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Results for “systematic analysis”

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At least 1,189 records · Page 66Linked to original sources
PubMed2006

Progesterone for the prevention of preterm birth among women at increased risk: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study was undertaken to determine whether progestational agents, initiated in the second trimester of pregnancy, reduce the risk of delivery less than 37 weeks, among women at increased risk of spontaneous preterm birth. STUDY DESIGN: Medline, pre-Medline, EMBASE, and Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials with less than 20% lost to follow-up were included. RESULTS: Three trials were eligible for inclusion. There was a significant reduction in risk of delivery less than 37 weeks with progestational agents (relative risk [95% CI] = 0.57 [0.36-0.90]). There was no significant effect on perinatal mortality or serious neonatal morbidity. CONCLUSION: Progestational agents, initiated in the second trimester of pregnancy, may reduce the risk of delivery less than 37 weeks' gestation, among women at increased risk of spontaneous preterm birth, but the effect on neonatal outcome is uncertain. Larger randomized controlled trials are required to determine whether this treatment reduces perinatal mortality or serious neonatal morbidity.

Drug Administration Schedule↗
PubMed2005

Three-day vs longer duration of antibiotic treatment for cystitis in women: systematic review and meta-analysis.

PURPOSE: We performed a meta-analysis to ascertain the efficacy and safety of the currently practiced 3-day antibiotic therapy for cystitis versus prolonged therapy (5 days or longer) to relieve symptoms and to achieve bacteriological cure. METHODS: The Cochrane Library, the Cochrane Renal Group's Register of trials, EMBASE and MEDLINE were searched to identify all randomized controlled trials comparing 3-day oral antibiotic therapy with prolonged therapy (5 days and longer) for uncomplicated cystitis in adult non-pregnant women. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. Relative risks (RR) with their 95% confidence intervals (CI) were estimated; a fixed effect model was used. An intention-to-treat analysis was performed whenever possible. RESULTS: Thirty-two trials and 9605 patients met inclusion criteria. For symptomatic failure rates no difference between 3-day and prolonged antibiotic regimens was found at short term (RR 1.16, 95% CI: 0.96-1.41) and long-term follow-up (RR 1.17, 95% CI: 0.99-1.38). Three-day treatment was less effective than prolonged therapy in preventing bacteriological failure, relative risk 1.37 (95% CI: 1.07-1.74) for short-term follow-up, and 1.47 (95% CI: 1.22-1.77) for long-term follow-up. Adverse effects were more common in the prolonged therapy group (RR 0.83, 95% CI: 0.79-0.91). The results were consistent for subgroup and sensitivity analyses. CONCLUSION: Antibiotic therapy for 3 days is similar to prolonged therapy in achieving symptomatic cure for cystitis, while the prolonged treatment is more effective in obtaining bacteriological cure.

Administration, Oral↗
PubMed2004

[A routine prospective survey process to detect nosocomial bacterial colonization in a neonatal unit: risk factors for acquisition].

UNLABELLED: A systematic analysis of weekly nasal and rectal swabs was carried out in a neonatal unit in order to detect colonization with multiresistant bacteria (MRB). PATIENTS AND METHODS: During a 6-month period, rectal and nasal samples were taken in 187 consecutively hospitalized newborns, the day of the admission (day 0) and every week until discharge, in order to detect MRB, mainly methicillin-resistant coagulase negative staphylococci (MRCoNS), Staphylococcus aureus and multi-resistant Gram-negative bacilli. RESULTS: Among 187 infants, 50 were already colonized at entrance and excluded from the study. In others, 49 (35%) were colonized by at least one MRB, with a total of 71 strains isolated. The most frequent was MRCoNS, especially Staphylococcus epidermidis (66.1%). Gram-negative bacilli accounted for 9.8%. Colonization began earlier with MRCoNS than with Gram-negative bacilli, 7.8 +/- 6 vs. 15.5 +/- 16 days, P=0.004, and finished earlier 22.7 +/- 15 vs. 38.5 +/- 16 days, P=0.03. Colonized children exhibited by univariate analysis a lower birth weight, more frequent parenteral nutrition or previous hospitalization in a neonatal unit and a younger age at admission. Odds ratio for colonization were 4.06 for prematurity and 43.83 for a previous hospitalization. MRCoNS at days 15 (P <0.05) and 22 (P <0.05) were correlated with the empiric use of antibiotics. No nosocomial infection occurred during the study. CONCLUSION: A high rate of newborns were colonized with MRB in our unit, especially MRCoNS, acquired earlier than Gram-negative bacilli, with a favoring action of empiric antibiotherapy.

Age Factors↗
PubMed2006

[Diuretics in preterm infants].

Diuretics are frequently used in preterm infants in various situations such as patent ductus arteriosus, respiratory distress syndrome, bronchopulmonary dysplasia or neonatal renal insufficiency. However, the beneficial effects reported in the literature are usually transient, without any obvious effect on important parameters such as duration of oxygen dependency, ventilator dependency, length of hospital stay, long-term outcome, or mortality. Moreover, these drugs may induce water-electrolyte disorders especially when used for a long-term period. Thus, we recommend a systematic analysis of the beneficial/risk ratio before any use of these drugs.

Bronchopulmonary Dysplasia↗
PubMed2004

Effects of statin therapy on the progression of carotid atherosclerosis: a systematic review and meta-analysis.

Observational studies suggested that the progression of carotid atherosclerosis and plaques might be an independent risk factor for coronary artery disease (CAD) and stroke, prior researches of different dosage of statins therapy on the progression of carotid atherosclerosis in patients had small sample sizes and different the results. We aimed to evaluate the efficacy and safety of statins therapy on the rate of carotid atherosclerosis progression through randomized controlled trials (RCTs). We searched MEDLINE (1980-September 2003), the Cochrane Controlled Trials Register, EMBASE (1985-September 2003), Science Citation Index and PUBMED (updated through December 2003). Additional articles were obtained from reference lists of relevant reviews and papers in manual searches. Ten studies (eight studies between statins and placebo, two studies between aggressive statins and conventional therapy) were included. Two reviewers extracted abstracts, and appraised the Jadad Score for Grading Quality of Randomized Controlled Trials independently, and discrepancies were resolved by consensus with a third reviewer. We analyzed the 10 trials with 3443 individuals age range from 30 to 70 years old and follow-up for 1-4 years. Eight studies showed that the rates of carotid IMT progression were consistently significantly different between statins and placebo, the Z score for overall effect of IMT was 10.41 (P<0.00001), Total 95%CI of weighted mean difference (WMD) between two groups was -0.02235 [-0.02656, -0.01614] (mm/y), the chi(2)-test for heterogeneity of IMT between eight studies was 685.33 (P<0.00001), two studies between aggressive statins and conventional statins demonstrated that the Z score for overall effect of IMT was 15.85 (P<0.00001), total 95%CI of WMD between two groups was -0.06326 [-0.07108, -0.05544], chi(2)-test for heterogeneity of IMT between two studies was 3.75 (P=0.05). Conventional statins were not significantly different of adverse events and withdrawal than placebo (P>0.05). Our findings suggest that conventional statins therapy are efficient and safe to decrease the rate of carotid atherosclerosis progression in a long-term, and aggressive statins may provide superior efficacy for carotid atherosclerosis regression.

Adult↗
PubMed2004

Evolutionary perspective on annexin calcium-binding domains.

Molecular systematic analysis of the annexin gene superfamily characterized the evolutionary origin, frequency and range of structural variation in calcium interaction domains that are considered intrinsic for membrane targeting and ion channel function. Approximately 36% of annexin repeat domains in an estimated 100 distinct subfamilies contained amino acid changes consistent with the functional loss of type two calcium-binding sites. At least 11% of annexin domains contained a novel K/H/RGD motif conserved in particular subfamilies and manifest in all phyla, apparently via convergent evolution. The first yeast annexin from Yarrowia lipolytica was classified in the ANXC1 subfamily with fungal and mycetozoan representatives. This clade had intact calcium-binding sites but disruption of the normally well-conserved, mid-repeat 4 region implicated in calcium channel regulation. Conversely, a tandem pair of novel annexins from the amphioxus Branchiostoma floridae resembled annexin A13 in gene structure and conserved the charged amino acids associated with the internal hydrophilic pore, but were devoid of external type 2 calcium-binding sites and incorporated K/RGD motifs instead, like annexin A9. The selective erosion of calcium-binding sites in annexin domains and the occurrence of alternate ligands in the same exposed, interhelical loops are pervasive features of the superfamily. This suggests greater complexity than previously appreciated in the mechanisms controlling annexin membrane interaction and calcium channel operation.

Amino Acid Sequence↗
PubMed2005

G alpha selectivity and inhibitor function of the multiple GoLoco motif protein GPSM2/LGN.

GPSM2 (G-protein signalling modulator 2; also known as LGN or mammalian Pins) is a protein that regulates mitotic spindle organization and cell division. GPSM2 contains seven tetratricopeptide repeats (TPR) and four Galpha(i/o)-Loco (GoLoco) motifs. GPSM2 has guanine nucleotide dissociation inhibitor (GDI) activity towards both Galpha(o)- and Galpha(i)-subunits; however, a systematic analysis of its individual GoLoco motifs has not been described. We analyzed each of the four individual GoLoco motifs from GPSM2, assessing their relative binding affinities and GDI potencies for Galpha(i1), Galpha(i2), and Galpha(i3) and Galpha(o). Each of the four GPSM2 GoLoco motifs (36-43 amino acids in length) was expressed in bacteria as a GST-fusion protein and purified to homogeneity. The binding of each of the four GST-GoLoco motifs to Galpha(i1)-, Galpha(o)-, and Galpha(s)-subunits was assessed by surface plasmon resonance; all of the motifs bound Galpha(i1), but exhibited low affinity towards Galpha(o). GDI activity was assessed by a fluorescence-based nucleotide-binding assay, revealing that all four GoLoco motifs are functional as GDIs for Galpha(i1), Galpha(i2), and Galpha(i3). Consistent with our binding studies, the GDI activity of GPSM2 GoLoco motifs on Galpha(o) was significantly lower than that toward Galpha(i1), suggesting that the in vivo targets of GPSM2 are most likely to be Galpha(i)-subunits.

Amino Acid Motifs↗
PubMed2006

Cellular uptake of S413-PV peptide occurs upon conformational changes induced by peptide-membrane interactions.

In face of accumulated reports demonstrating that uptake of some cell-penetrating peptides occurs through previously described endocytic pathways, or is a consequence of cell fixation artifacts, we conducted a systematic analysis on the mechanism responsible for the cellular uptake of the S4(13)-PV karyophilic cell-penetrating peptide. The results reviewed here show that the S4(13)-PV peptide is able to very efficiently accumulate inside live cells in a rapid, non-toxic and dose-dependent manner, through a mechanism distinct from endocytosis. Comparative analysis of peptide uptake by mutant cells lacking heparan sulfate proteoglycans demonstrates that, although not mandatory, their presence at cell surface facilitates the cellular uptake of the S4(13)-PV peptide. Furthermore, we demonstrate that upon interaction with lipid vesicles, the S4(13)-PV peptide undergoes significant conformational changes that are consistent with the formation of helical structures. Such conformational changes occur concomitantly with a penetration of the peptide into the lipid bilayer, strongly suggesting that the resulting helical structures are crucial for the non-endocytic cellular uptake of the S4(13)-PV peptide. Overall, our data support that, rather than endocytosis, the cellular uptake of the S4(13)-PV cell-penetrating peptide is a consequence of its direct translocation through cell membranes following conformational changes induced by peptide-membrane interactions.

Amino Acid Sequence↗
PubMed2006

Dissecting the ubiquitin pathway by mass spectrometry.

Protein modification by ubiquitin is a central regulatory mechanism in eukaryotic cells. Recent proteomics developments in mass spectrometry enable systematic analysis of cellular components in the ubiquitin pathway. Here, we review the advances in analyzing ubiquitinated substrates, determining modified lysine residues, quantifying polyubiquitin chain topologies, as well as profiling deubiquitinating enzymes based on the activity. Moreover, proteomic approaches have been developed for probing the interactome of proteasome and for identifying proteins with ubiquitin-binding domains. Similar strategies have been applied on the studies of the modification by ubiquitin-like proteins as well. These strategies are discussed with respect to their advantages, limitations and potential improvements. While the utilization of current methodologies has rapidly expanded the scope of protein modification by the ubiquitin family, a more active role is anticipated in the functional studies with the emergence of quantitative mass spectrometry.

Animals↗
PubMed2005

A survey of alternative transcripts of human tissue kallikrein genes.

Alternative splicing is prevalent within the human tissue kallikrein gene locus. Aside from being the most important source of protein diversity in eukaryotes, this process plays a significant role in development, physiology and disease. A better understanding of alternative splicing could lead to the use of gene variants as drug targets, therapeutic agents or diagnostic markers. With the rapidly rising number of alternative kallikrein transcripts, classifying new transcripts and piecing together the significance of existing data are becoming increasingly challenging. In this review, we present a systematic analysis of all currently known kallikrein alternative transcripts. By defining a reference form for each of the 15 kallikrein genes (KLK1 to KLK15), we were able to classify alternative splicing patterns. We identified 82 different kallikrein gene transcript forms, including reference forms. Alternative splicing may lead to the synthesis of 56 different protein forms for KLK1-15. In the kallikrein locus, the majority of alternative splicing events occur within the protein-coding region, and to a lesser extent in the 5' untranslated regions (UTRs). The most common alternative splicing event is exon skipping (35%) and the least common events are cryptic exons (3%) and internal exon deletion (3%). Seventy-six percent of kallikrein splice variants that are predicted to encode truncated proteins are the result of frameshifts. Eighty-nine percent of putative proteins encoded by splice variants are predicted to be secreted. Although several reports describe the identification of kallikrein splice variants and their potential clinical utility, this is the first extensive review on this subject. Accumulating evidence suggests that alternative kallikrein forms could be involved in many pathologic conditions or could have practical applications as biomarkers. The organization and analysis of the kallikrein transcripts will facilitate future work in this area and may lead to novel clinical and diagnostic applications.

Alternative Splicing↗
PubMed2026

Multi-omics profiling of cerebrospinal fluid in autoimmune encephalitis: insights into pathogenesis and therapeutic targets.

BACKGROUND: Autoimmune encephalitis (AIE) is a rare, severe inflammatory brain disease, with its pathogenesis not yet fully elucidated. This study aimed to characterize proteomic and metabolomic alterations in the cerebrospinal fluid (CSF) of AIE patients and identify potential therapeutic targets. METHODS: 65 consecutive AIE patients and age-matched concurrent controls were enrolled, respectively. Clinical characteristics, including blood and CSF laboratory findings, were compared between the two groups, and CSF samples were collected for multi-omics analysis. Differentially expressed proteins (DEPs) and metabolites (DEMs) between AIE patients and controls were identified using data-independent acquisition-based proteomics and targeted liquid chromatography-mass spectrometry-based metabolomics, followed by integrated multi-omics analysis. RESULTS: Compared with controls, AIE patients had lower levels of triglyceride and C1q, but higher HDL-CH levels, neutrophil counts, and eosinophil counts in blood. CSF leukocyte, erythrocyte, lymphocyte, and mononuclear cell counts were also elevated in AIE patients. Proteomic analysis identified 163 DEPs, with enrichment of 87 canonical pathways primarily associated with immune-inflammatory responses, neuronal-synaptic dysfunction, and cell signaling and metabolic pathways. Metabolomic analysis recognized 21 DEMs, predominantly amino acids, lipids, and carbohydrates, which were involved in lipid-carbohydrate metabolism and immune regulation. Integrated multi-omics analysis validated these findings and identified several potential therapeutic targets for AIE, including the IL6-STAT3 axis. CONCLUSIONS: Integrated multi-omics analysis systematically delineates cellular and molecular alterations underlying AIE. Immune-inflammatory response and lipid metabolism are pivotal in AIE progression and the IL6-STAT3 axis holds promise as a potential therapeutic target.

Humans↗
PubMed2005

Differential turnover of cortical and trabecular bone in transgenic mice overexpressing cathepsin K.

Cathepsin K is a major osteoclastic protease. We have recently shown that overexpression of mouse cathepsin K gene in transgenic UTU17 mouse model results in high turnover osteopenia of metaphyseal trabecular bone at the age of 7 months. The present report extends these studies to a systematic analysis of cortical bone in growing and adult mice overexpressing cathepsin K. Mice homozygous for the transgene locus (UTU17+/+) and their control littermates were studied at the age of 1, 3, 7, and 12 months. Bone properties were analyzed using peripheral quantitative computed tomography (pQCT), histomorphometry, histochemistry, radiography, and biomechanical testing. In addition, the levels of biochemical markers of bone turnover were measured in the sera. Unexpectedly, cortical thickness and cortical bone mineral density were increased in the diaphyseal region of growing and adult UTU17+/+ mice. This was associated with an increased number of vascular canals leading to increased cortical porosity in UTU17+/+ mice without changes in the ultimate bending force or stiffness of the bone. In UTU17+/+ mice, osteopenia of metaphyseal trabecular bone was observed already at the age of 1 month. In sera of 1-month-old UTU17+/+ mice, the activity of tartrate-resistant acid phosphatase 5b was decreased and the levels of osteocalcin increased. Our results support the role of cathepsin K as a major proteinase in osteoclastic bone resorption. Excessive production of cathepsin K induced osteopenia of metaphyseal trabecular bone and increased the porosity of diaphyseal cortical bone. The increased cortical thickness and bone mineral density observed in diaphyses of UTU17+/+ mice demonstrate the different nature and reactivity of trabecular and cortical bone in mice. These results suggest that the biomechanical properties of cortical bone are preserved through adaptation as outlined in Wolff's law.

Animals↗
PubMed2006

Crosstalk between cAMP-PKA and MAP kinase pathways is a key regulatory design necessary to regulate FLO11 expression.

Signal transduction pathways crosstalk with one another and play a central role in regulation of cellular events. Crosstalk brings complexity to the system, and hence, a systematic analysis of these crosstalks helps in relating the signaling network structure to its function. Here, we present a modular steady state approach to quantify the network comprising of cAMP-PKA and MAP kinase pathways involved in the regulation of FLO11, a gene which is required for pseudohyphae growth in Saccharomyces cerevisiae under nitrogen starvation. These two pathways crosstalk by converging on the same target, i.e., FLO11 and through Ras2p, an upstream activator of both cAMP and MAPK pathway. Analysis of crosstalk at the gene level revealed that cAMP-PKA and MAPK pathways are indispensable to FLO11 expression. The dose response was highly sensitive and primarily controlled by cAMP-PKA pathway. We demonstrate that the highly sensitive response in the cAMP-PKA pathway was due to crosstalk and inhibitor ultrsensitivity, key regulatory designs present at the downstream of cAMP-PKA pathway. The analysis of the role of Ras2p in the crosstalk between the cAMP-PKA and MAPK pathways indicated that crosstalk essentially helped in amplification of the Gpa2p signal, another upstream activator of the cAMP-PKA pathway. However, the effect of crosstalk due to Ras2p on FLO11 expression was minimal under normal activation levels of Ras2p. Whereas, the crosstalk itself can bring about FLO11 expression under the hyperactivated Ras2p conditions thereby eliminating the requirement for the other activator Gpa2p. We also observed the presence of system level properties such as amplification, inhibitor ultrasensitvity and bistability, which can be attributed to the regulatory design present in the FLO11 expression system. These system level properties might help the organism to respond to varying nutritional status.

Adenylyl Cyclases↗
PubMed2006

Glyoxal formation by Fenton-induced degradation of carbohydrates and related compounds.

In this paper, we provide a systematic analysis of glyoxal (1) formation from a range of monosaccharides and related compounds, to determine their potential role as sources of this alpha-oxoaldehyde in vivo. Substrates were reacted with the Fenton reagent (Fe(2+)/EDTA/H(2)O(2)) and the mixtures were analyzed by HPLC using the 6-hydroxy-2,4,5-triaminopyrimidine fluorimetric assay. The rank order of hexoses and their derivatives as glyoxal sources was found to be fructose > glucose = mannose = galactose > glucose-6-phosphate > mannitol. Within the pentose group, arabinose and ribose gave the higher yields of 1 followed by deoxyribose and its adenine N-glycosides and ribulose. Among the tested substrates, three-carbon compounds, that is, trioses and glycerol, but not glyceraldehyde-3-phosphate, were by far the most effective sources of 1. The effects of H(2)O(2) and Fe(2+)/EDTA concentrations as well as of other metal ions were also investigated.

Carbohydrate Metabolism↗
PubMed2004

Cell cycle goes global.

The cell division cycle is one of the most intensively studied biological processes, yet, in spite of great effort, many questions remain as to how the cell cycle is controlled by cyclin-dependent kinases and other critical regulators. Recent functional genomic and proteomic approaches have yielded new insights into almost all aspects of cell cycle control, including transcriptional circuits, DNA replication, sister chromatid separation and regulation by environmental signals. Perhaps most notably, systematic analysis has begin to reveal meta-level connections between previously distinct sub-processes. As the interconnections between these huge datasets are beyond intuition, mathematical representation and automated analysis of functional genomic data is an urgent mandate.

Animals↗
PubMed2006

Coding of odors by a receptor repertoire.

We provide a systematic analysis of how odor quality, quantity, and duration are encoded by the odorant receptor repertoire of the Drosophila antenna. We test the receptors with a panel of over 100 odors and find that strong responses are sparse, with response density dependent on chemical class. Individual receptors range along a continuum from narrowly tuned to broadly tuned. Broadly tuned receptors are most sensitive to structurally similar odorants. Strikingly, inhibitory responses are widespread among receptors. The temporal dynamics of the receptor repertoire provide a rich representation of odor quality, quantity, and duration. Receptors with similar odor sensitivity often map to widely dispersed glomeruli in the antennal lobe. We construct a multidimensional "odor space" based on the responses of each individual receptor and find that the positions of odors depend on their chemical class, concentration, and molecular complexity. The space provides a basis for predicting behavioral responses to odors.

Animal Structures↗
PubMed2025

Mitochondrial activity tunes nociceptor resilience to excitotoxicity.

The capsaicin receptor, TRPV1, mediates the detection of noxious chemical and thermal stimuli by nociceptors, primary sensory neurons of the pain pathway. Overactivation of TRPV1 leads to cellular damage or death through calcium entry and excitotoxicity. We have exploited this phenomenon to conduct a systematic analysis of excitotoxicity through a genome-wide CRISPRi screen, thereby revealing a comprehensive network of regulatory pathways. We show that decreased expression of mitochondrial electron transport chain (ETC) components protects against capsaicin-induced toxicity and other challenges by mitigating both calcium imbalance and the generation of mitochondrial reactive oxygen species via distinct pathways. Moreover, we confirm the regulatory roles of the ETC in sensory neurons through gain-of-function and loss-of-function experiments. Interestingly, TRPV1+ sensory neurons maintain lower expression of ETC components and can better tolerate excitotoxicity and oxidative stress compared with other sensory neuron subtypes, implicating ETC tuning as an intrinsic cellular strategy that protects nociceptors against excitotoxicity.

Mitochondria↗
PubMed2005

Modelling of ceramide interactions with porous graphite carbon in non-aqueous liquid chromatography.

Interactions of solutes on porous graphitic carbon (PGC) with non-aqueous mobile phases are studied by the linear solvation energy relationship (LSER). Studies have been carried out with eight binary mixtures composed of a weak solvent (acetonitrile or methanol) and a strong solvent (tetrahydrofuran, n-butanol, CH2Cl2, 1,1,2-trichloro-2,2,1-trifluoroethane). The systematic analysis of a set of test compounds was performed for each solvent mixture in isocratic mode (50:50). The results were compared to those obtained on PGC with hydro-organic liquids and supercritical fluids. They were then correlated with the observed retention behaviour of lipid compounds, more particularly ceramides.

Ceramides↗