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  • 1
    Abstract: Chronic lymphocytic leukemia is a malignancy of mature B cells that strongly depend on microenvironmental factors and their deprivation has been identified as promising treatment approach for this incurable disease. Cytokine array screening of 247 chronic lymphocytic leukemia serum samples revealed elevated levels of TNF receptor-1 which were associated with poor clinical outcome. We detected a microenvironment-induced expression of TNF receptor-1 in chronic lymphocytic leukemia cells in vitro and aberrantly high expression of this receptor in proliferation centers of patients' lymph nodes. Stimulation of TNF receptor-1 with TNF-alpha enhanced NFkappaB activity and viability of chronic lymphocytic leukemia cells which was inhibited by wogonin. Therapeutic effects of wogonin were analyzed in mice after adoptive transfer of Em-TCL1 leukemic cells. Wogonin treatment prevented leukemia development when given early after transplantation. Treatment of full-blown leukemia resulted in loss of TNF receptor-1 on chronic lymphocytic leukemia cells and their mobilization to blood. Targeting TNF receptor-1 signaling is therefore proposed for treatment of chronic lymphocytic leukemia.
    Type of Publication: Journal article epub ahead of print
    PubMed ID: 29326123
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  5th International Conference for Research in Medical Education (RIME 2017); 20170315-20170317; Düsseldorf; DOCP13 /20170307/
    Publication Date: 2017-03-07
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 3
    Abstract: Chronic lymphocytic leukemia is a malignancy of mature B cells that strongly depend on microenvironmental factors, and their deprivation has been identified as a promising treatment approach for this incurable disease. Cytokine array screening of 247 chronic lymphocytic leukemia serum samples revealed elevated levels of tumor necrosis factor (TNF) receptor-1 which were associated with poor clinical outcome. We detected a microenvironment-induced expression of TNF receptor-1 in chronic lymphocytic leukemia cells in vitro, and an aberrantly high expression of this receptor in the proliferation centers of patients' lymph nodes. Stimulation of TNF receptor-1 with TNF-alpha enhanced nuclear factor kappa-light-chain-enhancer of activated B cells (NFkappaB) activity and viability of chronic lymphocytic leukemia cells, which was inhibited by wogonin. The therapeutic effects of wogonin were analyzed in mice after adoptive transfer of Emu-T-cell leukemia 1 (TCL1) leukemic cells. Wogonin treatment prevented leukemia development when given early after transplantation. The treatment of full-blown leukemia resulted in the loss of the TNF receptor-1 on chronic lymphocytic leukemia cells and their mobilization to blood. Targeting TNF receptor-1 signaling is therefore proposed for the treatment of chronic lymphocytic leukemia.
    Type of Publication: Journal article published
    PubMed ID: 29326123
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  • 4
    ISSN: 1435-0130
    Keywords: Keywords Orbital volume ; Zygoma ; Enophthalmos ; Blow-out fracture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aims of this study were (1) to assess the difference between the volume of the traumatized and non-traumatized orbit, (2) to determine the critical change in orbital volume that will result in enophthalmos, and (3) to analyze the correlation between volume discrepancy and clinical outcome in maxillofacial trauma patients. Twenty-seven surgically managed patients with a fracture of the orbitozygomatic complex were included in this study. Preoperative and postoperative volume measurements of both orbits were compared, using software whose accuracy was confirmed in a preliminary experimental study in dry skulls. The correlation between volume discrepancy and clinical enophthalmos was statistically assessed before and after surgery. Preoperatively, there was an increase in orbital volume in 26 of 27 cases, with a range of 0.04–6.02 cc compared with the intact orbits. The mean volume difference between the orbits was 3.01±1.64 cm3 in the preoperative period, and this decreased to 1.02±1.29 cm3 following operation (P〈0.01). Five patients (19%) showed clinical enophthalmos with a mean volume difference of 4.77±0.18 cm3 preoperatively. Clinical enophthalmos persisted postoperatively in only one of five enophthalmic patients, in whom the volume discrepancy was greater than 4 cm3. Our data suggested that the technique described here is an easy and accurate method of assessing the volume of the orbit. Orbital volume measurement may help the surgeon to predict volume to be restored and to avoid probable complications.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1590-3478
    Keywords: Key words Atrial fibrillation ; Stroke ; Coagulation ; Fibrinolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Atrial fibrillation (AF) is a well-defined risk factor for ischemic stroke. Patients with lone AF represent a subgroup of AF patients with the lowest lifelong stroke risk. Nonvalvular atrial fibrillation (NVAF) confers a hypercoagulable state resulting in an increased risk of thromboembolism. This study was performed to determine the contributory role of alteration in the hemostatic markers of thrombin generation and fibrinolysis in patients with lone AF during acute ischemic stroke episode. We studied thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) concentrations in patients with acute middle cerebral artery ischemic stroke due to atherosclerotic large artery disease (n=50), lone AF (n=24) and cardioembolism (n=21). The values were compared with those of age-matched control subjects with lone AF and sinus rhythm (n=21 and 15, respectively). The mean F1+2 concentration was higher in the control subjects with lone AF in comparison with those without AF (p=0.014). Patients with stroke due to possible cardioembolism, from lone AF or other causes, had higher TAT (and marginally higher F1+2) concentrations than those with atherosclerotic stroke (p〈0.001). tPA concentrations were not different among groups (p=0.89). PAI-1 levels were marginally higher in stroke patients with lone AF and atherothrombotic large artery disease compared to the controls without AF (p=0.05). These results suggest that in the acute period of ischemic stroke secondary to lone AF, enhancement of the coagulatory activity occurs as a result of increased thrombin generation, similar to other possible sources of cardioembolism. Observed hemostatic alterations in acute ischemic stroke associated with lone AF may indicate some therapeutic and prognostic implications.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0006-3592
    Keywords: optical cell density probes ; turbidity probes ; on-line monitoring ; in situ probes ; mammalian cell bioreactors/fermentors ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: On-line optical cell density probes were implemented to continuously monitor the cell densities in mammalian cell bioreactor and to achieve advanced bioreactor controls. We tested cell density probes from six manufacturers in high cell density bioreactors. When externally calibrated, Aquasant and Ingold backscattering probes produced the most linear probe responses (PR) versus cell density (CD), followed by the ASR and Cerex laser probes. Monitek and Wedgewood transmission probes had lower resolutions. All probes were tested in two murine hybridoma fermentations. Cell densities varied between 1 × 106 cells/mL to 20 × 106 cells/mL and the bioreactors were operated for 5 to 7 weeks. For our bioreactors, Aquasant, Ingold, ASR, Wedgewood, and Monitek probes gave satisfactory responses. Little fouling was observed with any probe at the end of 2 weeks. Fouling was a possibility after 3 weeks in one bioreactor but its effect can be easily corrected. Cell density control and specific perfusion control of bioreactors based on the Aquasant probe were achieved. Implementation of cell density probe based perfusion control, instead of “step perfusion adjustments” based on manual hemacytometer control, will result in smoother operation, healthier cultures, increased medium delivery efficiency, and reduced operational excursions. © 1995 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0006-3592
    Keywords: glucose ; lactate ; on-line monitoring ; mammalian cell culture ; fermentation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: On-line monitoring and control of cell culture fermentation is important for optimal and consistent production of biologicals. In this work, glucose and lactate concentrations are monitored on-line using a commercially available analyzer (Model 2700, Yellow Springs Instruments, Yellow Springs, OH) during batch and perfusion hybridoma cell fermentation. Cell free samples from the reactor are obtained using a 0.45 μm hollow fiber filtering system placed in a circulation loop. The samples were analyzed at specified times and the data are collected on a computer. A process control strategy was developed to control the concentrations of glucose and lactate in a perfusion reactor where the feed rate is adjusted to maintain their concentrations at desired set points. Hybridoma cells (A10G10) were cultivated in a high density perfusion culture where cell density increased from 2 to 14 million cells/mL. During this period the control algorithm successfully adjusted the perfusion rate while maintaining constant glucose and lactate concentrations. Glucose consumption and lactate accumulation rates as well as net lactate yield on glucose were monitored continuously during perfusion culture. These metabolic rates were observed to be independent of cell concentration and were used for the estimation of viable cell density in the reactor. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 372-378, 1997.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0006-3592
    Keywords: one-line monitoring ; fermentation ; cell culture ; monoclonal antibodies ; real-time immunoassays ; BioCad/RPM ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: On-line, “real-time” monitoring of product concentration is important for mammalian cell culture fermentation. The continuous measurement of monoclonal antibodies allows for instantaneous determination of cell productivity and effective manipulation of the fermentor operating conditions for optimal production. This article will present the evaluation and application of a BioCad/RPM system (Per Septive Biosystems) for rapid analysis of lgG concentration for hybridoma cell cultivation. Several commercial crossflow filtration devices are tested for low protein retention and fouling properties. A protein G column is used successfully for analyzing about 400 samples of lgG1, without significant loss in separation efficiency. The Immuno Detection system is integrated into a computer-controlled 15-L fermentor. This fermentor could be operated in batch and perfusion modes with cell densities up to 20 million cells/mL. A continuous cell-free sample stream obtained by a hollow fiber filter system is introduced to the BioCad/RPM for analysis. The speed of this system allows for real-time monitoring even at high densities with fast dynamics. A murine hybridoma cell (A10G10) is cultivated in batch and continuous reactors and antibody concentration is measured continuously with complete sterility. The results are compared to offline measurements with good agreement. © 1995 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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