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Results for “knowledge accumulation”

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At least 109 records · Page 6Linked to original sources
PubMed2001

Rescue of the Friedreich's ataxia knockout mouse by human YAC transgenesis.

We have generated and characterised transgenic mice that contain the entire Friedreich's ataxia gene (FRDA) within a human YAC clone of 370 kb. In an effort to overcome the embryonic lethality of homozygous Frda knockout mice and to study the behaviour of human frataxin in a mouse cellular environment, we bred the FRDA YAC transgene onto the null mouse background. Phenotypically normal offspring that express only YAC-derived human frataxin were identified. The human frataxin was expressed in the appropriate tissues at levels comparable to the endogenous mouse frataxin, and it was correctly processed and localised to mitochondria. Biochemical analysis of heart tissue demonstrated preservation of mitochondrial respiratory chain function, together with some increase in citrate synthase and aconitase activities. Thus, we have demonstrated that human frataxin can effectively substitute for endogenous murine frataxin in the null mutant. Our studies are of immediate consequence for the generation of Friedreich's ataxia transgenic mouse models, and further contribute to the accumulating knowledge of human-mouse functional gene replacement systems.

Animals↗
PubMed2002

[Psychiatry as a profession].

With reference to Max Weber's timeless analysis of science and politics as a profession, the present paper describes the philosophical background and historical development of the tasks and tools, institutionalization, and socialization of psychiatry as a profession. In the mid twentieth century, psychiatrists' emergence from ideological confinement in asylums, where they were separated from urban culture and medicine in general, finally allowed them to benefit from accumulating knowledge and technological progress in the field of medicine. After its transition from a custodial to a therapeutic discipline, psychiatry has acquired a variety of new fields of action and duties that require a high degree of expertise on psychological and biological levels. At the same time, people have increasingly come to expect relief not only from disease, but also from manifold problems of everyday life. As a consequence, there has been an inflationary growth of professional psychiatric and psychotherapeutic and nonprofessional services. The professional requirements that psychiatrists should meet have also increased quantitatively and qualitatively in the wake of the historical change from a caring, paternalistic attitude towards the mentally ill to a therapeutic partnership. To a greater degree than physicians working in other medical fields, psychiatrists get personally involved with their patients. As a consequence, the mental burden of their profession is at times immense. For this reason, the ethics of a medical profession has special implications for psychiatrists. The fascinating advances in therapeutic methods, neurobiological knowledge, and the increasingly differentiated diagnostic tools, e.g., noninvasive investigation of the morphology and functioning of the brain, have turned psychiatry into one of the most interesting contemporary professions. Psychiatry is now facing an enormous challenge of meeting the standards of expertise.

Biological Psychiatry↗
PubMed1994

International Federation of Clinical Chemistry. Use of artificial intelligence in analytical systems for the clinical laboratory. IFCC Committee on Analytical Systems.

The incorporation of information-processing technology into analytical systems in the form of standard computing software has recently been advanced by the introduction of artificial intelligence (AI) both as expert systems and as neural networks. This paper considers the role of software in system operation, control and automation and attempts to define intelligence. AI is characterized by its ability to deal with incomplete and imprecise information and to accumulate knowledge. Expert systems, building on standard computing techniques, depend heavily on the domain experts and knowledge engineers that have programmed them to represent the real world. Neural networks are intended to emulate the pattern-recognition and parallel-processing capabilities of the human brain and are taught rather than programmed. The future may lie in a combination of the recognition ability of the neural network and the rationalization capability of the expert system. In the second part of this paper, examples are given of applications of AI in stand-alone systems for knowledge engineering and medical diagnosis and in embedded systems for failure detection, image analysis, user interfacing, natural language processing, robotics and machine learning, as related to clinical laboratories. It is concluded that AI constitutes a collective form of intellectual property and that there is a need for better documentation, evaluation and regulation of the systems already being used widely in clinical laboratories.

Artificial Intelligence↗
PubMed1995

Clinical applications of the p53 tumor suppressor gene.

The interest on the p53 gene has grown enormously in the last 4 years. It is now known that p53 is directly involved in important cellular functions including regulation of the cell cycle, and that its alteration may be one of the important steps in the initiation of cancer. In this review I will cover briefly basic and clinical aspects related to the p53 gene and protein and explore ways of using the accumulated knowledge for patient diagnosis and monitoring. The literature suggests that it is now appropriate to start assessing the p53 gene status of breast tumors for prognosis. Therapeutic options are at an infancy stage. A new diagnostic approach based on the immune response of cancer patients against mutant proteins is discussed, by using the p53 mutant protein as a model. Although the cancer patient has not as yet benefited directly from the enormous number of investigations on the p53 gene and protein, there is hope that in the long-term these studies will promote the understanding of cancer initiation and progression at the molecular level with a practical return at a later phase.

Autoantibodies↗
PubMed1995

Use of artificial intelligence in analytical systems for the clinical laboratory.

OBJECTIVE: To consider the role of software in system operation, control and automation, and attempts to define intelligence. METHODS AND RESULTS: Artificial intelligence (Al) is characterized by its ability to deal with incomplete and imprecise information and to accumulate knowledge. Expert systems, building on standard computing techniques, depend heavily on the domain experts and knowledge engineers that have programmed them to represent the real world. Neural networks are intended to emulate the pattern-recognition and parallel processing capabilities of the human brain and are taught rather than programmed. The future may lie in a combination of the recognition ability of the neural network and the rationalization capability of the expert system. In the second part of this paper, examples are given of applications of Al in stand-alone systems for knowledge engineering and medical diagnosis and in embedded systems for failure detection, image analysis, user interfacing, natural language processing, robotics and machine learning, as related to clinical laboratories. CONCLUSION: Al constitutes a collective form of intellectual property, and that there is a need for better documentation, evaluation and regulation of the systems already being used widely in clinical laboratories.

Artificial Intelligence↗
PubMed1992

The role of the nucleus and other compartments in toxic cell death produced by alkylating hepatotoxicants.

Hepatocellular necrosis occurs under a wide range of pathological conditions. In most cases, toxic cell death takes place over a finite span of time, delayed from the point of initial injury and accompanied by homeostatic counterresponses that are varied and complex. The present strategies for discovering critical steps in cell death recognize that (1) different toxins produce similar morphologic changes that precede killing in widely varied cell types, and that (2) lethal events are likely to involve one or more compartmentalized functions that are common to most cells. Investigations of the plasma membrane, endoplasmic reticulum, cytoplasm, mitochondrion, and nucleus have greatly advanced our understanding of acute hepatocellular necrosis. This report examines each compartment but emphasizes molecular changes in the nucleus which may explain cell death caused by alkylating hepatotoxicants. Accumulating knowledge about two distinct modes of cell death, necrosis and apoptosis, indicates that loss of Ca2+ regulation and subsequent damage to DNA may be critical steps in lethal damage to liver cells by toxic chemicals.

Alkylating Agents↗
PubMed1992

Levamisole, the story and the lessons.

The history of the use of levamisole in man is summarized, from its start as an anthelmintic in the early sixties, through its world-wide recognition as an immunotropic agent especially in the seventies and early eighties, and its return to clinical prominence in 1989-90 as an effective adjuvant treatment for operable colon cancer. The knowledge accumulated from experimental tumour models and from clinical use in various types of cancer, supplemented with the recent evidence obtained from large-scale controlled trials in resectable colon cancer is reviewed. It is speculated that we may not have seen the end of levamisole story yet; also, the role of serendipidity in drug research is emphasized.

Chemotherapy, Adjuvant↗
PubMed1984

Misleading concepts in the field of brain peptides.

Peptide research, like all of science, requires a careful balance between building upon previously accumulated knowledge and exploring perspectives that are in conflict with prevailing views. Many of the concepts discussed here originally stimulated certain lines of research. The downfall of most of these concepts, and thus their misleading nature, lies in the limitation of possible modes by which peptides are perceived to affect the functioning of the central nervous system (CNS).

Adrenocorticotropic Hormone↗
PubMed1987

AIDS as a social phenomenon.

AIDS is an infectious but also a social disease. Next to the major epidemiological question on the natural history of AIDS, important problems have been posed in various fields of social, political, ethical and legal areas extending far beyond traditional medical interest. These create polarization among public, politicians, press and also among physicians. As the situation changes, the gravity of the disease has become more prominent and the consensus on the effectiveness of the means used and proposed is not yet achieved. Social phenomena depend on societal values, the perception of fear and menace of disease to individuals versus perception of the collectivity. Among major risk groups this fear influenced by various ideologies and societal goals, is more pronounced than the response of the society warrant. It is not one of condemnation but of tolerance, and sympathy and has been directed not toward deterring people in engaging in certain kinds of sexual behaviour, but toward doing this with minimum risk. Conflict between the perception of rights (individual versus collective) is bound to grow although it is easy to distinguish in law legitimate epidemiological needs and their possible misuse. The present position of the main risk groups is changing in various ways. The reluctance of society to address openly issues of sexual behaviour has disappeared. There is rapidly accumulating knowledge on the social influence in the spread of the disease, but as yet, scant information on the influence of social factors on the control efforts and effectiveness of preventive behavioural strategies. The effects AIDS will have on the complex social structures in general, on health structures in particular, and on the problems which might shape future attitudes, values and morals cannot be delineated with any degree of precision but only vaguely guessed as the disease progresses now and into the next century.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Childhood amnesia and distinctions between forms of memory: a comment on Wood, Brown, and Felton.

Recently, Wood and his colleagues (1989) presented a case of childhood amnesia as evidence against the distinction between declarative and procedural memory that has sometimes been applied to human amnesia. Their argument was based on the observation that their patient showed some progress in school over the years, i.e., acquired some declarative knowledge, despite severely impaired day-to-day memory ability. We briefly review their case, together with a carefully studied second case of childhood amnesia not mentioned by Wood et al. Their argument is wrong in several ways. First, the utility of the declarative/procedural distinction for amnesia, or the utility of any other distinction between memory systems, depends on whether or not one kind of memory is impaired selectively, not on the severity of the impairment. In particular there is no requirement that one kind of memory be totally absent. Second, they have not provided the data necessary to support their argument; namely, data showing that the amount of declarative knowledge accumulated during years in school was better than would have been expected given the capacity for moment-to-moment or day-to-day memory. Indeed, the patient's moment-to-moment memory ability is better than represented, and the patient's progress in school was abnormally slow. Third, it is not clear that academic achievement scores provide a direct measure of declarative memory abilities (skill learning and recovery of function may also have contributed). We conclude that the evidence from childhood amnesia is fully consistent with the proposal that amnesia reflects a selective impairment in the formation of long-term declarative memory.

Achievement↗
PubMed1985

The structure of invertebrate extracellular hemoglobins (erythrocruorins and chlorocruorins).

The knowledge accumulated over the last 30 years concerning the subunit structures of the invertebrate extracellular hemoglobins permits us to classify them into four distinct groups. Single-domain, single-subunit hemoglobins consisting of single, heme-binding polypeptide chains which have a molecular mass of ca. 16 KDa. These molecules are found in multicellular parasitic organisms such as the trematodes Dicrocoelium and Fasciolopsis and in a few insects, namely in the adult Anisops and in the larvae of Chironomus and of Buenoa. Two-domain, multi-subunit hemoglobins consisting of 30-37 KDa polypeptide chains each containing two, linearly connected heme-binding domains, which form polymeric aggregates with molecular masses ranging from 250 to 800 KDa. These hemoglobins are found extensively among the carapaced branchiopod crustaceans: Caenestheria, Daphnia and Lepidurus hemoglobins have been found to consist of 10, 16 and 24 two-domain chains, respectively. Judging from their electron microscopic appearances, some of the hemoglobins may possess different molecular symmetries. Multi-domain, multi-subunit hemoglobins consisting of two or more polypeptide chains, each comprising many heme-binding domains of ca. 15-20 KDa each. Examples of this class are found among the carapaceless branchiopod crustaceans, the planorbid snails and the clams from the families Astartidae and Carditidae. Artemia hemoglobin consists of two chains of ca. 125 KDa, each containing 8 heme-binding domains. Planorbis and Helisoma hemoglobins possess a molecular mass of ca. 1700 KDa and consist of 10 chains of 170-200 KDa. Astarte and Cardita hemoglobins appear in electron micrographs as rod-like polymers of variable dimensions, 20-30 nm in diameter and 20-100 nm in length and consist of polypeptide chains of ca. 300 KDa. The crustacean and gastropod hemoglobins vary in their electron microscopic appearance and may possess different molecular symmetries. Single-domain, multi-subunit hemoglobins consisting of aggregates of several small subunits, some of which are disulfide-bonded and not all of which contain heme. These molecules are widely distributed among the annelids and possibly also among the pogonophores. They are characterized by a two-tiered, hexagonal electron microscopic appearance, with a vertex-to-vertex diameter of 30 nm and a height of 20 nm, an acidic isoelectric point, a sedimentation coefficient of 50-60 S and a low iron content of 0.24 +/- 0.03%.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

The surgical treatment of breast cancer.

Controversy regarding the efficacy of surgical treatment of breast cancer has persisted since the earliest descriptions of this disease in the first and second centuries AD. It has been acknowledged for many years that patients with untreated breast cancer survive for a surprisingly predictable period of 5 yr. Hence, in recommending extensive surgical procedures, the surgeon must recognize the unique biology of breast cancer and the need for long-term follow-up. In spite of a voluminous body of literature concerning the treatment of breast cancer, the distention and contention still continue. However, there is now increasing support for conservative treatment, including the less radical modified mastectomy, and in selected cases, wide local excision, axillary dissection and radiotherapy. As knowledge accumulates, it is clear that the treatment of breast cancer requires a multidisciplinary approach reflecting our understanding of the biology of this disease.

Aged↗
PubMed1996

Well-being, symptoms and the menopausal transition.

OBJECTIVES: This paper reviews the knowledge accumulated from published population studies of health and ill-health experiences during the menopausal transition. RESULTS: Well-being: mid-aged women are more likely to report positive moods than negative moods. Well-being is not associated with menopausal status but is associated with current health status, psychosocial and lifestyle variables. SYMPTOMS: SYMPTOMS vary greatly across cultures, with North American and European samples reporting higher rates of symptoms than Asian women. The most symptomatic women in the North American samples and Australian studies are those whose menstrual cycles have changed. Vasomotor symptoms increase through the menopausal transition. Other variables such as socio-demographic, health status, stress, premenstrual complaints, attitudes to ageing and menopause, and health behaviors are associated with the occurrence of symptoms. Psychological complaints: There is no increase in the incidence of major depression with the menopause. Negative moods are not associated with the natural menopausal transition. Factors associated with negative moods include surgical menopause, prior depression, health status, menstrual problems, social and family stressors and negative attitudes to menopause. Sexuality: Several studies suggest a decline in sexual functioning associated with menopausal status rather than ageing. Social factors and health status factors are also associated with sexual outcomes. RECOMMENDATIONS: Future research should bring together biomedical and sociological aspects. Positive aspects of health should be assessed as well as troubling symptoms. Longitudinal studies are needed with measures of hormonal change. Promoting positive attitudes to ageing and menopause, health lifestyles and stress reduction can be used as community interventions and as part of individual care.

Adult↗
PubMed1994

Measurement of condom use in 72 studies of HIV-preventive behaviour: a critical review.

Ninety-four distinct measures of condom use were identified in a review of 72 psychosocial studies of HIV-prevention. A coding scheme was developed which characterised each measure in terms of: (1) type of measure (e.g. frequency of use, use at last intercourse), (2) response alternatives (e.g. Likert scale), (3) recall period (e.g. lifetime, last month), (4) partner specification (e.g. 'new' partner), and (5) activity specification (e.g. vaginal or anal intercourse). Results show a great deal of inconsistency in measurements of condom use across studies. Single-item frequency or consistency measures were most common. Several difficulties with measures employed to date were identified. These included indeterminate reliability and validity of measures, lack of attention to the epidemiological significance of different types of use and terminological and self-presentational problems with items assessing use. Implications of extant measurement approaches for the accumulated knowledge base on predictors of 'safer' sex and suggestions for future research in this area are outlined.

Condoms↗
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↗
PubMed2006

Non-viral ocular gene therapy: potential ocular therapeutic avenues.

Non-viral vectors for potential gene replacement and therapy have been developed in order to overcome the drawbacks of viral vectors. The diversity of non-viral vectors allows for a wide range of various products, flexibility of application, ease of use, low-cost of production and enhanced "genomic" safety. Using non-viral strategies, oligonucleotides (ODNs) can be delivered naked (less efficient) or entrapped in cationic lipids, polymers or peptides forming slow release delivery systems, which can be adapted according to the organ targeted and the therapy purposes. Tissue and cell internalization can be further enhanced by changing by physical or chemical means. Moreover, a specific vector can be selected according to disease course and intensity of manifestations fulfilling specific requirements such as the duration of drug release and its level along with cells and tissues specific targeting. From accumulating knowledge and experience, it appears that combination of several non-viral techniques may increase the efficacy and ensure the safety of these evolving and interesting gene therapy strategies.

Animals↗
PubMed2006

Glutathione transferases in the genomics era: new insights and perspectives.

In the last decade the tumultuous development of "omics" greatly improved our ability to understand protein structure, function and evolution, and to define their roles and networks in complex biological processes. This fast accumulating knowledge holds great potential for biotechnological applications, from the development of biomolecules with novel properties of industrial and medical importance, to the creation of transgenic organisms with new, favorable characteristics. This review focuses on glutathione transferases (GSTs), an ancient protein superfamily with multiple roles in all eukaryotic organisms, and attempts to give an overview of the new insights and perspectives provided by omics into the biology of these proteins. Among the aspects considered are the redefinition of GST subfamilies, their evolution in connection with structurally related families, present and future biotechnological outcomes.

Animals↗
PubMed2004

The promise of human embryonic stem cells.

Pluripotency refers to the ability of a cell to give rise to cells that originate from all three germ layers. Among the available human pluripotent cells, human embryonic stem cells (hESCs) are considered to have the greatest probability for practical clinical application because of their simple propagation and stability in culture. Since their first derivation, issues concerning hESC maintenance and self-renewal have been widely addressed. The first part of this review presents the accumulated knowledge concerning the self-renewal of hESCs and discusses recent genetic profile data, which seem to shed light on hESC self-renewal and pluripotency mechanism. The second part deals with the regenerative potential of hESCs. Available lineage-specific differentiations of hESCs are presented, with detailed data on the ability of hESCs to differentiate into trophoblast cells, an observation that might broaden the definition of their developmental potential. Specific focus is given to vascular cell differentiation, including endothelial and smooth muscle cells. Transplantation limitations as well as current steps taken toward resolution conclude the review.

Blastocyst↗