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Biomedical subjects

A H Andersen

Publications and source records attributed to A H Andersen.

At least 55 records · Page 3Linked to original sources
PubMed1991

Molecular cloning, occurrence, and expression of a novel partially secreted protein "psoriasin" that is highly up-regulated in psoriatic skin.

Analysis of the protein patterns of normal and psoriatic noncultured unfractionated keratinocytes has revealed several low-molecular-weight proteins that are highly up-regulated in psoriatic epidermis. Here, we have cloned and sequenced the cDNA (clone 1085) for one of these proteins that we have termed psoriasin. The deduced sequence predicted a protein of molecular weight of 11,457 daltons and a pI of 6.77. The protein co-migrated with psoriasin as determined by two-dimensional (2D) gel analysis of [35S]-methionine-labeled proteins expressed by RK13 cells transfected with clone 1085 using the vaccinia virus expression system. Analysis of the predicted sequence revealed a potential calcium-binding sequence of the EF-hand type, as well as the absence of a signal sequence at its amino terminal. Psoriasin is not related to other proteins that migrate closely in 2D gels (MRP 14, also known as calgranulin B, L1 and calprotectin; MRP 8, or calgranulin A and cystatin A or stefin A), and bears no significant sequence homology with any other protein of known primary structure. Increased expression of psoriasin mRNA in psoriatic keratinocytes was confirmed by Northern blotting and in situ hybridization. Psoriasin showed a restricted occurrence in fetal human tissues as determined by 2D gel electrophoresis. Of 21 tissues analyzed, only ear, skin, and tongue showed significant levels of this protein. Psoriasin was not detected in normal human fibroblasts, lymphocytes, endothelial cells and transformed epithelial cells of keratinocyte origin. Granulocyte extracts contained this protein suggesting that its overexpression by psoriatic keratinocytes may be linked to the inflammatory stimuli.

Amino Acid Sequence↗
PubMed1990

Stimulation of topoisomerase II mediated DNA cleavage at specific sequence elements by the 2-nitroimidazole Ro 15-0216.

The effect of the 2-nitroimidazole Ro 15-0216 upon the interaction between purified topoisomerase II and its DNA substrate was investigated. The cleavage reaction in the presence of this DNA-nonintercalative drug took place with the hallmarks of a regular topoisomerase II mediated cleavage reaction, including covalent linkage of the enzyme to the cleaved DNA. In the presence of Ro 15-0216, topoisomerase II mediated cleavage was extensively stimulated at major cleavage sites of which only one existed in the 4363 base pair pBR322 molecule. The sites stimulated by Ro 15-0216 shared a pronounced sequence homology, indicating that a specific nucleotide sequence is crucial for the action of this drug. The effect of Ro 15-0216 thus differs from that of the clinically important topoisomerase II targeted agents such as mAMSA, VM26, and VP16, which enhance enzyme-mediated cleavage at a multiple number of sites. In contrast to the previous described drugs, Ro 15-0216 did not exert any inhibitory effect on the enzyme's catalytic activity. This observation might be ascribed to the low stability of the cleavage complexes formed in the presence of Ro 15-0216 as compared to the stability of the ones formed in the presence of traditional topoisomerase II targeted drugs.

Acetanilides↗
PubMed1990

Characterization of the interaction between topoisomerase II and DNA by transcriptional footprinting.

The interaction between calf thymus topoisomerase II and DNA has been characterized using a transcription assay. A highly preferred recognition sequence for topoisomerase II was inserted in either direction downstream from a promoter specific for a bacteriophage RNA polymerase. The presence of topoisomerase II-DNA complexes on the template provoked blockage of transcription, yielding RNA transcripts terminated 5' to the topoisomerase II binding site. A footprint of topoisomerase II, derived from transcription towards the complex from either side, revealed that eukaryotic topoisomerase II binds a region of 28 base-pairs with a highly protected central core of 22 base-pairs. The binding region was located symmetrically around the topoisomerase II-mediated cleavage site. In agreement with this result, optimal topoisomerase II-mediated cleavage was observed with a DNA substrate consisting of a 28-mer oligonucleotide homologous to the protected region. Stepwise removal of base-pairs from the ends of the 28-mer gradually reduced the level of enzyme-mediated cleavage.

Acetanilides↗
PubMed1990

Minimal DNA requirement for topoisomerase II-mediated cleavage in vitro.

The minimal DNA requirement for topoisomerase II-mediated DNA cleavage in vitro was determined by analyzing the interaction of the enzyme with sets of DNA substrates varying successively by single bases at the 5'- or 3'-end of either strand. A 16-base pair double-stranded region was established as the minimal duplex region required for topoisomerase II cleavage activity. The region was located symmetrically around the 4-base staggered cleavage site. Topoisomerase II-mediated cleavage within the 16-base pair core duplex, however, required single-stranded regions flanking the duplex to either the 5'- or 3'-sides, or an extension at both ends of the duplex with 1 or more base pairs.

Animals↗
PubMed1990

Minimal DNA duplex requirements for topoisomerase I-mediated cleavage in vitro.

The minimal DNA duplex requirements for topoisomerase I-mediated cleavage at a specific binding sequence were determined by analyzing the interaction of the enzyme with sets of DNA substrates varying successively by single nucleotides at the 5'- or 3' end of either strand. Topoisomerase I cleavage experiments showed a minimal region of nine nucleotides on the scissile strand and five nucleotides on the noncleaved strand. On the scissile strand, seven of the nine nucleotides were situated upstream to the cleavage site, while all five nucleotides required on the non-cleaved strand were located to this side. The results suggested that topoisomerase I bound tightly to this region, stabilizing the DNA duplex extensively. On minimal substrates which were partially single-stranded downstream to the cleavage site, cleavage was suicidal, that is, the enzyme was able to cleave the substrates, but unable to perform the final religation.

Base Sequence↗
PubMed1990

A ray tracing approach to restoration and resolution enhancement in experimental ultrasound tomography.

Recursive ray tracing is applied for experimental time-of-flight projection data to achieve a resolution enhancement over the initial straight-ray reconstructed velocity image. Curved-ray reconstruction is performed using the dedicated simultaneous algebraic reconstruction technique (SART). Tomographic reconstructions from experimental data are compared to images obtained from simulated projection data for a refractive field mimicking the actual tissue-equivalent phantom. The simulation study adequately explains the macrostructural geometric distortion and loss of resolution in the straight-ray image due to refraction effects that are unaccounted for.

Computer Simulation↗
PubMed1990

Quantification of oral epithelial hyperplasia in rats after topical application of the carcinogen 4-nitroquinoline 1-oxide.

Hyperplasia of the palatal epithelium was quantified in two groups of rats exposed thrice weekly to the carcinogen 4NQO for 2 weeks and 2 months, respectively. The lengths and areas of the epithelial layers were measured with a computerized line-following device. In the group treated for 2 weeks the maximum area of the nuclear layer was nearly three times and the maximum length of the epithelial/connective tissue interface almost twice the normal at the end of the carcinogen application period. The maximum area of the cornified layer was three times and the maximum lengths of the epithelial surface and the keratin/nuclear layer interface almost one and a half times the normal 1 week after painting with 4NQO. Thereafter the lengths and areas decreased gradually in both experimental groups. The area of the cornified layer and the length of the epithelial/connective tissue interface in the group treated for 2 months were significantly larger than those in animals treated for 2 weeks. These variables may be two of several indicators of prognostic significance in the assessment of dose-related premalignant epithelial hyperplasia.

4-Nitroquinoline-1-oxide↗
PubMed1989

Double-stranded DNA cleavage/religation reaction of eukaryotic topoisomerase II: evidence for a nicked DNA intermediate.

The DNA cleavage reaction of eukaryotic topoisomerase II produces nicked DNA along with linear nucleic acid products. Therefore, relationships between the enzyme's DNA nicking and double-stranded cleavage reactions were determined. This was accomplished by altering the pH at which assays were performed. At pH 5.0 Drosophila melanogaster topoisomerase II generated predominantly (greater than 90%) single-stranded breaks in duplex DNA. With increasing pH, less single-stranded and more double-stranded cleavage was observed, regardless of the buffer or the divalent cation employed. As has been shown for double-stranded DNA cleavage, topoisomerase II was covalently bound to nicked DNA products, and enzyme-mediated single-stranded cleavage was salt reversible. Moreover, sites of single-stranded DNA breaks were identical with those mapped for double-stranded breaks. To further characterize the enzyme's cleavage mechanism, electron microscopy studies were performed. These experiments revealed that separate polypeptide chains were complexed with both ends of linear DNA molecules generated during cleavage reactions. Finally, by use of a novel religation assay [Osheroff, N., & Zechiedrich, E. L. (1987) Biochemistry 26, 4303-4309], it was shown that nicked DNA is an obligatory kinetic intermediate in the topoisomerase II mediated reunion of double-stranded breaks. Under the conditions employed, the apparent first-order rate constant for the religation of the first break was approximately 6-fold faster than that for the religation of the second break. The above results indicate that topoisomerase II carries out double-stranded DNA cleavage/religation by making two sequential single-stranded breaks in the nucleic acid backbone, each of which is mediated by a separate subunit of the homodimeric enzyme.

Animals↗
PubMed1989

Strand specificity of the topoisomerase II mediated double-stranded DNA cleavage reaction.

The strand specificity of topoisomerase II mediated DNA cleavage was analyzed at the nucleotide level by characterizing the enzyme's interaction with a strong DNA recognition site. This site was isolated from the promoter region of the extrachromosomal rRNA genes of Tetrahymena thermophila and was recognized by type II topoisomerases from a variety of phylogenetically diverse eukaryotic organisms, including Drosophila, Tetrahymena, and calf thymus. When incubated with this site, topoisomerase II was found to introduce single-stranded breaks (i.e., nicks) in addition to double-stranded breaks in the nucleic acid backbone. Although the nucleotide position of cleavage on both the noncoding and coding strands of the rDNA remained unchanged, the relative ratios of single- and double-stranded DNA breaks could be varied by altering reaction conditions. Under all conditions which promoted topoisomerase II mediated DNA nicking, the enzyme displayed a 3-10-fold specificity for cleavage at the noncoding strand of its recognition site. To determine whether this specificity of topoisomerase II was due to a faster forward rate of cleavage of the noncoding strand or a slower rate of its religation, a DNA religation assay was performed. Results indicated that both the noncoding and coding strands were religated by the enzyme at approximately the same rate. Therefore, the DNA strand preference of topoisomerase II appears to be embodied in the enzyme's forward cleavage reaction.

Animals↗
PubMed1989

Dose-dependent bimodal effect of low-level lead exposure on the developing hippocampal region of the rat: a volumetric study.

The hippocampal region is known to accumulate experimentally applied and environmentally occurring lead and to be implicated in lead-induced behavioral deficits. With the intention of investigating morphological changes resulting from the lower range of exposures that produce behavioral alterations in laboratory animals, the volumes of hippocampal components were determined in groups of rats exposed from postnatal days 0-21 to different concentrations of lead through the maternal water supply (initially 109 ppm, subsequently replicated with 109, 218, 436 and 872 ppm). Significant effects were found in the mossy fiber zone, the granule cell layer and the commissural-associational zone of the dentate molecular layer of the group exposed to 109 ppm lead and the pyramidal cell layer of regio inferior (CA3) of Ammon's horn in the group exposed to 218 ppm lead. These results provide evidence that lead primarily affects newly formed neuronal components. In contrast to the results of previous studies, which used larger exposures to lead, the components affected in the group exposed to 109 ppm increased in volume. In addition, no significant effects were observed in the groups exposed to 436 and 872 ppm. Based on these findings and additional evidence from the literature, it is concluded that lead has a dose dependent bimodal influence on developing hippocampal components. While the volumetric changes related to lead were of the same magnitude and direction in the initial and replication studies, the absolute volumes of the affected hippocampal components were different. The differences in "baseline" values in the two studies are more likely related to differences in prenatal conditions.

Animals↗
PubMed1987

A quantitative evaluation of the neurotoxic effect of silver on the volumes of the components of the developing rat hippocampus.

The volumes of the components of the hippocampus of rats subjected to subcutaneous injections of silver during the first 4 postnatal weeks were compared to those of littermate controls. Of the 14 components measured, only the pyramidal cell layer was found to be significantly smaller in the treated animals. These findings indicate that the perikaria of the pyramidal cells are either the first elements in the developing hippocampus to show signs of silver toxicity or that they are the selective sites of silver neurotoxicity. The volumetric approach is shown to be a sensitive means by which small localized neurotoxic effects can be detected.

Animals↗
PubMed1985

Topoisomerase I has a strong binding preference for a conserved hexadecameric sequence in the promoter region of the rRNA gene from Tetrahymena pyriformis.

Topoisomerase I is in situ associated with DNaseI hypersensitive sites located in the promotor and terminator regions of the extrachromosomal rDNA in Tetrahymena thermophila at sites with sequences fitting the motif (sequence in text) Reconstitution experiments with purified topoisomerase I and cloned fragments of rDNA demonstrate that the enzyme exhibits the same binding and cleavage properties on naked DNA. These observations are striking as topoisomerase I previously has been found to exhibit low sequence specificity. The specific binding of the enzyme has an absolute requirement for divalent cations with a preference for Ca2+. The strong binding to the hexadecamer has been characterized by competition experiments, and it has been used to determine the molecular weight of the enzyme.

Animals↗
PubMed1984

Simultaneous algebraic reconstruction technique (SART): a superior implementation of the art algorithm.

In this paper we have discussed what appears to be a superior implementation of the Algebraic Reconstruction Technique (ART). The method is based on 1) simultaneous application of the error correction terms as computed by ART for all rays in a given projection; 2) longitudinal weighting of the correction terms back-distributed along the rays; and 3) using bilinear elements for discrete approximation to the ray integrals of a continuous image. Since this implementation generates a good reconstruction in only one iteration, it also appears to have a computational advantage over the more traditional implementation of ART. Potential applications of this implementation include image reconstruction in conjunction with ray tracing for ultrasound and microwave tomography in which the curved nature of the rays leads to a non-uniform ray density across the image.

Humans↗
PubMed1984

Degree of vertebral wedging of the dorso-lumbar spine.

From a random sample consisting of 164 persons, the degree of vertebral wedging was calculated as the ratio between the heights of the anterior and posterior aspects of the vertebrae Th8 to L3. The normal values and confidence limits are described. The degree of wedging was significantly greater at almost all levels in the male group than in the female group. No positive relationship to age was found.

Adolescent↗
PubMed1982

Development of thermotolerance during fractionated hyperthermia in a solid tumor in vivo.

The effect of 43.5 degrees water bath heating on a C3H mammary carcinoma inoculated into the foot of BALB/c x DBA F1 (hereafter called CD2F1 mice was investigated. A single heat treatment resulted in a linear dose-response relationship between heating time and tumor growth time (i.e., the time for tumors to reach 5 times the initial volume of the first treatment day). Recovery from hyperthermic damage, demonstrated by two-dose fractionation experiments (30 min + 60 min at 43.5 degrees), increased with increasing fractionation interval and reached its maximum at a 16-hr interval. Preheating for 30 min at 43.5 degrees induced thermal resistance to a second heat treatment at 43.5 degrees (thermotolerance) which was evidenced by a decrease in the slope of the dose-response curves. This thermotolerance gradually increased with increasing interval and reached a maximum at a 16-hr interval with a thermotolerance ratio of 5.2. Subsequently, the thermotolerance gradually decayed and completely disappeared at a 120-hr interval. No detectable repair of hyperthermic damage was found in this tumor. In principle, there data confirm the observations on thermotolerance reported previously for cell cultures in vitro and for several normal tissues in vivo.

Animals↗