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At least 721 records · Page 40Linked to original sources
PubMed2005

Extracorporeal shock wave lithotripsy in the management of chronic calcific pancreatitis: a meta-analysis.

CONTEXT: Main pancreatic duct stones may contribute to pain in chronic pancreatitis. Extracorporeal shock wave lithotripsy (ESWL) has been used alone or in combination with endoscopic therapy for fragmentation of stones. Published studies have shown mixed efficacy due to small sample size. OBJECTIVE: Systematic analysis of all published data evaluating ESWL with or without endoscopic therapy in pancreatic duct clearance and symptom relief. METHODS: Two investigators independently reviewed the computer databases. 31 potential studies were identified. Only studies using ESWL with or without endoscopic therapy were included. Completeness of the search was confirmed by an expert. Studies were independently coded by two investigators and differences rectified by mutual consent. MAIN OUTCOME MEASURES: Pain at follow-up and duct clearance. RESULTS: Seventeen studies published between 1989 and 2002 were included. Sixteen had a measure of pain at follow-up and duct clearance. All studies were case series with a total of 588 subjects, and included varying number of subjects undergoing endoscopic pancreatic sphincterotomy and stone extraction. The mean effect size (weighted correlation coefficient) for pain was 0.6215 and for duct clearance was 0.7432; thus indicating a large effect. All studies showed homogeneity suggesting similar effect size irrespective of the combinations of therapy. CONCLUSIONS: ESWL is effective in clearance of stones from the pancreatic duct and in relief of pain. Published studies showed homogeneity of the effect size of ESWL both in pancreatic duct clearance and relief of pain.

Calcinosis↗
PubMed2007

Mutational analysis of protein solubility enhancement using short peptide tags.

Protein aggregation is a common phenomenon. The preparation of highly concentrated protein samples, typically required for biophysical measurements, often involves a time consuming and tedious testing of solvent conditions for improving protein solubility. Here, in a systematic analysis, we have determined the increase in solubility upon the addition of SEP-tags (solubility enhancement peptide tags) containing, one, three, and five lysines or arginines (or six arginines) to either the N or C terminus of our low solubility model protein, bovine pancreatic trypsin inhibitor variant, BPTI-22 (a BPTI variant containing 22 alanines). As anticipated, the BPTI-22 solubility increased in direct relation to the number of charged residues contained in the SEP-tag, and without altering either the activity or the structure of the protein. The largest solubility increases were of 4.2-, 4.8-, and 6.2-folds produced by the addition, at the C terminus, of five lysine (BPTI-22-C5K), five and six arginine residues (BPTI-22-C5R and BPTI-22-C6R), respectively. The increased solubility of the tagged BPTI-22 yielded higher quality NMR spectra (hetero single quantum correlation HSQC spectra; with respect of the signal-to-noise and line shapes) in a much shorter time than for the untagged BPTI-22. Furthermore, tagged samples remained soluble for over ten days, as observed by their HSQC spectra. We believe that lysine- and arginine-based SEP-tags may provide an effective and versatile method for enhancing protein solubility.

Amino Acid Sequence↗
PubMed2001

Applications of yeast in drug discovery.

The yeast Saccharomyces cerevisiae is perhaps the best-studied eukaryotic organism. Its experimental tractability, combined with the remarkable conservation of gene function throughout evolution, makes yeast the ideal model genetic organism. Yeast is a non-pathogenic model of fungal pathogens used to identify antifungal targets suitable for drug development and to elucidate mechanisms of action of antifungal agents. As a model of fundamental cellular processes and metabolic pathways of the human, yeast has improved our understanding and facilitated the molecular analysis of many disease genes. The completion of the Saccharomyces genome sequence helped launch the post-genomic era, focusing on functional analyses of whole genomes. Yeast paved the way for the systematic analysis of large and complex genomes by serving as a test bed for novel experimental approaches and technologies, tools that are fast becoming the standard in drug discovery research

Antifungal Agents↗
PubMed2002

Microbial biodiversity: approaches to experimental design and hypothesis testing in primary scientific literature from 1975 to 1999.

Research interest in microbial biodiversity over the past 25 years has increased markedly as microbiologists have become interested in the significance of biodiversity for ecological processes and as the industrial, medical, and agricultural applications of this diversity have evolved. One major challenge for studies of microbial habitats is how to account for the diversity of extremely large and heterogeneous populations with samples that represent only a very small fraction of these populations. This review presents an analysis of the way in which the field of microbial biodiversity has exploited sampling, experimental design, and the process of hypothesis testing to meet this challenge. This review is based on a systematic analysis of 753 publications randomly sampled from the primary scientific literature from 1975 to 1999 concerning the microbial biodiversity of eight habitats related to water, soil, plants, and food. These publications illustrate a dominant and growing interest in questions concerning the effect of specific environmental factors on microbial biodiversity, the spatial and temporal heterogeneity of this biodiversity, and quantitative measures of population structure for most of the habitats covered here. Nevertheless, our analysis reveals that descriptions of sampling strategies or other information concerning the representativeness of the sample are often missing from publications, that there is very limited use of statistical tests of hypotheses, and that only a very few publications report the results of multiple independent tests of hypotheses. Examples are cited of different approaches and constraints to experimental design and hypothesis testing in studies of microbial biodiversity. To prompt a more rigorous approach to unambiguous evaluation of the impact of microbial biodiversity on ecological processes, we present guidelines for reporting information about experimental design, sampling strategies, and analyses of results in publications concerning microbial biodiversity.

Bacteria↗
PubMed1999

Mutational analysis of apolipoprotein B mRNA editing enzyme (APOBEC1). structure-function relationships of RNA editing and dimerization.

APOBEC1 is the catalytic subunit of an enzyme complex that mediates apolipoprotein (apo) B mRNA editing. It dimerizes in vitro and requires complementation factor(s) for its editing activity. We have performed a systematic analysis of the structure-functional relationship of APOBEC1 by targeted mutagenesis of various sequence motifs within the protein. Using in vitro RNA editing assay, we found that basic amino acid clusters at the amino-terminal region R15R16R17 and R33K34, are essential for apoB mRNA editing. Mutation of R15R16R17 to K15K16K17 and mutation of R33K34 simultaneously to A33A34 almost completely abolished in vitro editing activity. The carboxy-terminal region of APOBEC1 contains a leucine-rich motif. Deletion analysis of this region indicates that residues 181 to 210 are important for in vitro apoB mRNA editing. Single amino acid substitutions demonstrate that L182, I185, and L189 are important residues required for normal editing function. Furthermore, the double mutant P190A/P191A also lost >90% of editing activity which suggests that a beta turn in this region of the molecule may be essential for proper functioning of APOBEC1. It was suggested that dimerization of APOBEC1 creates an active structure for deamination of apoB mRNA. When we examined the dimerization potential of truncated APOBEC1s using both amino and carboxy termini deletion mutants, we found that amino-terminal deletions up to residue A117 did not impair dimerization activity whereas carboxy-terminal deletions showed diminished dimerization. The systematic and extensive mutagenesis experiments in this study provide information on the role of various sequence motifs identified in APOBEC1 in enzyme catalysis and dimerization.

APOBEC-1 Deaminase↗
PubMed1990

Structural analysis of the Hox-3.1 transcription unit and the Hox-3.2--Hox-3.1 intergenic region.

The mouse Hox gene family is a set of mammalian homeobox genes that may represent developmental control genes. Complete information about the primary structure of these genes is a prerequisite for a systematic analysis of the mechanisms that determine their complex tempero-spatial expression patterns. In this report we describe the complete sequence of the Hox-3.1 locus and provide evidence for several closely spaced transcriptional start sites. Sequence analysis of the 5' region of the Hox-3.1 gene extending to its nearest upstream neighbor, Hox-3.2, allowed us to identify sequences known to be capable of interactions with transcription factors. Several of these sequence motifs are similar to cis-regulatory elements found in the regulatory regions of other known developmentally regulated genes.

Amino Acid Sequence↗
PubMed2004

Does disinfection of environmental surfaces influence nosocomial infection rates? A systematic review.

OBJECTIVE: To review the evidence on the effects of disinfection of environmental surfaces in hospitals (as compared with cleaning without use of disinfectants) on the occurrence of nosocomial infections. METHODS: Systematic review of experimental and nonexperimental intervention studies dealing with environmental disinfection or cleaning in different health care settings. RESULTS: A total of 236 scientific articles were identified. None described a meta-analysis, systematic review, or randomized controlled trial. Only 4 articles described completed cohort studies matching the inclusion criteria. None of these studies showed lower infection rates associated with routine disinfection of surfaces (mainly floors) versus cleaning with detergent only. CONCLUSIONS: Disinfectants may pose a danger to staff, patients, and the environment and require special safety precautions. However, targeted disinfection of certain environmental surfaces is in certain instances an established component of hospital infection control. Given the complex, multifactorial nature of nosocomial infections, well-designed studies that systematically investigate the role of surface disinfection are required.

Cross Infection↗
PubMed2006

Identifying functional gene sets from hierarchically clustered expression data: map of abiotic stress regulated genes in Arabidopsis thaliana.

We present MultiGO, a web-enabled tool for the identification of biologically relevant gene sets from hierarchically clustered gene expression trees (http://ekhidna.biocenter.helsinki.fi/poxo/multigo). High-throughput gene expression measuring techniques, such as microarrays, are nowadays often used to monitor the expression of thousands of genes. Since these experiments can produce overwhelming amounts of data, computational methods that assist the data analysis and interpretation are essential. MultiGO is a tool that automatically extracts the biological information for multiple clusters and determines their biological relevance, and hence facilitates the interpretation of the data. Since the entire expression tree is analysed, MultiGO is guaranteed to report all clusters that share a common enriched biological function, as defined by Gene Ontology annotations. The tool also identifies a plausible cluster set, which represents the key biological functions affected by the experiment. The performance is demonstrated by analysing drought-, cold- and abscisic acid-related expression data sets from Arabidopsis thaliana. The analysis not only identified known biological functions, but also brought into focus the less established connections to defense-related gene clusters. Thus, in comparison to analyses of manually selected gene lists, the systematic analysis of every cluster can reveal unexpected biological phenomena and produce much more comprehensive biological insights to the experiment of interest.

Abscisic Acid↗
PubMed2006

Cross genome comparisons of serine proteases in Arabidopsis and rice.

BACKGROUND: Serine proteases are one of the largest groups of proteolytic enzymes found across all kingdoms of life and are associated with several essential physiological pathways. The availability of Arabidopsis thaliana and rice (Oryza sativa) genome sequences has permitted the identification and comparison of the repertoire of serine protease-like proteins in the two plant species. RESULTS: Despite the differences in genome sizes between Arabidopsis and rice, we identified a very similar number of serine protease-like proteins in the two plant species (206 and 222, respectively). Nearly 40% of the above sequences were identified as potential orthologues. Atypical members could be identified in the plant genomes for Deg, Clp, Lon, rhomboid proteases and species-specific members were observed for the highly populated subtilisin and serine carboxypeptidase families suggesting multiple lateral gene transfers. DegP proteases, prolyl oligopeptidases, Clp proteases and rhomboids share a significantly higher percentage orthology between the two genomes indicating substantial evolutionary divergence was set prior to speciation. Single domain architectures and paralogues for several putative subtilisins, serine carboxypeptidases and rhomboids suggest they may have been recruited for additional roles in secondary metabolism with spatial and temporal regulation. The analysis reveals some domain architectures unique to either or both of the plant species and some inactive proteases, like in rhomboids and Clp proteases, which could be involved in chaperone function. CONCLUSION: The systematic analysis of the serine protease-like proteins in the two plant species has provided some insight into the possible functional associations of previously uncharacterised serine protease-like proteins. Further investigation of these aspects may prove beneficial in our understanding of similar processes in commercially significant crop plant species.

Amino Acid Sequence↗
PubMed2001

Analysis of codon usage diversity of bacterial genes with a self-organizing map (SOM): characterization of horizontally transferred genes with emphasis on the E. coli O157 genome.

With increases in the amounts of available DNA sequence data, it has become increasingly important to develop tools for comprehensive systematic analysis and comparison of species-specific characteristics of protein-coding sequences for a wide variety of genomes. In the present study, we used a novel neural-network algorithm, a self-organizing map (SOM), to efficiently and comprehensively analyze codon usage in approximately 60,000 genes from 29 bacterial species simultaneously. This SOM makes it possible to cluster and visualize genes of individual species separately at a much higher resolution than can be obtained with principal component analysis. The organization of the SOM can be explained by the genome G+C% and tRNA compositions of the individual species. We used SOM to examine codon usage heterogeneity in the E. coli O157 genome, which contains 'O157-unique segments' (O-islands), and showed that SOM is a powerful tool for characterization of horizontally transferred genes.

Algorithms↗
PubMed2005

Analysis of the regulation of viral transcription.

Despite the small genomes and number of genes of papillomaviruses, regulation of their transcription is very complex and governed by numerous transcription factors, cis-responsive elements, and epigenetic phenomena. This chapter describes the strategies of how one can approach a systematic analysis of these factors, elements, and mechanisms. From the numerous different techniques useful for studying transcription, we describe in detail three selected protocols of approaches that have been relevant in shaping our knowledge of human papillomavirus transcription. These are DNAse I protection ("footprinting") for location of transcription-factor binding sites, electrophoretic mobility shifts ("gelshifts") for analysis of bound transcription factors, and bisulfite sequencing for analysis of DNA methylation as a prerequisite for epigenetic transcriptional regulation.

Cell Line, Tumor↗
PubMed2005

Residential radon and risk of lung cancer: a combined analysis of 7 North American case-control studies.

BACKGROUND: Underground miners exposed to high levels of radon have an excess risk of lung cancer. Residential exposure to radon is at much lower levels, and the risk of lung cancer with residential exposure is less clear. We conducted a systematic analysis of pooled data from all North American residential radon studies. METHODS: The pooling project included original data from 7 North American case-control studies, all of which used long-term alpha-track detectors to assess residential radon concentrations. A total of 3662 cases and 4966 controls were retained for the analysis. We used conditional likelihood regression to estimate the excess risk of lung cancer. RESULTS: Odds ratios (ORs) for lung cancer increased with residential radon concentration. The estimated OR after exposure to radon at a concentration of 100 Bq/m3 in the exposure time window 5 to 30 years before the index date was 1.11 (95% confidence interval = 1.00-1.28). This estimate is compatible with the estimate of 1.12 (1.02-1.25) predicted by downward extrapolation of the miner data. There was no evidence of heterogeneity of radon effects across studies. There was no apparent heterogeneity in the association by sex, educational level, type of respondent (proxy or self), or cigarette smoking, although there was some evidence of a decreasing radon-associated lung cancer risk with age. Analyses restricted to subsets of the data with presumed more accurate radon dosimetry resulted in increased estimates of risk. CONCLUSIONS: These results provide direct evidence of an association between residential radon and lung cancer risk, a finding predicted using miner data and consistent with results from animal and in vitro studies.

Adult↗
PubMedDate not supplied

[Modified nucleosides and nucleotides inhibiting HIV replication: analysis of the situation and potential prospects].

The results of an eight year search of blockaders of human immunodeficiency virus (HIV) among groups of modified nucleosides and nucleotides are reviewed. The molecular mechanism of action of these compounds is based on the inhibition of DNA polymerases activity. Attempts of systematic analysis of structure--anti-HIV activity relationship for modified substrates of DNA biosynthesis are made. In this analysis attention is focused on the evaluation of general properties of enzymes of the phosphorylation cascade and DNA polymerases. Such properties are analyzed on the basis of empiric rules which summarize electronic, steric and conformational properties of substrate analogs. The ability of phosphorylating nucleosides to block HIV reproduction are analyzed. The interdependence of structure of several most known inhibitors with their action on nucleic acids components metabolism as well as the structure--therapeutic properties relationship are discussed.

HIV↗
PubMed2004

Chlamydia trachomatis in the United Kingdom: a systematic review and analysis of prevalence studies.

OBJECTIVES: To undertake a systematic review to obtain estimates of genital Chlamydia trachomatis prevalence in various populations in the United Kingdom and Ireland; to determine which populations have the highest rates of infection; and to explore the most important determinants of infection. METHODS: Electronic databases were searched using the keywords "chlamydia" and "England," "Wales," "UK," "Scotland," "Ireland," or "Britain." Additional unpublished data and references were solicited from experts. Studies were included in the analysis if C trachomatis prevalence was reported, and if they met inclusion criteria. Nine variables identified as potentially important descriptors of chlamydia prevalence were extracted from each study and analysed using various logistic regression models. Only studies reporting prevalence in female populations were included in the models, because there were few data from males. RESULTS: 357 studies were identified using the search methods, 90 of which met inclusion criteria, and 19 of which contributed to the final model. The most influential variables on prevalence were age and setting of the population tested. In general practice surgeries, the under 20 year old age group had an estimated prevalence of 8.1% (95% CI 6.5 to 9.9), 20-24 year olds 5.2% (95% CI 4.3 to 6.3), 25-29 year olds 2.6% (95% CI 2.0 to 3.3), decreasing to 1.4% (95% CI 1.0 to 1.9) in those aged over 30 years. Overall, healthcare settings had higher prevalence estimates than population based studies. For example, among under 20 year olds, estimates were 17.3% (95% CI 13.6 to 21.8) in genitourinary medicine clinics, 12.6% (95% CI 6.4 to 23.2) in antenatal clinics, 12.3% (95% CI 9.8 to 15.3) in termination of pregnancy clinics, 10.7% (95% CI 8.3 to 13.8) in youth clinics, 10.0% (95% CI 8.7 to 11.5) in family planning clinics, and 8.1% (95% CI 6.5 to 9.9) in general practice, compared to 5.0% (95% CI 3.2 to 7.6) in population based studies. The type of test, specimen used, date, and location of test were not strongly associated with chlamydia prevalence. CONCLUSION: The chlamydia prevalence estimates by age and setting from the model may be used to inform chlamydia screening strategies. The systematic review revealed much heterogeneity in the studies identified, but with clear patterns of prevalence. It also indicated gaps in the knowledge about chlamydia prevalence in certain subgroups such as men and the general population.

Adolescent↗
PubMed1999

Analysis of the mouse proteome. (I) Brain proteins: separation by two-dimensional electrophoresis and identification by mass spectrometry and genetic variation.

The total protein of the mouse brain was fractionated into three fractions, supernatant, pellet extract and rest pellet suspension, by a procedure that avoids any loss of groups or classes of proteins. The supernatant proteins were resolved to a maximum by large-gel two-dimensional electrophoresis. Two-dimensional patterns from ten individual mice of the commonly used inbred strain C57BL/6 (species: Mus musculus) were prepared. The master pattern was subjected to densitometry, computer-assisted image analysis and treatment with our spot detection program. The resulting two-dimensional pattern, a standard pattern for mouse brain supernatant proteins, was divided into 40 squares, calibrated, and specified by providing each spot with a number. The complete pattern and each of the 40 squares are shown in our homepage (http://www.charite.de/ humangenetik). The standard pattern comprises 8767 protein spots. To identify the proteins known so far in the brain fraction investigated, a first set of 200 spots was analyzed by matrix-assisted laser desorption/ionization - mass spectrometry (MALDI-MS) after in-gel digestion. By screening protein databases 115 spots were identified; by extending the analysis to selected, genetically variant protein spots, 166 spots (including some spot series) were identified in total. This number was increased to 331 by adding protein spots identified indirectly by a genetic approach. By comparing the two-dimensional patterns from C57BL/6 mice with those of another mouse species (Mus spretus), more than 1000 genetically variant spots were detected. The genetic analysis allowed us to recognize spot families, i.e., protein spots that represent the same protein but that are post-translationally modified. If some members of the family were identified, the whole family was considered as being identified. Spot families were investigated in more detail, and interpreted as the result of protein modification or degradation. Genetic analysis led to the interesting finding that the size of spot families, i.e., the extent of modification or degradation of a protein, can be genetically determined. The investigation presented is a first step towards a systematic analysis of the proteome of the mouse. Proteome analysis was shown to become more efficient, and, at the same time, linked to the genome, by combining protein analytical and genetic methods.

Animals↗
PubMed1996

Investigations on the cell volumes of Azotobacter vinelandii by scanning electron microscopy.

Previous experiments by other investigators on the DNA content of Azotobacter vinelandii have demonstrated that the DNA content in these cells is several folds higher than that of E. coli. On the basis of this observation, it was hypothesized that A. vinelandii has at least 40 to 80 identical chromosomes per cell. However, the gene dosage analysis in A. vinelandii cells suggested that many genetic operations can be performed in these cells without the constraints expected in a polyploid bacterium. In an attempt to explain this apparent discrepancy, we have done systematic analysis of the relationship between the DNA content and the cell volume of this bacterium. Since a linear correlation is observed between the DNA content and the cell size in many other cell types, we hypothesized that if A. vinelandii is polyploid in nature, it should have a much larger cell volume to accommodate such a large amount of DNA. Our scanning electron microscopic analysis revealed that the cell volume of the vegetative cells of A. vinelandii is about 16 times larger than the cell volume of E. coli. This result is apparently consistent with the concept that the A. vinelandii is a polyploid bacterium. It was also reported that the encysted cells of A. vinelandii contain about 25% of the DNA content of the vegetative cells. This would mean that an encysted cell of A. vinelandii could contain about 10 copies of its chromosome. Since the estimated molecular weight of A. vinelandii chromosome is very similar to that of E. coli chromosome, the DNA content of the encysted cells also should be about 10 times higher than that of E. coli cells. If we assume that the relationship between the DNA content and the cell size is linear, then the encysted cells should have a cell volume larger than that of E. coli and smaller than that of the vegetative cells of A. vinelandii. However our scanning electron microscopic analysis showed that the cell volume of the encysted cells of A. vinelandii is in fact very similar to the cell volume of E. coli.

Azotobacter vinelandii↗
PubMed1991

Commingling analysis of generalized body mass and composition measures: the Québec Family Study.

Human body mass and composition are heterogeneous phenotypes resulting from the combined effects of genes, environmental factors, and their interactions. In order to gain an understanding of the individual genetic determinants leading to obesity, we have initiated a systematic analysis of several measures of fatness and its phenotypes including: the body mass index (wt/ht2), fat mass, fat-free (lean) mass, the ratio of fat mass over fat-free mass, percent body fat, and a fat mass index (fat mass/ht). In this report, we examine the distributions of these age and sex adjusted variables in a large family study from Québec in terms of evidence for commingling and skewness, and evaluate the inter-relationships among the measures. Fat mass, fat-free mass and the fat mass index conceptually represent primary variables in that they are quantitative measures of relevant components of total body weight; the hypothesis of a single distribution was inferred for each of these primary measures, with significant residual skewness except for fat mass. In general, offspring (8-26 years old) distributions were more positively skewed than parent (30-60 years old) distributions. The remaining variables (body mass index, fat mass to fat-free mass ratio, and percent body fat) are indexes combining information on fat and fat-free mass into single measures. Although offspring data were consistent with a single skewed distribution, commingling was found in the parents in each case. The prominent heterogeneity between generations suggests that there may be significant developmental (genetic or environmental) effects in the transition during growing years to adult pattern phenotypes, particularly for the complex indicators of body composition.

Adipose Tissue↗