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At least 505 records · Page 28Linked to original sources
PubMed1993

Vaccines to prevent enteric infections.

Considerable progress has been made in the last decade in developing vaccines against the enteric infections of greatest public health importance. A quadrivalent rotavirus vaccine consisting of rhesus rotavirus vaccine (which contains serotype 3 neutralization antigen) and three reassortant viruses (rhesus virus expressing neutralization antigens of serotypes 1, 2 or 4) is undergoing placebo-controlled field trials of efficacy in the USA and in two developing countries. Two new vaccines against typhoid fever (oral Ty21a and parenteral Vi polysaccharide) have been licensed in many countries. Even newer generations of typhoid vaccines are undergoing clinical testing, including new attenuated S. typhi strains and Vi polysaccharide-carrier protein conjugate vaccines. Two inactivated oral cholera vaccines, consisting of inactivated V. cholerae O1 bacteria alone or in combination with purified B subunit of cholera toxin, each conferred 50-53% protection over 3 years in a field trial in Bangladesh where subjects were immunized with a three-dose regimen. In extensive clinical trials in adults and children in less-developed countries, an engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown to be well tolerated and highly immunogenic following administration of just a single oral dose; a large-scale field trial in 70,000 subjects is underway to investigate the efficacy of this vaccine. Several candidate vaccines against Shigella and enterotoxigenic Escherichia coli are in clinical trials. Accumulating knowledge on pathogenesis of enteric infections and advances in mucosal and cellular immunology, coupled with the application of modern biotechnology, have resulted in a plethora of vaccine candidates. It is expected that in future years efforts will be directed to construct vaccines against other enteric pathogens.

Gastroenteritis↗
PubMed1993

Immunodeficiency-inducing retroviruses.

The plethora of disease syndromes (dystrophy of various organ systems, malignancies and opportunistic infections) caused by HIV are all potentiated by the profound virus-induced immunosuppression that accompanies this infection. The mechanism of this severe immunosuppression is poorly understood and the subject is currently being pursued in studies of HIV-infected patients and in animals infected with other immunodeficiency-inducing retroviruses.

Animals↗
PubMed1994

Transgenic and knockout models for studying diseases of the immune system.

The advance in transgenic animal technology, and in particular the use of germline manipulation for the creation of targeted gene mutations, has resulted in the generation of a plethora of murine models for the study of diseases of the immune system. In the past year, a number of studies have given us interesting, and sometimes unexpected, insights into the events that lead to immune dysregulation. Surprisingly, similar disease manifestations can arise in experimental animals with quite different immune abnormalities. This review is focussed on mice with mutations affecting T cells and T-cell function.

Animals↗
PubMed1992

Macrophages and nerve regeneration.

Macrophages are not only phagocytic cells but also secrete a plethora of growth factors that are potentially important for regeneration. This review will examine the emerging evidence of a likely contribution by macrophages to axonal regeneration.

Animals↗
PubMed1994

Screening mammography: interpretation of the data.

The literature on screening mammography includes a plethora of conflicting articles. More recently, individuals and various medical organizations have recommended and established their own guidelines for screening mammography. A review of salient breast screening randomized clinical trials in women over and under the age of 50 years is provided and compared with the more recent results of the Canadian National Breast Screening Study. In women under the age of 50 years, screening mammography cannot be supported from the results of these trials. In women over the age of 50 years, screening mammography leads to a significant reduction in breast cancer mortality and should be strongly recommended.

Adult↗
PubMed1995

Determination of carbonic anhydrase-III by enzyme-immunoassay in liver, muscle and serum of male rats with streptozotocin-induced diabetes mellitus.

Insulin has a plethora of metabolic effects but its action on carbonic anhydrase-III (CA-III), a key enzyme in acid-base regulation, has been little studied. The present studies examined the effects of streptozotocin induced diabetes on the concentrations of CA-III. The concentration of CA-III in the liver, muscles and serum of rats with experimental diabetes mellitus was measured by the method of enzyme-immunoassay. Streptozotocin-induced diabetes mellitus resulted in a reduction in concentration of CA-III in the liver and serum, but not in skeletal muscles, of adult male rats. A 98% reduction in hepatic CA-III content relative to control values was observed. The reduction in CA-III content in the liver was restored to control value by administration of insulin. The CA-III content in serum of diabetic rats declined to approx. 25% of control values, but the reduction was unaffected by administration of insulin. The concentration of CA-III in the liver and serum of diabetic rats was not influenced by administration of methyltestosterone. Although the content of CA-III in m. rectus femoris, m. tibialis craniaris and m. soleus differed, no significant difference of CA-III content was found between diabetes mellitus and control rats. The effect of chronic diabetes mellitus on CA-III content was obviously different between liver and muscle, suggesting that the regulation of CA-III biosynthesis differs between these two tissues. These results suggest that biosynthesis of CA-III in hepatocytes of rats is influenced by irregular patterns of GH secretion brought about by diabetes mellitus.

Animals↗
PubMed2005

Cold, salinity and drought stresses: an overview.

World population is increasing at an alarming rate and is expected to reach about six billion by the end of year 2050. On the other hand food productivity is decreasing due to the effect of various abiotic stresses; therefore minimizing these losses is a major area of concern for all nations to cope with the increasing food requirements. Cold, salinity and drought are among the major stresses, which adversely affect plants growth and productivity; hence it is important to develop stress tolerant crops. In general, low temperature mainly results in mechanical constraint, whereas salinity and drought exerts its malicious effect mainly by disrupting the ionic and osmotic equilibrium of the cell. It is now well known that the stress signal is first perceived at the membrane level by the receptors and then transduced in the cell to switch on the stress responsive genes for mediating stress tolerance. Understanding the mechanism of stress tolerance along with a plethora of genes involved in stress signaling network is important for crop improvement. Recently, some genes of calcium-signaling and nucleic acid pathways have been reported to be up-regulated in response to both cold and salinity stresses indicating the presence of cross talk between these pathways. In this review we have emphasized on various aspects of cold, salinity and drought stresses. Various factors pertaining to cold acclimation, promoter elements, and role of transcription factors in stress signaling pathway have been described. The role of calcium as an important signaling molecule in response to various stress signals has also been covered. In each of these stresses we have tried to address the issues, which significantly affect the gene expression in relation to plant physiology.

Acclimatization↗
PubMed2004

Computational modeling of the sugar-lectin interaction.

In the last few years numerous experimental studies have shed light onto the details of the lectin-carbohydrate interaction. X-ray crystallography and NMR spectroscopy have been used to elucidate the structures of lectins, sugars, and their complexes. In addition, an increasing number of experimental methods has been employed to determine the thermodynamic and kinetic parameters of the binding process. Based on this experimental data, computational methods have been developed to model and predict these interactions. A plethora of techniques from Molecular Modeling and Computational Chemistry have been applied to the problem and current models achieve high-quality predictions. These successes are based on both new theoretical approaches and reliable experimental data. The aim of the present article is to outline the most relevant computational and experimental methods applied in the field of lectin-carbohydrate interaction and to give an overview of the current state of the art in the modeling of these interactions with a focus on plant lectins.

Carbohydrates↗
PubMed2005

Novel target sites in bacteria for overcoming antibiotic resistance.

Resistance to marketed antibiotics continues to increase. During the last 10 years some 200 bacterial genome sequences have become available, giving rise to expectations that genomics would provide a plethora of novel targets and hence a flood of new therapeutic agents. Contrary to some predictions the genomic effort has yet to yield a substantial number of novel class agents in clinical development. What are the reasons for the differences between expectations and reality? This article reviews what has been achieved in the exploitation of bacterial genomes for the discovery of novel antibacterials.

Anti-Bacterial Agents↗
PubMed2004

Reactive oxygen species in hypertension; An update.

Hypertension is associated with an elevation of reactive oxygen species (ROS) and frequently also with an impairment of endogenous antioxidant mechanisms. Experimental manipulation of the redox state in vivo shows that ROS can be a cause of hypertension. During the development of the disease, ROS are generated by endogenous sources, notably the NADPH oxidase enzyme family and uncoupled nitric oxide synthase, due to a mutual reinforcement between ROS and humoral factors. The ROS affect multiple tissues, either directly or through nitric oxide depletion. In the vasculature, they induce contraction and endothelial dysfunction. In blood vessels and myocardium, they cause hypertrophic remodeling. In the kidneys, ROS promote salt reabsorption, decrease glomerular filtration, and lead to tissue damage. Finally, they also increase efferent sympathetic activity from the central nervous system. Progress in our understanding of the mechanisms of ROS formation and their plethora of pathophysiologic effects is expected to lead from simple antioxidant therapy to specific antihypertensive treatments.

Animals↗
PubMed2004

Malignant and benign lymphoid lesions of the lung.

Lymphoid lesions of the lung produce a complex of problems for the practicing pathologist. Although these lesions are eventually referred to hematopathologists, it is still the general surgical pathologist who first encounters them and confronts the problem of formulating an initial diagnosis. Over the last 20 years there has been a revolution in our knowledge of the classification and natural history of the pulmonary lesions, a plethora of information which warrants a thorough review. The purpose of this discussion is to report the clinical features and courses, pathologic features and, when known, etiologies or pathogenesis of the major "primary" pulmonary lymphoid lesions and present a brief approach to differential diagnosis. I will divide the lesions into malignant and benign, discussing each in turn.

Diagnosis, Differential↗
PubMed2005

The role of science in treaty verification.

Technologically advanced nations are currently applying more science to treaty verification than ever before. Satellites gather a multitude of information relating to proliferation concerns using thermal imaging analysis, nuclear radiation measurements, and optical and radio frequency signals detection. Ground stations gather complementary signals such as seismic events and radioactive emissions. Export controls in many countries attempt to intercept materials and technical means that could be used for nuclear proliferation. Nevertheless, we have witnessed a plethora of nuclear proliferation episodes, that were undetected (or were belatedly detected) by these technologies--the Indian nuclear tests in 1998, the Libyan nuclear buildup, the Iranian enrichment program and the North Korea nuclear weapons program are some prime examples. In this talk, we will discuss some of the technologies used for proliferation detection. In particular, we will note some of the issues relating to nuclear materials control agreements that epitomize political difficulties as they impact the implementation of science and technology.

International Cooperation↗
PubMed2004

Allophycocyanin and energy transfer.

Allophycocyanin is a biliprotein located in the core of the phycobilisome. The biliprotein is isolated and purified as a trimer (alpha3beta3), where a monomer is an alphabeta structure. Each alpha and beta subunit has a single noncyclic tetrapyrrole chromophore, called phycocyanobilin. The trimer of allophycocyanin has an unusual absorption maximum at 650 nm with a shoulder at 620 nm, while the monomer has an absorption maximum at 615 nm. Two explanations have been proposed for the 650-nm maximum. In one, this maximum is produced by the interaction of a particular local protein environment for three of the chromophores, causing them to red shift, while the other three chromophores are at a higher energy. Energy is transferred from the high- to the low-energy chromophores by Förster resonance energy transfer, the donor-acceptor model. In the second proposal, there is strong exciton coupling between two chromophores of the trimer that closely approach across the monomer-monomer interface. The strong interaction causes exciton splitting and a red shift in the absorption. There are three of these strongly coupled chromophore pairs, and energy is transferred between the two-exciton states of a pair by internal conversion. A variety of biophysical methods have been used to examine this question. Although evidence supporting both models has been produced, sophisticated ultra fast fluorescence results from a plethora of approaches now firmly point to the latter strong coupling hypothesis as being more likely. Between the different strongly coupled pairs, Förster resonance energy transfer should occur. For monomers of allophycocyanin, Förster resonance energy transfer occurs between the two chromophores.

Biopolymers↗
PubMed2004

ISWI complexes in Saccharomyces cerevisiae.

The imitation switch (ISWI) class of chromatin remodeling ATPase is ubiquitous in eukaryotes. It is becoming clear that these enzymes exist as part of larger complexes and the nature of the associated proteins dictate the function associated with a complex both in biochemical assays and in the cell. Much progress has been made in understanding these relationships in the budding yeast Saccharomyces cerevisiae, containing two ATPases, Isw1p and Isw2p. This has been aided by the ease of genetic manipulation, by a number of systematic screens designed to specifically detect ISWI function and by the plethora of data generated from a number of global screens for function. At present, many functions for yeast Isw1p and Isw2p are related to effects on RNA levels and are associated with the controlled repression of gene expression that crudely fall into three types: displacement of the basal transcription machinery to repress or silence transcription of genes (Isw2 complex and Isw1/Ioc3 complex); control of the activation of expression leading to coordination of transcription elongation; and efficient termination of transcription (Isw1/Ioc4/Ioc2 complex). The latter two functions are regulated by specific phosphorylation of residues within the carboxy terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAPII). Other functions may relate to the ability of ISWI complex to displace transcription factors or enzymes from the template. Other ISWI-containing complexes that have yet to be characterized indicate that much remains to be learnt about yeast ISWI itself and importantly, how the various forms cooperate with different classes of chromatin remodeling ATPase, complexes containing histone acetylases, deacetylases, methylases and both DNA and RNA polymerases.

Adenosine Triphosphatases↗
PubMed2005

Lipoprotein-mediated lipid transport in insects: analogy to the mammalian lipid carrier system and novel concepts for the functioning of LDL receptor family members.

In all animals, lipoproteins are used to transport lipids through the aqueous circulation. Lipids are delivered to mammalian cells by two different mechanisms: via endocytic uptake of the complete lipoprotein particle mediated by members of the low density lipoprotein (LDL) receptor (LDLR) family, or by selective delivery of lipoprotein-carried lipids at the cell surface, such as lipid uptake following the action of a lipoprotein lipase. Although many structural elements of the lipid transport system of insects are similar to those of mammals, insect lipoprotein-mediated lipid transport was thought to apply only to the latter concept, since the single lipoprotein acts as a reusable lipid shuttle. However, the recent identification of lipoprotein receptors of the LDLR family in insects suggests that lipid transport in these animals may also adopt the first concept. Yet, the endocytic properties of the insect LDLR homologue appear to deviate from those of the mammalian LDLR family members, resulting in the recycling of endocytosed lipoprotein in a transferrin-like manner. This indicates that a hitherto unknown as well as unexpected function can be added to the plethora of functions of LDLR family members. Analysis of the molecular mechanism of the ligand-recycling function of the insect receptor provides also new insight into the possible functioning of the mammalian family members. In the last several years, mammalian and insect lipoprotein-mediated lipid transport systems have been reviewed separately with respect to functioning and lipid delivery. This review, in which new and important developments in the insect field with respect to our understanding of lipid delivery are discussed with a particular focus on the involvement of the LDLR homologue, aims at comparing the two systems, also from an evolutionary biological perspective, and proposes that the two systems are more similar than assumed previously.

Amino Acid Sequence↗
PubMed2006

Transcriptional regulation of yeast phospholipid biosynthetic genes.

The last several years have been witness to significant developments in understanding transcriptional regulation of the yeast phospholipid structural genes. The response of most phospholipid structural genes to inositol is now understood on a mechanistic level. The roles of specific activators and repressors are also well established. The knowledge of specific regulatory factors that bind the promoters of phospholipid structural genes serves as a foundation for understanding the role of chromatin modification complexes. Collectively, these findings present a complex picture for transcriptional regulation of the phospholipid biosynthetic genes. The INO1 gene is an ideal example of the complexity of transcriptional control and continues to serve as a model for studying transcription in general. Furthermore, transcription of the regulatory genes is also subject to complex and essential regulation. In addition, databases resulting from a plethora of genome-wide studies have identified regulatory signals that control one of the essential phospholipid biosynthetic genes, PIS1. These databases also provide significant clues for other regulatory signals that may affect phospholipid biosynthesis. Here, we have tried to present a complete summary of the transcription factors and mechanisms that regulate the phospholipid biosynthetic genes.

CDP-Diacylglycerol-Inositol 3-Phosphatidyltransfer↗
PubMed2004

A hitchhiker's guide to the cullin ubiquitin ligases: SCF and its kin.

The SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase family was discovered through genetic requirements for cell cycle progression in budding yeast. In these multisubunit enzymes, an invariant core complex, composed of the Skp1 linker protein, the Cdc53/Cul1 scaffold protein and the Rbx1/Roc1/Hrt1 RING domain protein, engages one of a suite of substrate adaptors called F-box proteins that in turn recruit substrates for ubiquitination by an associated E2 enzyme. The cullin-RING domain-adaptor architecture has diversified through evolution, such that in total many hundreds of distinct SCF and SCF-like complexes enable degradation of myriad substrates. Substrate recognition by adaptors often depends on posttranslational modification of the substrate, which thus places substrate stability under dynamic regulation by intracellular signaling events. SCF complexes control cell proliferation through degradation of critical regulators such as cyclins, CDK inhibitors and transcription factors. A plethora of other processes in development and disease are controlled by other SCF-like complexes, including those based on Cul2-SOCS-box adaptor protein and Cul3-BTB domain adaptor protein combinations. Recent structural insights into SCF-like complexes have begun to illuminate aspects of substrate recognition and catalytic reaction mechanisms.

Amino Acid Sequence↗
PubMed2006

An update of the S100 nomenclature.

The plethora of names given to S100 proteins resulted in considerable confusion. Here we present the official and updated nomenclature of this protein family, approved by the HGNC (HUGO gene nomenclature committee) and ECS (European Calcium Society).

Chromosomes, Human↗