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PubMedDate not supplied

Towards understanding the control of the division cycle in animal cells.

The author reviewed the historical process by which classical knowledge of cell division accumulated, to give rise to the molecular biology of the cell cycle, and discussed the perspective of this field of research. The study of the control of cell division began at the turn of the century. It was hypothesized that cell division was a physiological regulation necessary for growing cells to maintain a proper nucleocytoplasmic ratio to survive, which was later substantiated by the finding that amoeba cells could be prevented from dividing by repeated excision of the cytoplasm. However, the observation in Tetrahymena that heat-shocked cells grow exceedingly, but fail to divide, suggested that the cell required the accumulation of a labile "division protein" to initiate division. Mechanisms that control the cell cycle were studied in oocytes by nuclear transplantation and cytoplasmic transfer, and in cultured mammalian cells, protozoa, and Physarum plasmodia by cell fusion. These experiments demonstrated the existence of cytoplasmic factors that control the cell cycle. Maturation promoting factor (MPF) thus discovered in frog oocytes became known to be an ubiquitous cytoplasmic factor that causes the transition from interphase to metaphase in all organisms. The insight into the molecular control of cell growth and division was gained from yeast cell genetics. For biochemical analysis of the cell cycle control, the method to observe the cell cycle in vitro was developed using frog egg extracts. Thus, MPF was identified as a cdc2--cyclin protein complex. Its activity was found to depend on synthesis and phosphorylation of these proteins. However, recently it was found that there were cell cycle phenomena that were difficult to explain in these terms. Various other cellular factors, including nucleocytoplasmic ratio and microtubule assembly, were also found to control MPF, as well as the cell cycle. It remained open to future how these factors control MPF to alter the pattern of the cell cycle.

Animals↗
PubMed1999

IMPROVING THE NUTRIENT COMPOSITION OF PLANTS TO ENHANCE HUMAN NUTRITION AND HEALTH1.

Plant foods contain almost all of the mineral and organic nutrients established as essential for human nutrition, as well as a number of unique organic phytochemicals that have been linked to the promotion of good health. Because the concentrations of many of these dietary constituents are often low in edible plant sources, research is under way to understand the physiological, biochemical, and molecular mechanisms that contribute to their transport, synthesis and accumulation in plants. This knowledge can be used to develop strategies with which to manipulate crop plants, and thereby improve their nutritional quality. Improvement strategies will differ between various nutrients, but generalizations can be made for mineral or organic nutrients. This review focuses on the plant nutritional physiology and biochemistry of two essential human nutrients, iron and vitamin E, to provide examples of the type of information that is needed, and the strategies that can be used, to improve the mineral or organic nutrient composition of plants.

Journal Article↗
PubMed1996

Physiological characterization of the hypertensive transgenic rat TGR(mREN2)27.

Transgenic techniques represent powerful tools for the study of gene-related mechanisms of diseases such as hypertension, which results from a complex interaction between genetic and environmental factors. The renin-angiotensin system, a biochemical cascade in which renin functions as the key enzyme in the formation of the effector peptide angiotensin II, plays a major role in the regulation of blood pressure. The renin gene, therefore, represents an important candidate gene for hypertension. Because rats are more suited than mice for a number of experimental settings often employed in cardiovascular research, we modified the transgenic technique to generate the transgenic rat strain TGR(mREN2)27 harboring the murine Ren-2 gene. These transgenic rats develop fulminant hypertension at an early age despite low levels of renin in plasma and kidney. In addition, high expression of the transgene in a number of extrarenal tissues is associated with increased local formation of angiotensin II. Thus the TGR(mREN2)27 rat represents a model of hypertension with a defined genetic background. Studies on the transgenic rat may not only provide new insights into pathophysiological mechanisms of hypertension in this animal model but also offer the unique possibility to investigate the function and regulation of renin-angiotensin systems in extrarenal tissues. The aim of this review is to compile the knowledge that has been accumulated to date on this transgenic rat and to discuss possible mechanisms responsible for its hypertensive phenotype.

Animals↗
PubMed2006

Investigating gene-to-behavior pathways in psychiatric disorders: the use of a comprehensive behavioral test battery on genetically engineered mice.

We have been investigating the relationships between genes and behaviors by conducting a systematic and well-defined behavioral test battery with mice that have a mutation on a gene of interest. The behavioral test battery covers a relatively broad range of various behavioral domains such as learning and memory, sensory-motor functions, emotion, motivation, and drug sensitivity/preference. Recently, we subjected mice lacking calcineurin (CN), a calcium/calmodulin protein phosphatase, to the comprehensive behavioral test battery. The mutant mice had a severe working memory deficit, increased locomotor activity, decreased social interaction, and impairments in prepulse and latent inhibition. The abnormalities of CN mutant mice were strikingly similar to those described for schizophrenic patients. Consistent with these findings, human genetics studies in a large sample of affected families detected a significant association of the PPP3CC gene, which encodes the CN gamma catalytic subunit with schizophrenia. The idea that abnormalities in the CN signaling pathway are involved in schizophrenia pathogenesis is consistent with traditional theories of schizophrenia and with many facts known about schizophrenia. A tremendous amount of knowledge about CN has accumulated and, by utilizing this information, the studies on the pathogenesis/pathophysiology of schizophrenia and its related mental disorders will be potentially accelerated. We discuss the potential impact of a large-scale mouse phenotyping project on the study of psychiatric disorders.

Animals↗
PubMedDate not supplied

Recent developments in the ENB framework and higher award.

The ENB Higher Award is designed to be flexible and clinically relevant, allowing practitioners to study to first degree and to masters if desired, or simply to follow individual units of learning in the programme to meet identified professional development needs. The structure of the ENB Higher Award is based on the 10 key characteristics of the ENB Framework; these encapsulate all the qualities that should make a good nurse and act as a reference point for practitioners. The aim of the Higher Award is to produce Quality Education for Quality Care, promoting higher standards of nursing care by the application of relevant skills and knowledge. The CAT (Credit Accumulation and Transfer) scheme has been introduced to give credit to existing qualifications and prevent replication of learning for all applicants. APEL (Assessment of Prior Experiential Learning) gives the practitioner the opportunity to claim further exemption from study based on relevant experience declared in a professional portfolio. Because this new scheme is deemed extremely cost-effective, no additional funds will be provided by regional health authorities or the ENB to fund this excellent continuing education initiative.

Clinical Nursing Research↗
PubMedDate not supplied

CATS: the way to academic qualifications?

At long last nurses are able to gain recognition for their academic achievements as well as their occupational skills. A working knowledge of the Credit Accumulation and Transfer Scheme (CATS) is of major importance to those wishing to make the most of this opportunity.

Accreditation↗
PubMed2002

Discovery of compounds that will prevent tau pathology.

Tau is certainly a reasonable target for the development of compounds to prevent neurofibrillary pathology, particularly in the fronto-temporal dementias. Although the mechanism of the filamentous accumulations remains unclear, sufficient knowledge is in place to move forward with high throughput screens. In fact, the development of compounds from such screens will ultimately be the only way to validate the target. The dichotomy for such screens is that in vitro screens are easier to design, but require more assumptions as to the mechanism, in contrast to cell-based screens that are more difficult to design, but make fewer assumptions about mechanism. We have designed a moderate throughput for tau binding that relies on fluorescence detection in living cells and an in vitro cdk5/p25 tau phosphorylation high throughput screen.

Animals↗
PubMed1999

New insights into signal recognition and elongation arrest activities of the signal recognition particle.

The signal recognition particle (SRP), a ubiquitous cytoplasmic ribonucleoprotein particle, plays an essential role in promoting co-translational translocation of proteins into the endoplasmic reticulum. Here, we summarise recent progress made in the understanding of two essential SRP functions: the signal recognition function, which ensures the specificity, and the elongation arrest function, which increases the efficiency of translocation. Our discussion is based on functional data as well as on atomic structure information, both of which also support the notion that SRP is a very ancient particle closely related to ribosomes. Based on the significant increase of knowledge that has been accumulating on the structure of elongation factors and on their interactions with the ribosome, we speculate about a possible mechanism of the elongation arrest function.

Alu Elements↗
PubMed2003

In vivo analysis of Nef function.

The nef gene is present in all primate lentiviruses (HIV-1, HIV-2, and SIVs). In vivo, Nef has been shown to be a major determinant of virus pathogenicity. In vitro, many different Nef activities have been reported, including CD4 and MHC I downregulation, enhanced virion infectivity, and T-cell activation. These four different activities have been extensively investigated and appear to increase the pathogenicity of the virus. However, the contribution that these activities (individually or together) make to the in vivo phenotype has not been elucidated. The mechanism(s) by which Nef modulates distinct host cell properties has provided great insights into the intricate interaction between virus and host. In this manuscript, we review the different model systems that have been used to study Nef function in vivo and the information that they have provided regarding the best characterized in vitro Nef activities. The knowledge that has been accumulated has provided clues to our understanding of Nef function but they have also left us with many unanswered questions that should be the focus of future in vivo analysis of Nef function.

Animals↗
PubMed2006

Changes in membrane conductance play a pathogenic role in osmotic glial cell swelling in detached retinas.

Detachment of the neural retina from the pigment epithelium may be associated with tissue edema; however, the mechanisms of fluid accumulation are not understood. Because retinal detachment is usually not accompanied by vascular leakage, we investigated whether the osmotic swelling characteristics of retinal glial (Müller) cells are changed after experimental detachment of the porcine retina. Osmotic stress, induced by application of a hypotonic bath solution to retinal slices, caused swelling of Müller cell bodies in 7-day-detached retinas, but no swelling was inducible in slices of control retinas. Müller cell somata in slices of retinal areas that surround local detachment in situ also showed osmotic swelling, albeit at a smaller amplitude. The amplitude of osmotic Müller cell swelling correlated with the decrease in the K+ conductance, suggesting a causal relationship between both gliotic alterations. Further factors implicated in Müller cell swelling were inflammatory mediators and oxidative stress. We propose that a dysregulation of the ion and water transport through Müller cells may impair the fluid absorption from the retinal tissue, resulting in chronic fluid accumulation after detachment. This knowledge may lead to a better understanding of the mechanisms involved in retinal degeneration after detachment.

Animals↗
PubMed1984

Injuries to car occupants--some aspects of the interior safety of cars. A study of a five-year material from an insurance company.

The purpose of this monograph is to describe trends in the interior safety of cars in terms of the frequency and severity of injuries among the car occupants, especially the drivers. Special references are made to the influence of the weight of the car, the starting year of production of the car, and some safety devices such as safety belts and head rest fittings. The material comprises all accident-involved private cars reported to an insurance company during a five-year period. The total number of such cars was 339,675 in which 8,592 drivers and 5,469 passengers were injured or killed. This represents approximately one-fourth of all accident-involved cars reported to insurance companies during a five-year period in Sweden. Data which are normally stored in the insurance files have been supplemented with data concerning car weight and starting year of production of the cars. In injury-producing accidents hospital records and doctors' certificates were available in the majority of cases, as well as reports from the police investigations. All data were computerised. An additive regression model was used to determine the influence of car weight, starting year of production of the car model, age of the car, safety belt usage and fitting of head rests, on the frequency of injuries. Data concerning car occupants with permanent medical disability and financial disability were specially investigated to gain information on what type of injuries lead to major problems in later years. A sample of car occupants with head injuries was investigated to study the frequency of problems remaining in later years. The main conclusions reached are that the weight of the striking car as well as of the struck car influences the injury frequency and severity of injuries among drivers. The knowledge of impact biomechanics accumulated since the middle of the sixties seems to have improved the interior safety of cars. The results of the regression analysis implied that some of the small new cars have the same safety level as large old ones. Safety-belt usage diminishes the severity of injuries and the risk of fatalities and it is proposed that the use of safety belts should also be compulsory in the rear seat.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdominal Injuries↗
PubMed1998

Role of the matrix in autosomal dominant polycystic kidney disease.

At present, even though we have accumulated a wealth of knowledge regarding structural, and molecular changes in ADPKD, the primary cause of the disease remains unknown. Obviously the gap in our understanding of the nature of the disease has been narrowed substantially over the past decade. With current techniques and efforts, the ultimate mystery of ADPKD should be resolved during the next decade.

Extracellular Matrix↗
PubMed1999

Identification of the archaeal NMN adenylytransferase gene.

Increasing evidence on the importance of fluctuations in NAD+ levels in the living cell is accumulating. Therefore a deeper knowledge on the regulation of coenzyme synthesis and recycling is required. In this context the study of NMN adenylyltransferase (EC 2.7.7.1),. a key enzyme in the NAD+ biosynthetic pathway, assumes a remarkable relevance. We have previously purified to homogeneity and characterized the protein from the thermophilic archaeon Sulfolobus solfataricus. The determination of partial sequence of the S. solfataricus enzyme, together with the recent availability of the genome sequence of the archaeon Methanococcus jannaschii, allowed us, based on sequence similarity, to identify the M. jannaschii NMN adenylyltransferase gene. As far as we know from literature, this is the first report on the NMN adenylyltransferase gene.

Amino Acid Sequence↗
PubMed1999

[Acquisition of evidence and facts for a consulting service in the department of clinical laboratory to support effective usage of laboratory tests].

We are developing an integrated laboratory information database to share the evidences and facts with clinicians for effective application of diagnostic laboratory tests for the care of individual patients. It includes high quality evidence acquired from the clinical trials and systematic reviews as well as basic information about the analytical method, related disorders and so on of each laboratory test. We should also have the skills to appropriately obtain information from articles about relevant subjects and obtain the original facts from the laboratory database combined with the database from the department of medical records to review diagnostic data of individual cases. These strategies to acquire and accumulate those kinds of knowledge and information are essential for the management of a consulting service room as part of the clinical laboratory department. We must contribute to the improvement of clinical diagnoses and treatments, and serve as professional consultants with the expertise.

Clinical Laboratory Information Systems↗
PubMed1993

[The medical philosophy of Choe Han-Ki].

Choe Han-Ki was a philosopher of the 19th century who resided in Seoul. He accumulated vast amount of knowledge of Western science and on the basis of them he built his own philosophical system different from those of the philosophers before him. Not only has he wrote books on philosophy, but many books on science as well. Among them Shin-Ki-Chon-Hum is a very unique medical book which reveals his original medical philosophy. He acquired medical knowledge through the medical books put into Chinese by missionary doctor Hobson and on the basis of them he criticized traditional medicine. He criticized traditional medicine because it explained vital phenomenon through the reductionist theory, such as Oh-Haeng (theory of five phases). And he also criticized it because it lacked in exact anatomical knowledge and that the exact origin of the disease was not known and it had limitations on treatment. He also criticized Western Medicine because it supposed God as a creator. He saw the possibility of communication between Western Medicine and traditional medicine. He didn't regard medicine as concerning disease and health only, but it included everything in it. His philosophy of medicine is just a part of his original system of science, Ki-Hak.

History, 19th Century↗
PubMed2005

A grand challenge for research: multimodal, multilevel and multiscale systems in medicine and biology.

Computational modelling, nano-bioscience and information technology in biology and medicine will play a major role in the interdisciplinary attempts to elucidate structures and functions of living systems. Developing tools capable to integrate the new advances and make benefit of them is crucial: accumulation of data and knowledge base with only storage and retrieval capabilities will have a poor impact if they are not made "active" or "operational". This is where models will play a central role in offering, not only sound ways for representation or simulation, but also the appropriate frames to put the players in the right place, with intra- and inter-level coupling and multisource handling. This paper advocated that sequential observations of multiple and complex mechanisms will be of limited interest to understand the inter-relations that are occurring at the same time, and therefore, that designing multimodal, multilevel and multiscale experiments, matched with these models, are of major importance.

Animals↗
PubMed1986

Replication and segregation of eukaryotic chromosomal DNA.

Transmission of the genetic information from the parental to the two daughter cells resulting from each cell division requires this genetic information to be duplicated prior to cell division. This ensures that each daughter cell will inherit an exact and complete copy of the information contained in the parental cell. The duplication of the genetic information, which is codified in deoxyribonucleic acid (DNA), is called "DNA replication". During the last 33 years, since the structure of DNA was discovered by Watson and Crick (1953), DNA replication has been investigated using genetical, cytological, and molecular techniques. The present review is an attempt to summarize most of the knowledge that has been accumulated throughout these years on eukaryotic DNA replication, with special emphasis on the methodologies that have been employed. Besides, some of the current "hot spots" in this subject, such as the controversy concerning whether or not there are specific DNA sequences which are recognized as replication origins, the existence of a close association between replication timing and gene expression, and the mechanisms operating at the time of nascent replicon maturation and segregation of sibling DNA molecules, are discussed with special deference.

Animals↗
PubMed1993

Sources of pollutants in indoor air.

In order to ensure an impeccable indoor air quality, it is important to do so, whenever possible, by means of source-control. In particular, this general principle should be applied with regard to contamination originating from building materials and furnishings. For such materials, quality requirements should be established to keep the concentration of emitted pollutants below admissible limits. In the case of building materials, a general declaration of all constituents should be mandatory and carcinogenic compounds like asbestos and benzene should be prohibited for use in indoor environments. If the emission of a specific pollutant cannot be avoided, its concentration in indoor air can be kept below the tolerated limit by increasing the ventilation. Increased concentrations of nitrogen dioxide due to the use of combustion appliances in kitchens and bathrooms can be avoided by exhausts. In geographical areas with high radon emission, however, corrective measures have to be evaluated individually. To eliminate the contaminants originating from human activities (e.g., carbon dioxide, body odours), adequate ventilation is required and depends on the occupancy and the use of the room; to maintain an acceptable air quality, the carbon dioxide concentration should not exceed 0.1-0.15%. Increased ventilation also reduces acute irritations if smoking is allowed. Here, the required air supply is dependent on the degree of annoyance which is considered to be acceptable to the user of the room. Acceptable indoor air quality can largely be maintained today because of the extensive knowledge and experience now accumulated in this field. However, the complex relationships between air quality and human health require further study. More research in the field of building materials is particularly desirable.

Activities of Daily Living↗