognition by T cells and T cell activation, we administered tumor bearing mice cell-based cancer vaccines with irradiated tumor cells alone or in combination with immunostimulating CpG-Oligonucleotides, a combination of Th1 cytokines and Th2 cytokine antibodies (IL-12, IFN-gamma, GM-CSF, Anti-IL-10) (after detecting a Th2 cytokine profile in G6BB), or the recall antigens diphtheria, pertussis, and tetanus.

Animals↗
PubMed1998

In situ microscopy for on-line determination of biomass.

A sensor is presented, which allows on-line microscopic observation of microorganisms during fermentations in bioreactors. This sensor, an In Situ Microscope (ISM) consists of a direct-light microscope with a measuring chamber, integrated in a 25 mm stainless steel tube, two CCD-cameras, and two frame-grabbers. The data obtained are processed by an automatic image analysis system. The ISM is connected with the bioreactor via a standard port, and it is immersed directly in the culture liquid-in our case Saccharomyces cerevisiae in a synthetic medium. The microscopic examination of the liquid is performed in the measuring chamber, which is situated near the front end of the sensor head. The measuring chamber is opened and closed periodically. In the open state, the liquid in the bioreactor flows unrestricted through the chamber. In closing, a defined volume of 2,2. 10(-8) mL of the liquid becomes enclosed. After a few seconds, when the movement of the cells in the enclosed culture has stopped, they are examined with the microscope. The microscopic images of the cells are registered with the CCD-cameras and are visualized on a monitor, allowing a direct view of the cell population. After detection, the measuring chamber reopens, and the enclosed liquid is released. The images obtained are evaluated as to cell concentration, cell size, cell volume, biomass, and other relevant parameters simultaneously by automatic image analysis. With a PC (486/33 MHz), image processing takes about 15 s per image. The detection range tested when measuring cells of S. cerevisiae is about 10(6) to 10(9) cells/mL (equivalent to a biomass of 0.01 g/L to 12 g/L). The calculated biomass values correlate very well with those obtained using dry weight analysis. Furthermore, histograms can be calculated, which are comparable to those obtained by flow cytometry.

Automation↗
PubMed1994

A prospective study of the migration of two acetabular components. PCA versus RM cups.

Fifty-nine PCA cups and 61 hydroxyapatite-coated RM cups were included in a prospective randomised study with a mean follow up of 5.2 years. Clinical evaluation revealed better results with the RM cup. Radiological criteria of loosening could be applied only with considerable restrictions as different parameters were assessed: progressively loosened beads in PCA cups and faded contour in RM cups. Migration was measured by a computer assisted method (EBRA). PCA cups showed significantly more longitudinal migration 2 years after operation and subsequently. High migration values correlated with a limp. Loosening as defined by migration was of clinical relevance, could be measured early and predicted the survival rate.

Activities of Daily Living↗
PubMed1990

Facial morphology and malocclusions.

The aim of this study was to determine whether sagittal and vertical aberrations in intermaxillary incisal tooth and jaw relationships were reflected in facial morphology. One hundred seventy-two children (79 girls and 93 boys), 12 to 14 years of age, were selected from the Orthodontic Department, University of Giessen. Pretreatment profile and frontal facial photographs as well as profile roentgenograms in centric occlusion for each child were made. The method consisted of (1) a personal appraisal of the existing incisal tooth and jaw relationship by visual inspection of facial photographs, (2) a validity assessment of these personal appraisals, and (3) a comparison of linear and angular measurements made from facial photographs and from lateral headfilms. The result of this investigation revealed that a large overjet and a Class II, Division 2 incisal tooth relationship were most often reflected in the face. A Class III incisal tooth relationship and an open bite, however, were difficult to detect. Sagittal maxillary and mandibular positions could only occasionally be determined on the basis of facial appearance, while a Class II jaw base relationship (large ANB angle) could easily be seen. The vertical jaw relationship (mandibular plane angle and anterior facial height index) could be determined with relatively high precision. When the measurements from the facial photographs were compared with those from the lateral headfilms, moderate to high correlations were found between skeletal and soft tissue readings: ANB angle (r = +0.63), mandibular plane angle (r = +0.93), and anterior facial height index (r = +0.86). It was concluded that sagittal and vertical dental and skeletal intermaxillary malrelationships were only partly reflected in the face.

Adolescent↗
PubMed1989

Antagonism of platelet activating factor-induced chemiluminescence in guinea-pig peritoneal macrophages in differing states of activation.

1. The effects of the platelet activating factor (Paf) antagonists alprazolam, BN 52021, kadsurenone, L 652,731 and SRI 63119 have been studied on Paf-induced chemiluminescence (CL) of guinea-pig, C. parvum-activated peritoneal macrophages in vitro. 2. All antagonists produced a shift to the right in the dose-response curve to Paf (0.001-10 mumol l-1). Schild plots for BN 52021, L 652,731, kadsurenone and SRI 63119 were linear, but only for BN 52021 and kadsurenone did the mean slope not differ significantly from unity. Mean pA2 values for BN 52021 and kadsurenone were 6.60 +/- 0.05 and 6.41 +/- 0.14 (mean + s.e.mean) respectively. Calculation of IC50 values for all antagonists (at 0.1 mumol l-1 Paf) gave an order of potency: L 652731 greater than kadsurenone greater than or equal to BN 52021 greater than alprazolam greater than SRI 63119. 3. When individual pA2 values for BN 52021 and kadsurenone were plotted against the maximal CL response to Paf of cell suspensions in the absence of antagonist (reflecting the degree of activation of the macrophages by the C. parvum), it was found that the affinity of both antagonists for macrophage Paf receptors remained relatively constant irrespective of the activation state of the cells. 4. We conclude that activation of guinea-pig peritoneal macrophages does not account for the increased affinity for macrophage Paf receptors previously observed for kadsurenone. Kadsurenone and BN 52021 presumably bind to a site on Paf receptors which is not affected by the activation process, while alprazolam and SRI 63119 are non-specific antagonists. The reason for the difference between the competitive nature of kadsurenone and its structural analogue L 652,731 is unclear.

Alprazolam↗
PubMed1989

[Coping strategies of adolescents and their significance for counseling].

This study investigated the problem solving strategies in adolescents. An anonymous, open questionnaire was employed. The descriptive analysis of the results show that personal discussion on the pertinent problems is the most common strategy, whereas other methods for overcoming problems (groups, institutions, financial and social aid etc.) are underrepresented. Approximately 1/6 of the adolescents are unable to comment on ways of solving problems specific to their age-group. Moreover, it is striking that only ca. 20% of the adolescents have realistic knowledge about the working methods of the respective institutions. The statistical analysis differentiates these effects according to the variables sex, age, and education. In the concluding section the consequences for institutional youth counselling are discussed. It is emphasized that ideas about counselling possibilities should become more realistic. In addition, the combination of social and psychotherapeutic interventions is suggested.

Adaptation, Psychological↗
PubMed1987

Changes in glutathione peroxidase activities and the oxidative burst of leukocytes during inflammation in the mouse and rat.

The relationship between glutathione peroxidase (GSH-Px) activity and opsonized zymosan-induced chemiluminescence (CL) has been studied with exudate leukocytes obtained at different times after induction of inflammatory responses in the mouse peritoneal cavity with heat-killed Corynebacterium parvum and in the rat pleural cavity with lambda-carrageenin. GSH-Px activity in mouse peritoneal exudate cells fell markedly after 2-4 h, returning to normal within 1-2 days. The lowered enzyme activity was associated with an increased ability of the cells to generate CL. Rat pleural exudate cells exhibited a slight fall in GSH-Px activity after 6 h which increased to supranormal levels within 1-2 days. During this period the ability of the cells to generate CL continually increased. The data indicate that during the early phase of increased generation of reactive oxygen species (ROS) by inflammatory leukocytes, the intracellular protective mechanism, represented by GSH-Px, is compromised. Subsequently, GSH-Px activity increases to or above initial levels possibly due to the presence of mononuclear cells and/or as a response to the increased generation of ROS.

Animals↗
PubMed1986

Pharmacological analysis of guinea-pig macrophage chemiluminescence responses to platelet activating factor and opsonized zymosan.

The luminol-dependent chemiluminescence (CL) response in vitro of guinea-pig C. parvum-activated peritoneal macrophages to platelet activating factor (PAF) has been compared with that to opsonized zymosan (OpZ). The response to PAF (5 X 10(-6) mol/l.) reached a peak within 1 min, that to OpZ (0.17 mg/ml) within 10-20 min. Peak responses to both stimuli were dose-dependently inhibited in a similar manner by p-hydroxymercuribenzoate (10(-5) - 10(-3) mol/l), sodium benzoate (10(-5) - 10(-3) mol/l.) and quinacrine (10(-6) - 10(-3) mol/l.). In contrast, the xanthine oxidase inhibitor allopurinol (IC50 vs OpZ, 220 mumol/l.; vs PAF greater than 1000 mumol/l.), the methylation-inhibiting combination homocysteine + 3-deazaadenosine (IC50 vs OpZ, 22 mumol/l.; vs PAF greater than 100 mumol/l.), the phospholipase A2 inhibitor and alkylating agent p-bromophenacylbromide (pBPB; IC50 vs OpZ, 2.6 mumol/l.; vs PAF 15 mumol/l.) and the beta-adrenoceptor agonist isoprenaline (IC50 vs OpZ, 0.1 mumol/l.; PAF greater than 10 mumol/l.) all exerted differential inhibitory effects on the CL responses to the two stimuli, though colour quenching by adrenochrome cannot be ruled out in the differential effect of isoprenaline. In screening studies, carried out with CL responses measured 2 or 5 min after PAF and OpZ, respectively, verapamil (less than or equal to 10(-4) mol/l.), trifluoperazine (less than or equal to 10(5) mol/l.) EDTA (less than or equal to 10(6) mol/l.), mannitol (less than or equal to 10(-2) mol/l.), metyrapone (less than or equal to 10(-5) mol/l.), SQ 22536 (less than or equal to 10 micrograms/ml.), iso-butyl methylxanthine (less than or equal to 10(-5) mol/l.).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Chemiluminescence from mouse resident macrophages: characterization and modulation by arachidonate metabolites.

Oxidative burst dependent chemiluminescence (CL), generated by mouse resident peritoneal and alveolar macrophages obtained by peritoneal and lung lavage, has been studied using a lumanol-dependent assay. Alveolar macrophages generated greater CL in response to opsonized zymosan (OpZ, 0.017-0.67 mg/ml) than did peritoneal cells, but the former were less sensitive to inhibition by joint cyclo-oxygenase/lipoxygenase inhibitors and superoxide dismutase. Responses of peritoneal macrophages to OpZ and calcium ionophore A23187 (0.1-0.5 microM) were small in comparison to responses of C. parvum-elicited cells, while FMLP (2-20 microM) was ineffective. Arachidonic acid alone (40-80 microM) generated slight CL from resident peritoneal macrophages. When added with OpZ (0.017 mg/ml), arachidonate (40 microM) initially enhanced, then inhibited CL, the inhibition being indomethacin (10 microM) sensitive. These data indicate that modulation of resident macrophage CL by arachidonate products differs somewhat from that reported for elicited macrophages.

Animals↗
PubMed1981

Macrophages from different sources, their production of chemiluminescence under various stimuli and the effects of PGE2 and drugs.

We are currently characterizing different macrophages sub-populations according to their release of oxygen free radicals (measured as chemiluminescence) under various stimuli and their responses to drugs and mediators. Mouse macrophages were obtained by peritoneal or lung lavage and stimulated in vitro with opsonized zymosan (OpZ) or the calcium ionophore A23187. Chemiluminescence was measured in a luminometer and responses obtained after 5 min expressed as percentages of standard responses to the stimuli. Almost identical dose-response curves to OpZ were obtained with peritoneal and alveolar macrophages, while the dose-response curve of peritoneal macrophages to A23187 was much shallower. The response to A23187 was generally much weaker than that to OpZ and in both types of macrophages PGE2 was a more effective inhibitor of OpZ-induced chemiluminescence than of that induced by A23187. The response to OpZ in peritoneal macrophages was inhibited in a dose-related manner by both PGE2 and superoxide dismutase, but not by indomethacin, d-penicillamine, piroxicam or phenylbutazone. OpZ but not A23187, is a suitable stimulus for pharmacological studies on macrophage chemiluminescence.

Animals↗