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Biomedical subjects

T Albrecht

Publications and source records attributed to T Albrecht.

At least 55 records · Page 3Linked to original sources

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↗

Prolongation and optimization of Doppler enhancement with a microbubble US contrast agent by using continuous infusion: preliminary experience.

PURPOSE: To investigate whether continuous infusion of an echo-enhancing contrast agent for up to 15 minutes can provide uniform and prolonged enhancement. MATERIALS AND METHODS: Six volunteers each received one bolus and three infusions of a microbubble contrast agent over 6-15 minutes at (a) a standard rate (mean, 2.08 mL/min), (b) a fast rate at twice the standard rate, and (c) a slow rate at half the standard rate. Spectral Doppler intensitometry of the femoral artery was performed for all infusions. Spectral Doppler ultrasound (US) scans of the femoral artery and color Doppler US scans of the carotid artery were subjectively assessed. RESULTS: All infusions provided an equilibrium plateau of constant prolonged enhancement starting after 1-2 minutes and lasting until the end of the infusion. Enhancement at the plateau was +13 dB (slow rate), +17.1 dB (standard rate), and +18.3 dB (fast rate) compared with baseline. Saturation artifacts with infusions were markedly fewer than those with bolus injections. Dose effectiveness (duration of enhancement that measured at least 7.5 dB per gram of contrast agent) was markedly improved with the infusions, from 0.8 min/g for the bolus to 2.6 min/g for the slow infusion. CONCLUSION: Continuous infusion of the microbubble contrast agent provided prolonged and uniform enhancement of Doppler signals and improved image quality by minimizing saturation artifacts.

Adult↗

Liver vascular transit time analyzed with dynamic hepatic venography with bolus injections of an US contrast agent: early experience in seven patients with metastases.

Spectral Doppler intensitometry to study transit of a bolus of an ultrasonographic (US) contrast agent in the hepatic veins was performed in seven patients suspected of having liver metastases and seven control subjects. All control subjects had a late response (rise time, > 25 seconds; time to peak intensity, > 45 seconds), whereas six of seven patients had an early response (rise time, < 25 seconds; time to peak intensity, < 45 seconds) (P < .01).

Adult↗

Three-dimensional spiral CT angiography in pancreatic surgical planning using non-tailored protocols: comparison with conventional angiography.

The aim of this study was to investigate three-dimensional spiral computed tomography (3DCT) as an adjunct to routine pancreatic CT scanning, with particular regard to the identification of surgically important hepatic arterial anomalies, correlated with conventional visceral angiography. 32 patients underwent spiral CT scans prior to pancreatic surgery using established protocols. Oral contrast medium was used throughout. 150 ml of intravenous contrast medium was given at 3 ml s-1 with a 24 s spiral CT sequence starting 35 s after the start of infusion. Two protocols were employed, both with a pitch of 1:3 mm table feed/collimation (n = 17) and 5 mm table feed/collimation (n = 15). Overlapping (1 mm minimum) axial reformats were reconstructed. 3DCT shaded-surface displays of the visceral arteries were assessed for visceral arterial anomalies. Visceral angiography (n = 23) was independently correlated. Satisfactory 3D angiograms were performed in all but one patient, in whom the coeliac axis was missed. (i) 3 mm protocol: 3DCT (n = 17) showed three anomalous right hepatic arteries (ARHA), one trifurcation anomaly and one splenic artery with an aortic origin. Angiography (n = 11) confirmed these findings, although one patient with an ARHA did not have angiography. A left gastric arterial supply to the left liver was not detected. (ii) 5 mm protocol: 3DCT (n = 15) showed two cases of ARHA. While confirming these findings, angiography (n = 12) showed a third case of ARHA, in which the coeliac and superior mesenteric artery had very close origins. A left gastric supply to the left liver was also missed. It is concluded that satisfactory 3DCT is possible without changing existing scanning protocols, although narrow sections are required for the confident assessment of right hepatic arterial anomalies, and any left hepatic supply via the left gastric artery was poorly assessed in this series.

Adolescent↗

Spiral computed tomography: principles and clinical use.

Spiral computed tomography (CT) has been the major advance in CT in the 1990s. Its high speed and the three-dimensional nature of the obtained data sets has considerably improved the clinical performance of CT in many areas. Furthermore it has led to new applications such as CT angiography and virtual endoscopy.

Angiography↗

Inhibition of cellular Cdk2 activity blocks human cytomegalovirus replication.

Human cytomegalovirus is a herpesvirus that induces numerous cellular processes upon infection. Among these are activation of cyclin-dependent kinase 2, which regulates cell cycle progression in G1 and S phase. We report here that inhibition of cellular Cdk2 activity blocks HCMV replication. Inhibition of Cdk2 activity by roscovitine inhibits HCMV DNA synthesis, production of infectious progeny, and late antigen expression in infected cells in a dose-dependent manner. HCMV replication is also inhibited by the expression of a Cdk2 dominant negative mutant, whereas expression of wild-type Cdk2 has no effect on viral replication. These data indicate that activation of cellular Cdk2 is necessary for HCMV replication.

Antigens, Viral↗