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Biomedical subjects

R Conrad

Publications and source records attributed to R Conrad.

At least 73 records · Page 4Linked to original sources

Diagnostic value of p53 immunohistochemistry in Barrett's esophagus: an endoscopic study.

The aim of this study was to establish the diagnostic utility of p53 immunohistochemistry in Barrett's esophagus. Three pathologists reviewed endoscopic biopsy specimens and one surgical specimen derived from 102 subjects in a prospective follow-up series. Dysplasia was graded as negative, indefinite, low grade and high grade. p53 staining was assessed as negative, weak or patchy and strong. Kappa coefficients for interobserver agreement for the three combinations of observer pairs were moderate to substantial (0.48, 0.55 and 0.68) for dysplasia and substantial to near perfect (0.77, 0.82 and 0.89) for p53 immunostaining. In the consensus grading achieved for dysplasia, strong p53 staining was recorded in 0/79 samples that were negative or indefinite for dysplasia, 5/15 (33%) examples of low grade dysplasia and 7/8 (87%) examples of high grade dysplasia. Non-dysplastic p53 positive glands were seen in specimens from two subjects harbouring dysplasia or cancer elsewhere. Two p53 positive specimens were, upon review and discussion, re-assigned from low- to high-grade dysplasia. It is concluded that p53 immunohistochemistry facilitates the interpretation of Barrett's epithelium but need only be employed to confirm a suspected diagnosis of dysplasia and assist with the distinction between low- and high-grade dysplasia.

Barrett Esophagus↗

[Radiologic changes following cement-free implantation of hip prostheses. 5-year follow-up and clinical experience with the cement-free hip prosthesis Autophor-900-S].

PURPOSE: To evaluate early reliable radiographic signs of loosening in cementless total hip arthroplasty compared to clinical follow-up. METHODS: Within a time interval of 5 years 89 patients with 101 hips underwent total hip arthroplasty using the Autophor 900 S-prosthesis. Clinical and radiographic follow-up were first performed retrospectively followed by a prospective investigation. RESULTS: Radiographic evaluation showed prosthesis fixation in 93%. Loosening of the prosthesis was identified in 4 cases of the acetabular component and in 4 cases of the femoral stem. Pain was associated with radiographically detectable loosening of the cementless arthroplastic components in only two cases. CONCLUSION: Within a follow-up period of up to five years, loosening of cementless total hip arthroplasty occurs in about 7%. The most reliable radiographic signs of loosening are complete radiolucent zones wider than 2 mm at the bone-component interface, progressive subsidence, migration, or tilt of the component. Pain and movement disorders are not specific symptoms and do not necessarily indicate a loosening of the prosthesis.

Adult↗

[Oral contrast media in CT: improvement by addition of guar?].

PURPOSE: To evaluate the additional effect of guar with iotrolan as an oral contrast medium. METHOD: In a clinical double-blind randomised study a viscous iotrolan (11.2 mg iodine/ml)/guar (4 g/l)-suspension was compared with aqueous solutions of pure iotrolan (11.2 mg iodine/ml) and meglumine ioxithalamate (12 mg iodine/ml). The contrast media were evaluated according to filling, distribution, transit time, artifacts, radiodensity, patient acceptance and side effects. RESULTS: The addition of guar delayed the transit time of the contrast media. Consequently a more homogeneous filling of the bowel with fewer artifacts was observed in comparison to the aqueous contrast media. The results of the pure iotrolan solution were comparable to meglumine ioxithalamate, except for a higher radiodensity in the distal small intestine. The colon showed a better filling with non-viscous contrast media in the given time frame. Pure iotrolan had the best patient acceptance. Two patients considered the iotrolan/guar-solution impossible to drink, the other 18 patients found taste and consistency just about acceptable. CONCLUSION: In spite of the discussed advantages, due to a less subjective acceptance the guar/iotrolan solution is not suitable in routine-diagnosis, unless taste and consistency are greatly improved. Individual use is recommended in selected cases and long-term examinations.

Administration, Oral↗

Detecting immobilized protein kinase C isozymes with RNA aptamers.

Nucleic acids that can bind tightly and specifically to protein targets can be selected from random sequence pools. Just as antibodies have been used to detect proteins in a variety of formats, it is possible the nucleic acid binding species (aptamers) could be used to specifically detect proteins. Using a simple filter binding assay, aptamers have been used to detect protein kinase C (PKC) introduced into a cell extract. Aptamers that were relatively nonspecific could be used to simultaneously detect different PKC isozymes, while aptamers with higher specificities could discriminate between related isozymes. These results demonstrate the feasibility of using aptamers as diagnostic tools to detect proteins.

Animals↗

Oxidation of nitric oxide by a new heterotrophic Pseudomonas sp.

A new bacterial strain isolated from soil consumed nitric oxide (NO) under oxic conditions by oxidation to nitrate. Phenotypic and phylogenetic characterization of the new strain PS88 showed that it represents a previously unknown species of the genus Pseudomonas, closely related to Pseudomonas fluorescens and Pseudomonas putida. The heterotrophic, obligately aerobic strain PS88 was not able to denitrify or nitrify; however, strain PS88 oxidized NO to nitrate. NO was not reduced to nitrous oxide (N2O). Nitrogen dioxide (NO2) and nitrite (NO2-) as possible intermediates of NO oxidation to nitrate (NO3-) could not be detected. NO oxidation was inhibited under anoxic conditions and by high osmolarity, but not by nitrite. NO oxidation activity was inhibited by addition of formaldehyde, HgCl2, and antimycin, and by autoclaving or disintegrating the cells, indicating that the process was enzyme-mediated. However, the mechanism remains unclear. A stepwise oxidation at a metalloenzyme and a radical mechanism are discussed. NO oxidation in strain PS88 seems to be a detoxification or a co-oxidation mechanism, rather than an energy-yielding process.

Nitric Oxide↗

A case of total peripheral aneosinophilia associated with complete deficiency of myeloperoxidase.

Complete and permanent absence of peripheral eosinophilic granulocytes was observed in a patient also presenting with total myeloperoxidase deficiency. The anomaly was suspected because of complete absence of the eosinophilic cluster in the display of a H*3 Technicon hematological automate and was confirmed by traditional staining of more than 100,000 leukocytes. A severe infectious problem during adolescence could be related to MPO deficiency in this patient. No specific disorder attributable to aneosinophilia was however observed subsequently.

Aged↗

Soil microorganisms as controllers of atmospheric trace gases (H2, CO, CH4, OCS, N2O, and NO).

Production and consumption processes in soils contribute to the global cycles of many trace gases (CH4, CO, OCS, H2, N2O, and NO) that are relevant for atmospheric chemistry and climate. Soil microbial processes contribute substantially to the budgets of atmospheric trace gases. The flux of trace gases between soil and atmosphere is usually the result of simultaneously operating production and consumption processes in soil: The relevant processes are not yet proven with absolute certainty, but the following are likely for trace gas consumption: H2 oxidation by abiontic soil enzymes; CO cooxidation by the ammonium monooxygenase of nitrifying bacteria; CH4 oxidation by unknown methanotrophic bacteria that utilize CH4 for growth; OCS hydrolysis by bacteria containing carbonic anhydrase; N2O reduction to N2 by denitrifying bacteria; NO consumption by either reduction to N2O in denitrifiers or oxidation to nitrate in heterotrophic bacteria. Wetland soils, in contrast to upland soils are generally anoxic and thus support the production of trace gases (H2, CO, CH4, N2O, and NO) by anaerobic bacteria such as fermenters, methanogens, acetogens, sulfate reducers, and denitrifiers. Methane is the dominant gaseous product of anaerobic degradation of organic matter and is released into the atmosphere, whereas the other trace gases are only intermediates, which are mostly cycled within the anoxic habitat. A significant percentage of the produced methane is oxidized by methanotrophic bacteria at anoxic-oxic interfaces such as the soil surface and the root surface of aquatic plants that serve as conduits for O2 transport into and CH4 transport out of the wetland soils. The dominant production processes in upland soils are different from those in wetland soils and include H2 production by biological N2 fixation, CO production by chemical decomposition of soil organic matter, and NO and N2O production by nitrification and denitrification. The processes responsible for CH4 production in upland soils are completely unclear, as are the OCS production processes in general. A problem for future research is the attribution of trace gas metabolic processes not only to functional groups of microorganisms but also to particular taxa. Thus, it is completely unclear how important microbial diversity is for the control of trace gas flux at the ecosystem level. However, different microbial communities may be part of the reason for differences in trace gas metabolism, e.g., effects of nitrogen fertilizers on CH4 uptake by soil; decrease of CH4 production with decreasing temperature; or different rates and modes of NO and N2O production in different soils and under different conditions.

Animal Population Groups↗

Aptamers as potential nucleic acid pharmaceuticals.

In vitro selection is a technique for the isolation of nucleic acid ligands that can bind to proteins with high affinity and specificity, and has potential applications in the development of new pharmaceuticals. This review summarizes the protein targets that have successfully elicited nucleic acid binding species (also known as "aptamers") and explores examples of how they might be developed for clinical use. In particular, the use of aptamers for the alleviation of blood clotting and the treatment of AIDS are considered.

Acquired Immunodeficiency Syndrome↗

Decreased catalase activity but unchanged superoxide dismutase activity in brains of patients with dementia of Alzheimer type.

"Oxidative stress" may be of significance in the etiopathogenesis of dementia of Alzheimer type (DAT). Therefore, we measured activities of the enzymes superoxide dismutase (SOD) and catalase (CAT), which detoxicate reactive oxygen species. Enzyme activities were measured postmortem in basal ganglia, cortical, and limbic brain regions of patients with DAT and age-matched controls. SOD activity increased with age in basal nucleus of Meynert. However, there was no significant difference in SOD activity between DAT and controls. CAT activity was independent of age and postmortem time. There were significant reductions in CAT activity in parietotemporal cortex, basal ganglia, and amygdala in DAT compared with controls (p < 0.05 to 0.01). Our findings are in line with the assumption that reactive oxygen species could contribute to the pathogenesis of DAT. Absence of these changes in basal nucleus of Meynert might reflect retrograde degeneration of cholinergic fibers.

Age Factors↗

Methanogenic and other strictly anaerobic bacteria in desert soil and other oxic soils.

Strictly anaerobic bacteria such as methanogenic, sulfate-reducing, and homoacetogenic bacteria could be enriched from all five oxic soils tested. The number of cells was lower than that in typical anoxic habitats. Spores did not always dominate the population of sulfate-reducing bacteria. In all soils, the methanogenic population displayed a long lag phase after anoxic conditions were imposed before methane production began.

Journal Article↗

SL1 trans-splicing specified by AU-rich synthetic RNA inserted at the 5' end of Caenorhabditis elegans pre-mRNA.

In Caenorhabditis elegans, pre-mRNAs of many genes are trans-spliced to one of two spliced leaders, SL1 or SL2. Some of those that receive exclusively SL1 have been characterized as having at their 5' ends outrons, AU-rich sequences similar to introns followed by conventional 3' splice sites. Comparison of outrons from many different SL1-specific C. elegans genes has not revealed the presence of any consensus sequence that might encode SL1-specificity. In order to determine what parameters influence the splicing of SL1, we performed in vivo experiments with synthetic splice sites. Synthetic AU-rich RNA, 51 nt or longer, placed upstream of a consensus 3' splice site resulted in efficient trans-splicing. With all sequences tested, this trans-splicing was specifically to SL1. Thus, no information beyond the presence of AU-rich RNA at least as long as the minimum-length C. elegans intron, followed by a 3' splice site, is required to specify trans-splicing or for strict SL1 specificity.

Adenine↗

Isozyme-specific inhibition of protein kinase C by RNA aptamers.

In vitro selection technology has been used to purify RNA aptamers from a random sequence pool that can bind to, and specifically inhibit, protein kinase C beta II. Two of the selected RNA aptamers bind to this isozyme of protein kinase C with nanomolar affinities and inhibit activation with unprecedented selectivity; the highly related, alternatively spliced beta I isozyme, which differs by 23 residues, is inhibited with 1 order of magnitude lower potency; the next most similar isozyme, alpha, shows no detectable inhibition. The production of isozyme-specific inhibitors of protein kinase C opens the possibilities for dissecting the roles of specific protein kinase Cs in the myriad of intracellular signalling pathways.

Amino Acid Sequence↗

[Pseudoaneurysm of the internal carotid artery following a peritonsillar abscess].

A pseudoaneurysm of the internal carotid artery is a rare major complication of peritonsillar abscess. We present a 95-year-old women, who had a persistent bleeding from peritonsillar fossa after a routine tonsillectomy and ligation of the external carotid artery. Postoperative performed intraarterial angiography verify the diagnosis of a pseudoaneurysm of the internal carotid artery. Subsequent ligation of the internal carotid artery superior the bifurcation stops the hemorrhage. Review of literature demonstrate the importance of angiography in such cases.

Aged↗

Functional analysis of a C. elegans trans-splice acceptor.

The rol-6 gene is trans-spliced to the 22 nt leader, SL1, 173 nt downstream of the transcription start. We have analyzed splicing in transformants carrying extrachromosomal arrays of rol-6 with mutations in the trans-splice acceptor site. This site is a close match to the consensus, UUUCAG, that is highly conserved in both trans-splice and intron acceptor sites in C. elegans. When the trans-splice site was inactivated by mutating the perfectly-conserved AG, trans-splicing still occurred, but at a cryptic site 20 nt upstream. We tested the frequency with which splicing switched from the normal site to the cryptic site when the pyrimidines at this site were changed to A's. Since most C. elegans 3' splice sites lack an obvious polypyrimidine tract, we hypothesized that these four pyrimidines might play this role, and indeed mutation of these bases caused splicing to switch to the cryptic site. We also demonstrated that a major reason the downstream site is normally favored is because it occurs at a boundary between A+U rich and non-A+U rich RNA. When the RNA between the two splice sites was made less A+U rich, splicing occurred preferentially at the upstream site.

Amino Acid Sequence↗

Conversion of a trans-spliced C. elegans gene into a conventional gene by introduction of a splice donor site.

In Caenorhabditis elegans, pre-mRNAs that are trans-spliced are distinguished by the presence of an 'outron', intron-like RNA at the 5' end followed by a splice acceptor. We report that trans-splicing of the rol-6 gene can be completely suppressed simply by introducing a donor site into its 173 nt outron, at a site 50 nt upstream of the trans-splice site, thereby converting rol-6 into a conventional gene with a spliced intron near its 5' end. When the consensus donor site was inserted at sites further upstream it was less effective in replacing transplicing with cis-splicing. Surprisingly, the length of the intron was not the important variable, since lengthening of the 50 nt intron to 250 nt did not restore trans-splicing. Apparently the context into which the splice site was introduced determined the efficiency of its use. These results support the conclusion that the sole signal for trans-splicing is the presence of an outron. Clearly, cis- and trans-splice acceptor sites are interchangeable, allowing the possibility of competition between the two types of splicing.

Animals↗

Metabolism of nitric oxide in denitrifying Pseudomonas aeruginosa and nitrate-respiring Bacillus cereus.

Suspensions of Pseudomonas aeruginosa and Bacillus cereus were continuously sparged with nitrogen to remove gaseous products of nitrate reduction. Under these conditions, P. aeruginosa denitrified nitrate to 4% NO, 47% N2O and 49% N2. B. cereus reduced nitrate to 94% nitrite, 2% NO and 5% N2O. B. cereus was unable to reduce NO or N2O as sole electron acceptor, whereas P. aeruginosa reduced NO stoichiometrically to N2O when the N2O reductase was inhibited by acetylene or when the formed N2O was immediately flushed out of the incubation vessel. The mechanism and the reason for NO production in nitrate-respiring B. cereus are unknown, but the amounts of NO released were in a similar range as in the denitrifying P. aeruginosa and thus may be of similar environmental importance.

Bacillus cereus↗