Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PLETHORA”

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 595 records · Page 33Linked to original sources
PubMed2004

ES-62, a filarial nematode-derived immunomodulator with anti-inflammatory potential.

Arthropod-transmitted filarial nematodes can survive for in excess of a decade via modulation of the vertebrate host immune system. Although human infection can result in very severe pathology, most infected individuals show remarkably little evidence of this. Analysis of the anti-nematode response indicates that apparently pathology-free individuals have an anti-inflammatory immunological phenotype and it has been suggested that this favours maintenance of host good health. It is considered that parasite-derived molecular secretions contribute to the anti-inflammatory phenotype and we have thus investigated the properties of a filarial nematode glycoprotein secreted in some abundance, ES-62. This molecule shows a plethora of immunomodulatory activities that can be classified as anti-inflammatory. It has been observed in a number of studies that several autoimmune disorders including rheumatoid arthritis (RA) exhibit reduced incidence and severity in geographic regions in which filarial nematodes are transmitted to humans. Furthermore, it has been speculated that these two observations are linked although molecular explanations for such an association have not been forthcoming. Although the aetiology of RA remains unknown a majority of data are consistent with it being mediated via excess pro-inflammatory cytokine production. Given that ES-62 is anti-inflammatory, we hypothesised that it might be able to counter the pathology associated with diseases like RA. Indeed, we found that exposure to ES-62 prevented initiation of collagen-induced arthritis (CIA) in a murine model and also suppressed progression of established disease. Ex vivo analyses demonstrated that these effects correlated with inhibition of TNF-alpha production and inhibition of collagen-specific TH-1 responses. The nematode product was also able to suppress pro-inflammatory cytokine release in vitro in synovial cells derived from RA patients. ES-62 thus constitutes a pathogen-derived immunomodulator with significant therapeutic potential.

Animals↗
PubMed2005

Ballistics: a primer for the surgeon.

The purpose of this paper is to review the literature on ballistics and to sort through the plethora of myth and popular opinion. The trauma surgeon is increasingly faced with gunshot wounds. Knowledge of ballistics is important to help in assessing the patterns of wounds that are seen. There are many factors that affect the flight of a bullet to its target. Many of these factors also affect the behaviour of the bullet after it strikes the target. It is primarily these factors that interest the surgeon.

Firearms↗
PubMed2005

Biological activity of bone morphogenetic proteins (BMP's).

Bone morphogenetic proteins are multifunctional molecules having effects in many tissue types. They are members of the transforming growth factor-beta superfamily. At least 40 different types have been described to date. Their potential use in tissue regeneration has led to extensive research leading to a plethora of articles being published. This article provides a brief overview of the biological activity of different BMP's involved in the fracture healing process.

Bone Morphogenetic Proteins↗
PubMed2006

Impact of interleukin-1 and interleukin-6 in murine primary schistosomiasis.

BACKGROUND: Immunization with schistosome antigens invariably elicits a plethora of cytokines and, hence, it is reasonable to assume that these cytokines influence host responses to challenge lung-stage larvae and, consequently, the adult worm burden, and may be responsible for the erratic data generally observed in protection studies against schistosome infection. METHODS: Schistosoma mansoni-infected mice were administered with recombinant interleukin (IL)-1beta or IL-6 to evaluate the impact of cytokines in host responses to lung-stage schistosomula, and subsequent effects on adult worm parameters. Plasma lipid levels were assayed by colorimetric enzymatic tests and antibody responses by ELISA. Cytokine profile in peripheral blood mononuclear cells was evaluated by RT-PCR. RESULTS: S. mansoni infection elicited, at the time of parasite residency in the lung, significant increase in free fatty acids (FA) and decrease in cholesterol plasma levels in C57BL/6 and CD1 mice, and stimulation of mRNA expression for cytokines of T helper type (Th) 2 in BALB/c, Th1 in C57BL/6, and Th1/Th2 in CD1 mice. However, no specific antibody production was evident in any mouse strain. In BALB/c mice, exogenous IL-1beta-related plasma free FA level significant increase, stimulation of expression of IL-1 and IL-12 mRNA, and considerable increase in percent of specific antibody-producing mice were associated with significant reduction in adult worm burden and egg load. In contrast, exogenous IL-1beta elicited decrease in free FA plasma levels, and down-regulation of cytokines' mRNA expression in C57BL/6 and CD1 mice, changes associated with aggravation of the worm burden. Likewise, exogenous IL-6 failed to stimulate increase in plasma free FA levels or percent of antibody-producing mice except in BALB/c mice, effects that were protective for the host in BALB/c and for the parasite in C57BL/6 and CD1 mice. CONCLUSION: These findings were discussed in relation to the erratic data of protection experiments with schistosome subunit antigens in different mouse strains.

Animals↗
PubMed2005

The 'supervirus'? Lessons from IL-4-expressing poxviruses.

Members of the Poxviridae family are particularly adept at avoiding the host immune system, encoding a plethora of immunomodulatory proteins that subvert host defense. With their large genome, poxviruses are also useful for studying the effect of exogenous genes on virus-host interactions and immune responses. The insertion of the Th2 cytokine interleukin-4 (IL-4) into several poxviruses significantly increases the efficiency of the recombinant virus as a pathogen by directly inhibiting the development of Th1 immunity, which is crucial for viral clearance. In an age in which the fear of genetically modified weaponized pathogens exists, the understanding of how to make viruses more pathogenic further blurs the distinction between fundamental academic research and bioweapons development. Here, the extent of immune evasion by IL-4-expressing poxviruses will be explored, as will the consequences of this increased pathogenicity on protective immune responses.

Animals↗
PubMed2006

The distinct temperament profiles of bipolar I, bipolar II and unipolar patients.

BACKGROUND: Despite a plethora of studies, controversies abound on whether the long-term traits of unipolar and bipolar patients could be differentiated by temperament and whether these traits, in turn, could be distinguished from subthreshold affective symptomatology. METHODS: 98 bipolar I (BP-I), 64 bipolar II (BP-II), and 251 unipolar major depressive disorder (UP-MDD) patients all when recovered from discrete affective episodes) and 617 relatives, spouses or acquaintances without lifetime RDC diagnoses (the comparison group, CG) were administered a battery of 17 self-rated personality scales chosen for theoretical relevance to mood disorders. Subsamples of each of the four groups also received the General Behavior Inventory (GBI). RESULTS: Of the 436 personality items, 103 that significantly distinguished the three patient groups were subjected to principal components analysis, yielding four factors which reflect the temperamental dimensions of "Mood Lability", "Energy-Assertiveness," "Sensitivity-Brooding," and "Social Anxiety." Most BP-I described themselves as near normal in emotional stability and extroversion; BP-II emerged as labile in mood, energetic and assertive, yet sensitive and brooding; MDD were socially timid, sensitive and brooding. Gender and age did not have marked influence on these overall profiles. Within the MDD group, those with baseline dysthymia were the most pathological (i.e., high in neuroticism, insecurity and introversion). Selected GBI items measuring hypomania and biphasic mood changes were endorsed significantly more often by BP-II. Finally, it is relevant to highlight a methodologic finding about the precision these derived temperament factors brought to the UP-BP differentiation. Unlike BP-I who were low on neuroticism, both BP-II and UP scored high on this measure: yet, in the case of BP-II high neuroticism was largely due to mood lability, in UP it reflected subdepressive traits. LIMITATION: We used self-rated personality measures, a possible limitation generic to the paper-and-pencil personality literature. It is therefore likely that BP-I may have over-rated their "sanguinity"; or should one consider such self-report as a reliable reflection of one's temperament? One can raise similar unanswerable questions about "depressiveness" and "mood lability." CONCLUSION: As contrasted to CG and published norms, the postmorbid self-described "usual" personality is 1) sanguine among many, but not all, BP-I; 2) labile or cyclothymic among BP-II; and 3) subanxious and subdepressive among UP. It is further noteworthy that with the exception of BP-II, the temperament scores of BP-I and MDD were within one SD from published norms. Rather than being pathological, these attributes are best conceived as subclinical temperamental variants of the normal, thereby supporting the notion of continuity between interepisodic and episodic phases of affective disorders. These findings overall are in line with Kraepelin's views and contrary to the DSM-IV formulation of axis-II constructs as being pathological and sharply demarcated from affective episodes.

Adult↗
PubMed2005

Antioxidant approach to disease management and the role of 'Rasayana' herbs of Ayurveda.

The disease preventive and health promotive approach of 'Ayurveda', which takes into consideration the whole body, mind and spirit while dealing with the maintenance of health, promotion of health and treating ailments is holistic and finds increasing acceptability in many regions of the world. Ancient Ayurvedic physicians had developed certain dietary and therapeutic measures to arrest/delay ageing and rejuvenating whole functional dynamics of the body system. This revitalization and rejuvenation is known as the 'Rasayan chikitsa' (rejuvenation therapy). Traditionally, Rasayana drugs are used against a plethora of seemingly diverse disorders with no pathophysiological connections according to modern medicine. Though, this group of plants generally possesses strong antioxidant activity, only a few have been investigated in detail. Over about 100 disorders like rheumatoid arthritis, hemorrhagic shock, CVS disorders, cystic fibrosis, metabolic disorders, neurodegenerative diseases, gastrointestinal ulcerogenesis and AIDS have been reported as reactive oxygen species mediated. In this review, the role of free radicals in these diseases has been briefly reviewed. 'Rasayana' plants with potent antioxidant activity have been reviewed for their traditional uses, and mechanism of antioxidant action. Fifteen such plants have been dealt with in detail and some more plants with less work have also been reviewed briefly.

Antioxidants↗
PubMed2005

Assessment of sensibility after nerve injury and repair: a systematic review of evidence for validity, reliability and responsiveness of tests.

Recovery of sensibility after peripheral nerve injury and repair needs to be assessed using psychometrically robust measures. In this study the literature was reviewed to identify what tests are available to quantify sensibility and to assess their validity, reliability and responsiveness. The databases Medline, CINAHL, Embase and AMED were searched for studies reporting the psychometric properties of sensibility tests. While there is a plethora of tests and studies reporting the outcomes after peripheral nerve suture only a few of the tests have evidence of validity, reliability and responsiveness. Currently the touch threshold test using monofilaments such as the Weinstein Enhanced Sensory Test (WEST) or Semmes-Weinstein Monofilament Test (SWMT) and the shape-texture identification (STI) test for tactile gnosis are the only tests which meet criteria for a standardized test and have had their psychometric properties evaluated and quantified.

Humans↗
PubMed2004

Studies on activities, cell up take and DNA binding of four multinuclear complexes of the form: [[trans-PtCl(NH(3))(2)](2)mu-[trans-Pd(NH(3))(2)-(H(2)N(CH(2))(n)NH(2))(2)]]Cl(4) where n=4-7.

The activity against human cancer cell lines including ovarian: A2780, A2780(cisR), cell up take, DNA-binding and nature of interaction with pBR322 plasmid DNA have been studied for four multinuclear complexes code named DH4Cl, DH5Cl, DH6Cl and DH7Cl, having the general formula: [[trans-PtCl(NH(3))(2)](2)mu-[trans-Pd(NH(3))(2)-(H(2)N(CH(2))(n)NH(2))(2)]]Cl(4) where n=4, 5, 6 and 7 for DH4Cl, DH5Cl, DH6Cl and DH7Cl, respectively. The compounds are found to exhibit significant anticancer activity against ovarian cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R). DH6Cl in which the linking diamine has six carbon atoms is found to be the most active compound. As the number of carbon atoms in the linking diamine is decreased below six and increased above six, the activity is found to decrease, illustrating structure-activity relationship. All the multinuclear compounds are believed to form a plethora of long-range interstrand GG adducts with DNA dictated by the sequence of bases in the DNA strands. Increasing prevention of BamH1 digestion with the increase in concentration of the compounds is due to global changes in DNA conformation brought about by interstrand long-range binding of the compounds with DNA.

Antineoplastic Agents↗
PubMed2003

Structural characterization of the GSK-3beta active site using selective and non-selective ATP-mimetic inhibitors.

GSK-3beta is a regulatory serine/threonine kinase with a plethora of cellular targets. Consequently, selective small molecule inhibitors of GSK-3beta may have a variety of therapeutic uses including the treatment of neurodegenerative diseases, type II diabetes and cancer. In order to characterize the active site of GSK-3beta, we determined crystal structures of unphosphorylated GSK-3beta in complex with selective and non-selective ATP-mimetic inhibitors. Analysis of the inhibitors' interactions with GSK-3beta in the structures reveals how the enzyme can accommodate a number of diverse molecular scaffolds. In addition, a conserved water molecule near Thr138 is identified that can serve a functional role in inhibitor binding. Finally, a comparison of the interactions made by selective and non-selective inhibitors highlights residues on the edge of the ATP binding-site that can be used to obtain inhibitor selectivity. Information gained from these structures provides a promising route for the design of second-generation GSK-3beta inhibitors.

Adenosine Triphosphate↗
PubMed2003

Improved Gō-like models demonstrate the robustness of protein folding mechanisms towards non-native interactions.

The use of simple theoretical models has provided a considerable contribution to our present understanding of the means by which proteins adopt their native fold from the plethora of available unfolded states. A common assumption in building computationally tractable models has been the neglect of stabilizing non-native interactions in the class of models described as "Gō-like." The focus of this study is the characterization of the folding of a number of proteins via a Gō-like model, which aims to map a maximal amount of information reflecting the protein sequence onto a "minimalist" skeleton. This model is shown to contain sufficient information to reproduce the folding transition states of a number of proteins, including topologically analogous proteins that fold via different transition states. Remarkably, these models also demonstrate consistency with the general features of folding transition states thought to be stabilized by non-native interactions. This suggests that native interactions are the primary determinant of most protein folding transition states, and that non-native interactions lead only to local structural perturbations. A prediction is also included for an asymmetrical folding transition state of bacteriophage lambda protein W, which has yet to be subjected to experimental characterization.

Archaeal Proteins↗
PubMed2004

Tracking the evolution of porphobilinogen synthase metal dependence in vitro.

Metal ions are indispensable cofactors for chemical catalysis by a plethora of enzymes. Porphobilinogen synthases (PBGSs), which catalyse the second step of tetrapyrrole biosynthesis, are grouped according to their dependence on Zn(2+). Using site-directed mutagenesis, we embarked on transforming Zn(2+)-independent Pseudomonas aeruginosa PBGS into a Zn(2+)-dependent enzyme. Nine PBGS variants were generated by permutationally introducing three cysteine residues and a further two residues into the active site of the enzyme to match the homologous Zn(2+)-containing PBGS from Escherichia coli. Crystal structures of seven enzyme variants were solved to elucidate the nature of Zn(2+) coordination at high resolution. The three single-cysteine variants were invariably found to be enzymatically inactive and only one (D139C) was found to bind detectable amounts of Zn(2+). The double mutant A129C/D139C is enzymatically active and binds Zn(2+) in a tetrahedral coordination. Structurally and functionally it mimics mycobacterial PBGS, which bears an equivalent Zn(2+)-coordination site. The remaining two double mutants, without known natural equivalents, reveal strongly distorted tetrahedral Zn(2+)-binding sites. Variant A129C/D131C possesses weak PBGS activity while D131C/D139C is inactive. The triple mutant A129C/D131C/D139C, finally, displays an almost ideal tetrahedral Zn(2+)-binding geometry and a significant Zn(2+)-dependent enzymatic activity. Two additional amino acid exchanges further optimize the active site architecture towards the E.coli enzyme with an additional increase in activity. Our study delineates the potential evolutionary path between Zn(2+)-free and Zn(2+)-dependent PBGS enyzmes showing that the rigid backbone of PBGS enzymes is an ideal framework to create or eliminate metal dependence through a limited number of amino acid exchanges.

Amino Acid Sequence↗
PubMed2006

Molecular details of cAMP generation in mammalian cells: a tale of two systems.

The second messenger cAMP has been extensively studied for half a century, but the plethora of regulatory mechanisms controlling cAMP synthesis in mammalian cells is just beginning to be revealed. In mammalian cells, cAMP is produced by two evolutionary related families of adenylyl cyclases, soluble adenylyl cyclases (sAC) and transmembrane adenylyl cyclases (tmAC). These two enzyme families serve distinct physiological functions. They share a conserved overall architecture in their catalytic domains and a common catalytic mechanism, but they differ in their sub-cellular localizations and responses to various regulators. The major regulators of tmACs are heterotrimeric G proteins, which transduce extracellular signals via G protein-coupled receptors. sAC enzymes, in contrast, are regulated by the intracellular signaling molecules bicarbonate and calcium. Here, we discuss and compare the biochemical, structural and regulatory characteristics of the two mammalian AC families. This comparison reveals the mechanisms underlying their different properties but also illustrates many unifying themes for these evolutionary related signaling enzymes.

Adenylyl Cyclases↗
PubMed2024

Exploring Regulatory Roles of Transposable Elements in EMT and MET through Data-Driven Analysis: Insights from regulaTER.

Gene expression is regulated at the transcriptional and translational levels and a plethora of epigenetic mechanisms. Regulation of gene expression by transposable elements is well documented. However, a comprehensive analysis of their regulatory roles is challenging due to the lack of dedicated approaches to define their contribution. Here, we present regulaTER, a new R library dedicated to deciphering the regulatory potential of transposable elements in a given phenotype. regulaTER utilizes a variety of genomics data of any origin and combines gene expression level information to predict the regulatory roles of transposable elements. We further validated its capabilities using data generated from an epithelial-mesenchymal and mesenchymal-epithelial transition cellular model. regulaTER stands out as an essential asset for uncovering the impact of transposable elements on the regulation of gene expression, with high flexibility to perform a range of transposable element-focused analyses. Our results also provided insights on the contribution of the MIR and B element subfamilies in regulating EMT and MET through the FoxA transcription factor family. regulaTER is publicly available and can be downloaded from https://github.com/karakulahg/regulaTER.

DNA Transposable Elements↗
PubMed2005

High throughput analysis of endogenous glutamate release using a fluorescence plate reader.

Recent discoveries of different modes of exocytosis and a plethora of molecules involved in neurotransmitter release has resulted in demand for more rapid and efficient methods for monitoring endogenous glutamate release from various tissue sources. In this article, we describe a high throughput microplate version of the enzyme-linked fluorescence detection method for the measurement of released glutamate, which utilises glutamate dehydrogenase, and the reduction of NADP to NADPH. Previous versions of this method rely upon cuvette-based fluorimeters for detection that are limited by large sample volumes and small numbers of samples that can be measured simultaneously. Comparison between the two methods shows that the microplate assay has comparable performance to the cuvette-based assay but has the capacity to analyse many times more samples in a given run. This increased capacity provides improved experimental design opportunities, higher experimental throughput and better comparison between experimental conditions.

Animals↗
PubMed2005

Epitope spread is not critical for the relapse and progression of MOG 8-21 induced EAE in Biozzi ABH mice.

Emerging autoimmunity (epitope-spreading) generated as a consequence of myelin damage is suggested to underlie the relapses in multiple sclerosis (MS). Myelin oligodendrocyte glycoprotein (MOG 8-21) induces relapsing EAE in ABH mice characterized by broadening of the autoimmune reportoire. Despite epitope spreading tolerance to the priming antigen, but not emerging epitope reactivities, resulted in long-term inhibition of clinical relapse. In contrast, spinal cord homogenate induced EAE was dominated by a proteolipid protein (PLP 56-70) autoreactivity despite the plethora of CNS antigens in the immunogen. This data suggests that during relapsing-remitting demyelinating disease the pathogenic process is dominated by the initiating antigen, with only a minor role played by emerging T-cell populations. These findings may have important implications for the efficacy of antigen-based immune therapies in autoimmune disorders.

Animals↗
PubMed2007

Neuronal plasticity and neuroregeneration in the skin -- the role of inflammation.

The skin develops probably the densest and most complex innervation of all mammalian organs, consisting of sensory and autonomic nerves loaded with a plethora of neuropeptides and neurotransmitters. Skin innervation, as well as the expression patterns of neurotrophins and their receptors, is subject to dramatic changes during not only morphogenesis but also adult tissue remodeling under physiological or inflammatory conditions. Bilateral neuroimmune interactions are the basis of adaptive responses to tissue remodeling (such as hair cycling), psycho-emotional stress or skin inflammation. Dermatitis and hair loss may be exacerbated by stress-induced neurogenic inflammation. In addition, selected inflammatory skin diseases are associated with increased innervation. Finally, inflammatory cytokines influence the cutaneous expression of neurotrophins, as well as neurotrophin-induced neurite outgrowth following axotomy. Here, we review key studies on bilateral neuroimmune interactions in the skin under both healthy and disease conditions to provide a basis for future research on the role of inflammation in peripheral nerve regeneration.

Animals↗
PubMed2006

A new approach to quantitative NMR: fluoroquinolones analysis by evaluating the chemical shift displacements.

Quantitative NMR spectroscopy is always an attractive goal as the identity and quantity could be simultaneously determined. Although significant advancements have been achieved in this field it is common that all reported quantitative NMR methods perform the analysis by utilizing the average integral intensities of selected signals. During the calculation of the area under NMR peaks several response problems can occur which should always be treated carefully to overcome inaccuracies. In the method proposed in this work the quantitative information is obtained utilizing the measurement of selected protons chemical shift displacements which is a quite straightforward and highly reproducible process. The (1)H NMR spectra of multiple fluoroquinolone (FQ) solutions revealed that the chemical shifts of protons, especially the aromatic ones, were concentration dependent for all tested compounds, as a result of extensive self-association phenomena. In the present work a novel methodology is described for the quantitation of several FQs based on this dependence. The proposed method was applied to Ciprofloxacin solutions over a wide range of concentrations. Evaluation of the obtained data presented acceptable characteristics regarding accuracy, precision, and robustness. The applicability limitations of this method were found to be posed by current instrumentation, mainly by the magnetic field frequency e.g. the slope of the response function achieved with a 400MHz instrument was twice the one achieved at 200MHz. The pH effect was negligible from pD 2.5 to 5.5. The phenomenon appeared in a pattern that can be applied for a plethora of drug categories revealing self-association phenomena in a range of concentration determined by the magnet strength of the instrument.

Anti-Infective Agents↗