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S Heiland

Publications and source records attributed to S Heiland.

65 records · Page 4Linked to original sources
PubMed1995

Transcription factor Oct1 binds to the AT-rich segment of the simian virus 40 replication origin.

A cellular protein that binds to the AT-rich late segment of the simian virus 40 (SV40) origin of replication has been identified as transcription factor Oct1. This conclusion is based on the following observations: the late origin binding protein has a molecular mass of about 100 kDa, like factor Oct1, and shares other biochemical properties with Oct1; its binding to the origin is inhibited by antibodies directed against the POU domain of factor Oct1; the isolated POU domain of Oct1 specifically binds to the SV40 late origin region. Thus, the SV40 genome contains binding sites for transcription factor Oct1 in the origin of replication in addition to the previously characterized octamer sites in the viral promoter enhancer. Oct1, bound to the viral origin, negatively affects the DNA unwinding reaction catalyzed by the viral replication initiator T antigen, suggesting that Oct1 may have a role in the regulation of viral replication.

Antigens, Polyomavirus Transforming↗
PubMed1995

The human topoisomerase I gene promoter is regulated by NF-IL6.

We investigated the expression of the human DNA topoisomerase I (hTOP1) gene in HeLa cells and in adenovirus-transformed 293 cells. A highly conserved proximal promoter element is essential for hTOP1 promoter activity in HeLa cells but not in 293 cells. This correlates with the presence of specific promoter-binding proteins in HeLa cells and their absence in 293 cells. We identified the HeLa binding protein by screening a cDNA expression library with the specific promoter site as a probe and demonstrate now that the activating protein is identical to the nuclear factor for interleukin-6 expression (NF-IL6), a member of the C/EBP family of transcription factors. Overexpression of NF-IL6 strongly stimulates hTOP1 promoter activity in HeLa cells, suggesting that NF-IL6 is a major hTOP1-regulating protein. Because of the presence of adenovirus protein E1A, 293 cells express the hTOP1 gene more efficiently than HeLa cells but do not contain NF-IL6 activity. E1A activation of the hTOP1 promoter is suppressed by NF-IL6 overexpression. This result supports previous observations concerning a functional interaction between viral protein E1A and NF-IL6. Finally, we show that hTOP1 gene expression in differentiating macrophages is correlated with the synthesis of NF-IL6-specific mRNA.

Adenoviruses, Human↗
PubMed1995

Decompressive craniectomy for cerebral infarction. An experimental study in rats.

BACKGROUND AND PURPOSE: Acute ischemia in the territory of the carotid artery can lead to massive cerebral edema with raised intracranial pressure and progression to coma and death due to uncal, cingulate, or tonsillar herniation. Thus far, only anecdotal experience with supratentorial ischemia treated by decompressive craniectomy has been reported; and there are no published experimental data dealing with this kind of therapy in acute supratentorial stroke. In this study, we present our results on the effect of decompressive craniectomy in an endovascular model of cerebral infarction in rats. METHODS: Focal cerebral ischemia was induced in 50 rats using an endovascular occlusion technique of the middle cerebral artery. Decompressive craniectomy was performed in 30 animals: in 15 animals after 1 hour and in the remaining 15 animals 24 hours after vessel occlusion. Twenty animals were not treated by decompressive craniectomy (control group). RESULTS: Mortality in the nontreated group was 35%, whereas none of the animals treated by decompressive craniectomy died. Neurological behavior, weight loss, and infarction size were all significantly better in the animals treated by decompressive craniectomy, regardless of whether they had been treated after 1 or 24 hours (P < .01). CONCLUSIONS: Our results suggest that decompressive craniectomy for cerebral ischemia not only reduces mortality but also significantly improves outcome and reduces infarction size, probably because of increased perfusion pressure through leptomeningeal collaterals. This experimental study suggests that a controlled study of decompressive craniectomy in patients with acute internal carotid or middle cerebral artery occlusion would be worthwhile. By performing decompressive craniectomy in a small, selected group of patients, neurosurgeons may play an important role in the management of these patients.

Acute Disease↗
PubMed1995

Early MR detection of experimentally induced cerebral ischemia using magnetic susceptibility contrast agents: comparison between gadopentetate dimeglumine and iron oxide particles.

PURPOSE: To evaluate early patterns of MR changes in a rat model of cerebral ischemia using the first pass of two magnetic susceptibility contrast agents. METHODS: One hours after endovascular middle cerebral artery occlusion, all animals were examined in an experimental MR unit. After bolus application of gadopentetate dimeglumine and, 10 minutes later, of iron oxide particles, the MR changes of the first pass of these contrast agents were followed using a T2*-weighted fast low-angle shot sequence. Time-density curves of both contrast agents were analyzed and compared. RESULTS: After bolus injection of either (paramagnetic) gadopentetate dimeglumine or superparamagnetic particles, nonischemic brain parenchyma decreased markedly in signal, whereas the ischemic brain area remained relatively hyperintense (and thus became clearly delineated). Only after application of gadopentetate dimeglumine did a mild reduction in signal occur in the ischemic hemisphere, although the main artery was occluded. An explantation for this phenomenon might be residual capillary perfusion (plasma flow), which is detectable only when the smaller (paramagnetic) contrast molecules are being used. CONCLUSIONS: Cerebral perfusion deficits can be detected 1 hour after vascular occlusion with T2*-weighted fast low-angle shot sequences and bolus injection of paramagnetic or superparamagnetic MR contrast agents. Gadopentetate dimeglumine may be used as a marker of microcirculatory plasma flow.

Animals↗
PubMed1994

Conserved regulatory elements in the type I DNA topoisomerase gene promoters of mouse and man.

The gene for mammalian type I DNA topoisomerase is constitutively expressed, but also regulated by a number of external stimuli. We compared the nucleotide sequences of the human and the mouse topoisomerase I gene promoters because promoter elements, essential for basic as well as regulated gene expression, should be conserved during evolution. We found that proximal upstream sequences are highly conserved and include potential binding sites for ubiquitous transcription factors, a regulatory CRE site as well as two novel promoter elements that have been shown to be important for the expression of the human gene. The more distal parts of the upstream sequences are less well conserved but include two regions that are almost identical in the human and the mouse gene. One of these regions contains a binding site for a basic-helix-loop-helix/leucine-zipper protein, and the other contains an AT-rich element with the potential for DNA bending.

Animals↗
PubMed1993

The promoter region of the human type-I-DNA-topoisomerase gene. Protein-binding sites and sequences involved in transcriptional regulation.

We examined the promoter of the human type-I-DNA topoisomerase gene (hTOP1) for regions protected against DNase I digestion by nuclear proteins from HeLa or from adenovirus-transformed 293 cells. We identified ten protected DNA sequences within 580 bp of DNA upstream of the transcriptional-start sites and one additional site, which is located between the two clusters of transcriptional-start sites. Several of these protein-binding sites have significant similarities to recognition sequences of known transcription factors including factors Sp1, octamer transcription factor, cAMP-responsive-element-binding protein (CREB/ATF), NF-kappa B and members of the Myc-related family of basic/helix-loop-helix/leucine-zipper proteins. Other protein-binding sites show less or no similarities to known consensus sequences. We investigated the physiological significance of these protein-binding sites using a set of deletion and nucleotide-exchange mutants. We conclude that the expression of the hTOP1 gene is regulated by a complex network of negatively and positively acting transcription factors.

Base Sequence↗
PubMed1993

MR imaging of fat-containing tissues: valuation of two quantitative imaging techniques in comparison with localized proton spectroscopy.

Since lipid protons, consisting mainly of triacylglycerols (TAG), are rather mobile, magnetic resonance imaging (MRI) is ideally suited for the examination of fat-containing tissues such as bone marrow. In contrast to water protons, however, lipid protons are chemically distinct and give rise to at least eight resonance peaks with different T1 and T2 relaxation times in the 1H spectrum. This is why the characterization of fat-containing tissues by quantitative MRI is much more difficult than that of most other tissues. In our study we wanted to examine the accuracy and the potential of a 1H chemical shift imaging (CSI) technique and a multiple spin-echo imaging (MSEI) technique. A stimulated-echo (STEAM) sequence for spatially localized proton spectroscopy was used as the reference method. In the first part of this paper, we describe quantitative imaging experiments which were performed to assess the accuracy of the fat-water separation according to the Dixon method and the bi-exponential decomposition of the MSEI data. For that purpose, we used a two-compartment phantom filled with either an aqueous Gd-DTPA solution and vegetable oil or with two different aqueous Gd-DTPA solutions, respectively. The analysis of the 1H CSI data revealed that the presence of non-methylen protons in neutral fats leads to a slight under-estimation (of about 15%) of the relative fat fraction. The error is described theoretically and verified quantitatively by STEAM measurements. The bi-exponential analysis of the transverse relaxation data, on the other hand, yields reliable T2 values if the relative proton density of both components is higher than 15%. IN the second part of our investigation, the same techniques were applied to acquire data from the subcutaneous fatty tissue, the femoral head, and the lumbar vertebrae of three healthy volunteers. In the bone marrow spectra, only two broad resonances could be resolved; they were superpositions of diverse molecular groups with different T1 and T2 relaxation times. In these cases, localized proton spectroscopy does not provide additional information with respect to 1H CSI. The MSEI data of the three examined fat containing tissue regions were adequately fitted by a bi-exponential function despite the fact that there were much more chemically distinct protons present in fatty tissues.

Adipose Tissue↗
PubMedDate not supplied

Perfusion-weighted MRI using gadobutrol as a contrast agent in a rat stroke model.

The purpose of this study was to examine the new nonionic contrast agent gadobutrol in MR perfusion-weighted imaging, including the influence of different concentrations and dosages of the agent on the sensitivity to perfusion alterations. Sixteen rats were examined within 35 to 105 minutes after endovascular occlusion of the middle cerebral artery. A fast T2*-weighted fast low-angle shot (FLASH) sequence was used to acquire four images before and 16 images after bolus injection of .1, .2, .3, and .4 mmol/kg gadobutrol as .5 molar and 1.0 molar formulation. From user-defined regions, we obtained the maximum signal decrease, the relative regional cerebral blood volume, and the bolus delay. Contrast between ischemic and nonischemic regions during bolus passage increased with dose and concentration of the contrast agent. For low doses (.1 and .2 mmol/kg), the ischemic lesion could not or could barely be discerned. For higher doses (.3 and .4 mmol/kg), administration of the 1 molar contrast agent yielded a better contrast between ischemic and nonischemic tissue. Our results suggest that administration of gadobutrol at higher dosage and higher concentration increases sensitivity to perfusion alterations. These results are potentially useful for perfusion-weighted imaging of the human brain, because the volume of contrast agent will be reduced if a solution with higher concentration is used. When using contrast agents in higher concentrations for human examinations, a significant signal decrease may be achieved also with the low doses (.1-.15 mmol/kg).

Animals↗
PubMedDate not supplied

Magnetization transfer measurements in normal-appearing cerebral white matter in patients with chronic obstructive hydrocephalus.

PURPOSE: The purpose of this work was to assess the presence of subtle changes in normal-appearing white matter on T2-weighted MR images in patients with chronic obstructive hydrocephalus using magnetization transfer (MT) measurements. METHOD: In 12 patients with chronic obstructive hydrocephalus, MT ratios (MTRs) of normal-appearing rostral (PR) and caudal (PC) periventricular white matter, of the genu (CG) and the splenium (CS) of the corpus callosum, and of the thalamus (TH) were measured and compared with those of 16 healthy control subjects. RESULTS: We found a significantly lower MTR in chronic obstructive hydrocephalus than in the normal group for PR, PC, CG, and CS but not for TH. CONCLUSION: Our study shows that MT measurements give additional information that cannot be gained by conventional SE MRI, suggesting that chronic obstructive hydrocephalus is associated with diffuse white matter damage that also affects normal-appearing cerebral white matter.

Adult↗
PubMedDate not supplied

MR enhancement of brain lesions: increased contrast dose compared with magnetization transfer.

PURPOSE: To compare image contrast and lesion conspicuity of enhancing intracranial lesions obtained with T1-weighted and magnetization transfer T1-weighted spin-echo sequences after administration of standard (0.1 mmol/kg body weight) and triple doses of gadobutrol. METHODS: Twenty-four patients with a total of 34 enhancing intracranial lesions were studied with T1-weighted and magnetization transfer T1-weighted spin-echo MR imaging. An incremental dose technique was used with intravenous injections of 0.1 and 0.2 mmol/kg body weight gadobutrol. Lesion-to-white matter contrast and white matter-to-edema contrast were calculated. RESULTS: The lesion-to-white matter contrast of the magnetization transfer T1-weighted studies was significantly higher than that of the T1-weighted studies when identical doses of gadobutrol were compared. The lesion-to-white matter contrast was not significantly different on the triple-dose T1-weighted study and the standard-dose magnetization transfer T1-weighted study. Two lesions were visible only on the standard-dose magnetization transfer T1-weighted and the triple-dose studies. CONCLUSION: Standard-dose magnetization transfer T1-weighted and triple-dose T1-weighted spin-echo MR studies are equally well suited to increase the lesion-to-white matter contrast in patients with enhancing intracranial lesions. Triple-dose magnetization transfer T1-weighted studies further increase lesion-to-white matter contrast but do not show additional lesions.

Adult↗