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Christian Fink

Publications and source records attributed to Christian Fink.

62 records · Page 4Linked to original sources

Comparing dynamic parameters of tumor vascularization in nude mice revealed by magnetic resonance imaging and contrast-enhanced intermittent power Doppler sonography.

RATIONALE: Angiogenesis is essential for spread and growth of malignant tumors. Because noninvasive methods for observing tumor vascularization are limited, most of previous results were based on histologic findings alone. In this study, dynamic parameters obtained using intermittent contrast-enhanced Doppler sonography and dynamic MRI were compared and correlated with microvessel density. METHODS: Eleven tumor-bearing nude mice were examined with dynamic T(1)-weighted sequences using Gd-DTPA in a 1.5 T magnetic resonance (MR) scanner and with intermittent power Doppler sonography after a single bolus of galactose based contrast agent. After examination 6 tumors were harvested for immunofluorescence microscopy using a CD31 stain. Using a 2-compartment model, the MR parameters amplitude (reflecting plasma volume) and k(ep) (influenced by the vessel permeability) were calculated and compared with maximal enhancement (max) and perfusion P measured with ultrasound. RESULTS: The MR amplitude correlated with the ultrasound parameter max significantly (r = 0.61; P = 0.01). Max (r = 0.67; P = 0.01), amplitude (r = 0.72; P = 0.01), and perfusion (r = 0.62; P = 0.05) correlated with the microvessel density. k(ep) moderately correlated with max, but not with perfusion and microvessel density. CONCLUSIONS: Dynamic MRI and contrast enhanced ultrasound are supplementing methods for examining perfusion and vascularity of experimental tumors.

Animals↗

Structure-activity profiles of complex biantennary glycans with core fucosylation and with/without additional alpha 2,3/alpha 2,6 sialylation: synthesis of neoglycoproteins and their properties in lectin assays, cell binding, and organ uptake.

The consideration of oligosaccharides and glycoconjugates as biopharmaceuticals is an emerging topic in drug design. Chemoenzymatic synthesis of N-glycans was performed to examine the influence of N-glycan core fucosylation on lectin-binding properties and biodistribution. As a first step in a systematic comparison of N-glycans, the core fucose moiety was chemically introduced into a complex-type biantennary heptasaccharide azide. After deprotection and attachment of a spacer, the terminal sections of the N-glycan were elongated enzymatically. Conversion of the amino group in the spacer to an isothiocyanate gave derivatives allowing convenient ligand attachment to bovine serum albumin (BSA). The resulting neoglycoproteins contained an average of 2.9-4.6 chains per carrier molecule. Relative to unsubstituted biantennary complex-type N-glycans, the core fucosylation appears to favor the extended orientation of the alpha 1,6-arm. This was deduced from an up to 5-fold alteration of affinity for lectins in solid-phase assays. Marked differences were also found for cell surface binding of cultured tumor cells, for staining of tumor cells in lung sections, and in organ distribution. In vivo, the alpha 2,6-sialylated neoglycoproteins showed a reduced serum half-life in mice relative to the alpha 2,3-sialylated isomer and the non-fucosylated congeners. These results support the notion that changing the shape of a glycan provides a promising strategy to optimize the affinity of protein-carbohydrate interactions. Overall, our study underscores the importance of chemoenzymatic synthesis to define the effect of chain orientation on the ligand properties of N-glycans.

Animals↗

Urea as a passive transport marker for arthritis biomarker studies.

OBJECTIVE: To develop a method to correct for the unknown dilution of synovial fluid that occurs during lavage of a joint, we evaluated the utility of urea, a molecule that is neither synthesized nor metabolized by joint tissues, as a means of correcting for the dilutional effects of lavage procedures and effusions. METHODS: Joint fluids were obtained from normal canine joints by direct aspiration (n = 41) and lavage (n = 10). Acute joint injury was induced in 4 joints by intraarticular injection of chymopapain. Serum and joint fluid levels of urea and joint fluid concentrations of glucose, lactate, cartilage oligomeric matrix protein (COMP), and keratan sulfate (KS) were measured in these 55 joints. RESULTS: Urea concentrations in joint fluid were directly proportional to those in serum throughout a wide range of concentrations in normal joints. From this relationship, the dilution factor introduced by joint lavage was determined. This method was applied to quantify biomarker concentrations in synovial lavage fluid and was found to successfully correct for lavage-induced dilution of glucose, lactate, COMP, and KS to levels equivalent to those in samples aspirated directly. In the context of chymopapain-induced joint effusion, urea concentrations continued to be proportional to serum concentrations, but were much lower, enabling an estimation of the change in the volume of distribution (V(d)) of a marker due to a change in joint water content in the setting of inflammation characterized by effusion. Lactate and KS levels rose markedly in response to chymopapain. After adjustment for the V(d), the glucose concentration in the chymopapain-injected joints did not change. CONCLUSION: Urea provides a robust method of quantifying and correcting for the dilution of synovial fluid due to joint lavage or inflammation. This method is potentially applicable to surrogate marker studies in human arthritis.

Animals↗

Interstitial magnetic resonance lymphography with gadobutrol in rats: evaluation of contrast kinetics.

RATIONALE AND OBJECTIVE: To evaluate the contrast kinetics of gadobutrol for interstitial MR lymphography. MATERIALS AND METHODS: In 11 rats, 0.5 mL undiluted gadobutrol was injected subcutaneously into the hind paw. Contrast kinetics were measured in lymph nodes, kidney, liver, muscle, and blood of six animals using a time-resolved 2D GRE sequence. Additionally, high-resolution 3D T1-weighted data sets were obtained in five animals. RESULTS: Immediately after injection, a pronounced signal intensity loss was observed in popliteal, inguinal and aorto-iliac lymph nodes, followed by a continuous signal intensity increase. From the data peak concentrations of up to 78 mmol/L were estimated for selected lymph nodes. A contrast enhancement was also observed in kidneys, liver, muscle, and blood. Regional lymphatic vessels, the thoracic duct, as well as popliteal, inguinal, aorto-iliac, and axillary lymph node groups could be visualized with the high-resolution 3D MRI. CONCLUSION: Gadobutrol is suitable for interstitial MR lymphography, as it rapidly appears in the lymphatic system. Based on estimates of local tissue concentrations future studies have to assess the optimal contrast agent dosage. Furthermore, the investigation of metastatic lymph nodes is required to evaluate the further potential of gadobutrol for interstitial MR lymphography.

Animals↗

Clinical comparative study with a large-area amorphous silicon flat-panel detector: image quality and visibility of anatomic structures on chest radiography.

OBJECTIVE: The objective of this study was to compare clinical chest radiographs of a large-area, flat-panel digital radiography system and a conventional film-screen radiography system. The comparison was based on an observer preference study of image quality and visibility of anatomic structures. MATERIALS AND METHODS: Routine follow-up chest radiographs were obtained from 100 consecutive oncology patients using a large-area, amorphous silicon flat-panel detector digital radiography system (dose equivalent to a 400-speed film system). Hard-copy images were compared with previous examinations of the same individuals taken on a conventional film-screen system (200-speed). Patients were excluded if changes in the chest anatomy were detected or if the time interval between the examinations exceeded 1 year. Observer preference was evaluated for the image quality and the visibility of 15 anatomic structures using a five-point scale. RESULTS: Dose measurements with a chest phantom showed a dose reduction of approximately 50% with the digital radiography system compared with the film-screen radiography system. The image quality and the visibility of all but one anatomic structure of the images obtained with the digital flat-panel detector system were rated significantly superior (p < or = 0.0003) to those obtained with the conventional film-screen radiography system. CONCLUSION: The image quality and visibility of anatomic structures on the images obtained by the flat-panel detector system were perceived as equal or superior to the images from conventional film-screen chest radiography. This was true even though the radiation dose was reduced approximately 50% with the digital flat-panel detector system.

Humans↗

Incidental finding of a mucinous carcinoma of the breast by dynamic MRI in a patient with a history of breast trauma (horse bite): incidental mucinous carcinoma after breast trauma.

Occasional reports on the coincidence of previous trauma of the breast and the development of invasive breast cancer have been published. Furthermore, traumatic changes of the breast tissue can clinically and radiographically mimic malignant breast disease. We report of a 52-year-old female presenting with increasing mammographic microcalcifications after a trauma of the breast due to a horse bite. Dynamic MRI was able to exclude malignancy at the site of the trauma but did detect a clinically and radiographically nonsymptomatic mucinous carcinoma of the breast.

Adenocarcinoma, Mucinous↗

Preoperative staging of renal cell carcinoma with inferior vena cava thrombus using multidetector CT and MRI: prospective study with histopathological correlation.

OBJECTIVE: To evaluate the accuracy of multidetector computed tomography (CT) and magnetic resonance imaging (MRI) in staging and estimating renal carcinomas with caval thrombus. METHODS: Initially, 23 patients with suspected caval thrombi were admitted into this prospective study. Triphasic CT imaging was performed using a multidetector CT with a reconstructed slice thickness of 2 mm. 3D CT reconstructions were used to improve surgical planning. MRI protocol included: a transversal T1-weighted GE sequence with and without Gd-DTPA, a transversal T2-weighted respiratory-gated TSE, and a coronal T1-weighted GE sequence with Gd-DTPA and fat saturation. In addition, a multiphase 3D angiography was performed after Gd-DTPA injection. Patients were divided into 3 groups: caval thrombus below the insertion of the hepatic veins, within the intrahepatic vena cava, and intra-atrial extension. The results the tumor thrombus extension and staging results of 2 independent readers were correlated with surgical and histopathological staging. RESULTS: Of the 23 patients admitted, CT and MR scans of 14/13 patients respectively were correlated with histopathological workup. CT thrombus detection sensitivity and specificity for both readers was 0.93 and 0.8 respectively. MRI sensitivity and specificity for both readers was 1.0/0.85 and 0.75. Readers I and II evaluated the uppermost extension of the cranial tumor thrombus by both CT and MRI. CT and MR accuracy was 78% and 72%, 88% and 76% respectively. CONCLUSION: In cases of a suspected tumor thrombus, MRI and multidetector CT imaging showed similar staging results. Consequently, these staging modalities can be used to assess the extension of the tumor thrombus.

Adult↗