Internal medicine and molecular biology--molecular medicine.
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Genetic Diseases, Inborn↗
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Synthesis of the neurotoxin quinolinic acid in apoptotic tissue from Suberites domuncula: cell biological, molecular biological, and chemical analyses.
Sessile marine animals, such as sponges, are prone to infection by prokaryotic as well as by eukaryotic attacking organisms. Using the sponge Suberites domuncula we document for the first time that in its apoptotic tissue a toxic compound is produced that very likely controls the elimination of the dying tissue. Apoptosis was induced by exposing the sponges to 2,2'-dipyridyl or by maintaining them under nonaeration conditions. After that treatment at least one eukaryotic epibiont (Bittium sp.) could be found grazing on apoptotic tissue. Cell proliferation assays demonstrated that aqueous extracts from unaffected sponge tissue displayed no cytotoxicity. However, addition of an extract from apoptotic tissue to neuronal cells from rat brain exerted strong toxicity. The underlying compound was identified as quinolinic acid; quantitative determination showed that quinolinic acid is present only in apoptotic tissue (4.8 mg/g dry wet weight). The complementary DNA encoding the key enzyme of the quinolinic acid pathway, 3-hydroxyanthranilate 3,4-dioxygenase, was cloned and characterized. The expression of this gene is up-regulated in apoptotic tissue. These data suggest that a complex molecular network controls apoptotic elimination of sponge tissue, which results in the synthesis of the bioactive compound quinolinic acid that controls the elimination of the tissue, perhaps via differential effects on grazing epibionts.
Journal Article↗
Ontologies for molecular biology.
Molecular biology has a communication problem. There are many databases using their own labels and categories for storing data objects and some using identical labels and categories but with a different meaning. A prominent example is the concept "gene" which is used with different semantics by major international genomic databases. Ontologies are one means to provide a semantic repository to systematically order relevant concepts in molecular biology and to bridge the different notions in various databases by explicitly specifying the meaning of and relation between the fundamental concepts in an application domain. Here, the upper level and a database branch of a prospective ontology for molecular biology (OMB) is presented and compared to other ontologies with respect to suitability for molecular biology (http:/(/)igd.rz-berlin.mpg.de/approximately www/oe/mbo.html).
Chromosome Mapping↗
Adding semantics to genome databases: towards an ontology for molecular biology.
Molecular biology has a communication problem. There are many databases using their own labels and categories for storing data objects and some using identical labels and categories but with a different meaning. Conversely, one concept is often found under different names. Prominent examples are the concepts "gene" and "protein sequence" which are used with different semantics by major international genomic and protein databases thereby making database integration difficult and strenuous. This situation can only be improved by either defining individual semantic interfaces between each pair of databases (complexity of order n2) or by implementing one agreeable, transparent and computationally tractable semantic repository and linking each database to it (complexity of order n). Ontologies are one means to provide such semantic repository by explicitly specifying the meaning of and relation between the fundamental concepts in an application domain. Here, heuristics for building an ontology and the upper level and a database branch of a prospective Ontology for Molecular Biology are presented and compared to other ontologies with respect to suitability for molecular biology (http:/(/)igd.rz-berlin.mpg.de/www/oe/mbo.html).
Computational Biology↗
The application of molecular biology.
Molecular biology methods have tremendous value not only in the investigation of basic scientific questions, but also in application to a wide variety of problems affecting the overall human condition. Disease prevention and treatment, generation of new protein products, and manipulation of plants and animals for desired phenotypic traits are all applications that are routinely addressed by the application of molecular biology methods. Because of the wide applicability of these methods, they are rapidly becoming a pervasive--some would argue invasive--aspect of our technologically based society. The public concerns that address the application of these methods should be addressed by informed public discussion and debate. While scientists can be extremely critical of the quality, interpretation, and significance of experimental results, they have a rather remarkable tendency to be non-judgmental of the relative social merits of many applications of scientific research. It remains a public responsibility to be sufficiently well-informed to critically assess the merits of applied science research and participate in a communal decision-making process regarding the extent to which a new technology will be allowed to affect society.
Animals↗
Recent advances in structure, binding sites with ligands and pharmacological function of beta-adrenoceptors obtained by molecular biology and molecular modeling.
The structure, binding sites interacting with ligands and the physiological functions of G-protein coupled beta-adrenoceptors (beta-ARs) are being elucidated by molecular biology and molecular modeling studies. The definition given amino acid sequences of beta-ARs in molecular biology and the analysis of three-dimensional and functional binding sites interacting with ligands by molecular modeling may be important for identifying other functional beta-ARs in various tissues and discovering new drugs. Thus, this review focuses on the interaction sites for receptor-ligand and roles of functional beta-ARs as studied by molecular biology and molecular modeling.
Adrenergic beta-Agonists↗
Sequence alignment in molecular biology.
Molecular biology is becoming a computationally intense realm of contemporary science and faces some of the current grand scientific challenges. In its context, tools that identify, store, compare and analyze effectively large and growing numbers of bio-sequences are found of increasingly crucial importance. Biosequences are routinely compared or aligned, in a variety of ways, to infer common ancestry, to detect functional equivalence, or simply while searching for similar entries in a database. A considerable body of knowledge has accumulated on sequence alignment during the past few decades. Without pretending to be exhaustive, this paper attempts a survey of some criteria of wide use in sequence alignment and comparison problems, and of the corresponding solutions. The paper is based on presentations and literature given at the Workshop on Sequence Alignment held at Princeton, N.J., in November 1994, as part of the DIMACS Special Year on Mathematical Support for Molecular Biology.
Algorithms↗
New therapeutic strategies for lung cancer: biology and molecular biology come of age.
The current understanding of the biology and molecular biology of lung cancer pathogenesis and progression is reviewed. Awareness of the influence of growth factors, oncogenes, and tumor suppressor genes as well as signal transduction and angiogenesis pathways on the natural history of cancer cells has led to attempts to develop new therapeutic strategies directed at interrupting tumor cell growth. Treatments utilizing monoclonal antibodies, matrix metalloproteinase inhibitors, and gene transfer and alteration are currently being investigated. The rationale and effectiveness of these treatments in early trials are explored, and recommendations for future directions in cell biology research are presented. Interest in the biology and molecular biology of tumor cells has led to some important findings that may provide opportunities for new treatments. Several of these new directions for anticancer therapy are already being examined in phase I clinical trials.
Antineoplastic Agents↗
[What can experimental research offer to rheumatology today--the viewpoint of molecular biology? Contribution of molecular biology to pathogenesis research in rheumatology using the example of rheumatoid arthritis].
Molecular biology plays an increasing role for the development of innovative approaches to analyze the pathogenesis of rheumatic diseases and to improve diagnosis and therapy of these disorders. Some of these approaches/techniques have recently yielded important results, e.g. the analysis of 1) chromosomal aberrations (numerical and, in part, structural aberrations in synovial fibroblasts/macrophages from chronic joint inflammation); 2) cell clonality (oligoclonal expansion of synovial T-cells, B-cells, but also fibroblasts); 3) the importance of genetic factors (genome-wide screening for arthritis susceptibility genes); 4) mutations in key genes of cell cycle and/or function (mutations in p53 and proto-oncogenes in the inflamed synovial membrane); and 5) gene expression patterns (e.g. by high-density microarrays, custom arrays, in situ hybridization, and real-time PCR). It can be expected that these analyses will result in central new findings concerning the understanding of the pathogenetic basis of chronic inflammatory rheumatic diseases, with the potential to develop differential diagnostic criteria for these hitherto extremely heterogeneous diseases, and to create the basis for individual-oriented therapy.
Arthritis, Rheumatoid↗
Biochemistry, cell biology and molecular biology of lipids of Saccharomyces cerevisiae.
The yeast Saccharomyces cerevisiae is a powerful experimental system to study biochemical, cell biological and molecular biological aspects of lipid synthesis. Most but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of this unicellular eukaryote have been cloned, and many gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes, turnover and degradation of complex lipids, regulation of lipid biosynthesis, and linkage of lipid metabolism to other cellular processes. Here we summarize current knowledge about lipid biosynthetic pathways in S. cerevisiae and describe the characteristic features of the gene products involved. We focus on recent discoveries in these fields and address questions on the regulation of lipid synthesis, subcellular localization of lipid biosynthetic steps, cross-talk between organelles during lipid synthesis and subcellular distribution of lipids. Finally, we discuss distinct functions of certain key lipids and their possible roles in cellular processes.
Biological Transport↗
Poor prognosis acute myelogenous leukemia 2--biological and molecular biological characteristics and treatment outcome.
Biological and molecular biological studies were performed on the marrow cells of 25 patients with poor prognosis AML to both characterize this type of leukemia and to assess the relationship between the parameters which were measured and treatment outcome. Treatment failure associated with high levels of telomerase activity and low levels of IL6 transcripts. Studies of the effects of amifostine on these parameters demonstrated that this agent reduced telomerase activity in aspirates of AML marrows. These data suggest that the beneficial effect associated with the administration of amifostine after the end of chemotherapy is likely, to be due to a reduction in the rate at which the surviving leukemia cells repopulate the marrow.
Amifostine↗
[Biological and molecular biology aspects of burn therapy].
Early wound closure, permanent skin replacement and management of postburn deformities are still unsolved problems in the treatment of burns. However, recent developments in biology and molecular biology provide new possibilities for improved therapy. This includes the enhancement of burn wound healing by growth factors and growth hormone, modulation of immunogenicity of skin allografts by gene transfer, cytokine treatment of burn sepsis and the use of cell membrane stabilizers in electrical injuries.
Animals↗
The role of European Molecular Biology Organization (EMBO) and European Molecular Biology Conference (EMBC) in European Molecular Biology (1970-1983).
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Europe↗
[Physiopathology of androgen insensitivity syndromes. Contribution of molecular biology].
Molecular genetic study of androgen insensitivity syndrome is now easier by the development of powerful molecular tools. Complementary DNA of the androgen receptor gene has been recently cloned and sequenced. The development of cDNA probes gave the opportunity to study DNA restriction fragment length polymorphisms of patients with complete or partial androgen insensitivity syndrome. These studies demonstrated that deletions are rarely observed. Using PCR and sequencing of exons, several groups described point mutations within the androgen receptor gene. Enzymatic amplification along with denaturing gradient gel electrophoresis and single strand conformational polymorphism study allowed the description of new mutations. These powerful tools together with mRNA study, expression of muted gene, anti-receptor study had also permitted to analyze correlations between structure-function activity of the androgen receptor gene in patients with androgen insensitivity syndrome.
Androgens↗
Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular Biology. Molecular biology and immunopathogenesis of rheumatoid arthritis. March 15-21, 1991.
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Arthritis, Rheumatoid↗
[Neurosurgery and molecular biology: (series 3) molecular biology of the brain-neurons].
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Animals↗
New contributions to clinical hypertension from molecular biology.
Molecular genetics is making enormous contributions to the understanding of complex biologic problems. Essential hypertension is a major health problem worldwide and it is a model of complex disease in which several genes must be affected simultaneously and environmental factors play an important role in the expression of the disease. Despite great progress in our understanding of the pathophysiology of hypertension and the development of an array of antihypertensive agents aimed at interfering with the major systems that control blood pressure, the main genetic determinants of hypertension remain elusive. The development of techniques and strategies for studying the structure and function of isolated genes or for studying genes on a genomewide basis may soon change this picture. The success of this approach is illustrated by the identification of the underlying molecular mechanisms responsible for rare monogenic forms of hypertension. Precise understanding of the molecular mechanisms involved with essential hypertension will allow unique opportunities for preclinical interventions and development of more rational and efficient forms of therapy.
Adolescent↗
The biology and molecular biology of scrapie-like diseases.
The transmissible spongiform encephalopathies (TSE's) are degenerative diseases of the central nervous system which naturally affect man (Creutzfeldt-Jakob disease [CJD], Gerstmann-Sträussler syndrome [GSS], kuru), sheep and goats (scrapie), cattle (bovine spongiform encephalopathy [BSE]), mink (transmissible mink encephalopathy), mule deer, elk and antelope (chronic wasting disease). Spongiform encephalopathies have also been diagnosed in captive species of zoo antelope and in domestic cats. Much has been written about these maladies in the wake of the BSE outbreak, the tragic cases of CJD in recipients of cadaver-derived human growth hormone, sex hormones or dura mater and this has stimulated a continuing public health debate about the transmissibility, prevalence and clinical variability of scrapie, CJD and related ("prion") diseases. Prions (Weissmann, Liautard, this volume) and the human (Kretzschmar, this volume) and cattle (Wilesmith, Marsh, this volume) diseases are described in more detail elsewhere. This article presents a brief overview of the biology and molecular cell biology of scrapie and rodent models of these diseases.
Animals↗