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At least 1,315 records · Page 73Linked to original sources
PubMed1998

Eukaryotic translation elongation factor 1 alpha: structure, expression, functions, and possible role in aminoacyl-tRNA channeling.

This review offers a comprehensive analysis of eukaryotic translation elongation factor 1 (eEF-1 alpha) in comparison with its bacterial counterpart EF-Tu. Altogether, the data presented indicate some variances in the elongation process in prokaryotes and eukaryotes. The differences may be attributed to translational channeling and compartmentalization of protein synthesis in higher eukaryotic cells. The functional importance of the EF-1 multisubunit complex and expression of its subunits under miscellaneous cellular conditions are reviewed. A number of novel functions of EF-1 alpha, which may contribute to the coordinate regulation of multiple cellular processes including growth, division, and transformation, are characterized.

Animals↗
PubMed2002

Comparative evaluation of indirect and sandwich ELISA for the detection of antibodies to bovine respiratory syncytial virus (BRSV) in dairy cattle.

Seroprevalence of bovine respiratory syncytial virus (BRSV) infection in both exotic and crossbred cattle were described. A baculovirus expressed recombinant purified nucleocapsid (N) protein was used in indirect and sandwich ELISA for screening of 499 bovine sera samples from all over the state for the presence of BRSV antibodies. The seroprevalence rate of BRSV was found to be 46.09% through indirect ELISA while it would found to be 65.33% by sandwich ELISA. The result also indicated that exotic breeds were more susceptible to BRSV infection compared to crossbred cattle. A comprehensive analysis on susceptibility to BRSV as regards to various factors like age and sex was also summarized.

Animals↗
PubMed2001

Yohimbine: a clinical review.

Although yohimbine (YOH) has been available for the treatment of male erectile dysfunction (ED) for longer than Viagra, there is a perception that little is known about the clinical performance of the drug. This review attempts, by comprehensive analysis of the literature, to cover the clinical, pharmacological, and therapeutic profiles of YOH, relevant to its potential utility in the management of patients with ED. Relatively few well-designed studies have been completed. From these, however, it can be concluded that YOH as monotherapy possesses only modest efficacy in ED patients. In acute and chronic (long-term) studies, YOH has been found to be relatively free of side effects over the dose range predicted to be effective in ED. At much higher doses, the most frequently observed effects, consistent with the primary pharmacological action of the drug, are elevation of blood pressure, a slight anxiogenic action, and increased frequency of urination. These side effects are all easily reversible on termination of YOH therapy. There is increasing evidence that the erectogenic action of YOH can be augmented by concomitant administration of agents that augment the release and/or action of nitric oxide in the corpus cavernosum. YOH has yet to be studied in female sexual dysfunction. Overall, the benefit risk profile of YOH would indicate that it has potential, more probably as part of a combination strategy, e.g., with a drug that enhances the nitric oxide pathway, in the treatment of ED.

Adrenergic alpha-Antagonists↗
PubMed2002

Pathways of straight and branched chain fatty acid catabolism in higher plants.

Significant advances in our knowledge of fatty acid breakdown in plants have been made since the subject was last comprehensively reviewed in the early 1990s. Many of the genes encoding the enzymes of peroxisomal beta-oxidation of straight chain fatty acids have now been identified. Biochemical genetic approaches in the model plant, Arabidopsis thaliana, have been particularly useful not only in the identification and functional characterisation of genes involved in fatty acid beta-oxidation but also in establishing the role of beta-oxidation at different stages in plant development. Advances in our understanding of branched chain amino acid catabolism have provided convincing evidence that mitochondria play an important role in this process. This work is discussed in the context of the long running debate on the sub-cellular localisation of fatty acid beta-oxidation in plants. A significant aspect of this review is that it provides the opportunity to present a comprehensive analysis of the complete Arabidopsis genome sequence for each of the different gene families that are known to be involved in beta-, alpha-, and omega-oxidation of fatty acids in plants. Inevitably, this increase in information, as well as providing many answers also raises many new intriguing questions, particularly as regards the regulation and physiological role of fatty acid catabolism throughout the higher plant life cycle.

Arabidopsis↗
PubMed2001

Recombinant tyrosine aminotransferase from Trypanosoma cruzi: structural characterization and site directed mutagenesis of a broad substrate specificity enzyme.

The gene encoding tyrosine aminotransferase (TAT, EC 2.6.1.5) from the parasitic protozoan Trypanosoma cruzi was amplified from genomic DNA, cloned into the pET24a expression vector and functionally expressed as a C-terminally His-tagged protein in Escherichia coli BL21(DE3)pLysS. Purified recombinant TAT exhibited identical electrophoretic and enzymatic properties as the authentic enzyme from T. cruzi. Both recombinant and authentic T. cruzi TATs were highly resistant to limited tryptic cleavage and contained no disulfide bonds. Comprehensive analysis of its substrate specificity demonstrated TAT to be a broad substrate aminotransferase, with leucine, methionine as well as tyrosine, phenylalanine, tryptophan and alanine being utilized efficiently as amino donors. Valine, isoleucine and dicarboxylic amino acids served as poor substrates while polar aliphatic amino acids could not be transaminated. TAT also accepted several 2-oxoacids, including 2-oxoisocaproate and 2-oxomethiobutyrate, in addition to pyruvate, oxaloacetate and 2-oxoglutarate. The functionality of the expression system was confirmed by constructing two variants; one (Arg389) being a completely inactive enzyme; the other (Arg283) retaining its full activity, as predicted from the recently solved three-dimensional structure of T. cruzi TAT. Thus, only one of the two strictly conserved arginines which are essential for the enzymatic activity of subfamily Ialpha aspartate and aromatic aminotransferases is critical for T. cruzi's TAT activity.

Amino Acids↗
PubMed1999

Experimental approaches to understanding virulence in toxoplasmosis.

Toxoplasma gondii is a widespread protozoan parasite that causes severe disease only in immunocompromised individuals. Equipped with excellent animal models and relatively advanced systems for genetics, T. gondii provides an excellent system for understanding pathogenesis. Resistance to toxoplasmosis is governed by rapid innate and adaptive immunity that is characterized by a Th1 type profile of cytokines. Despite this effective response, acute infections can cause considerable damage and the parasite effectively establishes a long-term chronic infection that predisposes the host to reactivation and provides a means of eventual transmission. This complex interaction is brought about by the differentiation of the parasite from a rapidly replicating, lytic form (known as the tachyzoite) to a slow-growing form (known as the bradyzoite) that gives rise to chronic infection. The population structure of T. gondii is remarkably clonal, consisting of just three predominant lineages that are geographically widespread and found in a variety of hosts including humans. Acute virulence is strongly associated with the type I genotype which exhibits an enhanced replication rate in vitro and higher tissue burdens in vivo relative to non-virulent lineages. The pathology associated with acute infection appears to be due to excessive production of acute inflammatory mediators, suggesting that disease is partly due to over-response of the host immune system. A combination of refined animal models and newly developed genetic tools for establishing the relative contribution of genes to pathogenesis will enable a comprehensive analysis of the molecular basis of virulence in toxoplasmosis.

Acute Disease↗
PubMed1997

Agricultural and horticultural chemical poisonings: mortality and morbidity in the United States.

STUDY OBJECTIVE: To provide a comprehensive analysis of morbidity and mortality from poisoning by agricultural and horticultural chemicals in the United States. METHODS: Descriptive analysis of national mortality data, National Hospital Discharge Survey data, and American Association of Poison Control Centers national data for 1985 through 1990. RESULTS: There were 341 fatalities from agricultural and horticultural chemicals over the 6-year period, of which 64% were suicides, 28% were unintentional, and 8% were of undetermined intent. There were 25,418 hospitalizations; 78% were reported to be unintentional. Both deaths and hospitalizations occurred more frequently in males, and rates were higher in nonwhites than in whites. There were 338,170 poison exposures reported to poison centers for fungicides, herbicides, pesticides/insecticides, and rodenticides. Life-threatening manifestations or long-term sequelae occurred in 782 cases, and 97 deaths were reported. Pesticides and insecticides accounted for 72% of the poison center cases and 63% of the fatalities. Although they accounted for only 8% of poison exposures, herbicide deaths were disproportionately high (25%). CONCLUSION: Poisonings with agricultural and horticultural chemicals are an important public health problem. Prevention efforts need to incorporate the fact that many serious cases, such as paraquat poisonings, are suicidal in nature.

Accidents, Home↗
PubMed2003

Stem cell transplantation for multiple sclerosis: what is the evidence?

Experimental and clinical observations have indicated that high-dose immunosuppression followed by autologous stem cell transplantation (ASCT) can induce remissions in severe, refractory, autoimmune diseases including multiple sclerosis (MS), a T cell-mediated autoimmune disorder against CNS myelin components, causing severe chronic disability. Control of the disease is unsatisfactory in most of the patients, especially those with rapidly evolving relapsing-remitting course and those with chronic progressive disease. The rationale for treating autoimmune diseases with ASCT is based on the immunosuppressive and immunomodulating effects of ASCT which may shift the immunological balance towards disease quiescence, a hypothesis supported by the results of ASCT in animal models of MS and by clinical observations in MS patients transplanted for concurrent malignancies. A number of phase I-II studies of ASCT in patients with active MS, conducted worldwide since 1995, and a comprehensive analysis of 85 patients, recently reported by the European Group for Blood and Marrow Transplantation (EBMT), have shown the feasibility of the method, a prominent anti-inflammatory effect on magnetic resonance imaging (MRI) disease, and a possible clinical benefit for active and refractory cases. The impact on MRI disease parameters appears superior with ASCT than with conventional therapies but the clinical results, in terms of stabilization of disease and prevention of disability, need to be validated in prospective, controlled trials. The procedure is also associated with a transplant-related mortality risk, of about 5% in high-risk cases, i.e., in older patients, those with high disability scores, those receiving strong myeloablative conditioning regimens and those undergoing intensive in vivo or ex vivo T cell-depletion. Therefore, it could be recommended for the treatment of a chronic, non-lethal, disease like MS only if it proved superior to standard therapies. A randomized trial is now launched by the EBMT to compare ASCT to mitoxantrone, currently regarded as one of the best available treatments, in properly selected patients having high chance of response at minimal mortality risk.

Humans↗
PubMed2000

Climate change: potential impact on plant diseases.

Global climate has changed since pre-industrial times. Atmospheric CO(2), a major greenhouse gas, has increased by nearly 30% and temperature has risen by 0.3 to 0.6 degrees C. The intergovernmental panel on climate change predicts that with the current emission scenario, global mean temperature would rise between 0.9 and 3.5 degrees C by the year 2100. There are, however, many uncertainties that influence these predictions. Despite the significance of weather on plant diseases, comprehensive analysis of how climate change will influence plant diseases that impact primary production in agricultural systems is presently unavailable. Evaluation of the limited literature in this area suggests that the most likely impact of climate change will be felt in three areas: in losses from plant diseases, in the efficacy of disease management strategies and in the geographical distribution of plant diseases. Climate change could have positive, negative or no impact on individual plant diseases. More research is needed to obtain base-line information on different disease systems. Most plant disease models use different climatic variables and operate at a different spatial and temporal scale than do the global climate models. Improvements in methodology are necessary to realistically assess disease impacts at a global scale.

Journal Article↗
PubMed2002

Emotion recognition via facial expression and affective prosody in schizophrenia: a methodological review.

Disturbances in affect recognition may be one of the most pervasive and serious aspects of the schizophrenic patient's interpersonal problems. Interest in the decoding of emotional information in schizophrenia has focused on facial affect recognition with 29 experimental papers on that topic published since 1987. A smaller literature exists on the topic of recognition of affect in speech and there are at least seven studies, which have examined both face and voice perception in the same individuals with schizophrenia. This paper includes a comprehensive analysis of the schizophrenia facial affect recognition research over the past decade and the schizophrenia literature on affective prosody, and provides the first review of the schizophrenia literature on multichannel emotion recognition research. The weight of evidence would suggest that individuals with schizophrenia experience problems in the perception of emotional material; however, the specificity, extent, and nature of the deficits are unclear. Emotion recognition research in schizophrenia should be informed by the general literature on emotion recognition with serious attention paid to methodological issues.

Affect↗
PubMed2003

Waste system implications for Mars missions.

Waste technologies for Mars missions have been analyzed, considering equivalent system mass and interface loads. Storage or dumping seems most appropriate for early missions with low food closure. Composting or other treatment of inedible biomass in a bioreactor seems most attractive for moderate food closure (50-75%). Some form of physicochemical oxidation of the composted residue might be needed for increased food closure, but oxidation of all waste does not seem appropriate due to excess of production of carbon dioxide over demand. More comprehensive analysis considering interfaces with other mission systems is needed. In particular, in-situ resource utilization is not considered, and might provide resources more cheaply than waste processing.

Biodegradation, Environmental↗
PubMed1998

Representing doctors: discourses and images in the Australian press.

Reports of incidents and issues related to members of the medical profession and the practice of medicine often feature in the western news media. Such intense coverage has incited the interest of both medical sociologists and members of the profession themselves. Thus far, however, very few detailed studies addressing the tenor of news reporting on the medical profession have been published, particularly in relation to the Australian media. This article presents the findings of a systematic and comprehensive analysis of the representation of doctors and the medical practice over a period of 15 months (January 1994 to March 1995) in metropolitan Australian newspapers and major news magazines. The method of critical discourse analysis was employed, including both quantitative analysis and interpretive analysis of the language and visual imagery of the news texts. The study revealed that negative portrayals of doctors were countered by positive representations. While cases of medical negligence, sexual assault and avarice on the part of doctors were often reported, medical successes were also frequently covered. Doctors were overwhelmingly reported as the major authorities on medical matters and as active agents in interacting with patients and other groups such as government officials. It is concluded that while the nature of reporting would suggest that members of the medical profession may be constantly under the spotlight of media scrutiny, they enjoy a significant degree of cultural and social authority in the Australian press.

Australia↗
PubMed2003

Isolation and structure elucidation of the major individual polyphenols in carob fibre.

Although it is already known that carob fibre contains several classes of polyphenolic substances, a comprehensive analysis of these has not been conducted to date. Therefore, the major polyphenolic compounds were extracted with organic solvents, and, following fractionation by normal-phase column chromatography on silicic acid, their structures were elucidated by liquid-chromatography electrospray-ionisation mass spectrometry (LC-ESI), nano-electrospray-ionisation mass spectrometry (ESI-MS), and gas-chromatography mass spectrometry (GC-MS). In addition, complete 1H and 13C NMR assignments were obtained for the isolated gallotannins 1,6-di-, 1,2,6-tri- and 1,2,3,6-tetra-O-galloyl-beta-D-glucose. Carob fibre was found to contain a rich variety of phenolic antioxidants. A total of 24 polyphenol compounds were identified with a yield of 3.94 g/kg (dry weight). The profile was dominated by gallic acid in various forms: free gallic acid (42% of polyphenols by weight), gallotannins (29%), and methyl gallate (1%), while simple phenols, mainly cinnamic acid, made up about 2% of the total. Flavonoids represented 26% of the polyphenols, and the major components were identified as the glycosides myricetin- and quercetin-3-O-alpha-L-rhamnoside (ca. 9% and 10%, respectively). These data indicate that carob fibre is rich in both amount and variety of phenolic antioxidant substances, and its inclusion in the diet may have chemopreventive properties.

Chromatography, Ion Exchange↗
PubMed2003

How low is the alpha/beta ratio for prostate cancer?

PURPOSE: It has been suggested recently that the alpha/beta ratio for human prostate cancer is low (around 1.5 Gy), and much debate on the evidence for such a low value is ongoing. Analyses reported so far ignored the contribution of tumor repopulation. Extremely low alpha values and unrealistic cell numbers of tumor clonogens are found in these studies. In this paper, we present a comprehensive analysis of the updated clinical data to derive a self-consistent set of parameters for the linear-quadratic (LQ) model. METHODS AND MATERIALS: The generalized LQ model, considering the effects of dose rate, sublethal damage repair, and clonogenic proliferation, was used to analyze the recently reported clinical data for prostate cancer using either external-beam radiotherapy or brachytherapy. Three LQ parameters, alpha, alpha/beta, and the repair time, were determined based on the clinical finding that the external-beam radiotherapy and the 125I and (103)Pd permanent implants are biologically equivalent. The tumor control probability model was used also to analyze the clinical data to obtain an independent relationship of alpha/beta vs. alpha and to estimate clonogenic cell numbers for patients in different risk groups. RESULTS: Based on the analysis of clinical data and a consideration of repopulation effect, we have derived a self-consistent set of LQ parameters for prostate cancer: alpha = 0.15 +/- 0.04 Gy(-1), alpha/beta = 3.1 +/- 0.5 Gy. Our analysis indicates the half-time of sublethal damage repair to be in the range from 0 to 90 min with a best estimate of 16 min. The best estimate of clonogenic cell numbers in prostate tumors is found to range from 10(6) to 10(7) according to the patient risk level. These values are more realistic than those derived previously (only 10-100). CONCLUSION: The effect of tumor repopulation is not negligible in determining the LQ parameters for prostate cancer, especially for the low-dose-rate permanent implants. Analysis of clinical data for prostate cancer with corrections for damage repair and repopulation effects results in a low alpha/beta ratio of 3.1 Gy. Unrealistic clonogenic cell numbers and extremely small values of alpha reported in the literature can be resolved by correcting for repopulation effect. The LQ parameters derived presently from the clinical data are consistent with reports of intrinsic radiosensitivity in vitro.

Dose Fractionation, Radiation↗
PubMed2000

EMBO workshop--"Molecular and Cellular Gerontology": Sepiano/Switzerland, September 18-22, 1999.

The EMBO Workshop "Molecular and Cellular Gerontology" provided a comprehensive analysis of recent developments in experimental gerontology. Various animal models for aging were presented. The focus of the conference was on the role of oxidative stress in aging at the cellular and organismal level. Evolution of aging was another topic discussed in the course of the meeting. Another focal point of the meeting was on age-related changes in cellular repair systems, in particular DNA repair and protein repair. Emphasis was also placed on the role of mitochondrial function and mitochondrial DNA mutations in the aging process. These molecular approaches were complemented by a session on age-related diseases, including aging of the immune system, cardiovascular disease and Alzheimer's disease.

Animals↗
PubMed1989

Patellofemoral instability in total knee arthroplasty.

Patellofemoral instability following total knee arthroplasty remains one of the major complications requiring operative intervention. In spite of recent advances in technique and instrumentation, the rate of this complication remains disturbingly high. A comprehensive analysis of cause reveals malalignment of any of the components to be potentially responsible, particularly valgus or internal rotation malalignment of either femoral or tibial component, as well as lateral displacement of the patellar component. Underresection of the patella or oversizing the femoral component may also contribute to excessive lateral retinacular tightness. When confronted with patellofemoral instability, the surgeon must first look for and correct the cause. Component malalignment requires component revision. Extensor mechanism imbalance requires either proximal or distal realignment. Lateral release alone invites recurrence of the problem.

Arthroplasty↗
PubMed2000

Comparative effects of carboxylic ionophores on membrane potential and resistance of NG108-15 cells.

Comparative analyses were conducted to determine the effects of Na(+) (monensin, MON), K(+) (nigericin, NIG) and Ca(2+) (A23187) selective carboxylic ionophores on differentiated NG108-15 (neuroblastoma X glioma hybrid) cells. Alterations in membrane potential (V(m)), input resistance (Rin) and electrically induced action potential generation were measured using intracellular microelectrode techniques in cells treated with 0.1-30 microM MON and NIG and 0.1-10 microM A23187. Responses to the ionophores were similar in that membrane hyperpolarization and unchanged R(in) predominated with all three compounds. However, significant differences between the ionophores were also detected. MON- and A23187-induced hyperpolarization was generally maintained throughout the 24-min superfusion whereas that produced by NIG diminished with time or was replaced by depolarization. In addition, action potential generation was blocked by NIG, whereas MON had no effect and action potential alterations were evident only with the highest A23187 concentration (10 microM). This study represents the initial comprehensive analysis of the effects of carboxylic ionophores on membrane electrical characteristics of an intact cell system and forms the basis for subsequent work using NG108-15 cells as a model system to evaluate potential therapeutic treatments against the carboxylic ionophores.

Calcimycin↗
PubMed2003

Evolution of the cystatin B gene: implications for the origin of its variable dodecamer tandem repeat in humans.

The human cystatin B gene contains a variable number of 12-bp tandem repeats in its promoter region, of which the common alleles contain two or three copies and unusual expansion causes progressive myoclonus epilepsy of the Unverricht-Lundborg type. We undertook a comprehensive analysis of the genomic sequence to address the evolutionary events of this variable repeat. By examination of a contiguous genome sequence spanning 5.0 kb and linkage analysis of detected polymorphic changes, we identified six major intragenic haplotypes in unrelated Japanese subjects. The number of normal repeats was closely correlated with these alleles, indicating that changes in the array should be comparatively rare events during human evolution. To examine the origin of the repeat array further, we also analyzed five primate genomes. Repetitive polymorphism was unlikely in hominoids, and the array originated with the dodecamer itself in the course of primate evolution. The variability conceivably developed after the separation to humans.

Cystatin B↗