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 991 records · Page 55Linked to original sources
PubMed2002

Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA.

Synthetic macromolecules such as copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(HPMA) was prepared for labelling by introducing biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of biotin-pHPMA was visualised using a streptavidin-alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated polymer could be easily detected in tissues fixed in 10% paraformaldehyde-phosphate buffer at 4 degrees C for 48 h. While biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate carcinoma (Dunning R3327-AT1). How biotin as a label influences the biodistribution of poly(HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(HPMA) with biotin-pHPMA. The organ distribution patterns of the two polymers correlated well, except with respect to kidney. It is assumed that the accumulation of biotin-pHPMA in the distal tubuli is due to a biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules.

Acrylamides↗
PubMed1995

Mutant p53 protein overexpression is associated with poor outcome in patients with well or moderately differentiated ovarian carcinoma.

BACKGROUND: It has been shown that the p53 gene is mutated in 30-80% of ovarian carcinomas and that the genetic alterations most often manifest as an accumulation of mutant p53 protein in tumor tissue. The prognostic significance of these findings for patients with ovarian cancer, however, must be established clearly. METHODS: Mutant p53 protein in 90 consecutive epithelial ovarian carcinomas was quantitatively analyzed using a time-resolved immunofluorometric procedure. In contrast to immunohistochemical techniques, this method uses two anti-p53 antibodies. The Cox model was used to evaluate the strength of the associations between the prognostic markers and disease relapse or death at univariate and multivariate levels. Kaplan-Meier survival curves were calculated for patients who were p53-positive or negative and for subgroups with a different clinical stage, histologic grade, or residual postsurgical tumor. RESULTS: The positivity rates for p53 included 1/21 (5%) with Stage I disease, 1/6 (17%) with Stage II, 29/51 (57%) with Stage III, and 8/12 (67%) with Stage IV (total = 39/90, 43%). Patients with p53-negative tumors had a significantly longer disease free survival than did patients with p53-positive tumors (P = 0.03); these results were similar for overall survival (P = 0.06). Multivariate analysis revealed that the presence of postsurgical residual tumor was the only predictor significantly associated with poor patient outcome. However, when patients were divided into groups based on histologic grade, patients with well (G1) and moderately (G2) differentiated tumors had a significantly higher risk of cancer relapse and death if mutant p53 protein was present in their tumors compared with patients who were negative for mutant p53 protein (< 0.01). CONCLUSIONS: The immunofluorometric measurement of mutant p53 protein accumulation in epithelial ovarian carcinomas of a low histologic grade was associated significantly with an increased risk for cancer relapse and death. A similar trend also was suggested for early stage disease and in the absence of residual tumor after surgery. These increased risks, however, were not found for patients with high grade or advanced stage cancer or for those with residual tumor. To the authors' knowledge, this is the first report suggesting that p53 tumor protein accumulation is a marker of poor prognosis in a subset of patients with ovarian cancer.

Adult↗
PubMed2006

Genome wide prediction of protein function via a generic knowledge discovery approach based on evidence integration.

BACKGROUND: The automation of many common molecular biology techniques has resulted in the accumulation of vast quantities of experimental data. One of the major challenges now facing researchers is how to process this data to yield useful information about a biological system (e.g. knowledge of genes and their products, and the biological roles of proteins, their molecular functions, localizations and interaction networks). We present a technique called Global Mapping of Unknown Proteins (GMUP) which uses the Gene Ontology Index to relate diverse sources of experimental data by creation of an abstraction layer of evidence data. This abstraction layer is used as input to a neural network which, once trained, can be used to predict function from the evidence data of unannotated proteins. The method allows us to include almost any experimental data set related to protein function, which incorporates the Gene Ontology, to our evidence data in order to seek relationships between the different sets. RESULTS: We have demonstrated the capabilities of this method in two ways. We first collected various experimental datasets associated with yeast (Saccharomyces cerevisiae) and applied the technique to a set of previously annotated open reading frames (ORFs). These ORFs were divided into training and test sets and were used to examine the accuracy of the predictions made by our method. Then we applied GMUP to previously un-annotated ORFs and made 1980, 836 and 1969 predictions corresponding to the GO Biological Process, Molecular Function and Cellular Component sub-categories respectively. We found that GMUP was particularly successful at predicting ORFs with functions associated with the ribonucleoprotein complex, protein metabolism and transportation. CONCLUSION: This study presents a global and generic gene knowledge discovery approach based on evidence integration of various genome-scale data. It can be used to provide insight as to how certain biological processes are implemented by interaction and coordination of proteins, which may serve as a guide for future analysis. New data can be readily incorporated as it becomes available to provide more reliable predictions or further insights into processes and interactions.

Algorithms↗
PubMed1993

Analytical and biological data of banked samples--a requirement to interpret accumulation and leaching of pollutants in biological specimens.

The accumulation of organic and inorganic pollutants in biological specimens depends, in many cases, not only on the atmospheric deposition or immission and contamination of the biotop, but also on the dynamic properties of the indicator. Thus the analytical data assume properties of process variables. In order to compare them in relation to space and time, it is often practical to refer them to defined conditions of the indicator (stationary phases, time cycles of low dynamics). If the accumulation varies consistently under identical conditions of contamination and if clear functional relations exist to the features of the indicator, for instance age, weight or ecological processes, it is necessary to normalize the analytical data, i.e. to refer them to a condition of the indicator which is defined meaningfully with regard to the ecology. Interactions with other inputs of substances may result in a differentiation of accumulation and leaching processes which is more or less specific for each element. Such knowledge is important for specifying the standard operation procedures and the evaluation as well as interpretation of analytic data, in particular, in the clarification of the ecotoxicological relations between the pollutant accumulation and the reaction of populations and ecosystems.

Animals↗
PubMed2002

Iodine-123-metaiodobenzylguanidine scintigraphy of total cardiac adrenergic denervation in Brugada syndrome.

A 22-year-old Japanese man with Brugada syndrome was resuscitated from cardiopulmonary arrest. In addition to the electrocardiographic evidence of the syndrome and the absence of apparent structural heart disease, no accumulation of iodine-123-metaiodobenzylguanidine (MIBG) was found anywhere throughout the heart. Thallium-201 (Tl) single photon emission computed tomography (SPECT) distribution showed no significant decrease in its uptake. To our knowledge, this is the first report that has demonstrated a homogeneous absence of cardiac accumulation of MIBG in Brugada syndrome.

3-Iodobenzylguanidine↗
PubMed2000

Noninfectious gas accumulation in an infarcted spleen.

BACKGROUND: Intentional selective occlusion of the arterial blood supply to tumors of abdominal organs is a well established therapeutic procedure. Several reports described gas accumulation at the infarcted sites. These gas collections are usually nonsuppurative; however, the differential diagnosis should include abscess formation. CASE REPORT: We present a 59-year-old patient in whom the splenic artery was accidentally ligated during gastrectomy surgery, with resultant splenic infarction. Gas accumulation was diagnosed by sonography and CT studies. To the best of our knowledge this is the first report ever published in the English medical literature describing nonsuppurative gas formation within an abdominal organ, caused by accidental ligation of its main arterial supply during surgery. SUMMARY: Possible theories regarding this noninfectious gas accumulation are discussed and the differential diagnosis between abscess formation and noninfectious gas accumulation is emphasized. Establishing the correct diagnosis is of big clinical importance as the treatment of choice is completely different in each one of these entities although the imaging features, in ultrasound as well as in CT, are somewhat similar.

Diagnosis, Differential↗
PubMed1993

Pathology of nonhuman spongiform encephalopathies: variations and their implications for pathogenesis.

Microscopic cavitation of the central nervous system (CNS) is a variable, non-specific feature of several different diseases of animals. In none, however, has it received more discussion than in scrapie, a naturally occurring disease of sheep, the clinical signs of which have been known for at least two centuries; yet consensus on the essential neurodegenerative pathology of scrapie emerged only three decades ago. The subsequent recognition of such changes in other species, including man, was a crucial factor in establishing the unifying concept of the transmissible spongiform encephalopathies (TSE). Recently these disorders have been recorded in several additional species, most significantly in domestic cattle as a foodborne epidemic. Although the TSE of animals present as infections, their pathology is confined to the CNS and has more in common with neuronal system degenerations with selective, usually symmetrical and progressive lesions, unaccompanied by inflammation. In a given host species the distribution of lesions may show variation, as in sheep scrapie or uniformity, as in bovine spongiform encephalopathy. Vacuolar or spongiform change is the most useful feature in routine diagnosis, in spite of variability in its prominence. The molecular pathology of the TSE is characterised by an abnormal isoform of a host-encoded membrane protein, the prion protein (PrP), accumulation of which is specially related to vacuolar change. There remain considerable deficits in our knowledge of the pathogenesis of the naturally occurring animal TSE, not least the extraneural events leading to CNS involvement and the relative roles of vacuolar change and PrP accumulation.

Acinonyx↗
PubMed2004

Down syndrome and beta-amyloid deposition.

PURPOSE OF REVIEW: Exciting new therapeutic approaches to the treatment or prevention of Alzheimer's disease involve preventing, slowing or reversing beta-amyloid accumulation. These interventions may also apply to the treatment of Alzheimer's disease in Down syndrome. The purpose of the current review is therefore to summarize developments and advances in our understanding of beta-amyloid pathogenesis in Down syndrome over the past year. RECENT FINDINGS: A shift in research to a focus on early events in beta-amyloid pathogenesis in Down syndrome has led to several novel observations. Several authors have reported the accumulation of both soluble and intracellular beta-amyloid before extracellular beta-amyloid (senile plaques) in Down syndrome. Increases in beta-amyloid levels in Down syndrome may reflect the increased expression and protein levels of beta-site amyloid precursor protein cleavage enzyme 2 on chromosome 21. The impact of the accumulation of beta-amyloid may have differential effects on development and aging in Down syndrome. SUMMARY: The past year has seen significant advances in our understanding of beta-amyloid pathogenesis and the functional consequences of beta-amyloid accumulation in Down syndrome. However, there are still large gaps in our knowledge of the pathways involved in beta-amyloid degradation and clearance. It will be critical to conduct clinical trials to test therapeutic strategies that may reduce beta-amyloid in Down syndrome directly to determine the optimal age and dose for specific interventions. Given the differences in the mechanism of beta-amyloid accumulation in Down syndrome, careful consideration needs to be given to potential clinical trials to treat this disorder.

Adult↗
PubMed2005

Cystinosis as a cause of noncirrhotic portal hypertension.

Cystinosis is a rare autosomal recessive storage disorder, characterized by the abnormal accumulation of cystine in cellular lysosomes. This accumulation, which can occur in any organ system, leads to crystallization of trapped cystine and ultimately cellular death. Hepatic manifestations of Cystinosis although rare, have been described in the literature. However, to our knowledge, only one other case of non-cirrhotic portal hypertension secondary to cystine accumulation in Kupffer cells has been reported. In this case and ours, portal hypertension was found in the absence of bridging fibrosis. Furthermore, in our case, for the majority of the patient's course, hepatic synthetic function remained normal. Cysteamine is therapeutic in this disorder, and can lead to significant removal of cystine, and thus to reversibility of disease, however, it requires high doses and must be taken regularly. Porto-systemic shunting in combination with aggressive medical therapy could potentially benefit patients who develop non-cirrhotic portal hypertension in this clinical setting.

Adult↗
PubMed1995

Optimal timing of granulocyte colony-stimulating factor (G-CSF) administration after bone marrow transplantation. A prospective randomized study.

The positive role of G-CSF in hastening the myeloid recovery of patients undergoing allogeneic bone marrow transplantation (ALLO-BMT) or autologous bone marrow transplantation (ABMT) has recently been established. Considerable knowledge about adequate doses and route of administration has been accumulated in the past few years. Nonetheless, the optimal time to start growth-factor administration remains undetermined. We have performed a stratified study according to the source of hematopoietic progenitors (ALLO-BMT or ABMT), underlying disease and its stage, and acute graft-versus-host disease (GVHD) prophylaxis regimen and randomized patients in two arms: group A, which started G-CSF on day 0 (36 patients), and group B, which started on day +7 post-BMT (39 patients). The same dose (5 micrograms/kg/day) and route of administration were employed in both groups. We found no significant differences in the time to reach an absolute neutrophil count (ANC) of 0.1, 0.5, and 1 x 10(9)/l and 50 x 10(9) platelets/l (medians: 10 and 11, 14.5 and 14, 17 and 16, 23 and 24 days, respectively, in groups A and B). We did not find differences in the days of fever or days on antibiotic treatment with less than 1 x 10(9)/l ANC, rate of bacteriemia, or days of hospitalization in both groups. In contrast, a considerable saving of G-CSF in B group was found (mean days of infusion in group A, 18, versus 11 in group B) (p < 0.0001). This is equivalent to a saving of 1120 $US per patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Experimental head trauma models: a clinical perspective.

The investigation of the biomechanics, biochemistry and functional changes occurring with significant head trauma is a very active and interesting area of scientific research by investigators of many disciplines. Using a variety of head trauma model systems, a tremendous amount of basic knowledge on what occurs to the injured brain has been accumulated over the last two to three decades. Ongoing research on the basic pathophysiology of head trauma as well as on the investigation of potentially useful therapeutic modalities is a current research trend. While a cross-disciplinary approach is necessary and useful in this rapidly expanding area of investigation, much of what is reported is technically difficult to understand and the clinical implications of the stated findings may not be clearly obvious. Some model systems are more suitable to study particular traumatic lesions that are others, and some systems have built-in limitations which must be acknowledged in data interpretation. This articles describes and evaluates some of the currently used head trauma model systems and reviews these systems from a clinician's standpoint.

Animals↗
PubMed2004

Concentrations of trace elements in muscle of sturgeons in the Caspian Sea.

Concentrations of 21 trace elements were determined in muscle of beluga (Huso huso), Persian sturgeon (Acipenser persicus), Russian sturgeon (Acipenser gueldenstaedtii), ship sturgeon (Acipenser nudiventris) and stellate sturgeon (Acipenser stellatus) collected from coastal regions of Azerbaijan, Iran, Kazakhstan and Turkmenistan, surrounding the Caspian Sea during 2000-2001. Concentrations of Mn, Co, Cu, Mo, Sn, Hg, Pb and Bi in the muscle were apparently different among the five species of sturgeons. Especially, beluga showed the highest concentrations of Hg, Pb and Mn in all the five species. In addition, more than half of the individuals of beluga exceeded the guideline level (0.3 microg/g wet wt.) of Hg for food in UK. However, V, Cr, Zn, Ga, Rb, Sr and Ba concentrations were similar among five sturgeons. Growth-dependent increase in Hg in beluga, Cu in Persian sturgeon, and Zn in Russian sturgeon were observed, whereas V, Mn, Co, Cu, Ga, Sr, Mo, Sn, Hg and Bi concentrations in Persian sturgeon, Pb in ship sturgeon, and Cr, Mn, and Rb in stellate sturgeon were negatively correlated with body length. All species of sturgeon in Azerbaijan showed the highest concentration of Sr and the lowest concentration of Rb, while the five sturgeons from Iran showed opposite trends. Concentration of V, which is present in oil, in sturgeons in the Caspian Sea was considerably lower than that of fish from Kuwait, but was comparable to that of Cambodia and the Gulf and Gulf of Oman. To our knowledge, this study provides the first extensive data on multielemental accumulation in sturgeons of the Caspian Sea.

Animals↗
PubMed2001

Uncertainty, variability and sensitivity analysis applied to the RAGENA model of radon generation, entry and accumulation indoors.

The application of a radon model is useful to understand the processes that drive the radon gas behaviour from its sources to its accumulation indoors. Since in a given inhabited house the detailed knowledge of the values of all the parameters that affect indoor radon levels is not available, the response of the model has to be explored in a reference site in which all the parameters are supposed to be known. We call this site the reference configuration. In this paper we report on the procedure followed to carry out uncertainty, sensitivity and variability analysis of the model response for a reference configuration that corresponds to a single family multi-zone house. We have obtained from the uncertainty analysis that, assuming a normal distribution of all the input parameters with a 10% relative standard deviation (R.S.D.), the model outputs present a R.S.D. in the range 17-22%. The sensitivity analysis reflects, in general, a good behaviour of the model, in the sense that its response describes a realistic behaviour of the system. The variability analysis has shown that the model is applicable to a wide range of situations, and that the most relevant parameters for the reference configuration are: the soil gas-permeability (obtained from the mean soil grain diameter); the ventilation rate of the rooms; the air-exchange rate between the basement and room 2; the soil-indoor pressure difference; the open area; and the concrete radium content.

Journal Article↗
PubMed2002

Endocytosis is involved in DNA uptake in yeast.

The transfection of mammalian cells by endocytosis is frequently hampered by low efficiency. To identify the bottlenecks, a system that allows the analysis of the intracellular pathway of DNA along the endocytic compartments in the eukaryote Saccharomyces cerevisiae was developed. DNA uptake in yeast cells was achieved by endocytosis when the cells were incubated with episomal DNA in the presence of 34% sucrose and subsequently shifted to a hypotonic medium to induce osmotical lysis of accumulated endocytic intermediates. The compartments of the endocytic pathway after the intersection of the endocytic and the vacuolar sorting pathway are preferred sites of DNA degradation. Either a transport blockade before this point or, even better, the presence of chloroquine, which is known as an adjuvant for transfection in mammalian cells, are required for successful transfection. The transport blockade can be achieved by deleting a GTPase of the endocytic pathway, Ypt51p, or ethanol. Chloroquine affects the compartments of the late endocytic pathway, and no effect is seen on transfection in a strain that is defective for YPT51 and accumulates the DNA in the early endocytic intermediates. To our knowledge, this is the first report on endocytic DNA uptake in S. cerevisiae.

Chloroquine↗
PubMed2001

Recent advances in methane fermentation technology.

In the past two decades, a number of biotechnologies for anaerobic (methanogenic) wastewater treatment have been created, and practical applications of these processes are now being extended to more recalcitrant wastewaters and to wastewaters at extreme temperatures. Our knowledge of methanogenic organic degradation associated with bioreactors is also accumulating at a rapid rate. The recent advancement of such fundamental understanding is attributed to modern molecular biology techniques applied to the study of microbial communities and to continuous challenges to the cultivation of many important but recalcitrant anaerobes in bioreactors.

Anaerobiosis↗
PubMed2002

Professional development in undergraduate medical curricula--the key to the door of a new culture?

CONTEXT: One of the most pressing requirements for contemporary medical education is to develop a framework for theory and practice of professional development which results in the attainment of professional competencies suitably robust for a lifetime's practice. The proposed content of a professional development curriculum may be reasonably straightforward to establish from policy documents and public expectations, but the process of achieving the desired outcomes is more complex, because professional development is largely based on attitudinal learning. Attitudes are at the interface between the personal and public psyche, relying more on individual experience and the accumulated impact of social and cultural interpretations than on propositional knowledge, and are therefore less amenable to factual or didactic teaching. AIMS: The purpose of this discussion paper is to develop thinking on the conceptual frameworks which need to underpin curriculum decision-making for professional development, especially in undergraduate medical training where models of good practice are less well-established. It brings together work from educational, sociological and psychological perspectives to elucidate the key principles which are most likely to result in acquisition of desirable professional attributes. IMPLICATIONS: The literature suggests that successful professional development needs to be based on explicit values, which are repeatedly demonstrated in the learning environment, and modelled by senior colleagues and tutors; that the curriculum should incorporate a clear model of emotional as well as cognitive development; should be a major component of summative assessment; and needs to include formative mentorship at all stages of training.

Curriculum↗
PubMed2003

History of tobacco and health.

Tobacco comes from plants that are native to the Americas around Peru and Ecuador,where it has been found since prehistoric times. It was brought back to Europe by early explorers where it was adopted by society and re-exported to the rest of the world as European colonization took place. Smoking tobacco in pipes of one sort or other gave way to handmade and then manufactured cigarettes, especially during the First World War. Smoking rates increased dramatically during the 20th century in developed countries until recently and rates are still increasing in underdeveloped countries. An epidemic of smoking-related diseases has followed the prevalence of smoking. Scientific knowledge of the harmful effects of active tobacco smoking has accumulated during the past 60 years since early descriptions of the increasing prevalence of lung cancer. The first epidemiological studies showing an association between smoking and lung cancer were published in 1950. In 1990 the US Surgeon General concluded that smoking was the most extensively documented cause of disease ever investigated but governments worldwide have been ambivalent and slow in taking action to reduce smoking. Tobacco smoking is now agreed to be a major cause of a vast number of diseases and other adverse effects. Since the 1980s passive smoking including exposure in utero has also been implicated as a significant cause of numerous diseases. In response, the tobacco industry has managed to forestall and prevent efforts to control this major health problem.

History, 15th Century↗
PubMed1999

Compensatory renal growth in uninephrectomized adult mice is growth hormone dependent.

UNLABELLED: Compensatory renal growth in uninephrectomized adult mice is growth hormone dependent. BACKGROUND: Growth hormone (GH) and insulin-like growth factors (IGFs) have been implicated as pathogenic factors in compensatory renal growth (CRG) following unilateral nephrectomy in rodents. CRG in adult rats has been suggested to be GH dependent and GH independent in immature rats. However, the exact role of GH as a regulating or permissive factor in CRG in adult rodents has not been fully resolved to date. METHODS: To elucidate a possible direct, permissive role of GH in CRG, we examined the effect of a newly developed specific GH receptor (GHR) antagonist (G120K-PEG) on kidney IGF-I accumulation and renal/glomerular hypertrophy over seven days after uninephrectomy in adult mice. RESULTS: Placebo-treated uninephrectomized mice were characterized by a transient increase in kidney IGF-I concentration preceding CRG and an increase in glomerular volume. In G120K-PEG-treated uninephrectomized animals, increased kidney IGF-I levels, kidney weight, and glomerular volume were fully abolished. No differences were seen between the two uninephrectomized groups with respect to body weight, food intake, blood glucose, serum GH, IGF-I, or IGFBP-3 levels. CONCLUSIONS: The administration of a GHR antagonist in uninephrectomized adult mice has renal effects without affecting circulating levels of GH/IGFs, indicating that the effect of G120K-PEG may be mediated through a direct inhibitory effect on renal IGF-I accumulation through the renal GHR. This study shows, to our knowledge for the first time, that CRG in adult mice is strictly GH dependent.

Age Factors↗