Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “systematic analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,279 records · Page 71Linked to original sources
PubMed2005

Ankyrin-G in skeletal muscle: tissue-specific alternative splicing contributes to the complexity of the sarcolemmal cytoskeleton.

Ankyrins are versatile adaptor proteins that join the spectrin-based cytoskeleton to transmembrane proteins, and have roles in organizing the microstructure of cell membranes. Molecular diversity of ankyrins in mammals arises from extensive alternative splicing of the products of three genes. There has been no systematic analysis of the diversity of expression of ankyrins-G, the widely expressed Ank3 gene products, in a complex tissue. We previously described Ank(G107), the first muscle-specific ankyrin-G. Here, we combined cDNA and database analyses to gain novel insight into the ankyrins-G of skeletal muscle. We find: (i) that Ank3 is composed of at least 53 exons, many of which are subject to tissue-specific splicing; (ii) five novel full-length cDNAs encoding two canonical (Ank(G197), Ank(G217)) and three small isoforms (Ank(G109), Ank(G128), Ank(G130)) bring to six the number of ankyrins-G expressed in skeletal muscle; (iii) a 76-residue insert in the C-terminal domain is a 'signature' for muscle ankyrins; (iv) variably spliced sequences of 17/18 and 195 residues increase diversity in the C-terminal domains. Comparison of endogenous ankyrins-G with in vitro translated cDNAs revealed that small ankyrins account for the majority of the immunoreactivity for ankyrin-G in soleus muscle. The small ankyrins, when expressed in vivo in the rat muscle, are all targeted to sarcolemmal costameres. Our results demonstrate the tissue-dependent alternative splicing of Ank3 in skeletal muscle and point to novel functions of small ankyrins-G in organizing microdomains of the plasma membrane.

Alternative Splicing↗
PubMed2004

Myostatin rapid sequence evolution in ruminants predates domestication.

Myostatin (GDF-8) is a negative regulator of skeletal muscle development. This gene has previously been implicated in the double muscling phenotype in mice and cattle. A systematic analysis of myostatin sequence evolution in ruminants was performed in a phylogenetic context. The myostatin coding sequence was determined from duiker (Sylvicapra grimmia caffra), eland (Taurotragus derbianus), gaur (Bos gaurus), ibex (Capra ibex), impala (Aepyceros melampus rednilis), pronghorn (Antilocapra americana), and tahr (Hemitragus jemlahicus). Analysis of nonsynonymous to synonymous nucleotide substitution rate ratios (Ka/Ks) indicates that positive selection may have been operating on this gene during the time of divergence of Bovinae and Antilopinae, starting from approximately 23 million years ago, a period that appears to account for most of the sequence difference between myostatin in these groups. These periods of positive selective pressure on myostatin may correlate with changes in skeletal muscle mass during the same period.

Amino Acid Sequence↗
PubMed2001

Predicting repeat DUI offenses with the alcohol interlock recorder.

The aim of this report has been to use information contained in the alcohol ignition interlock recorder to determine whether systematic analysis of it can be used to predict which DUI offenders will recidivate during the first 2 years after the interlock is removed. The interlock record was accumulated during a 4-year intervention study in Alberta, Canada. Data from more than 5.5 million breath tests collected during interlock use were analyzed retrospectively after allowing repeat DUI offenses to accumulate for up to 2 years post-interlock. The rate of interlock warns at low BAC (0.02-0.04%) and fails at higher BAC ( > 0.04%) were found to be predictive of later repeat DUI. The interlock record was used along with selected driver record variables and questionnaire data to identify predictor sets. CHAID segmentation analysis was used to identify combinations of predictor variables; these were joined with sensitivity analysis to compare different predictor combinations. Several variables, but primarily more prior DUIs and more interlock warns and fails logged during the first 5 months of interlock usage predict greater than 60% of repeat DUI with a false positive rate of less than 10%.

Adult↗
PubMed2000

Prevalence and characteristics of escape rhythms after radiofrequency ablation of the atrioventricular junction: results from the registry for AV junction ablation and pacing in atrial fibrillation. Ablate and Pace Trial Investigators.

BACKGROUND: Radiofrequency ablation of the atrioventricular junction is a well-established procedure for the management of atrial fibrillation refractory to medical therapy. However, there are few data available on the prevalence and characteristics of the escape rhythms that are present after the procedure. METHODS: The Ablate and Pace Trial was a prospective, multicenter registry of atrioventricular junction ablation and pacing in atrial fibrillation. Ablation of the atrioventricular junction was accomplished with radiofrequency energy with standard techniques. Before discharge from the hospital, patients underwent a systematic analysis of the rate and morphologic features of the escape rhythm, if any, that was present when the pacing rate was gradually decreased. RESULTS: There were 156 patients from 16 centers who underwent attempted radiofrequency ablation of the atrioventricular junction. The procedure was successful in 155 (99%) of 156 patients. An escape rhythm was present in 104 patients (67%) after radiofrequency ablation. The escape rate ranged from 11 to 65 beats/min (mean 39 +/- 10 beats/min). Only 49 patients (31%) had an escape rate >/=40 beats/min. Of the 104 patients with an escape rhythm, 53 patients (51%) had a QRS that was unchanged from baseline. There was no correlation between the number of radiofrequency applications and the presence of an escape rhythm. CONCLUSION: The majority of patients who undergo radiofrequency catheter ablation of the atrioventricular junction are pacemaker dependent after the procedure, as defined by lack of an escape rhythm or the presence of an escape rhythm that is <40 beats/min.

Adult↗
PubMed2000

A systematic review and meta-analysis of prospective studies on the association between maternal cigarette smoking and preterm delivery.

We have attempted to quantify the most up-to-date estimate of the association between cigarette smoking by the mother and preterm delivery. Studies were selected for inclusion in this review if they were prospective, reported data stratified across at least two levels of maternal smoking, and defined preterm delivery on the basis of gestational age. In a meta-analysis we combined results from multiple studies that reported on preterm delivery and maternal smoking during pregnancy. Pooled odds ratios were computed for various strata of smoking intensity with the Mantel-Haenszel fixed-effects model. Twenty studies met all inclusion criteria and were included in meta-analysis. The pooled point estimate from 20 prospective studies on any maternal smoking versus no maternal smoking was 1.27 (95% confidence interval, 1.21-1.33). Subgroup analyses stratifying maternal smoking on number of cigarettes per day suggest a dose-response relationship at low to moderate levels of smoking, which was not further increased at high levels of smoking. A nonsignificant level of publication bias appears to exist in the smoking-preterm delivery literature. Cigarette smoking is a preventable risk factor that is associated with preterm delivery. Consistent results across many study populations and research designs and evidence of a dose-response relationship support its causal role in preterm delivery.

Case-Control Studies↗
PubMed2003

Effectiveness of cervical cerclage for a sonographically shortened cervix: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to determine the effectiveness of cerclage for a shortened cervix on transvaginal ultrasound scanning in terms of the rates of preterm delivery and adverse neonatal and maternal outcomes. STUDY DESIGN: Pre-MEDLINE and MEDLINE, EMBASE, and the Cochrane Library were searched for human studies that compared cerclage placement to no cerclage on the basis of transvaginal ultrasound findings of a short cervix (< or =2.5 cm). Two authors independently determined eligibility and abstracted data. Meta-analyses were conducted when possible. RESULTS: Thirty-five studies were reviewed; 6 studies were eligible and were included in the analysis. There was no statistically significant effect of cerclage on the rates of preterm delivery (<37, <34, <32, and <28 weeks of gestation), preterm labor, neonatal mortality or morbidity, gestational age at delivery, or time to delivery. Birth weight was significantly higher with than without cerclage (P=.004). CONCLUSION: The available evidence does not support cerclage for a sonographically detected short cervix. A randomized controlled trial is needed to determine whether this intervention will reduce adverse neonatal outcomes.

Adolescent↗
PubMed1997

Biophysical characterization of cationic lipid: DNA complexes.

To better understand the structures formed by the interaction of cationic lipids with DNA, we undertook a systematic analysis to determine the biophysical characteristics of cationic lipid:DNA complexes. Four model cationic lipids with different net cationic charge were found to interact in similar ways with DNA when that interaction was compared in terms of the apparent molar charge ratio of lipid to DNA. When DNA was present in charge excess over the cationic lipid, the complex carried a net negative charge as determined by zeta potential measurements. Under these conditions, some DNA was accessible to ethidium bromide, and free DNA was observed in agarose gels and in dextran density gradients. Between a lipid:DNA charge ratio of 1.25 and 1.5:1, all the DNA became complexed to cationic lipid, as evidenced by its inaccessibility to EtBr and its complete association with lipid upon agarose gel electrophoresis and density gradient separations. These complexes carried a net positive charge. The transition between negatively and positively charged complexes a occurred over a very small range of lipid to DNA ratios. Employing a fluorescent lipid probe, the addition of DNA was shown to induce lipid mixing between cationic lipid-containing vesicles. The extent of DNA-induced lipid mixing reached a maximum at a charge ratio of about 1.5:1, the point at which all the DNA was involved in a complex and the complex became positively charged. Together with freeze-fracture electron micrographs of the complexes, these biophysical data have been interpreted in light of the existing models of cationic lipid:DNA complexes.

Cations↗
PubMed1999

The amino acid/auxin:proton symport permease family.

Amino acids and their derivatives are transported into and out of cells by a variety of permease types which comprise several distinct protein families. We here present a systematic analysis of a group of homologous transport proteins which together comprise the eukaryotic-specific amino acid/auxin permease (AAAP) family (TC #2. 18). In characterizing this family, we have (1) identified all sequenced members of the family, (2) aligned their sequences, (3) identified regions of striking conservation, (4) derived a family-specific signature sequence, and (5) proposed a topological model that appears to be applicable to all members of the family. We have also constructed AAAP family phylogenetic trees and dendrograms using six different programs that allow us to trace the evolutionary history of the family, estimate the relatedness of proteins from dissimilar organismal phyla, and evaluate the reliability of the different programs available for phylogenetic studies. The TREE and neighbor-joining programs gave fully consistent results while CLUSTAL W gave similar but non-identical results. Other programs gave less consistent results. The phylogenetic analyses reveal (1) that many plant AAAP family proteins arose recently by multiple gene duplication events that occurred within a single organism, (2) that some plant members of the family with strikingly different specificities diverged early in evolutionary history, and (3) that AAAP family proteins from fungi and animals diverged from the plant proteins long ago, possibly when animals, plants and fungi diverged from each other. The Neurospora protein nevertheless exhibits overlapping specificity with those found in plants. Preliminary evidence is presented suggesting that proteins of the AAAP family are distantly related to proteins of the large ubiquitous amino acid/polyamine/choline family (TC #2.3) as well as to those of two small bacterial amino acid transporter families, the ArAAP family (TC #2.42) and the STP family (TC #2.43).

Amino Acid Sequence↗
PubMed2001

Direct observation of domains in model stratum corneum lipid mixtures by Raman microspectroscopy.

Several studies on intact and model stratum corneum (SC), the top layer of the epidermis, have suggested the presence of crystalline domains. In the present work, we used micro-Raman mapping to detect lipid domains in model lipid mixtures formed by an equimolar mixture of ceramides, cholesterol, and palmitic acid, the three main lipid species of SC. We were able to determine the spatial distribution of the three compounds individually based on the systematic analysis of band areas. As a control, we studied freeze-dried lipid mixtures, and the Raman microspectroscopy reported faithfully the homogeneous distribution of the three compounds. Spectral mapping was then performed on hydrated equimolar mixtures carefully annealed. In this case, clear phase separations were observed. Domains enriched in cholesterol, ceramides, or palmitic acid with a size of a few tens of square microns were detected. These findings constitute the first direct evidence of the formation of heterogeneous domains in the SC lipid models in a bulk phase. Raman microspectroscopy is an innovative approach to characterize the conditions leading to the formation of domains and provides new insights into the understanding of the skin barrier.

Animals↗
PubMed1995

Photobleaching kinetics of fluorescein in quantitative fluorescence microscopy.

An investigation on the photobleaching behavior of fluorescein in microscopy was carried out through a systematic analysis of photobleaching mechanisms. The individual photochemical reactions of fluorescein were incorporated into a theoretical analysis and mathematical simulation to study the photochemical processes leading to photobleaching of fluorescein in microscopy. The photobleaching behavior of free and bound fluorescein has also been investigated by experimental means. Both the theoretical simulation and experimental data show that photobleaching of fluorescein in microscopy is, in general, not a single-exponential process. The simulation suggests that the non-single-exponential behavior is caused by the oxygen-independent, proximity-induced triplet-triplet or triplet-ground state dye reactions of bound fluorescein in microscopy. The single-exponential process is a special case of photobleaching behavior when the reactions between the triplet dye and molecular oxygen are dominant.

Fluorescein↗
PubMed1999

Structure-function study on a de novo synthetic hydrophobic ion channel.

Ion conduction properties of a de novo synthesized channel, formed from cyclic octa-peptides consisting of four alternate L-alanine (Ala) and N'-acylated 3-aminobenzoic acid (Aba) moieties, were studied in bilayer membranes. The single-channel conductance was 9 pS in symmetrical 500 mM KCl. The channel favored permeation of cations over anions with a permeability ratio (PCl-/PK+) of 0.15. The selectivity sequence among monovalent cations based on permeability ratio (PX+/PK+) fell into an order: NH4+(1.4) > Cs+(1. 1) >/= K+(1.0) > Na+(0.4) >> Li+(0). The conductance-activity relationship of the channel in K+ solutions followed simple Michaelis-Menten kinetics with a half-maximal saturating activity of 8 mM and a maximal conductance of 9 pS. The permeability ratio PNa+/PK+ remained constant ( approximately 0.40) under biionic concentrations from 10 to 500 mM. These results suggests that the channel is a one-ion channel. The pore diameter probed by a set of organic cations was approximately 6 A. The single-channel current was blocked by Ca2+ in a dose-dependent manner that followed a single-site titration curve with a voltage-dependent dissociation constant of 0.6 mM at 100 mV. The electric distance of the binding site for Ca2+ was 0.07 from both entrances of the channel, indicating the presence of two symmetrical binding sites in each vicinity of the channel entrance. Correlations between conduction properties and structural aspects of the channel are discussed in terms of a three-barrier and two-binding-site (3B2S) model of Eyring rate theory. All available structural information supported an idea that the channel was formed from a tail-to-tail associated dimer of the molecule, the pore of which was lined with hydrophobic acyl chains. This is the first report to have made a systematic analysis of ion permeation through a hydrophobic pore.

Binding Sites↗
PubMed1996

Differential expression of heat shock 70 proteins in primary cultures from rat cerebellum.

While a number of studies have described the heat shock response in established cell lines and in primary cultures of cells derived from the nervous system, there has been no systematic analysis comparing expression and localization of the inducible heat shock 70 (hsp70) proteins and the constitutively synthesized members of the family (hsc70) in neurons and glia. In the present communication, we utilized specific probes to compare the expression of hsp70 and hsc70 mRNAs and proteins in two types of primary cultures, astroglial and neuro-astroglial, from postnatal rat cerebellum. Conditions were adjusted to maintain physiological numbers of microglia in both types of culture, and cultures were analyzed at a number of different time points following a precisely defined heat shock. The northern, in situ hybridization and immunohistochemical analyses resulted in a number of novel observations concerning the nature of the heat shock response in these neuronal and glial cells. In postnatal day 4-5 cultures, hsp70 mRNA levels were elevated for at least 10 h in both types of culture, but in situ hybridization analysis showed no evidence for hsp70 mRNAs in neurons. Microglia were the only cell type in which hsp70 was detected in non-stressed cultures and this cell type contained the highest concentrations of hsp70 proteins in stressed cultures. Hsc70 mRNA levels were also increased after heat shock, but the increase was more transient. Hsc70 mRNAs and proteins were present in all cell types, again with the highest concentrations being present in microglia. Hsc70 mRNAs and proteins were localized in the cytoplasm at all time points examined, with hsc70 protein also being localized in nucleoli. Hsp70 mRNAs and proteins were diffusely localized over nuclei of astrocytes, as well as of most microglia. Hsp70, but not hsc70, was localized on chromosomes in glia once they had resumed cell division after heat shock, suggesting a role for hsp70 either in targeting damaged chromosomal proteins or in cell division. Some cytoplasmic hsp70 was observed in astrocytes of the mixed neuro-astroglial cultures and a delayed hsp70 immunoreactivity was observed in granule neurons in these cultures, suggesting either that translation of low levels of hsp70 mRNAs was more efficient in neurons, or that glial-neuronal translocation of hsp70 proteins had taken place. These results suggest that metabolism and functions of different heat shock protein family members may not always be identical and that care must be taken in extrapolation of results from one cell type to another.

Animals↗
PubMed1982

The symptomatology of abnormal appearance: an anecdotal survey.

From a systematic analysis of 54 anecdotal accounts written by patients with various abnormalities of appearance, a common pattern of experience has been discovered which is divisible into six parts: induction and development of self-consciousness, defence mechanisms, unavoidable distressing activities, downgrading of self-concept, difficulties with interpersonal relationships, and rationalisation. This scheme of symptomatology is presented as a basis for history-taking and as a base-line for future comparative studies of different types of abnormal appearance.

Congenital Abnormalities↗
PubMedDate not supplied

[Symptom variations in ADHD: importance of context, development and comorbidity].

Attention-deficit hyperactivity (ADHD) is a common disorder in school-aged children and is associated with significant impairment in social and academic functioning. Its recognition is based on congruent information from different sources, because most ADHD children and adolescents are not completely aware of impairments caused by inattention and/or hyperactivity/impulsivity. Fluctuations in symptom expression may complicate the diagnosis: during clinical examination or tests sessions, ADHD symptoms may be less severe than usual or completely absent. This review examines variations in ADHD symptoms due to environmental context, internal state, circadian factors, development, psychiatric comorbidity and discusses their clinical relevance. Generally, ADHD symptoms are pervasive and identified in different areas of functioning. Despite their chronicity, they show a relative context-dependency. An unfamiliar environment or situation may lessen symptoms. The same happens in dual relations or in calm settings, when the child receives attention and positive reinforcement from the adult. On the contrary, the classroom situation with its high stimulation level (noise, visual distractors, large class size) is likely to reveal or accentuate instability, impulsivity and inattention. Independently from objective symptom fluctuations, the impact of ADHD symptoms, and their consequences on self-esteem may also vary with the degree of environmental mismatch. Recent research in experimental psychology also draws attention to the motivational state of ADHD children: preference for immediate gratification and delay aversion may explain why most of them show satisfactory attentional capacities in certain activities (for instance video games or TV), while showing impairment in school work or in other effortful tasks. The diagnosis of the full ADHD syndrome requires significant impact on functioning in at least two areas. Some children with "situational" ADHD are impaired either in school setting or exclusively at home. Manuzza et al. report long-term outcome of "situational" versus "pervasive" ADHD. School-ADHD, in opposition to home-ADHD shows similarities with the full blown syndrome, as regards proportion of anti-social personality disorder, psycho-social functioning and academic/professional achievements. Moderate seasonal variations have also been identified with less ADHD symptoms in August. This result is likely to reflect a better fit between individual characteristics and environmental demands during school holidays rather than neurobiological changes, as there are no convincing arguments for seasonal fluctuations of serotoninergic tone in ADHD. Another cause for variations in ADHD symptom expression may be the co-occurrence of a mood disorder. Relationships between early-onset mania and ADHD are discussed. The appropriate definition of prepubertal mania is still in debate; its recognition is hindered by symptom overlap and high level of comorbid conditions. Chronic emotional dysregulation with irritability and frequent temper tantrums, sometimes viewed as characteristics of early-onset mania, might reflect a--possibly severe--sub-type of ADHD rather than a prodrome of bipolarity. A marked cyclicity of symptoms, with periodic accentuation of ADHD and mood symptoms, requires careful monitoring and systematic analysis of comorbid conditions. Clarification of the complex interrelations between ADHD and bipolar disorder will be obtained from long-term studies.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Angiotensin II type 1 receptor-function affected by mutations in cytoplasmic loop CD.

To explore peptide hormone-induced conformational changes, we attempted to engineer a metal-ion binding site between the cytoplasmic loops CD and EF in the angiotensin II type 1 (AT(1)) receptor. We constructed 12 double and six triple histidine mutant receptors, and tested the ability of each mutant and the wild-type to activate inositol phosphate (IP) production with and without ZnCl(2). Inhibition by ZnCl(2) in the double and triple His mutant receptors was not significant, but these mutations directly decreased the IP production. Systematic analysis of single His mutants demonstrated that the loop CD-mutants displayed 52-74% inhibition of IP production, whereas the loop EF-mutants did not affect IP production. These results indicate that the cytoplasmic loop CD-segment from Tyr(127) to Ile(130) is important for G(q/11) activation by the AT(1) receptor.

Amino Acid Sequence↗
PubMed2000

Functional genomics by mass spectrometry.

Systematic analysis of the function of genes can take place at the oligonucleotide or protein level. The latter has the advantage of being closest to function, since it is proteins that perform most of the reactions necessary for the cell. For most protein based ('proteomic') approaches to gene function, mass spectrometry is the method of choice. Mass spectrometry can now identify proteins with very high sensitivity and medium to high throughput. New instrumentation for the analysis of the proteome has been developed including a MALDI hybrid quadrupole time of flight instrument which combines advantages of the mass finger printing and peptide sequencing methods for protein identification. New approaches include the isotopic labeling of proteins to obtain accurate quantitative data by mass spectrometry, methods to analyze peptides derived from crude protein mixtures and approaches to analyze large numbers of intact proteins by mass spectrometry directly. Examples from this laboratory illustrate biological problem solving by modern mass spectrometric techniques. These include the analysis of the structure and function of the nucleolus and the analysis of signaling complexes.

Genome↗
PubMed1998

A novel system of peptidergic regulation.

Systematic analysis of structure and biological activity of peptide components of tissue extracts and biological fluids allows us to formulate a novel concept of a peptidergic regulatory system, complementary to the conventional regulatory systems (i.e. nervous, endocrine and paracrine systems). According to that concept, the proteolytic degradation of tissue proteins carried out by a specific and regulated system of tissue-specific enzymes and protein substrates gives rise to a large group of peptides, which we define as tissue-specific peptide pool. As a result, functional proteins provide their proteolytically derived fragments for maintaining tissue homeostasis.

Amino Acid Sequence↗
PubMed1998

Expression profile and structural divergence of novel human annexin 31.

Systematic analysis of expressed sequence tags in dbEST yielded an expression profile of the ten known human annexins and led to the discovery of a novel subfamily expressed mainly in differentiating tissues. Full-length cDNAs encoded a 338-amino acid protein with less than 40% identity to other annexins, an atypical amino acid composition, and an insertion and deletion in internal repeat 3. The most striking feature was a complete ablation of all four type II calcium-binding sites in the conserved tetrad core. Annexin 31 thus constitutes a unique, natural probe for investigating the role of membrane binding in annexin function.

Amino Acid Sequence↗