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Biomedical subjects

T Albrecht

Publications and source records attributed to T Albrecht.

At least 19 recordsLinked to original sources

[Stimulated acoustic emissions with the ultrasound contrast medium levovist: a clinically useful contrast effect with liver-specific properties].

PURPOSE: The purpose of this study was systematically to investigate stimulated acoustic emission (SAE) with the microbubble contrast agent Levovist (Schering AG, Berlin) in vivo with regards to reproducibility, distribution in various organs over time, dependence on technical factors, and influence on the delineation of focal liver lesions. PATIENTS AND METHODS: 2 intravenous injections of 1 g of Levovist were given to 2 dogs and 1-6 injections of 2.5 g Levovist to 5 healthy volunteers and 37 patients. The liver, spleen, large abdominal vessels, and kidney were intermittently scanned for up to 30 min. Studies were evaluated for the presence of SAE signals by 2 observers. In 20 patients with focal liver lesions (15 with metastases, 4 haemangiomata, 1 hepatocellular carcinoma, and 1 cyst) the influence on lesion visualization was also assessed. RESULTS: SAE effects, lasting up to 30 minutes, were seen in all subjects in the liver and spleen. Vascular and renal SAE signals were noted shortly after injection, lasting up to 6 minutes. SAE was absent or markedly reduced in focal liver lesions, which were seen as colour voids. This increased the conspicuity of focal lesions, and in 5 patients additional metastases were detected that could not be delineated on B-mode alone. CONCLUSION: A liver- and spleen-specific late phase of Levovist can be consistently demonstrated using SAE and the effect increases the conspicuity of focal liver lesions.

Adult↗

[Superparamagnetic iron oxide enhanced MR angiography of the portal vein system].

PURPOSE: Superparamagnetic iron oxide (SPIO) is used for the detection of focal liver lesions. The current study examines whether the blood-pool effect of an approved substance is adequate for contrast-enhanced MR angiography of the portal venous system. METHODS AND MATERIALS: Fifteen patients [9 women, 6 men, mean age 57 (34-73)] were examined with a breathhold 3D-FISP sequence (TR/TE/FA; 5 ms/2 ms/25 degrees) at 1.5 Tesla (Vision; Siemens, Erlangen) during the last third of a half-hour Infusion of a standard dose (15 mumol Fe/kg) of AMI-25 (Endorem, Guerbet Co., France). The image quality of source images and 3D reconstructions was evaluated by two examiners using a 3-point scale. RESULTS: Large vessels (portal vein, left and right branch of the portal vein, superior mesenteric vein, splenic vein) are visualized well or adequately in 80-93% of the cases, while this was achieved in only 53-60% of the small veins (vessels of the first order emptying into the superior mesenteric vein and the spleen). Venous arcades of the mesenterium are not visible by this technique. CONCLUSION: SPIO-supported MRA of the portal venous system yields usable results in the majority of patients. A possible indication is preinterventional angiography together with an SPIO examination for the detection of focal liver lesions.

Adult↗

B-mode enhancement at phase-inversion US with air-based microbubble contrast agent: initial experience in humans.

Pulse- or phase-inversion ultrasonography (US) sums the signals returned from two 180 degrees ultrasound pulses. Linear scattering from tissue results in a signal void while nonlinear signals from microbubbles stand out. The technique was applied with a US contrast agent in 39 human subjects. B-mode enhancement of vessels and organ parenchyma was seen in all cases. Enhancement occurred from flowing and stationary microbubbles. The flow-independent enhancement of normal and abnormal tissue represents a major advance in contrast material-enhanced US with many potential applications especially in tumor imaging.

Adult↗

Non-invasive diagnosis of hepatic cirrhosis by transit-time analysis of an ultrasound contrast agent.

BACKGROUND: Hepatic cirrhosis is accompanied by several haemodynamic changes including arterialisation of the liver, intrahepatic shunts, pulmonary arteriovenous shunts, and a hyperdynamic circulatory state. We postulated that the hepatic first pass of a bolus of an ultrasound contrast agent injected into a peripheral vein is accelerated in patients with cirrhosis. We investigated this first pass in patients with diffuse liver disease and in normal controls to assess whether it provides useful differential diagnostic information. METHODS: We enrolled 15 patients with biopsy-proven cirrhosis, 12 patients with biopsy-proven non-cirrhotic diffuse liver disease, and 11 normal controls. We carried out continuous spectral doppler ultrasonography of a hepatic vein from 20 s before to 3 min after a peripheral intravenous bolus injection of 2.5 g Levovist. The intensity of the doppler signal was measured and used to plot time-intensity curves. FINDINGS: Patients with cirrhosis showed a much earlier onset of enhancement (arrival time; mean 18.3 s) and peak enhancement (mean 55.5 s) than controls (49.8 s and 97.5 s) or patients with non-cirrhotic diffuse liver disease (35.8 s and 79.7 s). All patients with cirrhosis had an arrival time of the bolus of less than 24 s, whereas the arrival time was 24 s or more in 22 of the 23 other participants. Peak enhancement was higher in patients with cirrhosis (mean 48.7 units) than in the other two groups (12.5 and 12.3 units, respectively). We found highly significant differences between the patients with cirrhosis and each of the other two groups for all variables (p<0.005), whereas we found no significant differences between non-cirrhotic patients and controls. INTERPRETATION: Our preliminary study suggests that analysis of liver transit time of a bolus of ultrasound contrast agent provides useful information about haemodynamic changes in patients with cirrhosis. Measurement of the arrival time of the bolus allows discrimination of patients with cirrhosis from controls and from patients with non-cirrhotic diffuse liver disease, and has potential as a non-invasive test for cirrhosis.

Adult↗

MRI in neuro-Behçet's syndrome: comparison of conventional spin-echo and FLAIR pulse sequences.

We compared the sensitivity of a fluid-attenuated inversion-recovery (FLAIR) sequence with that of a conventional dual-echo spin-echo (SE) sequence) to brain lesions in 20 patients with Behçet's syndrome. They underwent 25 MRI examinations. The images were independently analysed for the number, type and anatomical location of lesions shown. There were 18 abnormal studies (13 initial and 5 follow-up). The FLAIR sequence detected significantly more lesions than the SE TE 80 (P < 0.05) and SE TE 20 (P < 0.01) sequences. It was particularly useful for demonstrating lesions in the juxtacortical white matter, which accounted for over half the lesions detected on the FLAIR images. Of patients presenting with nonspecific symptoms such as headache, seven had normal and five had abnormal studies. All patients presenting with focal neurological signs had abnormal imaging. We found supratentorial and, in particular, juxtacortical lesions to be more frequent than previously described.

Adult↗

Stimulated acoustic emission to image a late liver and spleen-specific phase of Levovist in normal volunteers and patients with and without liver disease.

Quantitative studies were performed to investigate liver- specific uptake of the microbubble Levovist, using stimulated acoustic emission (SAE), which can detect microbubbles even when stationary or slow-moving. These comprised studies of biodistribution comparing the liver and kidney in five normal volunteers, reproducibility in 34 patients, comparison between cirrhotics and controls (n = 9 each) and maximal depth of effect at different frequencies (180 measurements in 31 patients). Stimulated acoustic emission lasted beyond 30 min, with strongly liver-specific properties in each volunteer and was highly reproducible. No difference in the amount of SAE in the superficial liver was seen between cirrhotic and normal livers, but attenuation was higher in cirrhotics. This demonstrates a frequency-dependent effect on liver SAE penetration. We conclude that the liver uptake of Levovist lasts over 30 min, is reproducible, occurs even where diffuse liver disease is present and can be used to assess tissue attenuation in a novel fashion.

Adult↗

Functional renal perfusion imaging with colour mapping: is it a useful adjunct to spiral CT of in the assessment of abdominal aortic aneurysm (AAA)?

AIM: To ensure optimal timing with pre-operative spiral CT for abdominal aortic aneurysms (AAA), an initial 'timing' single level CT is commonly performed with a small bolus of contrast. This can be exploited to obtain adjunct functional information on renal perfusion. We have investigated the potential of this to measure renal perfusion, to produce colour renal perfusion maps and to predict surgical outcome in infrarenal aortic aneurysm assessment. METHODS: We studied 21 patients being assessed for repair of infrarenal AAA. Prior to the spiral CT, a single level through the renal hili and aorta was scanned after the intravenous injection of 25 ml of contrast given at 10 ml/s. Ten 1 s duration scans were performed from 8 to 30 s after injection. Optimal timing for CT angiography can then be determined. Time-density curves were then drawn for both kidneys and aorta using regions of interest (ROIs) or pixel-by-pixel analysis. Renal cortical perfusion was measured using both ROI analysis and pseudocolour perfusion images. Following previous work, perfusion was calculated as the peak upslope of the tissue time density curve divided by peak aortic enhancement. RESULTS: Cortical mean perfusion averaged 2.48 ml/min per ml (range 0.8-3.7 ml/min per ml n = 34) and the values obtained agreed with literature expectations. Follow up in the 10 patients proceeding to AAA repair suggest low mean perfusion values and predict a raised postoperative creatinine (P < 0.05) CONCLUSIONS: Additional functional data and imaging can be obtained from the initial timing scan of a CT study, without requiring a dedicated study.

Aged↗

Improved imaging of liver metastases with stimulated acoustic emission in the late phase of enhancement with the US contrast agent SH U 508A: early experience.

PURPOSE: To see whether stimulated acoustic emission (SAE) in the liver parenchyma in the late phase of enhancement with SH U 508A increases the conspicuity of occult metastases at ultrasonography (US). MATERIALS AND METHODS: Eighteen patients with known hypo- or hypervascular hepatic metastases underwent US after SH U 508A administration, after a delay of at least 5 minutes, to ensure decay of blood pool enhancement. In 16 patients with visible metastases, conspicuity was compared on registered SAE and gray-scale scans by two blinded readers and by using computerized analysis of relative gray-scale and color Doppler conspicuity scores inside and outside the lesion. In nine patients, areas suspected of being involved but without definite gray-scale masses were imaged in the same way. Paired sections were analyzed by two blinded readers looking for parenchymal color defects without corresponding gray-scale masses; nine control images from three healthy volunteers were also included. RESULTS: Intense, transient parenchymal SAE was seen in all subjects. All metastases appeared as areas of reduced or absent signal. The conspicuity score was 80% for SAE versus 9% for gray-scale US (P < .001, Wilcoxon signed rank test). SAE-specific defects were seen in all patients but in none of the volunteers. Metastases seen on SAE but undetectable on gray-scale images were proved in three patients. CONCLUSION: SAE with SH U 508A improves the conspicuity of metastases. SAE-specific defects may reveal isoechoic or subtle metastases.

Biopsy↗

MR angiography with superparamagnetic iron oxide: feasibility study.

Magnetic resonance (MR) angiography with blood-pool superparamagnetic iron oxide (SPIO) particles was evaluated in the whole-body vascular system. In 12 adult patients, three-dimensional fast imaging with steady-state precession was performed in successive steps from the lungs to the calves before and after a standard dose for liver imaging (15 mumol of iron per kilogram of body weight) of AMI-25. On SPIO-enhanced MR angiograms, visualization of the pulmonary arterial, whole-body, and lower extremity venous systems was graded as good or sufficient in all patients, and femoral vein thrombosis was clearly demonstrated in one patient.

Adult↗

The cyclin E promoter is activated by human cytomegalovirus 86-kDa immediate early protein.

Human cytomegalovirus (HCMV) activates cyclin E/Cdk2, which regulates cell cycle progression in G1 and S phase of the cell cycle. HCMV activation of cyclin E/Cdk2 can be demonstrated in cells that are refractory to normal mitotic stimuli. This observation suggests that the virus has some means to overcome the stringent control on expression of cell cycle progression factors that is characteristic of cells in the G0 state. One of the mechanisms involved in activation of cyclin E/Cdk2 is the induction of cyclin E expression. We report here that HCMV induces cyclin E expression through a transcriptional mechanism. The cyclin E gene is activated by the HCMV 86-kDa immediate early gene product (IE86), which directly binds to nucleotide sequences within the cyclin E promoter. An IE86 DNA-binding mutant neither binds nor activates the cyclin E promoter. IE86-binding sites within the cyclin E promoter are required for IE86-mediated activation, and deletion of the IE86-binding site inhibits IE86 activation of the cyclin E promoter. We also demonstrate that mutation of the known E2F-binding sites in the cyclin E promoter does not block activation by HCMV or IE86. These data provide a molecular mechanism for HCMV induction of cyclin E and represent the first report of IE86 directly binding to a cellular promoter.

Base Sequence↗

Homodimers and heterodimers of Pho1-type phosphorylase isoforms in Solanum tuberosum L. as revealed by sequence-specific antibodies.

Higher plants possess two types of glucan phosphorylase (EC 2.4.1.1). One isozyme type, designated as Pho1, is located in the plastid whereas the other type, Pho2, is restricted to the cytosol. For Solanum tuberosum L. two Pho1 type phosphorylases have been sequenced [Nakano, K. & Fukui, T. (1986) J. Biol. Chem. 261, 8230-8236; Sonnewald, U., Basner, A., Greve, B. & Steup, M. (1995) Plant Mol. Biol. 27, 567-576]. Both proteins (referred to as Pho1a and Pho1b, respectively) are highly similar (81-84% amino acid identity over most parts of the two sequences) with the exception of the N-terminal transit peptide and the large insertion located between the N- and the C-terminal domains. In this communication antibodies that bind specifically to either Pho1a or Pho1b were used to study both isoforms at the protein level. The antibodies were applied to both potato tuber and leaf extracts following either denaturing or non-denaturing electrophoresis. Pho1a but not Pho1b was immunochemically detectable in tuber extracts whereas leaf extracts contained both the Pho1a and Pho1b protein. During denaturing electrophoresis the two antigens comigrated. When the leaf Pho1 isoforms were separated by affinity electrophoresis three bands of activity were resolved; all of them were recognized by the anti-Pho1a antibodies, but only two of these reacted with the anti-Pho1b antibodies. The isoform binding exclusively to the anti-Pho1a antibodies comigrated with the Pho1 isozyme from potato tubers. Immunoprecipitation experiments performed with anti-Pho1a antibodies removed the entire Pho1 phosphorylase activity from both tuber and leaf extracts. Addition of anti-Pho1b antibodies to tuber extracts did not affect the enzyme pattern, whereas in leaf extracts one isoform remained unchanged but the two other bands were strongly retarded. This indicates that the Pho1a protein is present in all three forms and Pho1b is associated with Pho1a. Association of Pho1a and Pho1b was further demonstrated by cross-linking experiments using bis(sulfosuccinimidyl)suberate as linker. Immunoprecipitation experiments were also performed using extracts of transformed Escherichia coli cells that expressed either Pho1a or Pho1b or both simultaneously. Under these conditions a homodimeric Pho1b phosphorylase was observed that had a lower electrophoretic mobility than the heterodimer from leaves. In leaves of transgenic potato plants antisense inhibition of the Pho1a gene affected the formation of (Pho1a)2 more strongly than that of the heterodimer. Thus, in leaves, Pho1a exists both as a homodimer, (Pho1a)2 and as heterodimer, (Pho1a-Pho1b); a part of it appears to be covalently modified. Pho1b, in the homodimeric form, is often below the limit of detection. In tubers the homodimer, (Pho1a)2, is the only detectable Pho1-type enzyme. To our knowledge this is the first report on a heterodimeric structure of plant phosphorylase.

Amino Acid Sequence↗

Electrophoresis-related protein modification: alkylation of carboxy residues revealed by mass spectrometry.

In recent years, the combination of gel electrophoresis and mass spectrometry has developed into one of the most powerful approaches for the analysis of proteins. However, a number of gel electrophoresis-induced protein modifications have been described. Cysteine is the most endangered amino acid readily reacting with mercaptoethanol or free acrylamide. In the course of studies on glucan phosphorylases (E.C.2.4.1.1) from white potato (Solanum tuberosum L.) and the T cell receptor, we noticed that proteolytic peptides from these proteins can undergo an unexpected modification, giving rise to a mass increment of 14 Da. By post-source decay (PSD) analysis the modification was identified as methylation of the glutamic acid side chain carboxyl group. The methylation takes place during Coomassie blue staining of proteins if both trichloroacetic acid and methanol are present in the staining solution. Replacement of methanol by ethanol under otherwise unchanged conditions results in ethylation of the peptides. The in vitro alkylation was further studied by using synthetic peptides which contain, at different positions: glutamic acid, aspartic acid or the corresponding amides. The kinetic analysis of the observed reactions revealed that glutamic acid is preferentially methylated. The three other amino acid residues can be methylated but with a velocity at least one order of magnitude lower. Although these modifications complicate the interpretation of the spectra, they provide valuable structural information.

Alkylation↗