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C Wild

Publications and source records attributed to C Wild.

At least 37 records · Page 2Linked to original sources

An assessment of picture archiving and communication systems (PACS). The case study of the SMZO Project. Socialmedizinischenes Zentrum Ost.

In order to make rational decisions for further implementation of picture archiving and communication systems (PACS) in Viennese community hospitals, an assessment of the Sozialmedizinisches Zentrum Ost (SMZO) project was launched by the Viennese community hospital financing body. The aim of the technology assessment was to look at the experiences of day-to-day practice, organizational aspects of, and obstacles to developing the full potential of the PACS installation. The study analyzes the conditions for employment of digital radiology, gathers the experiences of national and international projects, and presents a view on critical points, from which options for further implementation can be derived. In the center of interest stood work organization, handling and user attitudes, perceptions of radiologists and clinicians, realism of expectations regarding economic efficiency, technical aspects, and influence of quality of medical care.

Austria↗

Nursing week 1998

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Journal Article↗

[Future developments in medicine: expert assessment].

In recent years studies forecasting the future such as Delphi expert surveys were carried out in various Western countries to make predictions on future developments in medicine and in the health care system. The answers draw a homogeneous picture: Cancer and dementia research as well as the development of materials for implantation and artificial organs are-in context of the demographic changes-of enormous relevance, whereas basic research receives less attention. Due to various technological developments in telecommunication and in diagnostics (sensors), sociomedical care at home is supported and will become more frequent.

Cross-Cultural Comparison↗

M.BssHII, a multispecific cytosine-C5-DNA-methyltransferase with unusual target recognizing properties.

A new multispecific cytosine-C5-DNA-methyltransferase (C5-MTase), M.BssHII, was identified in Bacillus stearothermophilus H3. The M.BssHII gene was cloned and sequenced. The amino acid sequence deduced shows the characteristic building plan of a C5-MTase. By sequencing bisulfite-treated DNA methylated by M.BssHII and by restriction enzyme analysis, we defined the following methylation targets of M.BssHII: ACGCGT/CCGCGG (MluI/SacII), PuGCGCPy (HaeII), PuCCGGPy (Cfr10I) and GCGCGC (BssHII). The relative location of the specificity determinants in the C5-MTase was derived from the analysis of M.BssHII derivatives carrying deletions within the variable region "V" and chimeric C5-Mtases constructed between M.BssHII and the related monospecific enzyme M.phi3TII. Four of the M.BssHII specificities (MluI, SacII, Cfr10I and BssHII) could be associated with amino acid segments within the variable region "V". The determinant for HaeII activity had to be assigned to sequences defining the enzyme core, the first example of a C5-MTase in which a sequence-specific methylation potential is mediated by structures outside of the variable region. Another intriguing result came from the analysis of one particular chimera made between M.BssHII and M.phi3TII. This construct showed a relaxation of the methylation capacity, both with respect to the target recognized and the targeting of methylation within this sequence.

Amino Acid Sequence↗

Identification of a subdomain within DNA-(cytosine-C5)-methyltransferases responsible for the recognition of the 5' part of their DNA target.

In previous work on DNA-(cytosine-C5)-methyltransferases (C5-MTases), domains had been identified which are responsible for the sequence specificity of the different enzymes (target-recognizing domains, TRDs). Here we have analyzed the DNA methylation patterns of two C5-MTases containing reciprocal chimeric TRDs, consisting of the N- and C-terminal parts derived from two different parental TRDs specifying the recognition of 5'-CC(A/T)GG-3' and 5'-GCNGC-3'. Sequences recognized by these engineered MTases were non-symmetrical and degenerate, but contained at their 5' part a consensus sequence which was very similar to the 5' part of the target recognized by the parental TRD which contributed the N-terminal moiety of the chimeric TRD. The results are discussed in connection with the present understanding of the mechanism of DNA target recognition by C5-MTases. They demonstrate the possibility of designing C5-MTases with novel DNA methylation specificities.

Amino Acid Sequence↗

McrB: a prokaryotic protein specifically recognizing DNA containing modified cytosine residues.

Restriction of DNA by the Escherichia coli K-12 McrBC restriction endonuclease, which consists of the two subunits McrB and McrC, depends on the presence of modified cytosine residues in a special constellation. From previous work by others it was known that restriction of 5-methylcytosine-containing DNA requires two methylated 5'-PuC sites separated by approximately 40-80 non-defined base pairs. Here we show that binding of the McrBC nuclease is mediated exclusively by the McrB subunit. McrB has a low affinity for non-methylated DNA, with which it forms low molecular weight complexes. The affinity for DNA is significantly increased, with variations depending on the sequence context, by hemi- or fully methylated 5'-PuC sites. Binding to such substrates yields high molecular weight complexes, presumably involving several McrB molecules. Methylation at unique 5'-PuC sites can be sufficient to stimulate DNA binding by McrB. As such substrates are not cleaved by the nuclease, restriction apparently requires the coordinated interaction of molecules bound to neighbouring 5'-PumC sites. The binding properties of McrB exhibit some similarities to recently identified eukaryotic proteins interacting in a non-sequence-specific manner with DNA containing methylated 5'-CpG sequences and might point to a common molecular origin of these proteins. In addition to DNA, McrB also binds GTP, an essential cofactor in DNA restriction by McrBC. McrC neither binds to DNA nor modulates the DNA binding potential of McrB. As McrC is essential for restriction it appears to predominantly function in catalysis.

Bacterial Proteins↗

M.BssHII: a new multispecific C5-DNA-methyltransferase.

M.BssHII is a new multispecific C5-DNA-methyltransferase recognizing five different targets. As the enzyme has been isolated from a thermophilic Bacillus, the protein should show enhanced intrinsic thermostability and therefore be a promising candidate for crystallizing a multispecific MTase.

Bacillus↗

Molecular and genetic epidemiology of hepatocellular carcinoma: studies in China and Senegal.

To identify environmental, viral, and genetic factors that may influence the risk of developing hepatocellular carcinoma (HCC), large prospective studies are being conducted in Haimen City, China and Senegal, and a case-control study of genetic variation in the detoxification of aflatoxin-B1 was carried out in Shanghai, China. Analysis of 78 HCCs that have occurred among 51,020 men enrolled in a large prospective study in Haimen City, China showed a strong association of HCC with chronic hepatitis B virus (HBV) infection. There were also significant associations of HCC risk with occupation (farming), history of a clinical episode of hepatitis in adulthood, and a family history of HCC. Study of 52 HCC cases and 116 controls for genetic polymorphisms and HCC risk showed a significant association with epoxide hydrolase (EPHX) mutant alleles (1/2, 2/2) and a borderline association with homozygous deletion of the glutathione-S-transferase mu (GSTM1) gene. There was a multiplicative interaction of these polymorphisms with chronic HBV infection such that HBsAg-positive persons who were GSTM1 null and were EPHX 1/2 or 2/2 had 135 times the risk of HCC as HBsAg-negative persons with the wild type genotypes for GSTM1 and EPHX. The risk of HCC is not uniform among persons with chronic HBV or HCV infections. Studies of genetic, viral, and environmental interactions may permit identification of those individuals at highest risk within groups at increased risk of HCC. Prevention strategies could then be targeted at those individuals.

Aflatoxin B1↗

Propensity for a leucine zipper-like domain of human immunodeficiency virus type 1 gp41 to form oligomers correlates with a role in virus-induced fusion rather than assembly of the glycoprotein complex.

For a number of viruses, oligomerization is a critical component of envelope processing and surface expression. Previously, we reported that a synthetic peptide (DP-107) corresponding to the putative leucine zipper region (aa 553-590) of the transmembrane protein (gp41) of human immunodeficiency virus type 1 (HIV-1) exhibited alpha-helical secondary structure and self-associated as a coiled coil. In view of the tendency of this type of structure to mediate protein association, we speculated that this region of gp41 might play a role in HIV-1 envelope oligomerization. However, later it was shown that mutations which should disrupt the structural elements of this region of gp41 did not affect envelope processing, transport, or surface expression (assembly oligomerization). In this report we compare the effects of amino acid substitutions within this coiled-coil region on structure and function of both viral envelope proteins and the corresponding synthetic peptides. Our results establish a correlation between the destabilizing effects of amino acid substitutions on coiled-coil structure in the peptide model and phenotype of virus entry. These biological and physical biochemical studies do not support a role for the coiled-coil structure in mediating the assembly oligomerization of HIV-1 envelope but do imply that this region of gp41 plays a key role in the sequence of events associated with viral entry. We propose a functional role for the coiled-coil domain of HIV-1 gp41.

Amino Acid Sequence↗

A synthetic peptide inhibitor of human immunodeficiency virus replication: correlation between solution structure and viral inhibition.

A peptide designated DP-107 was synthesized containing amino acid residues 558-595 of the envelope glycoprotein gp160 of human immunodeficiency virus type 1 strain LAI (HIV-1LAI). Algorithms for secondary structure have predicted that this region of the envelope transmembrane protein should form an extended alpha-helix. Consistent with this prediction, analysis by circular dichroism (CD) indicated that, under physiological conditions, DP-107 is approximately 85% helical. The high degree of stable secondary structure in a synthetic peptide of this size suggests self-association typical of a coiled coil or leucine zipper. In biological assays, the peptide efficiently blocked virus-mediated cell-cell fusion processes as well as infection of peripheral blood mononuclear cells by both prototypic and primary isolates of HIV-1. A single amino acid substitution in the peptide greatly destabilized its solution structure as measured by CD and abrogated its antiviral activity. An analogue containing a terminal cysteine was oxidized to form a dimer, and this modification lowered the dose required for antiviral effect from 5 to about 1 microgram/ml. These results suggest that both oligomerization and ordered structure are necessary for biological activity. They provide insights also into the role of this region in HIV infection and the potential for development of a new class of antiviral agents.

Algorithms↗

Characterization of the mcrBC region of Escherichia coli K-12 wild-type and mutant strains.

We have carried out an analysis of the Escherichia coli K-12 mcrBC locus in order to (1) elucidate its genetic organization, (2) to identify the proteins encoded by this region, and (3) to characterize their involvement in the restriction of DNA containing methylated cytosine residues. In vitro expression of recombinant plasmids carrying all or portions of the mcrBC region revealed that the mcrB and mcrC genes are organized as an operon. The mcrBC operon specifies five proteins, as evident from parallel in vitro and in in vivo expression studies. Three proteins of 53, 35 and 34 kDa originate from mcrB expression, while two proteins of 37 and 16 kDa arise from mcrC expression. Products of both the mcrB and mcrC genes are required to restrict the methylated substrate DNA used in this study. We also determined the nature of mutant mcrBC loci in comparison to the E. coli K-12 wild-type mcrBC locus. A major goal of these studies was to clarify the nature of the mcrB-1 mutation, which is carried by some strains employed in previous analyses of the E. coli K-12 McrBC system. Based on our analyses the mutant strains investigated could be divided into different complementation groups. The mcrB-1 mutation is a nonsense or frameshift mutation located within mcrB. It causes premature termination of mcrB gene product synthesis and reduces the level of mcrC gene expression. This finding helps to understand an existing conflict in the literature. We also describe temperature-sensitive McrA activity in some of the strains analysed and its relationship to the previously defined differences in the tolerance levels of E. coli K-12 mcrBC mutants to cytosine methylation.

Bacterial Proteins↗

Albuminuria in people at least 40 years old: effect of obesity, hypertension, and hyperlipidemia.

Concentrations of urinary albumin and the albumin:creatinine ratio were measured in early-morning urine specimens from 5670 people older than 40 years who participated in a health screening survey of a local workforce. Sex-specific reference intervals were determined in a subgroup of 3597 people after excluding 2073 individuals with Albustix-positive proteinuria; diabetes mellitus; bacteriuria; current hypertension; body mass index greater than or equal to 30 kg/m2; or serum triglyceride greater than or equal to 2.5 mmol/L. The 97.5 percentile concentration for urinary albumin was 28 mg/L in men and 29 mg/L in women; for the albumin:creatinine ratio this was 2.3 g/mol in men and 2.8 g/mol in women. In the study population, the degree of albuminuria showed piecewise log-linear relationships with diastolic blood pressure (P = 0.0001) and body mass index (P = 0.0001), log-linear relationships with hypertriglyceridemia (P = 0.0001) and hypercholesterolemia (P = 0.0001), and a negative piecewise linear relationship with high-density lipoprotein (HDL) cholesterol (P = 0.0461).

Adult↗