Biomedical subjects

Christoph Koch

Publications and source records attributed to Christoph Koch.

10 recordsLinked to original sources

PubMed2006

Identifying gene regulatory elements by genomic microarray mapping of DNaseI hypersensitive sites.

The identification of cis-regulatory elements is central to understanding gene transcription. Hypersensitivity of cis-regulatory elements to digestion with DNaseI remains the gold-standard approach to locating such elements. Traditional methods used to identify DNaseI hypersensitive sites are cumbersome and can only be applied to short stretches of DNA at defined locations. Here we report the development of a novel genomic array-based approach to DNaseI hypersensitive site mapping (ADHM) that permits precise, large-scale identification of such sites from as few as 5 million cells. Using ADHM we identified all previously recognized hematopoietic regulatory elements across 200 kb of the mouse T-cell acute lymphocytic leukemia-1 (Tal1) locus, and, in addition, identified two novel elements within the locus, which show transcriptional regulatory activity. We further validated the ADHM protocol by mapping the DNaseI hypersensitive sites across 250 kb of the human TAL1 locus in CD34+ primary stem/progenitor cells and K562 cells and by mapping the previously known DNaseI hypersensitive sites across 240 kb of the human alpha-globin locus in K562 cells. ADHM provides a powerful approach to identifying DNaseI hypersensitive sites across large genomic regions.

Algorithms↗

PubMed2006

Spinal dural arteriovenous fistula.

PURPOSE OF REVIEW: To summarize clinical key points, diagnostic features, and results of imaging and therapy of spinal dural arteriovenous fistula (SDAVF). RECENT FINDINGS: SDAVF accounts for 70% of spinal arteriovenous malformation with an annual incidence of 5-10 cases per million. At least 80% of patients are male, and more than 66% of patients are in the sixth and seventh decade of life indicating preponderance of gender and age. Thrombophilia is not a predisposing factor of disease. Clinical course is predominated by symptoms of congestive myelopathy, but subarachnoid hemorrhage may occur. Double SDAVF is a rare problem in the management of disease. Magnetic resonance imaging has replaced myelography as screening procedure. Contrast-enhanced magnetic resonance angiography and multislice computerized tomographic angiography may facilitate diagnostic procedure, however, spinal angiography is still required to confirm diagnosis. Treatment by permanent occlusion of fistula results in clinical improvement in 70% of cases. Microsurgical shunt interruption has proven secure and reliable. Endovascular shunt embolization has been established as a standardized procedure, but occlusion rates are still lower than in surgical treatment. SUMMARY: Advances have been made in diagnosis and treatment of SDAVF, but the disease is still not completely understood.

Age Distribution↗

PubMed2005

Binding sites for metabolic disease related transcription factors inferred at base pair resolution by chromatin immunoprecipitation and genomic microarrays.

We present a detailed in vivo characterization of hepatocyte transcriptional regulation in HepG2 cells, using chromatin immunoprecipitation and detection on PCR fragment-based genomic tiling path arrays covering the encyclopedia of DNA element (ENCODE) regions. Our data suggest that HNF-4alpha and HNF-3beta, which were commonly bound to distal regulatory elements, may cooperate in the regulation of a large fraction of the liver transcriptome and that both HNF-4alpha and USF1 may promote H3 acetylation to many of their targets. Importantly, bioinformatic analysis of the sequences bound by each transcription factor (TF) shows an over-representation of motifs highly similar to the in vitro established consensus sequences. On the basis of these data, we have inferred tentative binding sites at base pair resolution. Some of these sites have been previously found by in vitro analysis and some were verified in vitro in this study. Our data suggests that a similar approach could be used for the in vivo characterization of all predicted/uncharacterized TF and that the analysis could be scaled to the whole genome.

Base Pairing↗

PubMed2005

Aggressive therapy with intravenous abciximab and intra-arterial rtPA and additional PTA/stenting improves clinical outcome in acute vertebrobasilar occlusion: combined local fibrinolysis and intravenous abciximab in acute vertebrobasilar stroke treatment (FAST): results of a multicenter study.

BACKGROUND AND PURPOSE: A combined therapy of local recombinant tissue plasminogen activator (rtPA) fibrinolysis and intravenous Abciximab platelet inhibition with additional percutaneous transluminal angioplasty (PTA)/stenting may improve recanalization and neurological outcome in patients with acute vertebrobasilar occlusion. METHODS: Combined FAST therapy consisted on intravenous bolus of Abciximab (0.25 mg/kg) followed by a 12-hour infusion therapy (0.125 microg/kg per minute) and low-dose intra-arterial rtPA (median dosage: 20 mg, FAST cohort: N=47). The results were compared with a retrospective cohort, treated by intraarterial rtPA monotherapy (median dosage: 40 mg, rtPA cohort, N=41). Additional PTA/stenting was performed in case of severe residual stenosis. Recanalization success was classified according to the Trials in Myocardial Infarction (TIMI) criteria: TIMI0/1, failed recanalization; TIMI2/3, successful recanalization. Bleeding complications were evaluated according to severe extracerebral hemorrhage (ECH), asymptomatic intracerebral hemorrhage (AIH), and symptomatic intracerebral hemorrhage (SIH). RESULTS: Overall bleeding rate was higher under the combined therapy, but the SIH rate did not differ (FAST versus rtPA: ECH, 3% versus 0%; AIH, 32% versus 22%; SIH 13% versus 12%). Additional PTA/stenting was performed in 14 (FAST) versus 5 (rtPA) patients. TIMI2/3 recanalization rate was similar (FAST, 72%; rtPA, 68%), but TIMI3 rate was remarkably higher under combined therapy (FAST, 45%; rtPA, N=22%). Neurologic outcome appeared better under combined therapy (FAST versus rtPA: favorable outcome rate: 34% versus 17%) with a significantly lower mortality rate (FAST versus rtPA: 38% versus 68%; P=0.006). These results were consistent for embolic and atherothrombotic occlusions. CONCLUSIONS: Combined therapy of intravenous Abciximab and half dose intra-arterial rtPA with additional PTA/stenting appears to improve neurologic outcome in acute vertebrobasilar occlusion despite an increase of overall bleeding complications.

Abciximab↗

PubMed2004

Screening for cerebellopontine angle tumors: is a CISS sufficient?

This study attempted to evaluate the reliability of ultra-thin T2-weighted imaging with a constructive interference in steady state (CISS) sequence as a screening method for tumors in the cerebellopontine angle. A retrospective study of 200 CISS examinations was made by five investigators. The examinations were inspected on plain film supported by clinical information. The interobserver agreement in the detection of lesions was analyzed. Fourteen cases (50% of the contrast-enhancing lesions) were rated pathological by all five readers. One case of subarachnoid lymphoma infiltration was overlooked by all five readers. Overall, six pathological lesions (median = 6, range 1-9) were not identified. The interobserver agreement for all pathological lesions was moderate (kappa=0.53; 95% CI, 0.43-0.62). The mean sensitivity was 77.8% (range 72.0-96.3%), and the mean specificity was 97.6% (range 94.8-100%). The median sensitivity for pathological lesions concerning only patients with acute sensorineural hearing loss (n=148, patients with 20 contrast-enhancing cases) was 86.6% (range 80-100%), and median specificity was 95.2% (range 84.4-96.9%) with a moderate interobserver agreement (kappa=0.55; 95% CI, 0.44-0.66). In our opinion the CISS sequence is a valuable addition to the examination of the cerebellopontine angle but lacks sufficient reliability for the detection of tumors of small size or of tumors adjacent to brain parenchyma or the temporal bone.

Cerebellar Neoplasms↗

PubMed2004

DNA binding of methyl-CpG-binding protein MeCP2 in human MCF7 cells.

MeCP2 has been identified as a chromatin-associated protein that recognizes MAR elements as well as methyl-CpGs. To characterize target sequences of MeCP2 in human cells, we employed two complementary methods. First, by use of a preparative chromatin immunoprecipitation protocol, we created from MCF7 cells a library enriched with sequences bound to MeCP2. A total of 154 representative clones were sequenced and analyzed. A large fraction of clones was found to be associated with retrotransposons, mostly with Alu repeats. A subgroup of four clones is derived from putative MARs; one clone is associated with a CpG island, and four clones contain alphoid repeats. Classical satellite DNAs II and III are not represented among clones, although they are heavily methylated. Second, using indirect immunofluorescence microscopy, we show that MeCP2 staining of human metaphase chromosomes has a dotted to knobby appearance with a reduced level of staining of centromeric regions of some chromosomes. On the other hand, an anti-5-methylcytosine antibody preferentially stained the juxtacentromeric regions of chromosomes 1, 9, and 16, which habor highly methylated, classical satellite DNAs, and methylated alphoid sequences in centromeric regions of several other chromosomes with reduced intensity. In interphase MCF7 cells, the distribution of MeCP2 exhibits a granular appearance throughout the nucleus. This distribution does not parallel that of methylated cytosine and heterochromatin. The selective binding behavior of MeCP2 revealed by these results (preference for murine major satellite DNA, Alu sequences, MARs, and CpG islands) is explained by its ability to recognize the sequence information (guanine bases) adjacent to CpG (TpG) as demonstrated in previous footprinting experiments.

3T3 Cells↗

PubMed2004

Dural arteriovenous fistula of the lumbar spine presenting with subarachnoid hemorrhage. Case report and review of the literature.

The authors report on a patient presenting with subarachnoid hemorrhage (SAH) that was initially attributed to an aneurysm of the right internal carotid artery. During surgical exploration and placement of a clip, however, it was observed that the aneurysm had not ruptured. Diagnostic workup including spinal magnetic resonance imaging revealed a vascular malformation of the lumbar spinal canal within a subarachnoid hematoma. Spinal angiography demonstrated a spinal dural arteriovenous fistula (DAVF) (Type I spinal arteriovenous malformation) with a feeding vessel arising from the L-4 radicular artery. In the literature, SAH due to spinal DAVFs is rare; only cases of dural fistulas of the craniocervical junction and the cervical spine have been reported. This is the first case of SAH that can be attributed to a lumbar DAVF. Although unusual even in cases of cervical DAVF, SAH as a presenting symptom may occur in spinal DAVF of any location. Nontraumatic SAH should not be prematurely attributed to the rupture of an intracranial aneurysm if the clinical findings and imaging results are inconclusive.

Aneurysm, Ruptured↗

PubMed2003

Endovascular treatment of internal carotid artery stenosis: effect of primary stent application on debris particle release in human cadaveric specimens.

PURPOSE: To compare debris release with primary stent application (self-expanding stent application at stenosis and then balloon dilation through the opened stent) and that with secondary stent application (balloon angioplasty of stenosis and afterward additional stent application) for high-grade internal carotid artery stenosis in human cadaveric specimens. MATERIALS AND METHODS: Fresh human cadaveric internal carotid artery specimens were attached to a tube system. High-grade stenoses (>66%) were selected, randomized for primary or secondary stent application, and then treated, with fluoroscopic guidance, while the system was rinsed in a pulsating flow. Fluid was collected and filtered, and debris particles were examined with a light microscope. Particles were analyzed according to those consecutively caught by 100 x 100-microm and 11 x 11-microm mesh filters. Results were evaluated in relation to stent application. For statistical analyses of group differences, the exact Mann-Whitney U test was used. RESULTS: Thirteen high-grade human cadaveric internal carotid artery stenoses were analyzed. Five specimens were randomly assigned to secondary stent application, and eight were assigned to primary stent application. No significant difference could be demonstrated for debris release with primary or secondary stent application. P values ranged from.051 to.754. CONCLUSION: The reported superiority of primary stent application may not be related to debris reduction.

Arteriosclerosis↗

PubMed2002

Acute basilar artery occlusion treated with combined intravenous Abciximab and intra-arterial tissue plasminogen activator: report of 3 cases.

BACKGROUND: Acute vertebrobasilar occlusion remains a disease with a high mortality even after treatment by local intra-arterial fibrinolysis. Adjunctive treatment with platelet glycoprotein IIb/IIIa receptor inhibitors such as abciximab may facilitate recanalization and improve the neurological outcome. Results after treatment of 3 patients by combined intravenous abciximab and local intra-arterial tissue plasminogen activator (tPA) are reported. CASE DESCRIPTIONS: Treatment was performed within 6 hours of stroke onset. Angiography revealed embolic occlusion of the basilar artery in 2 patients and atherothrombotic occlusion at the vertebrobasilar junction in 1 patient. Therapy consisted of intravenous abciximab bolus administration (0.25 mg/kg) followed by 12-hour infusion therapy (0.125 microg/kg per minute) and local intra-arterial thrombolysis with tPA (10 mg/h). Heparin was only applied for catheter flushing (500 IU/h). The patient with the atherothrombotic occlusion was treated with additional percutaneous transluminal angioplasty and stenting. Complete recanalization of the basilar artery occurred in 2 patients, whose conditions improved clinically to functional independence. In the third patient only partial recanalization was seen, with only slight clinical improvement. This patient died of cardiac failure 2 months later. Besides a subtle subarachnoid hemorrhage (n=1), no intracranial or extracranial bleeding complication was observed. CONCLUSIONS: The combination of glycoprotein IIb/IIIa receptor inhibitor with local intra-arterial tPA might be a promising therapy for patients with acute vertebrobasilar occlusion. Further studies are necessary to define the clinical benefit and the bleeding rate of this new pharmacological approach.

Abciximab↗

PubMed2002

Correlation of apparent diffusion coefficient and computed tomography density in acute ischemic stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging is very sensitive for the detection of restricted molecular water diffusion in acute ischemic stroke. CT is sensitive to net water uptake in ischemic edema. We compared the decrease in the apparent diffusion coefficient (ADC) in diffusion-weighted MR imaging with CT density changes to study the correlation between diffusion restriction and water uptake in acute stroke patients. METHODS: Twenty-five patients with acute ischemic stroke of the anterior cerebral circulation underwent MR and CT imaging 1.3 to 5.4 hours after symptom onset. ADC and CT data were transferred into a common 3-dimensional space, and regions of decreased ADC (dADC) were superimposed onto the corresponding CT. Mean values of ADC and Hounsfield units (HU) were determined in comparison with the nonaffected hemisphere. RESULTS: Mean decrease in ADC (dADC) was 170+/-53x 10(-6) mm2/s and corresponded to a decrease (dCT) in CT density of 1.3+/-0.7 HU. dCT showed a continuous linear decrease of 0.4 HU/h (r=0.55, P<0.01), whereas the decrease is ADC was almost complete after 1.5 hours. A correlation between the decrease in ADC and dCT was found (r=0.41, P=0.04). CONCLUSIONS: The severity of diffusion restriction correlates with net water uptake in acute ischemic stroke. However, the underlying pathophysiology and different time courses indicate a common reason rather than a direct causality for both phenomena. The time delay and low value of CT density changes provide a reasonable explanation for the higher sensitivity of MR imaging in ischemic stroke.

Acute Disease↗