Biomedical subjects

C Weigel

Publications and source records attributed to C Weigel.

At least 19 recordsLinked to original sources

PubMed2005

[No detectable nephrotoxic side effect using a dimer, non-ionic contrast media in cerebral perfusion computed tomography in case of suspected brain ischemia].

PURPOSE: In suspected brain ischemia, the perfusion cerebral computed tomography (cCT) should be performed with the lowest amount of contrast media to avoid a contrast media induced nephropathy (CIN) even if the patient already is in renal failure. We were interested to find the best parameters for this examination. MATERIAL AND METHODS: From February 2000 to March 2003, 138 patients (58 females, 80 males, mean age 66.8 years) underwent cCT-perfusion immediately after the admission to our stroke unit. Of these patients, 62% (n = 86) had normal renal function and 38% (n = 52) renal failure (up to 381 micromol/l basic serum creatinine). We varied volume (20-80 ml), flow (5 vs. 7.2 ml/s) and concentration (270 vs. 320 ml/mg iodine) of a dimer, non-ionic contrast media (Visipaque) to establish 5 groups. So we got patients receiving 6 g, 12 g, 16 g, 19 g and 25 g of iodine. After generating the perfusion maps, two radiologists reviewed the quality of the maps and scored it (1-5). We measured the serum creatinine before contrast application and at follow up cCT (days 3 and 7). RESULTS: The quality of the maps increases with increasing amount of iodine. However, the diagnostic result was not significantly better using more than about 16 g of iodine (e. g., 60 ml--7.2 ml/s--270 mg/ml) in cCT-perfusion studies. Only one patient had a pathologic increase in serum creatinine (day 1: 93; day 4: 146 micromol/l) but died at day 5 because of massive co-morbidity and septic pneumonia. No CIN occurred even in the patient group with pre-existent renal failure. CONCLUSIONS: About 60 ml contrast media and a moderate flow rate of about 7 ml/s ensure good results in perfusion-cCT, even if the patients have poor blood circulation or arteriosclerosis. The use of a dimer, non-ionic contrast media (range of 6-25 g iodine) seems to minimize the risk of CIN in the daily routine.

Aged↗

PubMed2005

[Laser-induced thermotherapy (LITT) of tumors of the liver in central location: results and complications].

PURPOSE: To investigate whether laser-induced thermotherapy (LITT) for tumors of the liver in central location is a sufficient and safe therapeutic option. MATERIAL AND METHODS: According to predefined criteria, 23 of 136 patients were chosen to be treated with LITT because of malignant liver tumors. At the time of the first LITT, the patients had 28 central tumors (27 metastases, one HCC), which were treated in 34 sessions with 64 laser applications and had a clinical and imaging follow-up every 3 months. RESULTS: The primary effectiveness rate was 74.1% and the secondary effectiveness rate 82.1%. The mortality rate was 0%. Major complications occurred in one patient (hemorrhagic pleural effusion), while minor complications occurred in 10 patients. During the median follow-up of 20 months (range 3-57 months), local tumor progression developed in 22% of the tumors. The effectiveness rate was 78.6%, 71.4% and 64.3% after 3, 6 and 9 months. The median survival was 46.0 months (95% confidence interval: 28.6-47.1 months). CONCLUSION: In our patients, complications and ablation rate of laser-induced thermotherapy for central liver tumors do not differ from those in peripheral location as described in the literature.

Confidence Intervals↗

PubMed2004

Endogenous retroviral syncytin: compilation of experimental research on syncytin and its possible role in normal and disturbed human placentogenesis.

Placental syncytin was first described in the year 2000 as a fusogenic glycoprotein originally derived from a human endogenous retroviral envelope gene. Although the presence of stable integrated retroviral elements within the human genome has been known for many years, their biological significance is still obscure and has usually been designated as irrelevant or even harmful. Syncytin, however, demonstrates tissue-specific expression and distinctive receptor interaction during trophoblast cell differentiation and syncytium formation. These findings indicate an involvement of syncytin in the development of the human placenta. Disturbances in placental architecture leading to severe placental dysfunction, such as pre-eclampsia, may therefore be discussed as a consequence of an altered syncytin system. We evaluate the hypothesis that syncytin is essential for human placenta formation and may also have played an important role in human placental evolution.

Amino Acid Transport System ASC↗

PubMed2004

[Percutaneous thermoablation of lung metastases. Indication, performance, initial results, and imaging findings].

Not unlike thermoablation of liver metastases, thermoablation of metastases to the lungs is gaining clinical interest. Radiofrequency ablation and laser-induced interstitial thermotherapy are both used clinically. Initially it was suspected that percutaneous treatment of lung metastases would result in a rate of pneumothoraces and tissue reactions which would not be clinically acceptable. However, this did not prove true. Fear of pneumothoraces however did lead to the desire for an applicator with a maximally reduced diameter. While clinical results are not yet available, technical success rates of laser-induced interstitial thermotherapy of lung metastases are promising. The percentage of pneumothoraces does not differ significantly from that seen in diagnostic procedures. Large metastases may be treated by simultaneous use of multiple applicators or by repositioning of an applicator (pullback technique). Surgical experience is still guiding us in deciding which primaries' metastases may be successfully treated percutaneously. The literature indicates that lung metastases from colorectal primaries are especially suited. Radiotherapy is only an alternative method in cases of lung metastases if they cause symptoms (such as pain because of thorax infiltration or difficulty in breathing because of bronchial lesion). Due to the risk of radiation-induced pneumonia general radiotherapy is not to be recommended. The possibility of stereotactic ray treatment is being considered, but because breathing shifts the metastases it is not yet feasible. Therefore, percutaneous thermoablation could be used as a minimally invasive, rather riskless therapeutic option for a relatively high percentage of inoperable lung metastases.

Catheter Ablation↗

PubMed2004

[Percutaneous laser-induced thermotherapy of lung metastases: experience gained during 4 years].

We perform laser ablation of lung metastases for four years. In the following we report on technical success, ablation results and follow-up. 30 patients with a total of 42 lung metastases were treated. Patients were aged between 42 and 74 years. Primary tumors were mostly colorectal carcinomas, head and neck and uro-genital tumors. Technical success was achieved in 40, complete ablation in 14 metastases (33%); however, in 8 metastases follow-up was too short for a valid evaluation (4-8 weeks). Further analysis may improve the overall results: metastases located in the central parts of the lungs were more easily treated than those located peripherally, best results were achieved in metastases not larger than 3 cm, percutaneous ablation of lung metastases has potential as an additional therapeutic option if surgery is not possible.

Adult↗

PubMed2004

Does excessive occlusal load affect osseointegration? An experimental study in the dog.

AIM: The purpose of this study was to evaluate the effect of excessive occlusal load following placement of titanium implants in the presence of healthy peri-implant mucosal tissues. MATERIALS AND METHODS: Mandibular bilateral recipient sites in six Labrador dogs were established by extracting premolars and molars. After 3 months, two TPS (titanium plasma sprayed) implants and two SLA (sandblasted, large grit, acid etched) implants were placed on each side of the mandible in each dog. Three implants were lost in the initial healing phase, leaving 45 implants for evaluation. Following 6 months of healing, gold crowns were placed on implants on the test side of the mandible. The crowns were in supra-occlusal contact with the opposing teeth in order to create excessive occlusal load. Implants on the control side were not loaded. Plaque control was performed throughout the experimental period. Clinical measurements and standardised radiographs were obtained at baseline and 1, 3 and 8 months after loading. At 8 months, the dogs were killed and histologic analyses were performed. RESULTS: At 8 months, all implants were osseointegrated. The mean probing depth was 2.5+/-0.3 and 2.6+/-0.3 mm at unloaded and loaded implants, respectively. Radiographically, the mean distance from the implant shoulder to the marginal bone level was 3.6+/-0.4 mm in the control group and 3.7+/-0.2 mm in the test group. Control and test groups were compared using paired non-parametric analyses. There were no statistically significant changes for any of the parameters from baseline to 8 months in the loaded and unloaded implants. Histologic evaluation showed a mean mineralised bone-to-implant contact of 73% in the control implants and 74% in the test implants, with no statistically significant difference between test and control implants. CONCLUSION: In the presence of peri-implant mucosal health, a period of 8 months of excessive occlusal load on titanium implants did not result in loss of osseointegration or marginal bone loss when compared with non-loaded implants.

Acid Etching, Dental↗

PubMed2003

[Laser-induced thermotherapy (LITT) of lung metastases: description of a miniaturized applicator, optimization, and initial treatment of patients].

PURPOSE: A thin-caliber applicator system was developed for introducing a laser fiber under CT guidance into lung metastases with only minimal complications. MATERIALS AND METHODS: A space-saving 5.5 French Teflon cannula with a titanium trocar and connectors for a laser light guide (2 or 3 cm Dornier Diffusor-Tip H-6111-T2 or H-6111-T3 coupled to a Dornier Medilas Fibertom 5100 laser, wavelength of 1064 nm) and a perfusion line for physiologic saline solution were developed. After puncture the laser Diffusor-Tip remains in the cannula and is cooled during its tissue passage by slowly flowing saline solution. The miniaturized applicator system (Monocath) was calibrated in nonperfused bovine liver for maximum energy supply and necessary flow of the cooling saline solution in reference to a commercially available 9 French laser catheter with an 11.5 French inducer sheath (Power-Applicator). The new applicator system was used for treating lung metastases in 10 patients over a period of 21 months. RESULTS: The size of heat coagulation in bovine liver was 24 +/- 2 ml using the miniaturized system with application of 15 W for 20 min and a saline flow of 0.75 ml/min, in comparison to a size of 29 +/- 7 ml for the commercial applicator (30 W, 20 min, 60 ml/min). All metastases could be safely approached with the miniaturized applicator, except for two metastatic lesions at the lung base in two patients. A minor pneumothorax developed in three patients and intrapulmonary bleeding in two. Contrast-enhanced CT demonstrated necrosis of the treated metastatic areas in 6 patients. Follow-up of three patients after 5, 6, and 8 months showed complete tumor regression with minimal scarring in one patient. CONCLUSION: The miniaturized applicator system enables the introduction of a laser fiber into pulmonary metastases with only minor complications. Complete ablation seems to be achievable in suitable patients with the applied laser energy and a slow cooling fluid flow rate.

Adult↗

PubMed2001

Spring, a novel RING finger protein that regulates synaptic vesicle exocytosis.

The synaptosome-associated protein of 25 kDa (SNAP-25) interacts with syntaxin 1 and vesicle-associated membrane protein 2 (VAMP2) to form a ternary soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex that is essential for synaptic vesicle exocytosis. We report a novel RING finger protein, Spring, that specifically interacts with SNAP-25. Spring is exclusively expressed in brain and is concentrated at synapses. The association of Spring with SNAP-25 abolishes the ability of SNAP-25 to interact with syntaxin 1 and VAMP2 and prevents the assembly of the SNARE complex. Overexpression of Spring or its SNAP-25-interacting domain reduces Ca(2+)-dependent exocytosis from PC12 cells. These results indicate that Spring may act as a regulator of synaptic vesicle exocytosis by controlling the availability of SNAP-25 for the SNARE complex formation.

Amino Acid Sequence↗

PubMed2001

Bacterial replication initiator DnaA. Rules for DnaA binding and roles of DnaA in origin unwinding and helicase loading.

We review the processes leading to the structural modifications required for the initiation of replication in Escherichia coli, the conversion of the initial complex to the open complex, loading of helicase, and the assembly of two replication forks. Rules for the binding of DnaA to its binding sites are derived, and the properties of ATP-DnaA are described. We provide new data on cooperative interaction and dimerization of DnaA proteins of E. coli, Streptomyces and Thermus thermophilus, and on the stoichiometry of DnaA-oriC complexes of E. coli.

Bacterial Proteins↗

PubMed2001

The sequence requirements for a functional Escherichia coli replication origin are different for the chromosome and a minichromosome.

We have developed a simple three-step method for transferring oriC mutations from plasmids to the Escherichia coli chromosome. Ten oriC mutations were used to replace the wild-type chromosomal origin of a recBCsbcB host by recombination. The mutations were subsequently transferred to a wild-type host by transduction. oriC mutants with a mutated DnaA box R1 were not obtained, suggesting that R1 is essential for chromosomal origin function. The other mutant strains showed the same growth rates, DNA contents and cell mass as wild-type cells. Mutations in the left half of oriC, in DnaA boxes M, R2 or R3 or in the Fis or IHF binding sites caused moderate asynchrony of the initiation of chromosome replication, as measured by flow cytometry. In mutants with a scrambled DnaA box R4 or with a modified distance between DnaA boxes R3 and R4, initiations were severely asynchronous. Except for oriC14 and oriC21, mutated oriCs could not, or could only poorly, support minichromosome replication, whereas most of them supported chromosome replication, showing that the classical definition of a minimal oriC is not valid for chromosome replication. We present evidence that the functionality of certain mutated oriCs is far better on the chromosome than on a minichromosome.

Blotting, Southern↗

PubMed2000

Transcriptional regulation of gene expression of sec6, a component of mammalian exocyst complex at the synapse.

Sec6, an essential component of the mammalian brain exocyst complex, is believed to function in synapse formation and synaptic plasticity. During neuronal development, the expression of the Sec6 gene correlates temporally with neurite outgrowth and synaptogenesis. To understand the mechanisms that regulate the Sec6 gene expression, we have cloned and characterized the 5'-terminal region of the murine Sec6 gene. We have shown that the 5'-untranslated region of the murine Sec6 gene is encoded by two exons that are separated by a 1560-bp intron. Primer extension analysis demonstrates that Sec6 gene transcription is initiated from a unique site. The Sec6 promoter is embedded in a CpG island and lacks canonical TATA or CAAT boxes. Sequence analysis of the 5'-flanking region and the first intron reveals the presence of a number of binding sites for transcription factors AP-1, AP-2, AP-4, ATF, C/EBPbeta, GATA-1, Oct 1, SP1, STAT, and NRSF. Transfection experiments using Sec6-luciferase fusion genes demonstrate that the 5'-flanking sequence functions as a strong promoter in neuronal but not in nonneuronal cells. Deletion analysis reveals the presence of a core promoter between nucleotide position -139 and +53, and two enhancer and four silencer elements within the 5'-flanking region and the first intron sequence. These results indicate that neuronal expression of the Sec6 gene involves a relatively specific core promoter and interplay between multiple positive and negative regulatory elements.

5' Untranslated Regions↗

PubMed2000

Analysis of the DNA-binding domain of Escherichia coli DnaA protein.

The DNA-binding domain of the Escherichia coli DnaA protein is represented by the 94 C-terminal amino acids (domain 4, aa 374-467). The isolated DNA-binding domain acts as a functional repressor in vivo, as monitored with a mioC:lacZ translational fusion integrated into the chromosome of the indicator strain. In order to identify residues required for specific DNA binding, site-directed and random PCR mutagenesis were performed, using the mioC:lacZ construct for selection. Mutations defective in DNA binding were found all over the DNA-binding domain with some clustering in the basic loop region, within presumptive helix B and in a highly conserved region at the N-terminus of presumptive helix C. Surface plasmon resonance (SPR) analysis revealed different binding classes of mutant proteins. No or severely reduced binding activity was demonstrated for amino acid substitutions at positions R399, R407, Q408, H434, T435, T436 and A440. Altered binding specificity was found for mutations in a 12 residue region close to the N-terminus of helix C. The defects of the classical temperature sensitive mutants dnaA204, dnaA205 and dnaA211 result from instability of the proteins at higher temperatures. dnaX suppressors dnaA71 and dnaA721 map to the region close to helix C and bind DNA non-specifically.

Amino Acid Sequence↗

PubMed2000

The interaction domains of the DnaA and DnaB replication proteins of Escherichia coli.

The initiation of chromosome replication in Escherichia coli requires the recruitment of the replicative helicase DnaB from the DnaBC complex to the unwound region within the replication origin oriC, supported by the oriC-bound initiator protein DnaA. We defined physical contacts between DnaA and DnaB that involve residues 24-86 and 130-148 of DnaA and residues 154-210 and 1-156 of DnaB respectively. We propose that contacts between DnaA and DnaB occur via two interaction sites on each of the proteins. Interaction domain 24-86 of DnaA overlaps with its N-terminal homo-oligomerization domain (residues 1-86). Interaction domain 154-210 of DnaB overlaps or is contiguous with the domains known to interact with plasmid initiator proteins. Loading of the DnaBC helicase in vivo can only be performed by DnaA derivatives containing (in addition to residues 24-86 and the DNA-binding domain 4) a structurally intact domain 3. Nucleotide binding by domain 3 is, however, not required. The parts of DnaA required for replication of pSC101 were clearly different from those used for helicase loading. Domains 1 and 4 of DnaA, but not domain 3, were found to be involved in the maintenance of plasmid pSC101.

Bacterial Proteins↗

PubMed1999

ATP- and ADP-dnaA protein, a molecular switch in gene regulation.

DnaA protein functions by binding to asymmetric 9mer DNA sites, the DnaA boxes. ATP-DnaA and ADP-DnaA bind to 9mer DnaA boxes with equal affinity, but only ATP-DnaA protein binds in addition to an as yet unknown 6mer site, the ATP-DnaA box AGATCT, or a close match to it. ATP-DnaA protein binding to ATP-DnaA boxes is restricted to sites located in close proximity to DnaA boxes, suggesting that protein-protein interaction is required for its stabilization. We show that ATP-DnaA represses dnaA transcription much more efficiently than ADP-DnaA. DnaA is thus a regulatory molecule that, depending on the adenosine nucleotide bound, can bind to different sequences and thereby fulfill distinct functions.

Adenosine Diphosphate↗

PubMed1999

Preliminary results of simultaneous radiochemotherapy with paclitaxel for urinary bladder cancer.

BACKGROUND: Paclitaxel (Taxol) has been shown to be effective in metastatic bladder cancer as single agent and in combination with other cytotoxic drugs. Its efficacy seems to be comparable to cisplatin. We have used paclitaxel as alternative to cisplatin in selected patients with simultaneous radiochemotherapy. The objective of this article is to summarize the preliminary results with regard to feasibility and toxicity. PATIENTS AND METHODS: From 10/97 through 10/98 7 patients with locally advanced or recurrent urothelial bladder cancer were treated with radiotherapy and simultaneous paclitaxel + cisplatin. All patients had macroscopic irresectable residual tumor after transurethral surgery or cystectomy. Paclitaxel was given twice weekly in a daily dosage of 25 through 35 mg/m2 as 1-hour-infusion. Cisplatin was given in a dosage of 25 mg/m2 daily on days 1 to 5. RESULTS: All patients completed the scheduled therapy regimen. The acute toxicity consisted mainly of enteritis (Grade I to II CTC). As severe toxicity, 1 severe skin reaction in the groins (Grade III) after 20 Gy and 1 Grade-III enteritis were noted. Both patients with severe complications recovered within 4 weeks after treatment. Hematological toxicity was mild to moderate in all cases. CONCLUSIONS: This report suggests that paclitaxel is a promising agent for simultaneous radiochemotherapy protocols. The clinical value remains to be better defined especially the question whether paclitaxel may improve the results if used as alternative to standard cisplatin. At the moment paclitaxel offers at least an attractive alternative to cisplatin in patients with impaired renal function.

Adult↗

PubMed1999

The N-terminus promotes oligomerization of the Escherichia coli initiator protein DnaA.

Initiation of chromosome replication in Escherichia coli is governed by the interaction of the initiator protein DnaA with the replication origin oriC. Here we present evidence that homo-oligomerization of DnaA via its N-terminus (amino acid residues 1-86) is also essential for initiation. Results from solid-phase protein-binding assays indicate that residues 1-86 (or 1-77) of DnaA are necessary and sufficient for self interaction. Using a 'one-hybrid-system' we found that the DnaA N-terminus can functionally replace the dimerization domain of coliphage lambda cl repressor: a lambdacl-DnaA chimeric protein inhibits lambda plasmid replication as efficiently as lambdacI repressor. DnaA derivatives with deletions in the N-terminus are incapable of supporting chromosome replication from oriC, and, conversely, overexpression of the DnaA N-terminus inhibits initiation in vivo. Together, these results indicate that (i) oligomerization of DnaA N-termini is essential for protein function during initiation, and (ii) oligomerization does not require intramolecular cross-talk with the nucleotide-binding domain III or the DNA-binding domain IV. We propose that E. coli DnaA is composed of largely independent domains - or modules - each contributing a partial, though essential, function to the proper functioning of the 'holoprotein'.

Amino Acid Sequence↗

PubMed1998

Oxygenation of squamous cell carcinoma of the head and neck: comparison of primary tumors, neck node metastases, and normal tissue.

BACKGROUND: Most previous oxygenation measurements of head and neck tumors have mainly been performed in neck nodes. We investigated, therefore, the relationship between the pO2 status of primary tumors, cervical neck node metastases and normal tissues. PATIENTS AND METHODS: 30 patients with histologically proven advanced stage III-IV squamous cell carcinoma of head and neck underwent pretreatment polarographic pO2 measurements with a pO2 histograph (Eppendorf, Hamburg, Germany). We obtained data on oxygenation of 23 primary tumors, of 22 neck node metastases, and of 30 contralateral sternocleidomastoid muscles. In 15 cases, we were able to perform measurements in all three regions in the same individual. results: A highly significant correlation existed between the median pO2 of primary tumors and their neck node metastases (p=0.0001), as well as between the proportion of pO2 values < or =2.5 mmHg and +/-5.0 mmHg (p=0.0001, p=0.001) in both anatomic sites. The average pretreatment median PO2 was 14.7 mmHg (range 0.2-58.5 mmHg) in primary tumors, 13.7 mmHg (range 1.9-50.3 mmHg) in neck node metastases, and 43.8 mmHg (range 20.8-67.7 mmHg) in sternocleidomastoid muscles. In all cases, the oxygenation of malignant tissue was below that of the corresponding muscle. There was also a weak, but significant, correlation between hemoglobin level and the median pO2 of the primary tumors, as well as between hemoglobin concentration and the proportion of values below 5 mmHg at the primary site (p=0.017, p=0.003). CONCLUSIONS: Primary tumors and their regional lymph node metastases in advanced squamous cell carcinoma of the head and neck show comparable patterns of oxygenation in terms of the median pO2 and the proportion of hypoxic measurements. This report suggests that, in patients with such carcinomas, the oxygenation data obtained at one site are related to tumor oxygenation at other sites, so that measurements in any anatomic site would be sufficient to estimate a tumor's oxygenation status. The weak correlation between pO2 and hemoglobin level requires further investigation.

Adult↗

PubMed1998

Interaction of the Escherichia coli DnaA protein with bacteriophage lambda DNA.

Interaction of the Escherichia coli DnaA (replication initiator) protein with restriction fragments of phage lambda DNA demonstrated differential binding of DnaA along the whole lambda DNA. Interaction of DnaA with the lambda replication region (from the promoter pR to the origin of replication, orilambda) demonstrated a strong binding of DnaA to the region around the p(o) promoter where synthesis of a short antisense oop RNA is initiated. The four sequences protected by DnaA (two 9mers and two 5mers) are not related even to a relaxed DnaA box. The pattern of protection of these four sequences and the location of three DNase I hypersensitive sites in the lambda DNA r strand, together with results of mobility shift assays and electron microscopy studies, may indicate an interaction involving DnaA monomers bound to different DNA positions on one side of the helix and the formation of higher-order nucleoprotein structures. Therefore, it is tempting to suggest that DnaA, in addition to its activity in regulation of replication and transcription, could be considered as a factor which structures certain chromosomal regions.

Bacterial Proteins↗