| February 28,2003 |
Monoclonal Antibody Therapy For Cancer |
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Monoclonal antibody therapy has emerged as an important therapeutic modality for cancer. Unconjugated antibodies show significant efficacy in the treatment of breast cancer, non-Hodgkin’s lymphoma, and chronic lymphocytic leukemia.Numerous efforts to exploit the ability of antibodies to focus the activities of toxic payloads at tumor sites are under way and show early promise. |
| February 27,2003 |
Genetics and Arrhythmias |
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Genes have been identified for several
disorders responsible for arrhythmias and sudden death. These genes all encode ion
channels and are referred to as channelopathy genes. For example,Congenital long QT syndrome is caused by mutations in genes encoding sodium or potassium channels.Treatments based on knowledge of the molecular defect are being implemented for long QT syndrome and will probably provide paradigms for targeted treatment of acquired arrhythmias. |
| February 26,2003 |
Atheroprotective Effects of high density lipoprotein (HDL) |
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The high density lipoprotein (HDL) functions currently most widely held to account for the antiatherogenic effect include participation in reverse cholesterol transport, protection against endothelial dysfunction, and inhibition of oxidative stress. This review summarizes current views on the molecular mechanism underlying these atheroprotective effects of HDL. |
| February 25,2003 |
Discovery of immunopotentiatory drugs: current and future strategies |
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This review provides principal strategies and example serves to illustrate a general process in which, as more immune enhancing compounds are identified, more targets will be validated in an iterative refinement of targets and chemical ligands that will eventually provide the immunopotentiatory drugs of the future. |
| February 24,2003 |
The Current Status of Hematopoietic Cell Transplantation |
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Hematopoietic cell transplantation is the preferred therapy for a substantial proportion of patients with life-threatening diseases of the lymphohematopoietic system. Recent advances in donor identification, disease eradication, and supportive care measures have broadened the application of transplantation and improved
outcomes. This article provides a brief review of the major clinical principles of transplantation and results achieved to date. |
| February 23,2003 |
Molecular Genetic Risk Screening |
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If performed early enough, identification of these mutations by molecular genetic testing can be used not merely to diagnose disease but to predict risk of future disease.This chapter reviews the basic criteria to be considered before embarking on population genetic risk screening, and examines multiple disease-screening examples representing a variety of modes of inheritance and technical challenges. |
| February 22,2003 |
The structure and function of drug pumps: an update |
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Our understanding of the exact mechanisms used by the transmembrane protein pumps that confer cellular resistance to cytotoxic drugs has improved enormously with the recent determination of the structures of three Escherichia coli transporters.Information on the molecular basis of multidrug recognition has been provided by determining the structure of transcriptional regulators that can bind, often structurally unrelated, cytotoxic drugs and control the expression of drug pumps. |
| February 21,2003 |
Etiology of Chagas disease myocarditis:
autoimmunity, parasite persistence,or both? |
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Recent studies on parasite detection, however, suggest that parasite persistence is the main cause of Chagas disease. To date, there is no conclusive evidence for the pathogenic role of either autoimmunity or parasite-specific immunity.Here, the most recent evidence in favour of each hypothesis is discussed. |
| February 20,2003 |
Silence of the strands: RNA interference in eukaryotic pathogens |
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This versatile technique has remarkable promise as a tool for the study of eukaryotic pathogens. Protozoan parasites and pathogenic fungi often resist manipulation using standard molecular genetic approaches. Researchers studying these organisms need flexible molecular tools, particularly to exploit newly sequenced genomes; this review offers a practical guide to establishing RNAi in pathogenic eukaryotes. |
| February 19,2003 |
Bugs as drugs for cancer |
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Nowadays there are a wide range of viruses
and bacteria directly implicated in the transformation of normal cells and the eventual establishment of malignancy. However, the link between infection and cancer is not always causative and the subject of this review is to describe a number of key advances in cancer immunotherapy based upon microbes. Many of these have already been translated into significant benefit for the patient and it is hoped that the latest advances in research will yield more effective and safer therapies and vaccines. |
| February 18,2003 |
Molecular Versatility of Antibodies |
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The experimental data persuasively suggested that aggregation of the antibody was a necessary and likely sufficient initiating event, but this only begged the question: how does aggregation induce a response?Data from our own group and from many others led to a molecular model that appears to explain how a cell ‘senses’ that antigen has reacted with the IgE. |
| February 17,2003 |
The Road Ended Up at Stem Cells |
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This volume of Immunological Reviews is a rich testimony to the kinds of ideas and experiments on Human Stem Cell that, at least in retrospect, turned out to be critical. Many roads were taken, but only one ended up at stem cells.This paper is the heading review! |
| February 16,2003 |
Mobilizing the army |
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Armed with potent protein-digesting enzymes and oxidants, neutrophils are consummate microbe killers. But if these cells accumulate
and are activated in an uncontrolled way, they can cause excessive inflammation and
injure the very tissues they are designed to protect. So it is important to understand how
neutrophils find their way to, and so accumulate at, sites of injury. |
| February 15,2003 |
Artificial cells: Unique insights into exocytosis using liposomes and lipid nanotubes |
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Exocytosis is the fundamental process underlying neuronal communication. We describe the use of liposome–lipid nanotube networks to create an artificial cell model that undergoes the later stages of exocytosis.This model shows that membrane mechanics, without protein intervention, can drive expansion of the fusion pore to the final stage of exocytosis and can affect the rate of transmitter release
through the fusion pore. |
| February 14,2003 |
RNA sets the standard |
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One way of finding out what genes do is to inactivate them, and to study the effects, in ‘model’ organisms. That has now been done for many
thousands of worm genes in two large-scale analyses.Two groups' work sets a new standard for
systematic, genome-wide genetic studies. |
| February 13,2003 |
Stem Cell Molecular Blueprint: “Life, the Universe, and Everything” |
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Despite significant advances in enrichment protocols, the continuous propagation (i.e., expansion) of human HSCs ex vivo has not yet been achieved. One reason for this failure is the difficulty in obtaining pure populations of HSCs. Because of this dilemma, the genetic programs involved in HSC self-renewal and lineage commitment have remained poorly understood product. |
| February 12,2003 |
Herbal Remedies |
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Herbal medicine is an increasingly common form of alternative therapy in the United States. A 1997 survey estimated that 12.1 percent
of adults in the United States had used an herbal medicine in the previous 12 months (as compared with 2.5 percent in 1990), resulting in out-of-pocket payments of $5.1 billion. |
| February 11,2003 |
Nuclear protein synthesis: A re-evaluation |
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It has been reported that nuclei from HeLa cells are responsible for ~10%–15% of total cellular protein synthesis. We suggest that the nascent polypeptides observed in nuclei of permeabilized cells may have been due to “overpermeabilization” and consequent damage to the cells. Based on this information,we conclude that nuclear protein synthesis,if it exists,is limited to less than 1% of that in cells. |
| February 10,2003 |
Nuclear translation: What is the evidence? |
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Recently, several reports have been published in support of the idea that protein synthesis occurs in both the nucleus and the
cytoplasm. This proposal has generated a great deal of excitement because, if true, it would mean that our thinking about the compartmentalization of cell functions would have to be re-evaluated. The significance and broad implications of this phenomenon require that the experimental evidence used to support it be carefully evaluated. |
| February 09,2003 |
Flexibility and molecular recognition in the immune system |
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Photon echo spectroscopy has been used to measure the response of three antibody-binding sites to perturbation from electronic
excitation of a bound antigen, fluorescein. The three antibodies show motions that range in time scale from tens of femtoseconds to nanoseconds.The binding site flexibilities may result in varying mechanisms of antigen recognition including lock-and-key, induced-fit, and conformational selection. |
| February 08,2003 |
Genome-based peptide fingerprint scanning |
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We have implemented a method that identifies the genomic origins of sample proteins by scanning their peptide-mass fingerprint
against the theoretical translation and proteolytic digest of an entire genome. Unlike previously reported techniques, this method requires no predefined ORF or protein annotations.This genome fingerprint scanning method has the potential to aid in genome annotation, identify proteins for which annotation is incorrect or missing, and handle cases where sequencing errors have caused framing mistakes in the databases. |
| February 07,2003 |
Decoding the literature on genetic variation |
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A survey of scientific and patent literature on single-nucleotide variants(up to the end of 2001,covered 1987-2001) reveals the dominance of research centers of United States and the prolific patenting of SNP technology by a selected group of biotechnology companies. |
| February 06,2003 |
Sensing heart stress |
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Heart failure and pathological overgrowth of the heart often occur hand in hand.Although the performance of the heart is well maintained over a wide range of physiological stressors, increased biomechanical stress
from either exercise or disease can drive morphological changes in the heart muscle, known as cardiac hypertrophy.New data on a biomechanical sensor challenge the viewpoint that cardiac hypertrophy causes heart failure. |
| February 05,2003 |
Immunotherapy for AIDS virus infections |
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Highly active antiretroviral therapy
(HAART) limits HIV-1 replication and retards disease progression, but drug toxicities
and emergence of drug-resistant viruses are challenges for long-term control in infected persons. Alternative treatment strategies are clearly needed.A vaccine that is able to work as a treatment for HIV-infected patients has been an elusive goal. |
| February 04,2003 |
RNA-guided Nucleotide Modification of Ribosomal and Other RNAs |
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One of the exciting frontiers in the field of RNA editing is the phenomenon of RNA-guided nucleotide modification. In this type of editing, a nucleotide in a precursor RNA is converted to another form by an RNA-protein complex (RNP)1. In this minireview we describe the present state of knowledge about the various RNP-modifying complexes, the processes they mediate, where in the cell these reactions occur, and the range of substrates. |
| February 03,2003 |
Alzheimer disease therapy: Can the amyloid cascade be halted? |
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Recent and expected advances in (a)
understanding the pathogenesis of AD, (b) identifying the genetic factors that confer risk for AD, (c) validating potential biomarkers for AD, and (d) developing therapeutic agents that target both Aβ and downstream pathological changes greatly increase the likelihood that AD will be managed successfully in the future. |
| February 02,2003 |
Tumour banks: well-guarded
treasures in the interest of patients |
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Tumour banks are facilities that are organized to collect, store and distribute samples In order for the genomics revolution to
change how we diagnose, categorize and treat cancer, scientists and clinicians must have access to tumour samples. There has therefore never been a better time to create banks of tumour tissue. Collecting and storing tumour samples and their associated data, however, creates numerous methodological, ethical, legal and technical problems. How can we leap these
hurdles in a responsible manner and still make full use of the wealth of information that can be obtained from them? |
| February 01,2003 |
Is proteomics heading in the
wrong direction? |
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Proteomics is now considered to be one of the most important ‘post-genome’ approaches to help us understand gene function. In fact, several genomics companies have launched large-scale proteomics projects, and have started to annotate the entire human proteome. The ‘holistic view’ painted by a human
proteome project is seductive, but is it realistic? |