Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “knowledge accumulation”

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 559 records · Page 31Linked to original sources
PubMed2004

Knowledge modeling and acquisition of traditional Chinese herbal drugs and formulae from text.

Traditional Chinese medicine has developed over more than 4000 years. A tremendous amount of medical knowledge has been accumulated, among which herbal drugs and formulae are an important portion. This paper presents an ontology for traditional Chinese drugs and formulae, and an ontology-based system for extracting knowledge of drugs and formulae from semi-structured text. The system consists of two components: an executable knowledge extraction language (or EKEL) for specifying knowledge-extracting agents, and a support machine for executing EKEL programs. Experiments show that the system is adequate of extracting knowledge of herbal drugs and formulae from semi-structured text.

Automation↗
PubMedDate not supplied

The tuberculosis epidemic. Scientific challenges and opportunities.

One in every three people on Earth is believed to be infected with Mycobacterium tuberculosis, leading to seven to eight million cases of active tuberculosis (TB) per year and approximately three million deaths annually. this epidemic, like those of most infectious diseases, creates scientific challenges and opportunities as it raises the demand for public health solutions. The currently available weapons for fighting TB are inadequate. The ultimate goal of biomedical TB research is to lessen the public health burden of this disease by developing improved diagnostic, therapeutic, and intervention strategies. Achieving this goal requires a base of knowledge about the biology of M. tuberculosis and related mycobacteria, their interactions with human and animal hosts, and the nature of an effective host-protective immune response. TB researchers are applying this accumulating base of knowledge to developing rapid, easy-to-use diagnostic assays appropriate for low-as well as high-income countries, improving the current complicated therapeutic regimen, identifying potential new drugs to combat multidrug-resistant TB, and creating more effective vaccines.

Animals↗
PubMed1988

The extracellular matrix of the central and peripheral nervous systems: structure and function.

The extracellular matrix (ECM) is the naturally occurring substrate upon which cells migrate, proliferate, and differentiate. The ECM functions as a biological adhesive that maintains the normal cytoarchitecture of different tissues and defines the key spatial relationships among dissimilar cell types. A loss of coordination and an alteration in the interactions between mesenchymal cells and epithelial cells separated by an ECM are thought to be fundamental steps in the development and progression of cancer. Although a substantial body of knowledge has been accumulated concerning the role of the ECM in most other tissues, much less is known of the structure and function of the ECM in the nervous system. Recent experiments in mammalian systems have shown that an increased knowledge of the ECM in the nervous system can lead to a better understanding of complex neurobiological processes under developmental, normal, and pathological conditions. This review focuses on the structure and function of the ECM in the peripheral and central nervous systems and on the importance of ECM macromolecules in axonal regeneration, cerebral edema, and cerebral neoplasia.

Brain Edema↗
PubMed1996

Cytokines and bacterial infections.

During the recent 10-15 years a growing amount of knowledge has been accumulated on the role of cytokines in the pathogenesis and resistance to infections caused by nonviral agents, including a wide range of bacteria. Cytokines can be major mediators of the pathogenic effect in some diseases, and represent important defense mechanisms in others. Detailed knowledge on the role of the growing number of recognised cytokines is important, because it may represent means to combat and to prevent diseases caused by such infections.

Animals↗
PubMed1995

[Public health risk caused by emissions from refuse incinerators].

An irresponsible "approval on request" in favour of waste incineration written by a consulting committee of the German Federal Board of Physicians has meanwhile been widely distributed both nationally and internationally. The aim of this politically motivated paper is to dramatically increase the present number of 49 waste incinerators in Germany. It is our duty to warn of this intention. Health problems are known to exist both in workers at waste incinerators and in humans living in their vicinity. Furthermore, in the long run negative impact also to ecosystems should be expected from the emissions. Health problems in patients living downwind of waste incinerators repeatedly have been reported on by physicians. "Lack of statistical significance", often used as counter-argument, is only due to absence of funding of comprehensive epidemiological studies in Germany. Analyses of soil samples reveal the pollution from waste incineration. Considering the pre-load of the region, additional emissions caused by waste incineration and other sources have to be assessed. The application of preventive limit values is imperative. The presently used "limit values", being about 100 times too high, bear an unacceptable risk. Therefore, reliable regional registers of emissions have to be established immediately. Limit values continuously have to be adjusted to the progress of scientific knowledge. In this respect it is imperative to consider that the actual composition of emissions is unknown; isolated risk assessment of single compounds underestimates the total risk; the negative impact, e.g. of dioxins, on both the immune and hormone systems occurs at concentrations 100 times lower than those causing carcinogenic effects; the assumption of "threshold values" is obsolete; a considerable lack of knowledge exists about accumulation in food webs and in ecosystems; the demand of preservation of natural, geogenic situations is indispensable in assessments of soil and water pollution. Essential prerequisites for risk assessments of emissions from waste incineration are 1. actual, continual and comprehensive qualitative and quantitative analytical knowledge of the composition of emissions; 2. region-specific meteorologic dispersion models of the emissions; 3. evaluation of the complex mixtures in emissions for their kinetics in and toxicity for ecosystems and humans. Neither of these demands is so far fulfilled. Facing these problems, the present propagation of waste incineration must be stopped. As an alternative, efforts to optimize waste-avoiding and recycling concepts considerably have to be reinforced, and low-risk procedures, like compost and other decomposing methods, hydrogenation or freeze-griding of plastics, have to be widely promoted.

Air Pollution↗
PubMed2002

Neurological function-based research.

Function of the nervous system has been the main domain of interest of an elite group of philosophers, scientists and physicians. This topic may only be understood within a historical perspective, since the progression of knowledge of the function of the nervous system has always paralleled the expansion of our understanding of the outer world and of biological organisms observed. However, data gained from functional experimental and clinical researches in neurosurgery, neurology and neuroscience constitute not only a traditional and historical accumulation of this knowledge but also serve as one of the most important aspects of experimental and clinical neuroscience in the future. This article summarizes the basic principles and methods used in neurological function-based research. In order to elucidate the topic, the text was practically divided into three main sections: (1) historical perspective regarding functional research models in clinical and experimental neuroscience; (2) neurological function-based clinical studies in humans; and (3) experimental research models on animals.

Animals↗
PubMed1999

[Hereditary hemochromatosis--new developments after discovery of the HFE gene].

Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism, resulting in an increased iron deposition and multiorgan failure. Recently a candidate gene of HH, termed HFE, has been identified on chromosome 6, coding for a protein homologous to major histocompatibility complex (MHC) class I molecules. Two mutations of the hemochromatosis gene leading to an exchange of cysteine to tyrosine at aminoacid 282 and histidine to asparagine at aminoacid 63, are retained responsible for the development of hereditary hemochromatosis. The Cys282Tyr-mutation disrupts a disulfid bond and thus abrogates binding of the mutant HFE-protein to beta 2-microglobulin and its presentation on the cell surface. The His63Asp-mutation seems to play a role in pH-regulated dissociation of the transferrin receptor/transferrin complex in the lysosome. Mutations of the HFE-protein alter the affinity of the transferrin receptor for its ligand transferrin and may thus cause an intracellular accumulation of iron. Knowledge of the responsible gene allows a molecular diagnosis of HH. The new genetic marker can be used for screening and confirmation of HH reducing the need for confirmatory liver biopsies. Compared to standard screening parameters like ferritin and transferrin saturation genetic testing will allow the diagnosis of HH in an early, asymptomatic state before iron accumulation has occurred. As a normal life expectancy of patients with HH can be achieved if iron reduction is initiated early, genetic testing may thus be of great benefit for patients with HH.

Algorithms↗
PubMed1999

[Diagnosis of hepatic enzyme activities of drug metabolizing enzymes-phenotyping and genotyping].

Drug metabolizing enzymes (DMEs) play an important role in the biotransformation of various xenobiotics, generally by detoxifying and eliminating substrates by converting them to more hydrophilic derivatives, or in some cases, activating substrates by conversion to intermediates that are highly reactive with biological macromolecules. It is widely accepted that the enzymatic activities of hepatic DMEs are one of the most important determinants of the concentration of drugs at their site of action or in the blood. Wide inter-individual variability in drug concentrations in the blood has been demonstrated even after the administration of the same doses on the basis of body weight, and in many cases the wide differences in plasma drug concentrations have been attributed to the individual differences in the enzymatic activities of DMEs. Attempts have therefore been made to estimate the hepatic DME activities of each individual before administration of drugs clinically. Three different approaches were taken to estimate patients' hepatic DME activities: 1) the use of probe drugs (phenotyping); 2) molecular diagnosis of genetic DME deficiency (genotyping); 3) examination of DME levels/activities in peripheral blood leukocytes/lymphocytes on the assumption that their activities in leukocytes/lymphocytes are well correlated with hepatic enzyme activities. A great number of data have been accumulated concerning the specificity of certain DME for candidate probe drugs, and searches have been made for mutated alleles of DME genes that indicate whether an individual is deficient in DMEs. Gene expression is measured by sensitive methods such as the reverse-transcriptase polymerase chain reaction and/or immunochemical methods in peripheral blood leukocytes/lymphocytes, which are less invasive tissues. Knowledge is being accumulated that will allow the development of useful methods of predicting the activities of hepatic DMEs that affect individual pharmacokinetics/pharmacodynamics. In this article, various reported methods of assessing hepatic DME activities are reviewed for the purpose of maximizing the efficacy and safety of pharmacotherapy.

Arylamine N-Acetyltransferase↗
PubMed1977

Regulation of hemoglobin synthesis during the development of the red cell (third of three parts).

In this article we have surveyed the current state of knowledge regarding the accumulation of globin mRNA and hemoglobin in red cells. We have attempted to examine the interplay of numerous processes that seem to be necessary to achieve this highly differentiated state. Finally, we have made an effort to formulate some of the mechanisms whereby individual red cells may come to contain varying proportions of specific hemoglobins. The past several years have been characterized by a veritable explosion of knowledge concerning the globin structure genes, and the structure, transcription, processing and function of globin mRNA in erythroid cells. It now seems possible to analyze the earlier stages of erythropoiesis by cultivation and examination of erythroid colonies in vitro. The primary differentiation events leading to the production of specific globins, especially for hemoglobin F production in man, are now experimentally accessible. There is good reason to hope that these advances will soon permit achievement of the long desired therapeutic goal of enhancing hemoglobin F synthesis in patients with severe beta-chain hemoglobinopathies. Our aim has been to review the scientific information that might provide the rationable for amelioration of the clinical phenotypes in patients inheriting abnormal globin genes.

Adult↗
PubMed1967

Recent advances in techniques for tsetse-fly control.

With the advent of modern persistent insecticides, it has become possible to utilize some of the knowledge that has accumulated on the ecology and bionomics of Glossina and to devise more effective techniques for the control and eventual extermination of these species.The present article, based on experience of the tsetse fly problem in Northern Nigeria, points out that the disadvantages of control techniques-heavy expenditure of money and manpower and undue damage to the biosystem-can now largely be overcome by basing the application of insecticides on knowledge of the habits of the particular species of Glossina in a particular environment. Two factors are essential to the success of a control project: the proper selection of sites for spraying (the concept of restricted application) and the degree of persistence of the insecticide used. Reinfestation from within or outside the project area must also be taken into account.These and other aspects are discussed in relation to experience gained from a successful extermination project carried out in the Sudan vegetation zone and from present control activities in the Northern Guinea vegetation zone.

Insect Control↗
PubMed1983

Clinical implications of population-based studies in Europe.

The cross-fertilization of epidemiology and clinical medicine is a continuous process. The impressive progress in cardiovascular disease (CVD) epidemiology of the last 30 years was substantially reinforced by large population-based intervention studies in the last decade. As a result, guidelines for prevention are emerging with relatively clear implications for clinical medicine in general. Two such guidelines were recently published by the Royal College of General Practitioners (2, 5). However, the application of these general principles in day-to-day doctor-patient interaction is not easy. General health promotion counseling in the family, conscientious case findings, and regular follow-up are the main points of agreement between epidemiologists and progressive clinicians. Preventive treatment with drugs, however, needs to be decided in each case individually. The ever-increasing new epidemiological knowledge, the intimate knowledge of the individual and his family, and the careful balancing of potential benefits and possible side effects of treatment coupled with the art of the clinician are helping physicians to make these difficult decisions correctly. In order to maximally diminish the current need for such difficult decision making, when the patient's risk is already high, generally adopted, sound, and safe health promotion efforts should be pursued by clinicians in their everyday activities. WHO will continue to encourage the accumulation of sound knowledge in prevention of CVD and other chronic diseases. The future calls for comprehensive health promotion policies focused on the individual and on the community, not only in regard to single diseases.

Coronary Disease↗
PubMed2005

Muscle function and dysfunction in health and disease.

Skeletal muscles of the trunk and limbs developmentally originate from the cells of the dermomyotomal compartment of the somite. A wealth of knowledge has been accumulated with regard to understanding the molecular regulation of embryonic skeletal myogenesis. Myogenic induction is controlled through a complex series of spatiotemporal dependent signaling cascades. Secreted signaling molecules from surrounding structures not only initiate the myogenic program, but also influence proliferation and differentiation decisions. The proper coordination of these molecular events is thus critical for the formation of physiologically functional skeletal muscles. Hereditary congenital skeletal muscle defects arise due to genetics lesions in myogenic specific components. Understanding the mechanistic routes of congenital skeletal muscle disease therefore requires a comprehensive knowledge of the developmental system. Ultimately, the application of this knowledge will improve the diagnostic and therapeutic methodologies for such diseases. The aim of this review is to overview our current understanding of skeletal muscle development and associated human congenital diseases.

Animals↗
PubMed2002

Butterfly-shaped pattern dystrophy: a genetic, clinical, and histopathological report.

OBJECTIVES: To identify the disease-causing mutation in a large family segregating dominantly inherited butterfly-shaped pattern dystrophy (BPD) and to describe the microscopic pathological changes observed in a member of this family. METHODS: Seventeen individuals at risk for dominantly inherited BPD in a family were examined and blood samples obtained. Linkage analysis and mutation screening of the human retinal degeneration slow (RDS)/peripherin locus were performed. Light and electron microscopic examinations were performed on 1 postmortem eye of 1 affected individual. RESULTS: Four individuals demonstrated macular degenerative changes with diminished visual acuity, and 3 others exhibited early signs of atrophy without visual deficits. Microscopic examination of the left eye of 1 patient revealed an area of total loss of the retinal pigment epithelium (RPE) and photoreceptor cell layer with intact choriocapillaris and lipofuscin-containing cells in the subretinal space. Outside the area of RPE atrophy, the RPE was greatly distended by lipofuscin. The disease locus in this family was mapped to 6p21.2, the region of the RDS/peripherin gene. Further analysis identified a G-->A change at nucleotide position 637 of RDS/peripherin, predicting a novel Cys213Tyr substitution in all affected members of the family. CONCLUSIONS: This study describes a new RDS/peripherin mutation for BPD and provides the first combined genetic-pathological study of this condition, to our knowledge. CLINICAL RELEVANCE: Accumulation of lipofuscin in RPE is a prominent feature of several retinal disorders, including age-related macular degeneration. Further elucidation of the cellular and molecular mechanism of BPD may provide insight into pathogenesis and lead to novel treatment approaches for this and other macular degenerations.

Adult↗
PubMed2002

Understanding dry eye syndrome.

It was my great pleasure to have had the opportunity to give the conference address in addition to being honored by the Professor Dohlman Award. I am proud of the progress in the understanding of dry eye that has been made over the past couple of decades. However, the clinical application of the knowledge that has accumulated lies in the future. Thus far no effective medication has ever been developed for the treatment of severe dry eye. Cyclosoporine may become the first eyedrops to be used, and a series of new drugs containing androgens, immunomodulators, secretagogues, P2Y2 receptor agonists, and others may follow. I believe that medication for the treatment of dry eye will be developed in the not to distant future, and I hope that at the 4th conference in a few years time, we will be able to share these new treatments for the management of dry eye patients.

Dry Eye Syndromes↗
PubMed1996

Keeping in mind the mind: mental functions, networks and neurosurgery.

The object of the neurosurgeons daily endeavour, the human brain, is less well understood in its overall organization than any other organ. This puts the neurosurgeon in a very difficult position. However, a substantial body of knowledge has been accumulated during recent years, and scientists from a variety of different disciplines have worked out theoretical frameworks to accomodate the available data. Here we present some of the evolving concepts on the organization of the substrate of the mind. Review of the literature shows that application of mathematical neural network models to the nervous system is very successful in explaining function. An implicit aspect of neural network models is that information storage is not localized in certain neurons but that the information is stored as the global pattern of activity in the network. Because networks of the brain involve often millions of neurons, exact identification and comparison with the theoretical models is not possible today.

Brain↗
PubMedDate not supplied

Lentiviral vectors.

Vectors based on lentiviruses have reached a state of development such that clinical studies using these agents as gene delivery vehicles have now begun. They have particular advantages for certain in vitro and in vivo applications especially the unique capability of integrating genetic material into the genome of non-dividing cells. Their rapid progress into clinical use reflects in part the huge body of knowledge which has accumulated about HIV in the last 20 years. Despite this, many aspects of viral assembly on which the success of these vectors depends are rather poorly understood. Sufficient is known however to be able to produce a safe and reproducible high titre vector preparation for effective transduction of growth-arrested tissues such as neural tissue, muscle and liver.

Genetic Therapy↗
PubMed2006

Differential functions of Ras for malignant phenotypic conversion.

Among the effector molecules connected with the group of cell surface receptors, Ras proteins have essential roles in transducing extracellular signals to diverse intracellular events, by controlling the activities of multiple signaling pathways. For over 20 years since the discovery of Ras proteins, an enormous amount of knowledge has been accumulated as to how the proteins function in overlapping or distinct fashions. The signaling networks they regulate are very complex due to their multiple functions and cross-talks. Much attention has been paid to the pathological role of Ras in tumorigenesis. In particular, human tumors very frequently express Ras proteins constitutively activated by point mutations. Up to date, three members of the Ras family have been identified, namely H-Ras, K-Ras (A and B), and N-Ras. Although these Ras isoforms function in similar ways, many evidences also support the distinct molecular function of each Ras protein. This review summarizes differential functions of Ras and highlights the current view of the distinct signaling network regulated by each Ras for its contribution to the malignant phenotypic conversion of breast epithelial cells. Four issues are addressed in this review: (1) Ras proteins, (2) membrane localization of Ras, (3) effector molecules downstream of Ras, (4) Ras signaling in invasion. In spite of the accumulation of information on the differential functions of Ras, much more remains to be elucidated to understand the Ras-mediated molecular events of malignant phenotypic conversion of cells in a greater detail.

Amino Acid Sequence↗
PubMed2002

Bcr-Abl is a "molecular switch" for the decision for growth and differentiation in hematopoietic stem cells.

Chronic myeloid leukemia (CML) is a clonal disorder originating in the pluripotent hematopoietic stem cell (HSC), the hallmark of which is the constitutively activated p210-type of Bcr-Abl tyrosine kinase protein. Studies in recent years have helped us to understand the molecular processes involved in the initiation and progression of CML. Although a great amount of knowledge has been accumulated, the effect of Bcr-Abl on the HSC is still unclear. We have developed an in vitro system that mirrors the chronic phase of CML with a combination of in vitro embryonic stem cell differentiation and tetracycline-inducible Bcr-Abl expression. Enforced Bcr-Abl expression was sufficient to increase the number of both multilineage progenitors and myeloid progenitors. The current system is powerful for analyzing the genetic changes in hematopoietic development. This review focuses on how Bcr-Abl affects HSCs and how Bcr-Abl expression alters the properties of HSCs.

Animals↗