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Biomedical subjects

D Strobel

Publications and source records attributed to D Strobel.

33 records · Page 2Linked to original sources
PubMed1996

K-ras point mutations are rare events in premalignant forms of Barrett's oesophagus.

OBJECTIVE: In Barrett's adenocarcinomas, in contrast to squamous oesophageal carcinomas, K-ras point mutations are thought to be a frequent event. The frequency of K-ras point mutations in premalignant forms of Barrett's oesophagus (metaplasia, dysplasia) leading to adenocarcinoma with increased risk is currently not known. To establish the frequency of K-ras mutations in premalignant forms of Barrett's oesophagus, we investigated oesophageal biopsy specimens with Barrett's metaplastic and dysplastic epithelium for point mutations in the K-ras gene/codons 12, 13. DESIGN: A total of 412 biopsies from patients with Barrett's oesophagus were histologically classified into biopsies with metaplasia (n = 252), dysplasia (n = 105) and adenocarcinoma (n = 11), as well as biopsies distant from disease (normal, n = 37 and hyperplastic squamous epithelium, n = 7). METHODS: DNA from biopsy specimens was amplified by polymerase chain reaction (PCR) with a modified primer for generating a restriction site in the case of wild type in codon 12. Wild-type or point mutations in the K-ras gene/codons 12, 13 were detected by restriction fragment length analysis of the PCR products. RESULTS: Point mutations in K-ras/codon 12 were found in 9 biopsies (n = 1 in metaplasia, n = 4 in dysplasias, n = 4 in adenocarcinomas). All the other biopsies showed the wild type of K-ras/codon 12. No K-ras/codon 13 mutation (GGCgly-->GACasp) was observed. CONCLUSION: Mutations in K-ras/codon 12 were rarely found in premalignant forms of Barrett's oesophagus. Whereas the screening for K-ras point mutations in metaplastic sites of Barrett's epithelium seems not to be of practical value, the screening for mutations in dysplastic lesions might be helpful to estimate the individual risk for progression of Barrett's epithelium to adenocarcinoma. A further evaluation in larger numbers of patients is needed.

Adenocarcinoma↗
PubMed1993

Temperature sensitivity of aberrant RNA splicing with a mutation in the G+5 position of intron 37 of the gene for type III procollagen from a patient with Ehlers-Danlos syndrome type IV.

A single-base mutation in intron 37 of the gene for type III procollagen (COL3A1) was found in a proband with the type IV variant of Ehlers-Danlos syndrome. Probe-protection experiments with S1 nuclease and RNA from fibroblasts incubated at 37 degrees C demonstrated that about 35% of the total mRNA or about 70% of the mRNA from mutated allele was spliced by exon skipping. The effects of the mutation were temperature-sensitive in that the amount of RNA from the mutated allele that was spliced by exon skipping was 87.1 +/- 7.7% at 31 degrees C, 70.1 +/- 6.5% at 37 degrees C, and 85.4 +/- 11.1% at 42 degrees C. The effects of temperature on aberrant RNA splicing were, therefore, the reverse of those reported for four previous mutants in collagen genes. The increase in abnormal RNA splicing when the temperature was raised from 31 degrees to 37 degrees C seen with previously reported mutants suggested that RNA-RNA hybridization of U1snRNA to the 5'-splice site in the substrate may be limiting in the processing of transcripts from the mutated alleles, since RNA-RNA hybridizations become less favorable at higher temperatures. The decrease in abnormal RNA splicing seen here when the temperature was raised from 31 degrees to 37 degrees C suggested that protein-RNA or protein-protein binding steps become rate limiting with the G+5 mutation in intron 37 of the COL3A1 gene.

Adolescent↗
PubMed1991

Heterozygous mutation in the G+5 position of intron 33 of the pro-alpha 2(I) gene (COL1A2) that causes aberrant RNA splicing and lethal osteogenesis imperfecta. Use of carbodiimide methods that decrease the extent of DNA sequencing necessary to define an unusual mutation.

Cultured skin fibroblasts from a proband with osteogenesis imperfecta were found to synthesize normal and shortened alpha 2(I) chains of type I procollagen. A cDNA library was prepared using mRNA isolated from the proband's fibroblasts. Partial nucleotide sequencing of five clones demonstrated that two clones lacked the 54 base pairs (bp) of coding sequences found in exon 33 of the pro-alpha 2(I) gene (COL1A2). To reduce the amount of nucleotide sequencing required, heteroduplexes were prepared from two of the clones, one normal and the other lacking exon 33, and reacted with a water-soluble carbodiimide under conditions in which nonbase-paired G and T nucleotides are specifically modified by the reagent. Analysis of the heteroduplexes by immunoelectron microscopy suggested that the sequence variation near the codons of exon 33 was the only sequence difference in the cDNA clones. Amplification of cDNA from the proband by polymerase chain reaction gave products of two sizes, one of the expected size for the normal sequence and the other of the expected size for a product lacking the 54 bp in exon 33. To define the mutation in genomic DNA, a 1.6-kilobase region spanning exons 32 and 34 was amplified by the polymerase chain reaction and DNA heteroduplexes were prepared from the products. The heteroduplexes were treated with a water-soluble carbodiimide and then used as templates for primer extension under conditions in which extension terminates at the site of a carbodiimide-modified base. The results suggested a mismatch near the exon-intron boundary of exon 33 and a second mismatch near the 3' end of intron 33. Nucleotide sequencing of the polymerase chain reaction products revealed a single-base substitution in one allele that changed the moderately conserved G at position +5 of the 5' splice site of intron 33 to an A. In addition, there was an apparently neutral single-base substitution that placed both a G and T at position +661 of intron 33. The results provide only the third example of a mutation in the G at the +5 position of an intron that causes aberrant RNA splicing. Also, the results demonstrate that use of techniques involving carbodiimide modification of DNA heteroduplexes can reduce the amount of nucleotide sequencing necessary to define mutations in large and complex genes.

Adult↗
PubMed1990

Adult scurvy.

Explore the source record for details and available documents.

Ascorbic Acid↗
PubMed1985

Basal cell carcinoma arising at the site of venipuncture.

Basal cell carcinoma has been reported to occur in sites of chronic trauma, inflammation, or scarring, and even after a single injury. We report on a patient in whom a nodular basal cell carcinoma developed at the site of venipuncture. The venipuncture occurred six months earlier and the site never healed but gradually progressed to a nodule of basal cell carcinoma. Single injuries may provoke or aggravate the growth of basal cell carcinoma.

Bloodletting↗
PubMed1985

Iododerma occurring during thyroid protection treatment.

A patient with rheumatoid arthritis developed nodules and ulcers shortly after treatment with supersaturated potassium iodide (SSKI) drops. The SSKI was administered for thyroid protection during an iodide fibrinogen uptake test to detect phlebothrombosis of the legs. Discontinuation of SSKI was accompanied by regression of all lesions. Previous case reports include other patients who experienced iododerma after receiving low doses of iodides. This should be borne in mind if ever a mass iodide prophylaxis program is undertaken following a nuclear event.

Aged↗
PubMedDate not supplied

Cellular and vascular reactions in the liver to radio-frequency thermo-ablation with wet needle applicators. Study on juvenile domestic pigs.

UNLABELLED: The aim of this animal experiment was to investigate the cellular and vascular reactions in the liver of juvenile domestic pigs produced by a radio-frequency thermoablation (RFTA) applicator perfused with saline solution. METHODS: A total of 13 coagulation necroses were produced in the liver of 3 anesthetized domestic pigs using RFTA. The pigs were dissected and the coagulations examined. RESULTS: The mean macroscopical length and width of the coagulation zones with a hemorrhagic marginal zone after a 5-minute application time were 34.1 +/- 8 mm (22-46 mm) and 20.8 +/- 4 mm (12 +/- 28 mm) respectively. The sonographically determined diameters correlated significantly (r(length) = 0.741 and r(width) = 0.923). Three areas in the coagulation zones could be histologically distinguished: (1) central necrosis zone, (2) hemorrhagic marginal zone, (3) sublethal damage zone. Large vessels did not show any substantial changes after RFTA. Venous vessels less than 1 mm were completely thermally denatured or destroyed. CONCLUSIONS: Tumors in close proximity to large blood vessels can be treated by RFTA with 'wet electrodes'.

Animals↗
PubMedDate not supplied

Radiofrequency ablation of liver tumors: how to enlarge the necrotic zones?

In an attempt to increase necrotic zones in liver tissue by radiofrequency ablation fresh bovine liver was coagulated by means of a needle electrode continuously perfused with NaCl solution. Power output (60 W) and application time (15 min) were kept constant while the perfusion was varied in terms of saline concentration (0.9, 5.85 and 10%) and perfusion rate (40 or 80 ml/h). Our results showed that the use of higher osmolar saline solutions in radiofrequency ablation with perfused needle electrodes did not lead to significantly larger coagulation volumes. By contrast, increasing the perfusion rate produced significantly larger necrotic zones. Doubling the perfusion rate made it possible to reach higher temperatures (>60 degrees C) within significantly shorter time.

Animals↗
PubMedDate not supplied

Radiofrequency ablation using perfused needle electrodes - study of intermittent and continuous triple needle application ex vivo.

To increase necrotic zones, bovine livers were treated by means of three parallel-oriented radiofrequency ablation (RFA) needles spaced at 3 cm using a puncture guide. The triple application was varied as a continuous and intermittent energy application compared to a single needle applicator. In all three study arms the applied energy (60 W) and the perfusion rate (240 ml/h) were kept constant. After treatment the smallest necrosis diameter was determined. In addition, temperature and the device's power output were monitored. Our study shows that synchronous use of three RFA application needles achieves significantly larger necrosis zones ex vivo than does single needle application. Intermittent energy application heats up the necrosis faster and more evenly with highest average temperature than continuous energy application.

Animals↗