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PubMed2003

Pharmacologic treatment of poststroke depression: a systematic review of the literature.

UNLABELLED: CLINICAL QUESTION/OBJECTIVE: A systematic evaluation of the literature published from 1966 until December 2001 on pharmacologic interventions for poststroke depression (PSD). DESIGN: Articles were selected from a computer-based search and were independently reviewed by three evaluators using a standardized criteria including internal validity items as well as descriptive and quantitative items. RESULTS: Fifty studies were preliminarily reviewed and 10 randomized controlled trials (RCTs) were included for systematic analysis. CONCLUSION: Selective serotonin reuptake inhibitors (citalopram and fluoxetine) may be effective in the treatment of PSD. There is some evidence for a beneficial effect of the tricyclic antidepressant nortriptyline, however, the RCTs for this medication lack sufficient validity, and reports on side effects are contradictory.

Antidepressive Agents↗

PubMed1989

Analysis of cytotoxic T cell precursor frequencies directed against individual HLA-A and -B alloantigens.

We describe here a limiting dilution analysis to determine cytotoxic T lymphocyte precursor (CTLp) frequencies against individual HLA-A or -B antigens. This assay is reproducible and showed that the CTLp frequency of an individual remains stable with time. Significant variations in CTLp frequency against the same alloantigen were found in different individuals and even in monozygotic twins, showing that these differences were not (completely) genetically determined. Within an individual, a wide range of CTLp frequencies can be found against different allo-antigens. Serologically cross-reactivity seems not to interfere in this assay. This LDA is a practicable tool for a systematic analysis of CTLp response against selected individual HLA-A or -B antigens and can be used for the selection of HLA mismatched donors for transplantation patients.

Cross Reactions↗

PubMed2002

Controversial medical and agri-food biotechnology: a cultivation analysis.

Whether biotechnology is one or several developments is not clear. Once distinctions are required, the question is: Which one prevails? When the good, the bad, and the ugly settle, where do they fall? Evaluation implies distinction, and representation drives attitude. The controversies over biotechnology are fertile ground on which to study these issues. The imports of genetically modified (GM) soya into Europe in 1996-97 and the cloning of Dolly the sheep from adult cells in 1997 changed the symbolic environment for genetic engineering. The ensuing public controversies came to focus mainly on field trials of GM crops and food labeling. This paper will explore the relationship between quality press coverage and public perception, in particular the cultivation of the contrast between "desirable" biomedical (RED) and "undesirable" agri-food (GREEN) biotechnology in Britain. The argument draws on a systematic analysis of the British press coverage of biotechnology from 1973 to 1999 and analysis of public perceptions in 1996 and 1999. The paper concludes that the debate over GM crops and food ingredients fostered the RED-GREEN contrast among the newspaper-reading public, thereby shielding RED biotechnology from public controversy, and ushered in a realignment of the regulatory framework in 2000.

Biotechnology↗

PubMed2003

Comparative analysis of the ATP-binding sites of Hsp90 by nucleotide affinity cleavage: a distinct nucleotide specificity of the C-terminal ATP-binding site.

The 90-kDa heat shock protein (Hsp90) is a molecular chaperone that assists both in ATP-independent sequestration of damaged proteins, and in ATP-dependent folding of numerous targets, such as nuclear hormone receptors and protein kinases. Recent work from our lab and others has established the existence of a second, C-terminal nucleotide binding site besides the well characterized N-terminal, geldanamycin-sensitive ATP-binding site. The cryptic C-terminal site becomes open only after the occupancy of the N-terminal site. Our present work demonstrates the applicability of the oxidative nucleotide affinity cleavage in the site-specific characterization of nucleotide binding proteins. We performed a systematic analysis of the nucleotide binding specificity of the Hsp90 nucleotide binding sites. N-terminal binding is specific to adenosine nucleotides with an intact adenine ring. Nicotinamide adenine dinucleotides and diadenosine polyphosphate alarmones are specific N-terminal nucleotides. The C-terminal binding site is much more unspecific-it interacts with both purine and pirimidine nucleotides. Efficient binding to the C-terminal site requires both charged residues and a larger hydrophobic moiety. GTP and UTP are specific C-terminal nucleotides. 2',3'-O-(2,4,6-trinitrophenyl)-nucleotides (TNP-ATP, TNP-GTP) and pyrophosphate access the C-terminal binding site without the need for an occupied N-terminal site. Our data provide additional evidence for the dynamic domain-domain interactions of Hsp90, give hints for the design of novel types of specific Hsp90 inhibitors, and raise the possibility that besides ATP, other small molecules might also interact with the C-terminal nucleotide binding site in vivo.

Adenosine Triphosphate↗

PubMed2005

Meta-analysis of bacterial resistance to macrolides.

OBJECTIVES: Understanding changing resistance patterns is important in determining appropriate antibiotic treatments. This meta-analysis systematically evaluated resistance of Streptococcus pneumoniae and Streptococcus pyogenes to macrolide antibiotics among patients with community-acquired respiratory tract infections. METHODS: MEDLINE and EMBASE databases were searched and experts were consulted to identify published and unpublished literature reporting macrolide resistance rates. Identified studies were evaluated by two independent reviewers; those meeting a priori specified criteria (resistance by patient condition and strain, resistance thresholds, 1997-2003 isolates) were included. Data from included studies were abstracted by two independent reviewers using a standard review form. Discrepancies in abstracted data were resolved by the study investigator. RESULTS: Random-effects meta-analysis was performed for outcomes present in at least four studies overall and for specified subgroups. We identified 3849 studies and performed detailed review on 407; of these 29, published between 1998-2003, met the inclusion criteria. Mean resistance of S. pneumoniae isolates to azithromycin was 27.2% [95% confidence interval (CI) 24.6-29.7]; mean resistance to erythromycin was statistically equivalent (30.4%; 95% CI 28.1-32.7). Resistance of S. pyogenes to erythromycin (30.0%; CI 18.6-41.5) was similar to that of S. pneumoniae. Too few studies of clarithromycin were included to allow evaluation of resistance. In subgroup analyses, substantial variation in resistance to erythromycin was seen by geographic area. CONCLUSIONS: Reported macrolide resistance of S. pneumoniae varies substantially and may be a significant issue in certain regions. Use of meta-analysis to aggregate individual studies enabled determination of robust values for macrolide resistance. This information is useful for clinical and policy decision makers in developing appropriate antibiotic strategies.

Anti-Bacterial Agents↗

PubMedDate not supplied

Serological assessment of type I collagen burden in scleroderma spectrum disorders: a systematic review.

RATIONALE: The aim of the study was to evaluate the validity of collagen type I metabolites as markers of disease activity in scleroderma (SSc), through a systematic review of the literature and by validating the results by measuring collagen type I metabolites in well characterized patients with scleroderma spectrum disorders and in Raynaud's phenomenon. METHODS: A systematic review was performed of studies of collagen type I metabolites in scleroderma spectrum disorders published from 1980 to 2003. The collected results from the literature were compared with our own measurements of collagen type I metabolites (PINP and ICTP) in a small number of well characterized patients within the scleroderma spectrum and in patients with primary and "autoimmune" Raynaud's phenomenon. Peptide concentrations from all sources, including the present study, were compared. Reported correlations between peptide concentrations and clinical variables were also analysed. RESULTS: Of 19 papers identified by an extensive Medline search, 12 were eligible for systematic analysis. There was a considerable heterogeneity in the results with a wide range of metabolite concentrations. Values from disease groups and healthy controls overlapped. These findings were confirmed by our study where, similarly, there was a large range of values in all groups, but particularly in the diffuse SSc subset. When the correlation between peptide levels and clinical variables was assessed, large discordance between the studies was observed. CONCLUSIONS: We have not found sufficient evidence to support the use of serum markers of collagen turnover in the assessment of scleroderma activity and severity, in view of their low specificity and the heterogeneity of the results of various studies. Lack of standardized routine evaluation of SSc patients in clinical studies might have accounted for the variability of the findings. However, due to the small sizes of most published studies, demonstration of no effect should come from large-scale randomised trials. Longitudinal serial analysis of these molecules in individual patients may play a future role in the evaluation of the response to fibroblast-targeting therapeutic strategies in scleroderma patients.

Biomarkers↗

PubMed2026

Protective association of the ELMO1 rs741301 variant against diabetes mellitus and diabetic nephropathy: a systematic meta-analysis of case-control studies.

CONTEXT: Diabetes mellitus (DM), an endocrine disorder, is characterised by persistently elevated blood glucose levels due to inadequate insulin production. Diabetic nephropathy (DN), is a critical complication associated with DM, often leading to end-stage renal failure and increased mortality. OBJECTIVE: This meta-analysis aimed to evaluate the association between the ELMO1 rs741301 polymorphism and susceptibility to DN among individuals with diabetes. METHOD: A systematic literature search was conducted for studies published between 2014 and 2024 using Embase, Google Scholar, and PubMed. Eligible case-control studies investigating the association between ELMO1 rs741301 and DN among individuals with DM were selected according to predefined inclusion criteria. Nine case-control studies comprising 880 individuals with DM and 1008 individuals with DN were included in the meta-analysis. RESULTS: The pooled analysis demonstrated a significant protective association between the ELMO1 rs741301 polymorphism and DN under the allelic model (OR = 0.77, 95% CI: 0.67-0.88), recessive model (OR = 0.74, 95% CI: 0.61-0.90), and dominant model (OR = 0.68, 95% CI: 0.53-0.88). In contrast, no statistically significant association was observed under the over-dominant model. CONCLUSION: The findings suggest that the ELMO1 rs741301 polymorphism may be associated with a reduced susceptibility to DN among individuals with DM. These findings provide evidence for a potential genetic contribution of ELMO1 to DN susceptibility and may help improve understanding of the genetic factors underlying diabetic complications. Further well-designed studies in diverse populations are warranted to validate this association.

Humans↗

PubMed2003

A method for in-vivo analysis for regional arterial wall material property alterations with atherosclerosis: preliminary results.

Atherosclerosis is a diffuse arterial disease developing over many years and resulting in a complicated three-dimensional arterial morphology. The arterial wall material properties have been demonstrated to show regional alterations with atheroma development and growth. We present a mechanical analysis of diseased arterial segments reconstructed from intravascular ultrasound images in order to quantitatively identify regional alterations in the elastic constants with atherosclerotic lesions. We employ a finite element and a displacement sensitivity analysis to divide the arterial segment into regions with different material properties and use an optimization algorithm to identify the elastic constants in these regions. The results with regional variations identified with this method correlated qualitatively with the extent and location of atherosclerotic lesions identified by visual inspection of the affected arteries. The optimized elastic modulus in regions affected by early atherosclerotic lesions ranged from 90.9 to 93.0 kPa where as the corresponding magnitudes in normal arterial segments ranged from 97.9 to 101.0 kPa. This method can be potentially employed to identify the extent and location of atherosclerotic lesions in a systematic analysis and may potentially be used for the early detection of lesion growth.

Animals↗

PubMed2006

Optimal frequency ranges for extracting information on cardiovascular autonomic control from the blood pressure and pulse interval spectrograms in mice.

The analysis of blood pressure (BP) and heart rate (HR) variability by spectral methods has proven a useful tool in many animal species for the assessment of the vagal and sympathetic contributions to oscillations of BP and HR. Continuous BP measurements obtained in mice by telemetry were used to characterize the spectral bandwidths of autonomic relevance by using an approach with no a priori. The paradigm was based on the autonomic blockades obtained with conventional drugs (atropine, prazosin, atenolol). The spectral changes were estimated in all of the combinations of spectral bandwidths. The effect of hydralazine was also tested using the same systematic analysis, to detect the zones of sympathetic activation resulting reflexly from the vasodilatory action of the drug. Two zones of interest in the study of the autonomic control of BP and HR were observed. The first zone covered the 0.15-0.60 Hz range of the systolic BP spectrum and corresponds to the low-frequency zone (or Mayer waves). This zone reflects sympathetic control since the power spectral density of this zone was significantly reduced with alpha1-adrenoceptor blockade (prazosin), while it was significantly amplified as a result of a reflex sympathetic activation (hydralazine). The second zone covered the 2.5-5.0 Hz range of the pulse interval spectrum and corresponded to the high-frequency zone (respiratory sinus arrhythmia) under vagal control (blocked by atropine). These zones are recommended for testing the autonomic control of circulation in mice.

Animals↗

PubMed1989

In vitro splicing analysis of mini-gene constructs of the alternatively processed human calcitonin/CGRP-I pre-mRNA.

The human calcitonin/CGRP-I (CALC-I) gene can be alternatively expressed into calcitonin mRNA in thyroid C-cells and into CGRP-I mRNA in particular nerve cells. Formation of calcitonin mRNA requires splicing of exons 1, 2, 3 and 4 and addition of poly(A) at exon 4, whereas splicing of exons 1, 2, 3, 5 and 6 and addition of poly(A) at exon 6 yields CGRP-I mRNA. The calcitonin and CGRP-I mRNA-specific splicing reactions were investigated in vitro, in nuclear extracts of HeLa cells, using model precursor RNAs containing the exon 3 to exon 5 region of the gene. A precursor RNA containing the full-length exon 3 to exon 5 region was only poorly spliced in vitro. Therefore, a systematic analysis was performed of the effect of deletions introduced in the intron 3, exon 4 and intron 4 of this precursor RNA on calcitonin/CGRP mRNA-specific splicing. The deletions increased the efficiency of splicing considerably. In all cases CGRP mRNA-specific splicing is strongly favoured over calcitonin mRNA-specific splicing. In addition, splicing reactions using cryptic 5' splice sites were detected which interfered with the usage of processing signals for calcitonin and CGRP mRNA-specific splicing. The results imply a major regulatory role for the exon 4 poly(A) addition reaction in the generation of calcitonin mRNA.

Calcitonin↗

PubMed2006

Variables contributing to the coordination of rapid eye/head gaze shifts.

In this article results of several published studies are synthesized in order to address the neural system for the determination of eye and head movement amplitudes of horizontal eye/head gaze shifts with arbitrary initial head and eye positions. Target position, initial head position, and initial eye position span the space of physical parameters for a planned eye/head gaze saccade. The principal result is that a functional mechanism for determining the amplitudes of the component eye and head movements must use the entire space of variables. Moreover, it is shown that amplitudes cannot be determined additively by summing contributions from single variables. Many earlier models calculate amplitudes as a function of one or two variables and/or restrict consideration to best-fit linear formulae. Our analysis systematically eliminates such models as candidates for a system that can generate appropriate movements for all possible initial conditions. The results of this study are stated in terms of properties of the response system. Certain axiom sets for the intrinsic organization of the response system obey these properties. We briefly provide one example of such an axiomatic model. The results presented in this article help to characterize the actual neural system for the control of rapid eye/head gaze shifts by showing that, in order to account for behavioral data, certain physical quantities must be represented in and used by the neural system. Our theoretical analysis generates predictions and identifies gaps in the data. We suggest needed experiments.

Algorithms↗

PubMed2005

Correlation-associated peptide networks of human cerebrospinal fluid.

Profiling of peptides and small proteins from either human body fluids or tissues by chromatography and subsequent mass spectrometry reveals several thousand individual peptide signals per sample. Any peptide is an intermediate in the course of biosynthesis, post-translational modification (PTM), proteolytic processing and degradation. Changes in the concentration of one peptide often affects the concentration of the other, hence a challenge consists in the development of suitable tools to turn this large amount of data into biologically relevant information. Comprehensive statistical analysis of the peptide profiling data allows associating peptides, which are closely related in terms of peptide biochemistry. Here, the bioinformatic concept of peptide networks, correlation-associated peptide networks (CANs), is introduced. Peptides with statistical similarity of their concentrations are grouped in form of networks, and these networks are interpreted in terms of peptide biochemistry. The spectrum of functional relationships found in cerebrospinal fluid CAN covers PTM and proteolytic degradation of peptides, clearance processing in the complement cascade, common secretion of peptides by neuroendocrine cells as well as ubiquitin-mediated degradation. Our results indicate that CAN is a powerful bioinformatic tool for the systematic analysis and interpretation of large peptidomics and proteomics data and helps to discover novel bioactive and diagnostic peptides.

Chemical Fractionation↗

PubMed2026

Effect of walking training on blood glucose control and metabolic health in patients with type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the improvement effect of walking training on blood glucose control and metabolic health indicators in type 2 diabetes patients, and to explore the effect of different intervention program characteristics on the efficacy through subgroup analysis. METHOD: The system searched PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO databases, with a search period from the establishment of the database to March 15, 2026. Include a randomized controlled trial with the main intervention measures of walking behavior, with an intervention period of ≥8 weeks. Two researchers independently conducted literature screening, data extraction, and bias risk assessment. Meta-analysis was conducted using RevMan 5.4 software, with mean difference (MD) and its 95% confidence interval (CI) as effect measures for continuous variables. Select fixed effects model or random effects model for combined analysis based on heterogeneity size, and conduct subgroup analysis according to intervention program characteristics. RESULTS: Totally 5 randomized controlled trials were included, including 483 patients with type 2 diabetes (241 cases in the intervention group and 242 cases in the control group). Participants had a mean age of 54.2 ± 6.5 years, BMI of 29.1 ± 3.2 kg/m2, and 48.5% were male. The meta-analysis results showed that walking training significantly reduced glycated hemoglobin levels, with a combined effect of -0.48% (95% CI: -0.60 to -0.36, P < 0.00001), There is moderate heterogeneity among the studies (I2 = 67%). Subgroup analysis showed that the "walking + other interventions" subgroup (combined effect size -0.58%, 95% CI: -0.96 to -0.20) and the "clear step target" subgroup (combined effect size -0.52%, 95% CI: -0.65 to -0.39) had larger effect sizes and lower heterogeneity within the subgroups. The bias risk assessment shows that the overall quality of the included research methodology is good. CONCLUSION: Walking training can significantly improve the blood glucose control in patients with type 2 diabetes. Combined with diet or behavioral intervention, setting clear goals for the number of steps may achieve better results. Walking training can be used as an effective auxiliary treatment for the management of type 2 diabetes in clinical promotion. Due to limitations in the number and quality of studies included, the above conclusions still require more high-quality research to validate.

Humans↗

PubMedDate not supplied

[Diagnostic performance of mammography in patients with clinically impercetible tumors. Analysis of 1005 tumors].

UNLABELLED: Breast cancer is an important public health problem. Early diagnosis is the only method of efficient secondary prevention in the control of the illness as it permits rapid and effective treatment. The objective of this study was to carry out a methodical analysis that would enable us to increase the diagnostic performance of the mammogram and to diminish the number of unnecessary surgical biopsies. MM: We selected impalpable mammary tumors in patients with radiological suspicion of breast cancer, on which surgical biopsy by harpoon had been practiced in the Lozano Blesa Hospital, Zaragoza, between October 1991 and January 2005. RESULTS: We analyzed a total of 1005 tumors in 965 patients, with an average age of 57 years. In our series of 1005 tumors, 40% were PVV. CONCLUSIONS: The diagnosis of radiological suspicion and the indication for biopsy or mammographic control are subjective and personal appreciations, but based on the systematic analysis of radiological signs of incipient tumors. This analysis enables us to establish a cut-off point to include the tumors in BIRADS.

Adult↗

PubMed2026

Divergent evolutionary strategies in spider venoms: A comparative proteomic profiling of four sympatric species from Yunnan.

Spider venoms comprise complex cocktails of bioactive molecules evolved for predation and defense, representing a valuable resource for biological research and pharmaceutical discovery. In this study, we performed a systematic analysis of venom gland extracts from four common spider species indigenous to Yunnan, China: Agelena limbata, Hippasa lycosina, Lycosa grahami, and Sinopoda pengi. Using an integrated transcriptomic and proteomic targeted profiling approach, we successfully annotated 141 distinct toxins. Comparative analysis revealed significant interspecific heterogeneity, suggesting distinct evolutionary trajectories and "weapon system economics." Both A. limbata and L. grahami exhibited a "peptide-dominant" profile anchored by neurotoxic peptides and isomerases, optimized for rapid chemical paralysis. In contrast, S. pengi displayed a distinct "protein-dominant" signature enriched with high-molecular-weight enzymes and CAP superfamily proteins, likely functioning to facilitate tissue degradation and toxin diffusion. Occupying an intermediate position, H. lycosina demonstrated a hybrid composition. These findings suggest that although these species share the same geographical range, their venom systems have undergone divergent evolutionary adaptations driven by specific ecological niches and hunting strategies. This study represents the first systematic proteomic characterization of these venom components, providing a valuable reservoir of molecular candidates while highlighting the bioinformatic nuances of analyzing whole-gland homogenates.

Animals↗

PubMed2001

Immunohistochemical analysis of diethylstilbestrol-induced renal tumors in adult male Syrian hamsters: evidence for relationship to peripheral nerve sheath tumors.

Estrogen-induced Syrian hamster kidney tumors (SHKT) are widely used as experimental models for the study of hormonal and renal carcinogenesis. In order to characterize the direction of differentiation of SHKT, kidney sections of diethylstilbestrol (DES)-treated hamsters (1-11 months) were analyzed by immunohistochemistry using a panel of lineage-specific markers. The first tumorous buds found in animals exposed to DES for 4-6 months exhibited prominent S100, Leu-7, and vimentin immunoreactivities. Immunopositivities for neuron-specific enolase, PGP 9.5, desmin, and glial fibrillary acidic protein were mostly detected in medium-sized and large tumors after prolonged exposure to DES (> 6 months). All neoplasms, irrespective of the size and the duration of treatment, appeared negative for cytokeratin, neurofilaments, synaptophysin, and CD99 antibodies. Western blotting confirmed to a large extent the immunohistochemical observations. The systematic analysis of serial kidney sections by confocal microscopy after double immunostaining for S100 and neurofilaments revealed that early neoplastic buds could stem from S100-positive cells associated with nerves bundles. Altogether, these observations suggest that DES-induced SHKT could be related to malignant peripheral nerve sheath tumor and originate from a yet unidentified precursor cell present in the sheath of peripheral nerves.

Animals↗

PubMed2004

Identification of genes preferentially expressed during wood formation in Eucalyptus.

Wood is the most abundant biological resource on earth and it is also an important raw material for a major global industry with rapidly increasing demand. The genus Eucalyptus includes the most widely used tree species for industrial plantation, mainly for making pulp and paper. With the aim of identifying major genes involved in wood formation in Eucalyptus , we have developed a targeted approach of functional genomics based on the isolation of xylem preferentially expressed genes by subtractive PCR. Transcript profiling using cDNA arrays and analysis of variance (ANOVA) were used to identify differentially expressed ESTs between secondary xylem and leaves. Real-time RT-PCR was performed to confirm the differential expression of representative EST. Of 224 independent EST sequences obtained, 81% were preferentially expressed in xylem. One-third of the ESTs exhibiting homologies with proteins of known function fell into two main classes highlighting the importance of the auxin signalling through ubiquitin-dependent proteolysis on one hand, and of the enzymes involved in cell wall biosynthesis and remodelling, on the other. The functions of the genes represented by the remaining 61% of ESTs should be of great interest for future research. This systematic analysis of genes involved in wood formation in Eucalyptus provides valuable insights into the molecular mechanisms involved in secondary xylem differentiation as well as new candidate-genes for wood quality improvement.

DNA, Complementary↗

PubMed2007

A portrait of Aristotle as an anatomist: historical article.

Aristotle is principally known as a theoretical philosopher and logician but he was also an eminent natural scientist. In particular, he should be considered probably the first anatomist in the modern sense of this term and the originator of anatomy as a special branch of knowledge. Although it seems certain that he did not perform dissections of human adult cadavers, he examined human fetal material and, above all, made systematic analysis of animal bodies. His contribution to comparative anatomy, as well as to human anatomy, was enormous. He founded the anatomical discipline on precise descriptive and scientific ground. He also coined a series of technical terms, which are still in use in the modern nomenclature. His observational skill was astounding. Although many of his physiological concepts turned out to be wrong, still his structural description of organs and body parts was often first-rank. The present study will chiefly focus on Aristotle's anatomical work and will provide only essential mention of his complex physiological and philosophical doctrine. The main purpose of this article is indeed to offer to today's anatomists a systematic account of the extraordinary achievements of this great pioneer of our discipline.

Anatomy↗