[Identification of tumor antigens: strategies and perspectives].
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Antigens, Neoplasm↗
Biomedical subjects
C Renner
Publications and source records attributed to C Renner.
[Functional outcome after decompressive craniectomy: a retrospective and prospective clinical study].
Decompressive craniectomy has been revived as a radical surgical treatment in increased ICP. While the life saving effect is undisputable, reports about the functional outcome are controversial. Furthermore, there are no data comparing the outcome of craniectomised patients with different aetiologies. In a retrospective and prospective study we assessed the functional outcome of craniectomised patients (41 stroke and 24 traumatic brain injury (TBI) patients). The majority of patients considerably benefits from the rehabilitation process. Nevertheless, most of them remained dependent upon caregivers. In stroke patients there was a significant negative correlation between age and outcome. Even though TBI were younger than stroke patients there were no outcome differences between these groups. We found no correlation between the side of the hemisphere injured and outcome.
Adult↗
Application of intraoperative 3D ultrasound during navigated tumor resection.
Intraoperative 3D ultrasound (3D-iUS) may enhance the quality of neuronavigation by adding information about brain shift and tumor remnants. The aim of our study was to prove the concept of 3D ultrasound on the basis of technical and human effects. A 3D-ultrasound navigation system consisting of a standard personal computer containing a video grabber card in combination with an optical tracking system (NDI Polaris) and a standard ultrasound device (Siemens Omnia) with a 7.5 MHz probe was used. 3D-iUS datasets were acquired after craniotomy, at different subsequent times of the procedure and overlaid with preoperative MRI. All patients underwent early postoperative 3D MRI including contrast agent within 24 hours after surgery. Acquisition of 3D iUS and the fusion with preoperative MRI was successful in 22/23 patients. The expenditure of time was at least 5 minutes for one intraoperative 3D US dataset. The technique was used three to seven times during surgery. The quality of the ultrasound images was superior in cases of metastasis, meningeoma and angioma over those in malignant glioma. Brain shifting ranged from 2-25 mm depending on localization and kind of tumor. A resection control was possible in 78%. All six neurosurgeons demonstrated a learning curve. The introduction of 3D ultrasound has increased the value of neuronavigation substantially, making it possible to update several times during surgery and minimize the problem of brain shift. Configuration of both the 3D iUS based on a standard ultrasound system and the MR navigation system is time- and especially cost-effective. Faster navigational datasets and more intuitive image-guided surgery enable novel and user-friendly display techniques.
Adult↗
New compact scrubber for odour removal in wastewater treatment plants.
This work presents the performances of a new odour scrubber. The reactor is packed with a new structure which enables co-current operations at high gas velocities. Energy consumption and removal efficiency of sulphur compounds by oxidative alkaline scrubbing were studied. The influence of both superficial gas (U(SG)) and liquid (U(SL)) velocities, ranging from 5.6 to 28 m.s(-1) and 0.016 to 0.055 m.s(-1) respectively, were quantified. Thus, the range of 0.5 to 5 liquid-to-gas mass ratio (L/G) was studied. A comparison has been made with a previous study on static mixers (SM) and with classical random packed towers (PT). It has been shown that superficial liquid and gas velocities have a significant influence on these parameters. Hydrogen sulphide (H2S) abatement reached values up to 99%. As concerns methylmercaptan (CH3SH), the maximal removal efficiency was 87%. As a result, if well scaled-up, our reactor can be a small single stage efficient apparatus for the elimination of low concentrations of sulphur compounds as H2S and CH3SH in high flow rates of polluted gas effluents.
Air Pollutants↗
Expression of RHAMM/CD168 and other tumor-associated antigens in patients with B-cell chronic lymphocytic leukemia.
Antigen targeted immunotherapies might represent a novel treatment for B-cell chronic lymphocytic leukemia (B-CLL). We screened the mRNA expression of tumor-associated antigens (TAAs) from the literature (fibromodulin, survivin, OFA-iLRP, BAGE, G250, MAGE1, PRAME, proteinase, syntaxin, hTERT, WT-1) and TAAs defined previously by serological analysis of cDNA expression libraries from leukemic cells (PINCH, HSJ2, MAZ, MPP11, RHAMM/CD168, NY-Ren60). Peripheral blood mononuclear cells from 43 B-CLL patients and 20 healthy volunteers (HVs) were examined by conventional and quantitative RT-PCR. mRNA of RHAMM/CD168, fibromodulin, syntaxin and NY-Ren60 was expressed in 55-90%, and mRNA of HSJ2, MAZ and OFAiLRP was expressed in 90-100% of the patients. No expression of WT-1, hTERT, BAGE, G250, MAGE1 or survivin was observed. Low (2-20%) expression frequencies of MPP11, PINCH, PRAME and proteinase were detected. RHAMM/CD168, fibromodulin, PRAME and MPP11 showed expression in B-CLL patients, but not in HVs. Because of the exquisite tissue expression of RHAMM/CD168 and its high expression frequency in CLL patients, mixed lymphocyte peptide culture (MLPC), enzyme-linked immunosorbent spot (ELISPOT) and flow cytometry were performed for antigen specific T-cells. In MLPC, RHAMM specific responses by CD8+HLA-A2/R3tetramer+CCR7-CD45RAhigh effector T-cells were detected. RHAMM/CD168 might be a possible target for future immunotherapies in both ZAP-70(+) and ZAP-70(-) B-CLL patients.
Adult↗
Engineering and characterisation of chimeric monoclonal antibody 806 (ch806) for targeted immunotherapy of tumours expressing de2-7 EGFR or amplified EGFR.
We report the generation of a chimeric monoclonal antibody (ch806) with specificity for an epitope on the epidermal growth factor receptor (EGFR) that is different from that targeted by all other anti-EGFR therapies. Ch806 antibody is reactive to both de2-7 and overexpressed wild-type (wt) EGFR but not native EGFR expressed in normal tissues at physiological levels. Ch806 was stably expressed in CHO (DHFR -/-) cells and purified for subsequent characterisation and validated for use in preliminary immunotherapy investigations. Ch806 retained the antigen binding specificity and affinity of the murine parental antibody. Furthermore, ch806 displayed enhanced antibody-dependent cellular cytotoxicity against target cells expressing the 806 antigen in the presence of human effector cells. Ch806 was successfully radiolabelled with both iodine-125 and indium-111 without loss of antigen binding affinity or specificity. The radioimmunoconjugates were stable in the presence of human serum at 37 degrees C for up to 9 days and displayed a terminal half-life (T(1/2beta)) of approximately 78 h in nude mice. Biodistribution studies undertaken in BALB/c nude mice bearing de2-7 EGFR-expressing or amplified EGFR-expressing xenografts revealed that (125)I-labelled ch806 failed to display any significant tumour retention. However, specific and prolonged tumour localisation of (111)In-labelled ch806 was demonstrated with uptake of 31%ID g(-1) and a tumour to blood ratio of 5 : 1 observed at 7 days postinjection. In vivo therapy studies with ch806 demonstrated significant antitumour effects on established de2-7 EGFR xenografts in BALB/c nude mice compared to control, and both murine 806 and the anti-EGFR 528 antibodies. These results support a potential therapeutic role of ch806 in the treatment of suitable EGFR-expressing tumours, and warrants further investigation of the potential of ch806 as a therapeutic agent.
Animals↗
Azobenzene as photoresponsive conformational switch in cyclic peptides.
Over the last decades azobenzene has been the most widely used optical trigger for the synthesis of photoresponsive systems ranging from poly-alpha-amino acids to innovative materials with light-controlled mechanical and optical properties. More recently, its use in form of appropriate derivatives allowed to generate cyclic peptide structures of constraint conformational space and thus to exploit its reversible photoisomerization to induce well defined transitions between different conformational states. These can be characterized in detail in both photostationary states making such systems ideal substrates for ultrafast spectroscopic analysis of conformational transitions. Moreover, the changes in biophysical properties that occur as a consequence of the different conformational states can be exploited for a photo-control of a large variety of molecular recognition processes.
Azo Compounds↗
Evaluation of intra-operative ultrasound imaging in brain tumor resection: a prospective study.
AIMS: The purpose of our study was to evaluate intra-operative ultrasound (IOUS) as a tool of resection control after brain tumor surgery. In addition, we looked for tumor species suitable for ultrasound representation. METHODS: Using a Siemens Omnia Sonoline Ultrasound, 36 tumors were examined, high-grade gliomas (62%), metastases (22%) and others (16%). We focused on tumor imaging by ultrasound with regard to its reliability of tumor expansion and margins. Evaluation of the images was carried out by correlating the ultrasound-based intra-operative measured tumor volume before and after resection with a pre- and post-operative (within 48 hours) measured volume by MRI. The IOUS measurements were performed by the neurosurgeon and the MRI measurements by the neuroradiologist. Thus, the measurement procedures were blinded. Corresponding to a deviation of the ultrasound volume by 10, 20 and > 20% from the MRI volume, the correlation was ranked good, moderate and poor. For assessing the agreement between these two methods of imaging, the statistical analysis was conducted using a method described by Bland and Altman. RESULTS: High-grade gliomas mostly showed a moderate or poor correlation in comparing IOUS- and MRI-tumor volumetry resulting in incomplete resection. Metastases resulted in a good to moderate correlation with a satisfactory extent of resection. The other tumors had poor images with larger tumor residues. The MRI measured volumes tended to be larger on average; the deviation grew with tumor size . CONCLUSION: The reliability of IOUS depends on tumor type. It is beneficial to use IOUS for the resection of metastases and a few high-grade gliomas. Concerning the volumetric accuracy, the value of IOUS is worse than its value of navigation and resection control.
Adolescent↗
Fatal bihemispheric intracerebral hemorrhage after burrhole evacuation of chronic subdural hematoma in a bone marrow-transplanted patient: case report and review of the literature.
BACKGROUND: Intracranial hemorrhage seems to be a relatively frequent complication following bone marrow transplantation (BMT). The neurosurgical management of these patients can be problematic. CASE DESCRIPTION: We report about a 46-year-old patient, who had BMT because of a Pre-T-ALL and who developed symptomatic bihemispheric chronic subdural hematomas (cSDHs). Pre-T-ALL is a form of an acute lymphatic leukemia of T cell type characterized by certain immunologic markers with a worse prognosis. A few hours after evacuation of the cSDHs, the patient developed a fulminant intracerebral hemorrhage on each hemisphere and expired 2 days later. We reviewed the literature reporting similar cases to discuss the indication for a neurosurgical intervention. CONCLUSION: We presume a higher incidence of intracranial hemorrhage in BMT patients than reported. This is caused by the pathologically altered parenchyma related to the extensive therapy in these patients. BMT patients are typically at high risk for intracranial bleeding and are treated conservatively or surgically. We cannot generally recommend the conservative management for symptomatic subdural hematomas/hygromas. The risk for an acute worsening, secondary to repeated hemorrhage, is equivalent to the risk of surgical intervention. Although the outcome of our case is tragic, it should not deter surgical intervention.
Bone Marrow Transplantation↗
Ultrafast conformational dynamics in cyclic azobenzene peptides of increased flexibility.
Structural changes of peptides containing the azobenzene dye 4-aminomethyl-phenylazobenzoic acid (AMPB) are studied with ultrafast spectroscopy. AMPB peptides are a new class of molecules where the photoisomerizable dye azobenzene is linked to the peptide moiety via a flexible methylene spacer. The ultrafast reactions in the femtosecond to nanosecond time domain are investigated for the optical switch AMPB, a linear and cyclic octapeptide, and a bicyclic octapeptide containing an additional disulfide bridge. These molecules with increasing conformational constraints are studied for the cis to trans and the trans to cis photoreactions. For the cis to trans reaction the isomerization of the chromophore occurs fast in the 1-ps range, whereas it is slower (10-ps range) in the trans to cis reaction. In all peptides the structural changes of the chromophore lead to modifications in the peptide structure in the 10-ps-1-ns time range. The results indicate that the chromophore AMPB acts simultaneously as a fast molecular switch and as a sensor for initial conformational dynamics in the peptide. Experiments in the mid-infrared range where the structural changes of the peptide backbone are directly observed demonstrate that the essential part of the structural dynamics in the bicyclic AMPB peptide occurs faster than 10 ns.
Amino Acid Sequence↗
Repetitive training of compensatory steps: a therapeutic approach for postural instability in Parkinson's disease.
BACKGROUND: Postural instability (PI) is a common and serious problem in Parkinson's disease (PD). Dopaminergic medication is of negligible use and a positive effect of deep brain stimulation on this issue has not been reported. OBJECTIVE: To develop a method of repetitive training of compensatory steps to enhance protective postural responses by using training strategies based on recent neurophysiological research. METHODS: Fourteen patients with PD took part in a multiple baseline design study and were trained for 14 days in an ambulant setting consisting of two daily sessions. RESULTS: After training, the length of compensatory steps increased and the step initiation shortened. In a gait analysis, the cadence and the step length increased, gait velocity improved, and the period of double support shortened. The "mobility" subscore of a quality of life questionnaire (PDQ-39) also improved. All these changes were significant (p < 0.05). These effects were stable for two months without additional training. CONCLUSION: The repetitive training of compensatory steps is an effective approach in the treatment of PI and should be applied if PI is evident clinically or in a patient's history.
Adult↗
Influence of cerebral oxygenation following severe head injury on neuropsychological testing.
Despite recent advances in the management of severe head injury the mortality and morbidity remains high. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are crucial parameters for the correct management at the intensive care unit, due to their therapeutic and prognostic importance. In addition, regional brain tissue oxygenation (ptiO2) seems to be of importance. While different studies demonstrated the impact of cerebral hypoxia on outcome (mortality), no data are available focusing on morbidity (neuropsychological deficits). Therefore, our study is carried out to demonstrate a possible relationship between amount of cerebral oxygenation during acute stage after severe head injury and neuropsychological outcome. Besides ICP and CPP, ptiO2 was monitored in 40 severely head injured patients during the ICU stay from the day of admission until day 10. Monitoring data were stored and amount of hypoxic episodes were calculated. Besides outcome using the Glasgow Outcome Scale neuropsychological testing was performed 2-3 years after injury. Analysing the quality of brain tissue oxygenation, a relationship to the performance in neuropsychological tests could be found. Patients with low brain tissue oxygenation had a worse outcome in neuropsychological testing, especially concerning intelligence and memory. Associated with these deficits patients showed a reduced performance in their profession. Our data suggest a possible predictive value of brain tissue oxygen on morbidity analysing neurocognitive function after head injury. This may implicate monitoring and treatment of cerebral hypoxia.
Adolescent↗
A33scFv-cytosine deaminase: a recombinant protein construct for antibody-directed enzyme-prodrug therapy.
A recombinant fusion protein of colon carcinoma binding A33 single chain antibody with cytosine deaminase displayed specific antigen binding and enzyme activity in surface plasmon resonance and is catalytic activity assay. In vitro, it selectively increased the toxicity of 5-FC to A33 antigen-positive cells by 300-fold, demonstrating the potency of this ADEPT strategy.
Antigens, Neoplasm↗
Clinical and epidemiological picture of B pertussis and B parapertussis infections after introduction of acellular pertussis vaccines.
AIMS: To investigate the clinical picture and frequency of Bordetella pertussis and B parapertussis infections after introduction of acellular pertussis (acP) vaccines in Germany. METHODS: Prospective surveillance for B pertussis and B parapertussis in 14 144 toddlers. Pertussis vaccination coverage was 86%, either with acP (75%) or whole cell pertussis (wcP) vaccine (11%). All children presenting with cough for more than seven days were examined for B pertussis and B parapertussis by culture, PCR, and serology (for cough duration > or =21 days). RESULTS: There were 180 Bordetella infections; 116 (64%) were caused by B pertussis and 64 (36%) by B parapertussis. Incidence rates were 4.8 and 2.8 per 1000 person-years, respectively. Paroxysmal cough, post-tussive whooping, and vomiting > or = 21 days was found in 53%, 22%, and 8% of all B pertussis cases and in 22%, 5%, and 0% of all B parapertussis cases, respectively. A total of 81/116 (70%) B pertussis cases and 56/64 (87.5%) B parapertussis cases had received at least one dose of pertussis vaccine. Typical pertussis with paroxysmal cough > or = 21 days was present in 29/35 (83%) unvaccinated B pertussis cases, in contrast to 33/81 (41%) vaccinated B pertussis cases. CONCLUSION: Following the increase of pertussis vaccination coverage, we observed a relative increase of B parapertussis cases in comparison to B pertussis cases. In vaccinated children B pertussis disease frequently presented as a mild disease, clinically difficult to distinguish from diseases associated with coughing caused by B parapertussis and other viral or bacterial infections.
Bordetella Infections↗
Stromal antigen targeting by a humanised monoclonal antibody: an early phase II trial of sibrotuzumab in patients with metastatic colorectal cancer.
BACKGROUND: A novel immunological approach to colon cancer therapy is the antibody targeting of the fibroblast activation protein (FAP), which is highly expressed by stroma cells of this tumour. Unconjugated sibrotuzumab (BIBH 1), which is a humanised version of the murine anti-FAP mAb F19, was investigated for its anti-tumour activity, safety and pharmacokinetics. PATIENTS AND METHODS: Patients with metastatic colorectal cancer received weekly intravenous infusions of unconjugated sibrotuzumab at a dose of 100 mg over 12 scheduled weeks. The study was implemented as an open-label, uncontrolled, multicentre trial. RESULTS: 25 patients were enrolled. Patients had one or more measurable lesions, predominantly liver lesions, at baseline. At least 8 repeated weekly infusions of sibrotuzumab in 17 evaluable patients did not result in complete or partial remission. Rather, ongoing tumour progression was noted in all patients except for 2 patients with stable disease. However, progressive disease was also observed post-study in these 2 patients who received 1 and 6 additional infusions, respectively, of sibrotuzumab. Sibrotuzumab exhibited 2-compartment pharmacokinetics with a dominant terminal phase and t1/2 beta = 5.3 +/- 2.3 days. Adverse drug reactions (rigors/chills, nausea, flushing and one incidence of bronchospasm) were observed in 5 patients. Of the 24 patients given 2 or more infusions of sibrotuzumab, antibodies against sibrotuzumab were found in 3 patients (12.5%) after 4-12 infusions. CONCLUSIONS: Sibrotuzumab was well tolerated and safe. The minimal requirement for the continuation of this exploratory trial, of at least one complete or partial remission, or equivalently, of 4 patients with stable disease, was not met.
Aged↗
[Minimally invasive therapy of obstruction of the kidney pelvis].
We report on 109 patients with ureteropelvic junction obstruction (UPJO) treated according to the following algorithm: intrinsic stenoses were treated by laser endopyelotomy (LEP). We used retroperitoneoscopy with ureterolysis to manage significant extrinsic UPJO due to a crossing vessel and either non-dismembered pyeloplasty in cases of an anterior vessel or dismembered pyeloplasty in cases of a posterior crossing vessel. Children were mostly treated by open dismembered pyeloplasty. Analysis of the factors that influence the postoperative results in the group of 64 patients treated by LEP showed significance for the presence of extrinsic causes of UPJO and the underlying grade of hydronephrosis. Based on our own results and the review of the literature, minimally invasive approaches for the management of UPJO have been proven safe and effective with results comparable to open surgery.
Adolescent↗
Systematic search and molecular characterization of the antigenic targets of myeloma immunoglobulins: a monoclonal IgA from a female patient targeting sperm-specific cylicin II.
The identification of the antigenic stimuli of B-cell neoplasms might be of considerable importance since a causal relationship between these neoplasms and antigenic stimulation has been suggested. To date the identification of such antigens has been erratic and accidental. For a systematic search and molecular characterization of human proteins that are antigenic target structures of myeloma-associated immunoglobulins, we applied SEREX (serological analysis of antigens by recombinant cDNA expression cloning) using a testis cDNA expression library and myeloma proteins from 42 patients. A monoclonal IgA from a female patient was shown to target sperm-specific cylicin II. The specificity of the reaction was confirmed by the characteristic staining of the equatorial belt of human sperm heads by the patient's myeloma protein. Serological analysis of recombinantly expressed cDNAs is a straightforward and high throughput approach for the molecular characterization of the targets of myeloma-associated immunoglobulins. The analysis of the antigenic spectrum of immunoglobulins associated with B-cell neoplasms will provide valuable information for the understanding of the pathogenesis of these diseases.
Aged↗
Linear and field-independent relation between vortex core state energy and gap in Bi(2)Sr(2)CaCu(2)O(8+delta).
We present a scanning tunneling spectroscopy study on quasiparticle states in vortex cores in Bi(2)Sr(2)CaCu(2)O(8+delta). The energy of the observed vortex core states shows an approximately linear scaling with the superconducting gap in the region just outside the core. This clearly distinguishes them from conventional localized core states and is a signature of the mechanism responsible for their discrete appearance in high-temperature superconductors. The energy scaling of the vortex core states also suggests a common nature of vortex cores in Bi(2)Sr(2)CaCu(2)O(8+delta) and YBa(2)Cu(3)O(7-delta). Finally, these states do not show any dependence on the applied magnetic field between 1 and 6 T.
Journal Article↗