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At least 1,207 records · Page 67Linked to original sources
PubMed2002

The doctrine of signatures in the medieval and Ottoman Levant.

This study traces the use of the Doctrine of Signatures among medieval and Ottoman physicians and its subsequent appearance in the pharmacological literature of the Levant. Close examination of the historical sources of the Levant seems to support the claim that although this theory did not originate in the region, it was certainly practised there. These sources have revealed 23 substances with medicinal uses based on the Doctrine, bearing witness to the extent of its influence at the time. The main categories of the Doctrine uncovered were: similarity between the substance used and the human organ; resemblance in shape or behaviour to a specific animal; correlation between the colour of a substance and the colour of the symptoms; similarities between the substance and the patient's symptoms and the use of a substance that might produce symptoms of a particular disease in a healthy person to remedy those same symptoms in one who is sick.

History, Medieval↗
PubMed2002

The bioenergetic signature of cancer: a marker of tumor progression.

Mitochondrial H+-ATP synthase is required for cellular energy provision and for efficient execution of apoptosis. Almost one century ago, Otto Warburg proposed the hypothesis that mitochondrial function might be impaired in cancer cells. However, his hypothesis was never demonstrated in human carcinomas. In this study, we have analyzed the expression of the beta-catalytic subunit of the H+-ATP synthase (beta-F1-ATPase) of mitochondria in carcinomas of the human liver, kidney, and colon. We show that carcinogenesis in the liver involves a depletion of the cellular mitochondrial content, as revealed by reduced content of mitochondrial markers, whereas in kidney and colon carcinomas, it involves a selective repression of the expression of the beta-F1-ATPase concurrent with an increase in the expression of the glycolytic glyceraldehyde-3-phosphate dehydrogenase. Both mechanisms limit mitochondrial cellular activity in cancer, strongly supporting Warburg's hypothesis, and suggest a mechanism for the resistance and compromised apoptotic potential of tumor cells. Furthermore, we show that the metabolic state of the cell, as defined by a bioenergetic mitochondrial index relative to the cellular glycolytic potential, provides a signature of carcinogenesis of prognostic value in assessing the progression of colorectal carcinomas.

Animals↗
PubMed2002

Valid informed consent: a process, not a signature.

Surgeons have dutifully used "consent forms" for most of the last century. But only in the last two decades have we begun to understand the difference between a patient's legalistically signed form and the meaningful process of communicating the reasons for considering surgical or other invasive intervention. Furthermore, we must be reasonably assured that the patient is legally competent, understands the situation and alternatives, and is not coerced (by family or medical professionals) in the decision-making. To accomplish this, time-consuming patient education and negotiation are necessary. To limit this process to a brief agreement that the procedure should be done and the patient is willing (as evidenced by a signature) is to return to paternalism. Little evidence suggests that such signing is valid. Of more importance, patients want and are owed a clear understanding of what is probably ahead including risks and preventive measures to limit complications. This article analyzes the components of "consent," suggests methods to ensure the validity of the agreement, and proposes that an educated patient benefits greatly by an appropriate process.

Communication↗
PubMed2003

Identification of signature genes by microarray for acute myeloid leukemia without maturation and acute promyelocytic leukemia with t(15;17)(q22;q12)(PML/RARalpha).

Acute myeloid leukemia (AML) has distinct subgroups characterized by different maturation and specific chromosomal translocation. In order to gain insight into the gene expression activities in AML, we carried out a gene expression profiling study with 21 AML samples using cDNA microarrays, focusing on acute promyelocytic leukemia with specific translocation t(15;17)(q22;q12) [French-American-British or FAB-M3 with t(15;17)] and AML without maturation (FAB-M1) characterized by morphologically and phenotypically immature AML blasts and no recurrent chromosomal abnormalities. Using a multivariate sigma-classifier algorithm, we identified 33 strong feature genes that distinguish FAB-M3 with t(15;17) from other AML samples, and 24 strong feature genes that classify FAB-M1. A direct comparison between FAB-M3 with t(15;17) and FAB-M1 led to selection of 13 strong feature genes. Those genes include some known to be related to leukemogenesis and cell differentiation. RIN1, a gene in the ras pathway, was up-regulated in FAB-M3 with t(15;17). Growth factor-binding protein 2 gene was down-regulated in FAB-M1. Huntingtin gene was up-regulated in FAB-M1. Others include syndecan 4, interleukin-2 receptor beta, folate receptor beta, low affinity immunoglobulin gamma, Fc receptor IIC precursor, insulin-like growth factor binding protein 2, and myeloperoxidase, which are involved in cell differentiation. Overexpression of myeloperoxidase in FAB-M3 cells with t(15;17) compared to FAB-M1 cells is consistent with the conventional cytochemical staining pattern. Thus, the study revealed that a morphologically-defined FAB-M1 subtype has a distinct gene expression signature that contributes to its cell differentiation and proliferation as well as FAB-M3 with a recurrent cytogenetic abnormality t(15;17)(q22;q12).

Algorithms↗
PubMed2002

A novel bioinformatic strategy for unveiling hidden genome signatures of eukaryotes: self-organizing map of oligonucleotide frequency.

With the increasing amount of available genome sequences, novel tools are needed for comprehensive analysis of species-specific sequence characteristics for a wide variety of genomes. We used an unsupervised neural network algorithm, Kohonen's self-organizing map (SOM), to analyze di- and trinucleotide frequencies in 9 eukaryotic genomes of known sequences (a total of 1.2 Gb); S. cerevisiae, S. pombe, C. elegans, A. thaliana, D. melanogaster, Fugu, and rice, as well as P. falciparum chromosomes 2 and 3, and human chromosomes 14, 20, 21, and 22, that have been almost completely sequenced. Each genomic sequence with different window sizes was encoded as a 16- and 64-dimensional vector giving relative frequencies of di- and trinucleotides, respectively. From analysis of a total of 120,000 nonoverlapping 10-kb sequences and overlapping 100-kb sequences with a moving step size of 10 kb, derived from a total of the 1.2 Gb genomic sequences, clear species-specific separations of most sequences were obtained with the SOMs. The unsupervised algorithm could recognize, in most of the 120,000 10-kb sequences, the species-specific characteristics (key combinations of oligonucleotide frequencies) that are signature representations of each genome. Because the classification power is very high, the SOMs can provide fundamental bioinformatic strategies for extracting a wide range of genomic information that could not otherwise be obtained.

Animals↗
PubMed2004

Proteomic signatures for daunomycin and adriamycin in Bacillus subtilis.

The influence of the two anthracyclin antibiotics daunomycin and adriamycin on the proteome of Bacillus subtilis was investigated. They intercalate in the double helix causing strand breaks. Both compounds induce proteins related to DNA damage and oxidative stress as indicated by the induction of some members of the PerR and the DinR-regulon. The mild induction of some members of the HrcA- and the CtsR-regulon may indicate protein oxidation as well. Furthermore, an influence on the sigmaB-dependent general stress response was shown. These data show that the proteomic signature is a valuable experimental tool for a comprehensive evaluation of the action of different drugs.

Anti-Bacterial Agents↗
PubMed2004

Signatures of environmental exposures using peripheral leukocyte gene expression: tobacco smoke.

Functional biological markers of environmental exposures are important in epidemiological studies of disease risk. Such markers not only provide a measure of the exposure, they also reflect the degree of physiological and biochemical response to the exposure. In an observational study, using DNA microarrays, we show that it is possible to distinguish between 85 individuals exposed and unexposed to tobacco smoke on the basis of mRNA expression in peripheral leukocytes. Furthermore, we show that active exposure to tobacco smoke is associated with a biologically relevant mRNA expression signature. These findings suggest that expression patterns can be used to identify a complex environmental exposure in humans.

Adult↗
PubMed1992

Basics of abdominal and pelvic duplex: instrumentation, anatomy, and vascular Doppler signatures.

The capabilities and limitations of color duplex sonography are briefly discussed in this article. Following this, basic Doppler and hemodynamic principles are reviewed, with emphasis on the concept of arterial pulsatility, as reflected in Doppler velocity waveforms. The bulk of the article is devoted to abdominal vascular anatomy and a review of the Doppler signatures that facilitate identification to abdominal vessels. This subject is complex, and an intimate command of abdominal vascular anatomy can only be achieved when detailed study is coupled with sonographic experience. It is hoped that the anatomic drawings and sonographic illustrations included in this work will assist the neophyte sonographer with the difficult task of mastering the anatomy and normal Doppler characteristics of abdominal vessels.

Abdomen↗
PubMed2005

Detecting the historical signature of key innovations using stochastic models of character evolution and cladogenesis.

Phylogenetic evidence for biological traits that increase the net diversification rate of lineages (key innovations) is most commonly drawn from comparisons of clade size. This can work well for ancient, unreversed traits and for correlating multiple trait origins with higher diversification rates, but it is less suitable for unique events, recently evolved innovations, and traits that exhibit homoplasy. Here I present a new method for detecting the phylogenetic signature of key innovations that tests whether the evolutionary history of the candidate trait is associated with shorter waiting times between cladogenesis events. The method employs stochastic models of character evolution and cladogenesis and integrates well into a Bayesian framework in which uncertainty in historical inferences (such as phylogenetic relationships) is allowed. Applied to a well-known example in plants, nectar spurs in columbines, the method gives much stronger support to the key innovation hypothesis than previous tests.

Adaptation, Biological↗
PubMed2005

In chronic myeloid leukemia white cells from cytogenetic responders and non-responders to imatinib have very similar gene expression signatures.

BACKGROUND AND OBJECTIVES: Imatinib induces complete cytogenetic responses (CCR) in the majority of patients with chronic myeloid leukemia (CML) in chronic phase (CP). However, a subgroup of patients is refractory at the cytogenetic level. Clinically, it would be advantageous to identify such patients a priori, since they may benefit from more aggressive therapy. DESIGN AND METHODS: To elucidate mechanisms underlying cytogenetic refractoriness, we used Affymetrix oligonucleotide arrays to determine the transcriptional signature associated with cytogenetic refractoriness in unselected white blood or bone marrow cells from 29 patients with CML in first CP prior to treatment with imatinib. Patients with CCR within 9 months were defined as responders (n = 16) and patients lacking a major cytogenetic response (> 35% Philadelphia-positive metaphases) after 1 year were defined as non-responders (n = 13). RESULTS: Differences in gene expression between responders and non-responders were subtle. Stringent statistical analysis with multiple comparison adjustments revealed very few differentially expressed genes. Differentially expressed genes could not be confirmed in an independent test set. INTERPRETATION AND CONCLUSIONS: We conclude that transcriptional profiling of unselected white cells is of limited value for identifying genes consistently associated with cytogenetic refractoriness to imatinib.

Adult↗
PubMedDate not supplied

1H MR spectroscopic characteristics of kernicterus: a possible metabolic signature.

BACKGROUND AND PURPOSE: MR examination of infants with kernicterus shows abnormal changes in signal intensity in various parts of the brain, including the globus pallidus and subthalamic regions. The purpose of this study was to retrospectively analyze proton ((1)H) MR spectroscopic data to see if the MR spectroscopic profiles of infants with hyperbilirubinemia and symptoms of kernicterus provide new insights into the pathophysiology of bilirubin neurotoxicity. METHODS: Six patients aged 3 days to 3 weeks, with hyperbilirubinemia and symptoms of kernicterus underwent MR imaging and MR spectroscopy with a single-voxel point-resolved spectroscopic sequence. The voxel of interest was centered in the basal ganglia with CSF excluded. Quantitative analysis was done by using LCModel. Between-subject comparisons were based on metabolite ratios relative to creatine. RESULTS: Ratios of taurine, glutamate and glutamine, and myoinositol relative to creatine were significantly elevated (P < .001), whereas the ratio of choline to creatine was significantly decreased (P < .001) compared with normal values published for this age group. Lactate levels were not significantly elevated. CONCLUSION: Kernicterus has a characteristic signature that is detectable on (1)H-MR spectroscopy. Our results are generally in agreement with what is known about bilirubin pathology, and the finding of increased glutamate and glutamine and decreased choline ratios indicates a possible link between hepatic encephalopathy and kernicterus. This observation may help in elucidating the pathophysiology of bilirubin neurotoxicity.

Female↗
PubMed2002

[A novel approach to study pathogenesis of pathogens in vivo--signature-tagged mutagenesis].

Signature-tagged mutagenesis (STM) is a novel approach to study pathogenesis of pathogens and to screen virulence genes with high throughput in vivo,which is based on whole genome of pathogen in question. In recent years, more than ten species of microbial pathogens have been screened with this technology. There are also unknown virulence factors being identified with exception of known virulence genes identified in all these screens. This article reviews the principle, advantages and current limitations,the requirements, modifications of STM, and to date virulence genes identified by this technology.

English Abstract↗
PubMed2005

The signature of positive selection on standing genetic variation.

Considerable interest is focused on the use of polymorphism data to identify regions of the genome that underlie recent adaptations. These searches are guided by a simple model of positive selection, in which a mutation is favored as soon as it arises. This assumption may not be realistic, as environmental changes and range expansions may lead previously neutral or deleterious alleles to become beneficial. We examine what effect this mode of selection has on patterns of variation at linked neutral sites by implementing a new coalescent model of positive directional selection on standing variation. In this model, a neutral allele arises and drifts in the population, then at frequency f becomes beneficial, and eventually reaches fixation. Depending on the value of f, this scenario can lead to a large variance in allele frequency spectra and in levels of linkage disequilibrium at linked, neutral sites. In particular, for intermediate f, the beneficial substitution often leads to a loss of rare alleles--a pattern that differs markedly from the signature of directional selection currently relied on by researchers. These findings highlight the importance of an accurate characterization of the effects of positive selection, if we are to reliably identify recent adaptations from polymorphism data.

Biological Evolution↗
PubMed2006

Novel strategies to identify relevant molecular signatures for complex human diseases based on data of identical-by-decent profiles and genomic context.

OBJECTIVE: To develop novel strategies to identify relevant molecular signatures for complex human diseases based on data of identical-by-decent profiles and genomic context. METHODS: In the proposed strategies, we define four relevancy criteria for mapping SNP-phenotype relationships-point-wise IBD mean difference, averaged IBD difference for window, Z curve and averaged slope for window. RESULTS: Application of these criteria and permutation test to 100 simulated replicates for two hypothetical American populations to extract the relevant SNPs for alcoholism based on sib-pair IBD profiles of pedigrees demonstrates that the proposed strategies have successfully identified most of the simulated true loci. CONCLUSION: The data mining practice implies that IBD statistic and genomic context could be used as the informatics for locating the underlying genes for complex human diseases. Compared with the classical Haseman-Elston sib-pair regression method, the proposed strategies are more efficient for large-scale genomic mining.

Alcoholism↗
PubMed2006

Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumors.

Chemotherapy (CT) resistance in ovarian cancer is related to multiple factors, and assessment of these factors is necessary for the development of new drugs and therapeutic regimens. In an effort to identify such determinants, we evaluated the expression of approximately 21,000 genes using DNA microarray screening in paired tumor samples taken prior to and after CT treatment from 6 patients with predominantly advanced stage, high-grade epithelial ovarian cancer. A subset of differentially expressed genes was selected from all microarray data by initial filtering on confidence at p=0.05, followed by filtering on expression level (>or=2-fold). Using these selection criteria, we found 121 genes to be commonly up-regulated and 54 genes to be down-regulated in the post-CT tumors, compared to primary tumors. Up-regulated genes in post-CT tumors included substantial number of genes with previously known implication in mechanisms of chemoresistance (TOP2A, ETV4, ABCF2, PRDX2, COX2, COX7B, MUC1, MT3, MT2A), and tumorigenesis (SCGB2A2, S100A9, YWHAE, SFN, ATP6AP1, MGC5528, ASS, TACC3, ARHGAP4, SRA1; MGC35136, PSAP, SPTAN1, LGALS3BP, TUBA4, AMY2B, PPIA, COX1, GRB2, CTSL). Down-regulated genes in post-CT samples mostly included genes implicated in chemosensitivity (GRP, TRA1, ADPRTL1, TRF4-2), cell proliferation and cell cycle control (NGFRAP1, TPD52L1, TAX1BP1) and tumor suppression and apoptosis (SMOC2, TIMP3, AXIN1, CASP4, P53SCV). Additionally, gene clustering analysis revealed the existence of two distinct expression signatures of chemoresistant tumors, which was further confirmed by assessment of some genetic (p53 gene mutation status) and clinical parameters (CT regimens). Our data suggest that intrinsic and acquired chemoresistant phenotypes of post-CT tumors may be attributed to the combined action of different factors implicated in mechanisms of chemoresistance, tumor invasion/progression and control of cell proliferation. This type of molecular profiling could have important clinical implications in resolving chemoresistance and the development of novel treatment strategies designed to prevent its emergence.

Adult↗
PubMed2006

Identification of gene expression signatures for molecular classification in human leukemia cells.

Although the methods by which leukemia is classified have been improved for effective therapies, leukemia patients occasionally exhibit diverse, sometimes unpredictable, responses to treatment. Consequently, these patients also evidence individually different clinical courses when administered with anti-leukemia drugs. In order to find new, more precise molecular markers for leukemia classification, we have analyzed the gene expression profiles from 65 diagnostic bone marrow specimens of adult patients with AML, ALL, CML or CLL by using high-throughput DNA microarrays harboring approximately 8,300 unique human genes or expression sequence tags. In the present study, we identified a group of leukemia-specific genes, which manifest gene expression profiles distinctly representative of normal bone marrow samples, as determined by a significance analysis of microarray (SAM) and GeneSpring 6.1 programs. We also determined the minimal number of genes showing a difference between acute and chronic leukemia patient groups. Furthermore, the unsupervised cluster analysis revealed a gene subset which can be used to distinguish between AML, ALL, CML and CLL patient groups, based on expression signatures. The expression levels of differentially regulated genes were verified via the principle component analysis (PCA). Our results may provide a novel set of molecular criteria for the classification of leukemia patients, and may also facilitate effects to discovery new targets, allowing for more effective treatment of leukemia patients.

Adolescent↗
PubMed2006

Delineation of a chemical and biological signature for stormwater pollution in an urban river.

Stormwater is a major source of Escherichia coli in urban waterways. This study assessed the chemical and bacterial contaminant load in stormwater entering an urban river using chemical analyses, E. coli enumeration and antibiotic resistance testing. Inline monitoring of five major stormwater outfalls revealed that E. coli concentrations can range from 100 to >240,000 CFU 100ml(-1) in stormwater; 15% of the samples contained >240,000 CFU 100 ml(-1). E. coli levels increased from <200 CFU 100ml(-1) to between 1,500 and >20,000 CFU 100ml(-1) in the receiving waters following storm events. Metals and nutrients were significantly elevated (p < 0.05) in inline stormwater samples compared with baseflow river water. Chromium, zinc, lead and total phosphorus were co-ordinately elevated in stormwater, but E. coli levels did not correlate to this chemical signature. E. coli isolates from stormwater and river water samples (n = 2,478) were tested for resistance to 10 antibiotics and compared with over 1,800 isolates from human and non-human sources. The antibiotic resistance frequencies of isolates from human sources were considerably higher than those found in non-human sources. Isolates from human sources were resistant to multiple antibiotics; however, no specific multiple resistance pattern was found. One of five stormwater outfalls tested contained E. coli resistant to antibiotics at frequencies that were not significantly different from those of E. coli isolates from wastewater treatment plant influent (p < 0.05). The results from antibiotic resistance testing suggested that the elevated E. coli levels observed after storm events are a mixture of human and non-human sources. The results of this study demonstrate that there is a considerable E. coli load to receiving waters from stormwater and that sanitary sewage inputs may not be limited to recognized sewer overflows.

Anti-Bacterial Agents↗
PubMed2006

[Analysis of the characters of organic matter in water using spectral fluorescence signature and fitting Gaussian].

A sort of analytical method of fast diagnosis of organic matter in water is discussed. The total luminescence spectra (TLS) of water samples in combination with laser induced fluorescence (LIF) measurements using 532 nm wavelength excitation source were measured in the laboratory. The spectra of dissolved organic matter (DOM) and chlorophyll a (Chl a) were pointed out and obtained with spectral fluorescence signature (SFS) technique. The spectrum of water Raman scattering and fluorescence of DOM and Chl a were separated from TLS with fiting Gaussian of the least squares method, and a high correlation coefficient excelling 0.996 4 was obtained. The results indicated the possibilities of water quality monitoring in real time and on line based upon SFS technique and fitting Gaussian of the least squares method.

Environmental Monitoring↗