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Biomedical subjects

G Seidel

Publications and source records attributed to G Seidel.

At least 55 records · Page 3Linked to original sources
PubMed1998

Molecular cloning of hSLP-1, a novel human brain-specific member of the band 7/MEC-2 family similar to Caenorhabditis elegans UNC-24.

We have isolated and characterized cDNA clones encoding a stomatin-like protein (hSLP-1) from a human cerebral cortex cDNA library. The deduced amino acid sequence (394 residues) revealed that hSLP-1 is a bipartite protein, containing a major stomatin-like part, starting at the N-terminus, and a non-specific lipid transfer protein (nsLTP)-domain at the C-terminal end, similar to the Caenorhabditis elegans protein UNC-24. Therefore, we conclude that hSLP-1 is the human homologue of UNC-24. In addition, the identification of an alternatively spliced variant demonstrated that two exon/intron boundaries are conserved in the hSLP-1 and unc-24 genes. Northern blot and RNA dot blot analyses showed that the 2. 2-kb transcript is mainly expressed in the brain, with the highest levels in the frontal lobe, cerebral cortex, caudate nucleus, amygdala, temporal lobe, putamen, substantia nigra, and hippocampus. This high-level expression of hSLP-1 in the basal ganglia may also reflect the evolutionary link to UNC-24.

Amino Acid Sequence↗
PubMed1998

The influence of different gases on acoustic properties of a spherosome-based ultrasound contrast agent (BY963). A transcranial Dopplersonography study.

Ultrasound contrast agents improve the signal-to-noise ratio of reflected ultrasound, enhancing the diagnostic value of transcranial Doppler (TCD). In dog studies, we investigated the time course of TCD signal amplitude after application of a phospholipid-containing ultrasound contrast agent (BY963) filled with different gases. The median time of Doppler amplitude enhancement exceeding 5 dB was determined using isoflurane-, isopentane-, trichlortrifluoroethane-, air-, argon-, and perfluoropentane-filled BY963 (69, 72, 75, 78, 88, and 245 seconds respectively). The decrease of time-intensity curve and the duration of signal enhancement showed significant differences comparing the different gases (p = 0.04 and 0.03, respectively). The time course of in vitro stability of BY963 agitated with the different gases measured by absorbance of light (500 nm) showed a retarded decay for perfluoropentane, a rapid decrease for air, isopentane, trichlortrifluoroethane, and argon, and a very rapid decrease using isoflurane. The time course of the different gases depended on the physiochemical properties (lipophilicity and the solubility in water) of the gas encoated in the phospholipid shell. Perfluoropentane-filled BY963 showed the highest in vitro stability and the longest duration of TCD enhancement compared with the other gases used.

Acoustics↗
PubMed1998

Administration of modified spherosome suspension (BY963) leads to an increase of acoustic impedance in dog brain tissue.

Ultrasound contrast agents change the acoustic properties of brain tissue. This can be quantified with acoustic densitometry. In a dog model, the authors examined changes in acoustic impedance in the thalamic and parietal white-matter regions of the brain after intravenous injection of the spherosome containing an ultrasound contrast agent (BY963) filled with perfluoropentane gas. The authors examined six sedated mongrel dogs with a Hewlett-Packard Sonos 1500 device. BY963 filled with perfluoropentane (0.2 ml/kg body weight) was injected three times with a time interval between injections of 5 minutes. Time-dependent changes in mean acoustic impedance were calculated. The authors found a significant increase in peak acoustic impedance after fractional injection of 0.6 ml/kg body weight (3 x 0.2 ml/kg body weight) in the thalamus region up to 7.0 IU (p = 0.006). In the parietal white matter the increase in peak acoustic impedance was not significant (p = 0.06). Statistical comparison of the increase in peak acoustic impedance between placebo and BY963 injection in the thalamus region showed a significant difference after the first injection (p = 0.01) but showed no significance after the second and third injections. The authors concluded that thalamus and parietal white matter of the brain showed different accumulations of BY963.

Animals↗
PubMed1998

Overexpression and structural characterization of the phage T4 protein DsbA.

The double strand binding protein A (DsbA) of bacteriophage T4 is one of several viral gene products participating in transcriptional regulation. These proteins interact or associate with the host RNA polymerase core enzyme, enabling the enzyme to successively initiate transcription at different classes of viral promoters: early, middle and late. This leads to a temporally controlled expression of the T4 gene products. The DsbA binding site overlaps the late promoter region, and DsbA binding seems to intensify transcription of late genes in vitro, possibly acting as an enhancer protein (Molecular Biology of Phage T4, Karam, 1994). To further investigate the function and structure of DsbA, we overexpressed the protein in E. coli and purified it to homogeneity. Physiological functionality of the recombinant protein was shown by gel retardation experiments and by circular dichroism (CD) spectroscopy. DsbA shows strong bands in the near UV-CD spectra. The far UV-CD spectroscopy analysis shows alpha-helices to be the main secondary structure elements. This is in agreement with secondary structure predictions. A possible helix-turn-helix motif in the center of the protein could be identified. Results from crosslinking and sedimentation analyses show that DsbA forms a dimer in solution. The thermal unfolding curve fits a dimer-two-state-folding-model, and the unfolding temperature was concentration dependent. Therefore, dimerization should supply the main portion of the free energy of stabilization of deltaG0 = 42 kJ/mol.

Binding Sites↗
PubMed1997

Solution structure of porcine delta sleep-inducing peptide immunoreactive peptide A homolog of the shortsighted gene product.

The 77-residue delta sleep-inducing peptide immunoreactive peptide (DIP) is a close homolog of the Drosophila melanogaster shortsighted gene product. Porcine DIP (pDIP) and a peptide containing a leucine zipper-related partial sequence of pDIP, pDIP(9-46), was synthesized and studied by circular dichroism and nuclear magnetic resonance spectroscopy in combination with molecular dynamics calculations. Ultracentrifugation, size exclusion chromatography, and model calculations indicated that pDIP forms a dimer. This was confirmed by the observation of concentration-dependent thermal folding-unfolding transitions. From CD spectroscopy and thermal folding-unfolding transitions of pDIP(9-46), it was concluded that the dimerization of pDIP is a result of interaction between helical structures localized in the leucine zipper motif. The three-dimensional structure of the protein was determined with a modified simulated annealing protocol using experimental data derived from nuclear magnetic resonance spectra and a modeling approach based on an established strategy for coiled coil structures. The left-handed super helical structure of the leucine zipper type sequence resulting from the modeling approach is in agreement with known leucine zipper structures. In addition to the hydrophobic interactions between the amino acids at the heptade positions a and d, the structure of pDIP is stabilized by the formation of interhelical i to i' + 5 salt bridges. This result was confirmed by the pH dependence of the thermal-folding transitions. In addition to the amphipatic helix of the leucine zipper, a second helix is formed in the NH2-terminal part of pDIP. This helix exhibits more 310-helix character and is less stable than the leucine zipper helix. For the COOH-terminal region of pDIP no elements of regular secondary structure were observed.

Acetylation↗
PubMed1997

Transcranial Doppler echo contrast studies using different colour processing modes.

OBJECTIVES: To study the effects of different colour imaging modes on the contrast-medium-enhanced image of the intracranial cerebral arteries. METHODS: Twelve healthy volunteers were studied transcranially after administration of 10 ml BY963 successively with Power Doppler (p-TCCS) and with colour Doppler frequency imaging mode (f-TCCS) in a randomized order. RESULTS: The latency time (mean+/-SD) from the injection until the signal enhancement in the middle cerebral artery was 17.1+/-5.8 s for p-TCCS and 17.8+/-4 s for f-TCCS, and the duration of the optimal diagnostically useful signal enhancement was 44.2+/-8.2 s and 40.2+/-12.6 s respectively. CONCLUSIONS: Based on the measured parameters, both imaging modes were of equal value. Theoretical differences in sensitivity of the two methods play no particular role facing the immense signal enhancement after echo contrast application.

Adult↗
PubMed1997

Characteristics of transcranial Doppler signal enhancement using a phospholipid-containing echocontrast agent.

BACKGROUND AND PURPOSE: Ultrasound attenuation caused by the skull is a major limitation of transcranial Doppler. Echocontrast agents (EAs) may solve this problem. The aim of the present study was to investigate the characteristics of a new echocontrast agent (BY963) containing air bubbles stabilized by phospholipids. METHODS: Nine healthy volunteers received three different doses (2.5, 5.0, and 10 mL) of BY963 at an injection rate of 0.25 mL/s. The Doppler signal amplitude obtained from the middle cerebral artery was recorded with a 2-MHz pulsed-wave Doppler system. After complete decay of the signal enhancement, upward stroking of the veins of the upper arm was performed to evaluate the stability of the EA in the venous system. RESULTS: A dose-dependent increase of at least 30 dB in the Doppler signal amplitude lasted 19 to 47, 35 to 64, and 48 to 126 heart cycles (68% range) after 2.5, 5.0, and 10 mL EA, respectively. In 6 cases, there was a biphasic increase in EA enhancement. Upward stroking of the forearm, in general 12 to 18 minutes after administration, caused a Doppler signal enhancement of at least 30 dB in 6 cases. CONCLUSIONS: Each injection of BY963 caused a diagnostically relevant Doppler signal enhancement. A considerable amount of EA remained stable in the venous system for at least 12 minutes. The biphasic dose-response fits to models of dilution-indicator theory and indicates free recirculation, as well as a nonlinear washout curve.

Adult↗
PubMed1997

Harmonic imaging of the vertebrobasilar system.

BACKGROUND AND PURPOSE: Gas bubbles of ultrasound contrast agents resonate at frequencies used for diagnostic ultrasound and produce harmonics or multiples of the transmitted frequency. Processing of the second harmonic frequency results in a reduction of the signal-to-noise ratio and the signal-to-tissue artifacts. This study is the first to evaluate second harmonic imaging in the cerebral circulation. METHODS: We used a duplex system (HP SONOS 2500) in connection with a 1.8/3.6-MHz (second harmonic) and a 2.5-MHz (conventional) sector transducer. Levovist (6.5 mL; 400 mg/mL) was injected intravenously for second harmonic and conventional color duplex imaging in 13 healthy volunteers (age range, 23 to 34 [median, 29] years). RESULTS: When second harmonic imaging was compared with conventional color duplex imaging, more cerebellar arteries were detected (35 versus 31), the duration of blooming artifact was significantly reduced (7.9 versus 29.9 seconds; P = .03), and the duration of diagnostically useful signal enhancement was increased (248.5 versus 117.4 seconds; P = .0003), but the maximal investigation depth was reduced (8.4 versus 9.3 cm; P = .001). When conventional and second harmonic duplex were compared, there was a significant (P < .04) difference in the systolic blood flow velocity in the vertebral and basilar arteries. CONCLUSIONS: Second harmonic color duplex imaging in the vertebrobasilar system increases the time of diagnostic useful signal enhancement and produces a better spatial resolution compared with conventional color duplex imaging.

Adult↗
PubMed1996

Pharmacokinetic studies of different echo-contrast agents in the cerebral circulation of dogs.

Ultrasound contrast agents (UCAs) are improving the signal-to-noise ratio of the reflected ultrasound so that Doppler frequency spectra can be recorded even under poor sonographic conditions. This is of particular diagnostic value in transcranial Doppler sonography. Depending on specific pharmacologic properties, echo-contrast agents may cause different increase and duration in Doppler signal amplitude. We used a dog model to study the temporal profile of Doppler signal amplitude after application of a phospholipid-containing echo-contrast agent (BY 963). In addition, we compared it with a contrast agent containing albumin (Albunex). Spherosome suspension BY 963 resulted in a dose-dependent increase in the duration of ultrasound amplification (Doppler enhancement of 1 mL, 3 mL and 10 mL of BY 963 per animal: 62.4 +/- 8.4, 72.8 +/- 9.2 and 67.7 +/- 4.2 s, respectively, n = 6). Detection of BY 963 in the extracranial jugular vein demonstrated that the UCA passes through the cerebral microcirculation (cerebral transit time was 2.2 +/- 0.2 s, n = 4). The signal enhancement lasted longer using the spherosome suspension compared with the albumin-containing solution (77.2 +/- 11.6 and 31.1 +/- 3.7 s, respectively, n = 6), and the maximum increase in intensity was more pronounced (27.0 +/- 2.0 and 17.5 +/- 2.2 dB, respectively, n = 6).

Albumins↗
PubMed1996

Confidentiality and HIV status in Kwazulu-Natal, South Africa: implications, resistances and challenges.

This article provides a contextualized comparison and analysis of the former Kwazulu and the new Kwazulu-Natal policy documents on HIV confidentiality, the differing practices within the region, and their implications for support and gender. It is based on interviews with key players in the regional NACOSA (National AIDS Convention of South Africa), and participation in meetings between August and November 1995. The main division is between those influenced by other rural African models, especially the Zambian concept of "shared confidentiality' as a way of ensuring support, and who have gone on to develop more community-based practices to destigmatize the disease, in contrast with the stronger emphasis in the new document on individual rights, assuming a more urban constituency, and where "shared confidentiality' is much more circumscribed. One of the difficulties of the new policy in which "confidentiality' is interpreted as "secrecy', is that it would seem to foreclose and neutralize lay and community support, as distinct from the earlier and unacknowledged policy of former Kwazulu. It also seeks to provide an enhanced role for professional counsellors. This psychologizing of the infection and the distancing from "community', and from women's groups, is surprising in a country in whose townships "community' remains a powerful motivating symbol, and where NGOs and peer groups have been identified everywhere as central to effective HIV/AIDS related prevention, care and support for behavior change.

Confidentiality↗
PubMed1996

Transcranial duplex monitoring discloses hemorrhagic complication following rt-PA thrombolysis.

INTRODUCTION: Transcranial color-coded sonography (TCCS) allows imaging of basal cerebral arteries as well as brain parenchyma. It may therefore serve to monitor thrombolysis in acute stroke. CASE DESCRIPTION: rt-PA thrombolysis was performed in a patient, suffering from paradoxical embolism causing MCA occlusion. Hemorrhage immediately after completion of rt-PA infusion as well as delayed MCA recanalization could be monitored by TCCS. CONCLUSION: TCCS is useful to improve monitoring and safety of systemic thrombolytic treatment.

Adult↗
PubMed1996

Dislocation of the third ventricle due to space-occupying stroke evaluated by transcranial duplex sonography.

Transcranial color-coded duplex sonography is a recently introduced method for visualizing (1) the blood flow velocity of the basal cerebral arteries and (2) the brain parenchyma as an acoustic impedance image. Dislocation of the third ventricle due to space-occupying stroke is an important clinical marker. This study evaluated the dislocation of the third ventricle from the brain midline by transcranial duplex sonography in 10 healthy volunteers. The mean dislocation was 0.2 +/- 0.3 mm. Eighteen stroke patients were investigated within 12 hours by both duplex sonography and computed tomography (CT) and the dislocation of the third ventricle was measured. Correlation between the two methods was high (r = 0.87, N = 27). Twelve stroke patients divided into three subgroups according to the extent of the space-occupying effects of the lesion were followed for 3 weeks. The increase and decrease of the dislocation of the third ventricle over the time were monitored. In conclusion, transcranial duplex sonography is a reliable tool to monitor dislocation of the third ventricle due to space-occupying stroke.

Adult↗
PubMed1995

Is there a hemispheric side preference of cardiac valvular emboli?

Microaggregates arising from prosthetic cardiac valves offer the opportunity to examine the distribution of valvular emboli in the human cerebral circulation. Forty-four patients with different kinds of prosthetic valves underwent bilateral transcranial Doppler monitoring for 1 h to detect high intensity Doppler signals representing microemboli. Comparing the total number of embolic signals in both middle cerebral arteries (N = 1066), a side preference was not statistically evident. However, clear side preferences were obvious in some individuals. The lack of statistical evidence for hemispherical preferences of cardiac microembolism in general does not exclude selective streaming in individuals, explaining the clinical observation of lodging preferences of recurrent cardiac embolism. A cardiac source of microembolism may mimic disease activity of extracranial carotid artery stenosis and bias the localization of embolic source.

Adult↗
PubMed1995

[Current status of transcranial color duplex ultrasound in the adult].

Technical improvements accomplished over the last few years allow imaging of intracranial parenchymal structures as well as of basal cerebral arteries by ultrasound. Low frequency probes (2-2.5 MHz) and colour Doppler technology are required for these examinations. Recent experience in clinical practice proves that perfusion patterns in basal cerebral arteries can be depicted more accurately and with better reproducibility compared to conventional transcranial Doppler sonography. Simultaneous B-Mode imaging allows detection of cerebral haemorrhage, brain tumours and ventricular enlargement. Preliminary data on the sensitivity and specificity are promising and encourage further prospective studies.

Adult↗