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M Schmitt

Publications and source records attributed to M Schmitt.

At least 37 records · Page 2Linked to original sources
PubMed2005

[T-cells activated with a trifunctional bi-specific antibody in head and neck cancer].

BACKGROUND: The trifunctional bi-specific antibody Removab bridges and activates CD3 positive T cells to EpCAM on carcinoma cells and simultaneously binds to an accessory immune cell, thus inducing tumor cell lysis. Following intravenous application, Removab may induce cytokine-related side effects resulting in a sepsis like syndrom. It was questioned, if peripheral mononuclear blood cells (PBMN) already opsonized with Removab could retain antitumor activity and induce less cytokine release than the mere antibody. METHODS: PBMN of patients with head and neck cancer were incubated with Removab and the released cytokines were washed out. Then the Removab-opsonized PBMN were coincubated with genuine tumor cells of the same patient on a chorioallantois membrane for 24 h (T 24) and 48 h (T 48). Tumor cells coincubated with Cisplatin or solely cell culture medium served as control. RESULTS: Coincubation of tumor cells with opsonized PBMN resulted in a 32 % decrease of viable cells at T 24 and a 37 % decrease at T 48, whereas viable cells increased by 10 % at T 24 or 3 % at T 48 when incubated with medium alone (p < 0.05). This tumor cytotoxicity was similar to that of Cisplatin (35 % at T 24/37 % at T 48). CONCLUSION: In an autologous human ex vivo tumor system, Removab-opsonized PBMN induce tumor cell lysis with significantly reduced cytokine release after i. v. application.

Adult↗
PubMed2005

Measurement of plasminogen activator system components in plasma and tumor tissue extracts obtained from patients with breast cancer: an EORTC Receptor and Biomarker Group collaboration.

The plasminogen activator (PA) system comprises the 2 serine proteases, urokinase PA (uPA) and tissue PA (tPA), the 2 serpin inhibitors, PAI-1 and PAI-2 and the uPA receptor (uPAR; CD87). High levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR in breast cancer tissue are associated with poor prognosis, while high levels of tPA or PAI-2 correlate with good prognosis. In this study, pre-operative plasma levels of uPA, PAI-1, uPAR, tPA, uPA-PAI-1 complex, and tPA-PAI-1 complex were measured in patients with benign (n=103) and malignant breast disease (n=113) by immunoenzymatic assays (ELISA). While plasma antigen levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR were not significantly different in the 2 groups, antigen levels of tPA and tPA-PAI-1 complex were significantly higher in patients with breast carcinoma compared to the control group. In plasma from the breast cancer patients, uPA levels correlated weakly but significantly with those of tPA (r=0.20, p=0.035) and uPAR (r=0.208, p=0.028). tPA levels correlated strongly with tPA-PAI-1 complex (r=0.972, p=0.0001) while uPA-PAI-1 levels were significantly associated with PAI-1 levels (r=0.534, p<0.0001), tPA levels (r=0.348, p=0.0003) and tPA-PAI-1 levels (r=0.356, p=0.002). However, no significant correlation was found between plasma and tumor tissue levels of uPA, PAI-1, uPA-PAI-1 complex, tPA or tPA-PAI-1. Our findings indicate that determination of these factors in plasma do not reflect their concentration in tumor tissue. Therefore, measurement of PA components in blood cannot be recommended for assessing prognosis in breast cancer.

Biomarkers, Tumor↗
PubMed2004

The application of a SERS fiber probe for the investigation of sensitive biological samples.

The applicability of an etched and silver or gold coated SERS fiber probe in combination with a commercially available laboratory micro-Raman setup or a home built mobile micro-Raman setup to perform on-site field measurements was evaluated and successfully tested on different biological samples. The SERS fiber probe allows one to perform measurements with high spatial resolution. Simultaneously, the laser power used for Raman spectroscopy on biological samples as compared with conventional Raman experiments can be reduced by more than two orders of magnitude. This experimental arrangement was tested to investigate sensitive biological samples like mint plants (Bergamot mint, spear mint) and citrus fruits (kumquat). Furthermore, traces of fungicides on wine leaves were detected by means of such a SERS fiber probe setup.

Animals↗
PubMed2004

Multimode pumped continuous-wave solid-state Raman laser.

We demonstrate the continuous-wave operation of a solid-state Raman laser containing a barium nitrate crystal as the Raman medium. The Raman laser, which has a singly resonant cavity, is pumped by multimode radiation. The Raman oscillation threshold is reached at approximately 2 W of pump power. As much as 500 kW/cm2 of Stokes power density at 60-kW/cm2 pump power density is obtained in the cavity.

Journal Article↗
PubMed2004

Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy.

A highly versatile setup, which introduces an optical gradient trap into a Raman spectrometer, is presented. The particular configuration, which consists of two lasers, makes trapping independent from the Raman excitation laser and allows a separate adjustment of the trapping and excitation wavelengths. Thus, the excitation wavelength can be chosen according to the needs of the application. We describe the successful application of an optical gradient trap on transparent as well as on reflective, metal-coated microparticles. Raman spectra were recorded from optically trapped polystyrene beads and from single biological cells (e.g., erythrocytes, yeast cells). Also, metal-coated microparticles were trapped and used as surface enhanced Raman spectroscopy (SERS) substrates for tests on yeast cells. Furthermore, the optical gradient trap was combined with a SERS fiber probe. Raman spectra were recorded from trapped red blood cells using the SERS fiber probe for excitation.

Erythrocytes↗
PubMed2004

[Comparison of urokinase type plasminogen activators (uPA) and plasminogen activator inhibitors (PAI-1) in primary resection of oral squamous cell carcinoma].

This article examines the distribution and prognostic importance of urinase type plasminogen activators (uPA) and of plasminogen activator inhibitors (PAI-1) in cases of primary oral squamous cell carcinoma. Tissue from the primary tumor was taken from 79 patients. In order to make an intra-individual comparison, tissue from the healthy mucous membrane of the mouth was taken from 50 patients and metastatic tissue from lymph glands in the neck from 16 patients. The content of uPA and PAI-1 was determined using ELISA. After follow-up, 58 patients with primary surgical therapy were included. Statistical evaluation was carried out using the Kruskal-Wallis test, the Mann-Whitney U-test and the Wilcoxon test. Pearson's product moment correlation was used to determine the relationship between uPA and PAI-1 levels. The median uPA value was 3.43 ng/mg in primary tumor, and for PAI-1 47.1 ng/mg ( n=79). There was a significant correlation between uPA and PAI-1 both in the cancerous as well as the healthy tissue ( P<0.01). The intra-individual comparisons showed uPA and PAI-1 differed significantly between cancerous and healthy tissue ( P<0.0001) with the mean uPA and PAI-1 values being nine times higher in the cancerous tissue ( n=58). The correlation for between uPA and PAI-1 in tumors, healthy tissue and metastatic lymph node tissue ( n=16) showed highly significant values in the tumors ( P<0.001). The comparison between cancerous tissue in the primary tumor and the lymph nodes was not significant for PAI-1. For uPA, the values in the lymph nodes were significantly lower ( P<0.049). There were also significantly higher levels in metastatic lymph node tissue compared with healthy mucous membrane ( P=0.005 for uPA and P=0.003 for PAI-1). There was no significant correlation of PAI-1 and uPA ( n=79) with the patient's sex, size of the tumor (T stage), nodal status (N stage), differentiation (grade), or residual tumor status. If the patients were divided into two groups (< or =58 years and >58 years), the older patients had higher uPA ( P<0.017) and PAI-1 ( P<0.02) levels. The was no significant association between tumor localisation and uPA content in the tumor; for PAI-1 the association was significant ( P<0.02) in the individual areas of the mouth. A total of 23 (40%) patients relapsed (local n=13, lymph node n=3, local and lymph node n=1, lymph node and skin n=1, other locations n=5). Such patients had raised uPA ( P=0.012) and PAI-1 ( P=0.014) levels in the primary tumor. The high variability of the normal clinical parameters in tumors only has a limited prognostic value because it is not taken into account in individual cases. Thus determination of the PAI-1 level directly after surgery could provide an indication of the likelihood of a relapse and thus aid in determining the adjuvant therapy. This confirms a trend in that tumor associated proteases can also play a key role in oral squamous cell carcinoma as new, independent, prognostic factors. Whether or not uPA and PAI-1 will play such a role will be determined in additional multicentre clinical studies.

Carcinoma, Squamous Cell↗
PubMed2004

[The prognostic importance of urinase type plasminogen activators (uPA) and plasminogen activator inhibitors (PAI-1) in the primary resection of oral squamous cell carcinoma].

This article examines the prognostic importance of urinase type plasminogen activators (uPA) and of plasminogen activator inhibitors (PAI-1) in cases of primary oral squamous cell carcinoma. Tissue samples were taken from the core of the tumour in 58 such primary surgical patients. The levels of uPA and PAI-1 were determined using ELISA. Statistical significance was calculated using the chi2- and log-rank tests. The mean follow-up (n=58) was 23 months. In order to determine prognostic value, the time before relapse was used. The mean time before relapse was 19 months. A total of 28 (40%) patients relapsed (local n=13, lymph node n=3, local and lymph node n=1, lymph node and skin n=1, other locations n=5). Such patients had significantly raised uPA (P<0.012) and PAI-1 (P<0.014) levels in the primary tumour. A optimal cutoff value for uPA (4.58 ng/mg) and PAI-1 (106.3 ng/mg) was determined using the multiple log-rank test. There was no significant correlation for patients with low or high levels (i.e. lower or higher than the cutoff value, respectively) with the usual clinical parameters such as localisation, N-stage, T-stage, differentiation and residual tumor status. Older patients (>58 years) had significantly higher levels of uPA and PAI-1 (P<0.017 and P<0.02, respectively). The likelihood of relapse was significantly higher in patients with high levels (uPA P<0.009, PAI-1 P<0.008). If the patients were divided into three groups depending on uPA and PAI-1 levels (group 1: uPA and PAI-1 low, n=35; group 2: uPA or PAI-1 high, n=12; group 3: uPA and PAI-1 high, n=11), relapses were more common in group 3 than in groups 1 or 2 (P<0.023). Patients with only surgical therapy (n=29) and those with postoperative radiotherapy (n=29) were used to evaluate postoperative follow-up. Cutoff levels were calculated for both groups. In the surgical therapy group this was uPA=5.63 ng/mg and PAI-1=106.3 ng/ml and in the surgical therapy plus radiotherapy group uPA=4.13 ng/mg and PAI-1=97.02 ng/mg. Kaplan-Meier curves showed a marked tendency for patients with higher levels to relapse more often. This is significant for surgical patients for PAI-1 (P<0.01) and for radiotherapy patients for uPA (P<0.04)

Carcinoma, Squamous Cell↗
PubMed2004

[Feasibilities and limitations of high field parallel MRI].

In medical magnetic resonance imaging (MRI) it is standard to use MR scanners with a field strength of 1.5 Tesla. Recently, an ongoing development to higher field strength can be observed and a new clinical standard at 3.0 Tesla seems to be established. High field MRI with its intrinsic higher signal to noise ratio (SNR) can enable new applications of MRI in medical diagnosis, or can serve to improve existing methods. It is important to note, that the use of high field MRI is not without its limitations. Besides the SNR, other unwanted effects increase with a higher field strength. Without correction, these high field problems cause a serious loss in image quality. An elegant way to address these problems is the use of parallel imaging. In many clinical applications, parallel MRI (pMRI) is part of the standard protocol, because pMRI can enhance virtually every MRI application, without necessarily affecting the contrast behavior of the underlying imaging sequence. In high field MRI, besides the speed advantage of pMRI, the positive influence on high field specific problems and therefore on the image quality will be of major importance.

Artifacts↗
PubMed2004

Comparative analysis between the HER2 status in primary breast cancer tissue and the detection of isolated tumor cells in the bone marrow.

The presence of isolated tumor cells in the bone marrow (ITC-BM) of breast cancer patients is an independent prognostic parameter, indicating hematogenous tumor cell dissemination. While the HER2 status of breast cancer tissue has predictive value for the efficacy of different therapies, its prognostic relevance is controversial. To investigate the relationship between HER2 and ITC-BM, we retrospectively analyzed tumor tissues of 327 patients who underwent bone marrow aspiration at primary diagnosis or during the disease-free interval. Screening for ITC-BM was performed immunocytochemically, using the anti-cytokeratin antibody A45 B/B3. HER2 was determined by immunohistochemistry (IHC) with the antibody CB 11 (n = 277) and by fluorescence in situ hybridization (FISH, PathVision, Vysis, n = 206). ITC-BM were found in 83 of 327 patients (25.4%), with a median of 2.0 per 2 x 10(6 ) mononuclear cells. HER2 positivity (2+ /3+ ) was demonstrated in 18.8% of the tumors, amplification by FISH in 56 of 206 cases (27.2%). Established pathological parameters,tiviathological parameters, such as tumor size (p = 0.15), lymph node status (p = 0.93) and HER2 did not predict the presence of ITC-BM. After a median follow-up of 49 months (1-255), the presence of ITC-BM was a significant prognostic factor for distant disease free and overall survival, as well in univariate (log-rank-test, p = 0.024) as in multivariate analysis (cox-regression, p = 0.033 ). This also was confirmed in subgroups of patients by aease free survival (p = 0.013) and local recurrence (p = 0.003). The detection of ITC-BM is superior in predicting overall survival, compared to the HER2 status of the primary tumor. The direct identification of HER2 on ITC-BM is the aim of ongoing research, potentially synergizing the prognostic relevance of ITC-BM and the predictive value of the HER2 status.

Adult↗
PubMed2004

Comparative study of the Yang-Monti channel and appendix for continent diversion in the Mitrofanoff and Malone principles.

PURPOSE: Continent conduits for Mitrofanoff and Malone procedures are widely used for incontinence management. Because the appendix is not always suitable or available, Monti proposed a transversely retubularized short segment of ileum. We present our experience and compare outcomes according to the type of conduit. MATERIALS AND METHODS: In a retrospective study from 1988 to 2003 case notes were reviewed specifying conduit characteristics, underlying disease, overall surgical management of incontinence and subsequent complications. Comparison was based on followup, details of complications and treatments. RESULTS: In 32 men and 14 women with a total of 65 conduits (Mitrofanoff in 41 and Malone procedure in 24) the condition was spina bifida in 29, bladder exstrophy in 5 and sacral agenesia in 3. Other cases included various origins. Mean age at operation was 14.2 years (range 1 to 31). Mean followup was 5.3 years (range 1 to 14.7). Appendix was used in 23 cases and a Yang-Monti channel was performed in 18 (ileum in 7 and sigmoid in 11) for urinary diversion. The Malone procedure was performed using appendix in 11 cases and a Yang-Monti tube in 13. At followup 61 conduits (93.8%) were in use and 4 (6.2%) were abandoned. Complications were cutaneous stenosis, kink blockage and stomal leakage. No significant differences were observed between the types and purposes of the conduit. CONCLUSIONS: With constant availability and various possibilities of construction the Yang-Monti channel is recommended for continent diversion creation when appendix does not look suitable or is already in use or absent.

Adolescent↗
PubMed2004

Terminal deletion of the long arm of chromosome 10.

The case of two female patients with de novo terminal deletion of the long arm of chromosome 10, one with del(10)(q26.2) and the other with del(10)(q26.3), is reported. Both presented with megabladder associated with urinary tract abnormalities. The case of four similar patients has been previously reported with bladder dilatation secondary to urinary obstruction. These new cases highlight the possible involvement of the bladder and the urethra in the syndrome of chromosome 10q terminal deletion, suggesting a careful renal and urinary tract evaluation in such situations. Moreover, the possibility of monosomy 10qter syndrome should be borne in mind in the case of prenatal diagnosis of apparently isolated bladder obstruction, especially in females.

Abnormalities, Multiple↗
PubMed2004

A novel test method for evaluation of the abrasive wear behaviour of total hip stems at the interface between implant surface and bone cement.

After total hip replacement, some cemented titanium stems show above-average early loosening rates. Increased release of wear particles and resulting reaction of the peri-prosthetic tissue were considered responsible. The objective was to develop a test method for analysing the abrasive wear behaviour of cemented stems and for generating wear particles at the interface with the bone cement. By means of the novel test device, cemented hip stems with different designs, surface topographies and material compositions using various bone cements could be investigated. Before testing, the cemented stems were disconnected from the cement mantle to simulate the situation of stem loosening (debonding). Subsequently, constant radial contact pressures were applied on to the stem surface by a force-controlled hydraulic cylinder. Oscillating micromotions of the stem (+/- 250 microm; 3 x 10(6)cycles; 5 Hz) were carried out at the cement interface initiating the wear process. The usability of the method was demonstrated by testing geometrically identical Ti-6A1-7Nb and Co-28Cr-6Mo hip stems (n= 12) with definite rough and smooth surfaces, combined with commercially available bone cement containing zirconium oxide particles. Under identical frictional conditions with the rough shot-blasted stems, clearly more wear particles were generated than with the smooth stems, whereas the material composition of the hip stems had less impact on the wear behaviour.

Biocompatible Materials↗
PubMed2004

Opsonization with a trifunctional bispecific (alphaCD3 x alphaEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM positive tumor cells by cytotoxic T lymphocytes.

Removab is a trifunctional bispecific antibody which can bridge CD3+ T cells and epithelial cell adhesion molecule positive (EpCAM+) tumor cells, and binds with its Fc fragment to antigen presenting cells. To explore a new approach for the treatment of patients with carcinoma of the upper aerodigestive tract, we investigated whether Removab can induce specific cellular responses to the EpCAM+ carcinoma cell line BHY. Particular emphasis was put on the opsonization of peripheral blood mononuclear cells (PBMN) with respect to clinical application. Tumor cells and allogeneic PBMN of healthy volunteers were incubated with or without Removab. In a third group, PBMN were opsonized with Removab and washed before incubation with tumor cells. Inverse microscopy, ELISPOT, flow cytometry analysis and cytotoxicity assays on the chorioallantois membrane (CAM) were performed. In comparison with PBMN alone, opsonization with Removab resulted in: a) activation of CD83+ antigen presenting cells, b) secretion of interferon gamma, and c) granzyme B mediated lysis of targeted BHY cells by EpCAM specific CD8+ T cells. The secretion of tumor necrosis factor alpha, interferon gamma and interleukin-2 by opsonized PBMN was significantly reduced after 24 h. Washed opsonized PBMN maintained their lytic activity against tumor cells as tested on the CAM. Removab is an appropriate agent for the therapeutic amplification of T cell responses against EpCAM+ tumor cells by opsonization of PBMN without putting patients at risk for severe adverse events caused by a cytokine storm.

Antibodies, Bispecific↗
PubMed2003

Efficient anti-Stokes generation through phase-matched four-wave mixing in higher-order modes of a microstructure fiber.

Phase-matched four-wave mixing in higher-order modes of microstructure fibers allows unprecedentedly high efficiencies of anti-Stokes frequency conversion to be achieved for subnanojoule femtosecond laser pulses. 70-fs pulses of 790-nm radiation were used to generate an anti-Stokes component at 520-530 nm in a higher-order mode of a microstructure fiber with a 4.8-microm core. The maximum ratio of the anti-Stokes signal energy to the energy of the pump component in the output spectrum is estimated as 1.7.

Journal Article↗
PubMed2003

Inhibition of cytochrome P450 3A: relevant drug interactions in gastroenterology.

Cytochrome P450 3A (CYP3A) is involved in biotransformation of more than half of all drugs currently available. Drug interactions by inhibition of CYP3A are of major interest in patients receiving combinations of drugs. Some interactions with CYP3A inhibitors also involve inhibition of the multidrug export pump, P-glycoprotein. An increasing number of adverse drug reactions might be avoided on the basis of knowledge about CYP3A substrates and inhibitors. This article summarizes some examples of such interactions relevant to gastroenterologists. Serious cases by coadministration of CYP3A inhibitors resulting in acute hepatitis, hypotension, rhabdomyolyis, torsade de pointes, sedation, or ergotism are presented: interactions with azole antifungals (ketoconazole, itraconazole, fluconazole), HIV protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir), macrolide antibiotics (clarithromycin, erythromycin), and grapefruit juice. In addition, 1 case is reported who presented the highest trough levels of the CYP3A substrate budesonide in serum ever measured. Practitioners have to be aware of the high potential of metabolic drug interactions when they prescribe a CYP3A inhibitor. It is wise to check carefully comedication in patients complaining of side effects with substrates of CYP3A.

Anti-Bacterial Agents↗