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 1,189 records · Page 66Linked to original sources
PubMed1998

The metabolism of phytanic acid and pristanic acid in man: a review.

The branched-chain fatty acid phytanic acid is a constituent of the diet, present in diary products, meat and fish. Degradation of this fatty acid in the human body is preceded by activation to phytanoyl-CoA and starts with one cycle of alpha-oxidation. Intermediates in this pathway are 2-hydroxy-phytanoyl-CoA and pristanal; the product is pristanic acid. After activation, pristanic acid is degraded by peroxisomal beta-oxidation. Several disorders have been described in which phytanic acid accumulates, in some cases in combination with pristanic acid. In classical Refsum disease, the enzyme that converts phytanoyl-CoA into 2-hydroxyphytanoyl-CoA--phytanoyl-CoA hydroxylase--is deficient, resulting in highly elevated levels of phytanic acid in blood and tissues. Also in rhizomelic chondrodysplasia punctata, phytanic acid accumulates, owing to a deficiency in the peroxisomal import of proteins with a peroxisomal targeting sequence type 2. In patients affected with generalized peroxisomal disorders, degradation of both phytanic acid and pristanic acid is impaired owing to absence of functional peroxisomes. In bifunctional protein deficiency, the disturbed oxidation of pristanic acid results in elevated levels of this fatty acid and a secondary elevation of phytanic acid. In addition, several variant peroxisomal disorders with unknown aetiology have been described in which phytanic acid and/or pristanic acid accumulate. This review describes the discovery of phytanic acid and pristanic acid and the initial attempts to elucidate the origins and fates of these fatty acids. The current knowledge on the alpha-oxidation and beta-oxidation of these branched-chain fatty acids is summarized. The disorders in which phytanic acid and/or pristanic acid accumulate are described and some remarks are made on the pathogenic mechanisms of elevated levels of phytanic acid and pristanic acid.

Animals↗
PubMed2004

High-density lipoprotein as a key component in the prevention of premature atherosclerotic disease in the insulin resistance syndrome.

The occurrence of insulin resistance syndrome (IRS), which is also called the metabolic syndrome, has rapidly increased over the last decade. IRS involves such major clinical features as premature atherosclerosis and its related complications. The major proatherogenic phenotype includes elevated plasma levels of apolipoprotein B-containing lipid particles. Another lipid particle of high-density lipoprotein (HDL) plays a key role in the prevention of atherosclerotic disease. Decreased levels of HDL cholesterol are found in IRS; however, little is known about metabolic pathways related to HDL antiatherogenic properties in this pathological condition. Hitherto, in other dyslipidemic populations, the antiatherogenic properties of HDL have been most frequently characterized in vitro. Recently, knowledge about antiatherogenic pathways in which HDL particles are involved in vivo has been accumulating. Consistent with these developments, new therapeutic strategies can be envisaged for IRS, including treatment with recombinant HDL particles and inhibitors of cholesteryl ester transfer protein.

Apolipoproteins B↗
PubMed1996

Cytophilic immunoglobulins revisited via natural killer cells.

Cytophilia is one of the biologic properties of the Fc region of immunoglobulins operationally defined as the ability of an antibody molecule to attach to certain cell types before combination with antigen. By attachment of cytophilic antibody to membrane Fc receptors, cells become "armed" with antibodies and able to interact specifically with soluble or particulate antigens. In contrast to this cytophilia, the so-called opsonic antibody binds to FcR of various cell types only after it has complexed with antigen. In spite of knowledge of cytophilic properties of immunoglobulins for more than 30 years and an impressive accumulation of facts regarding the structure and function of cell-surface FcR binding IgG, IgE, or IgA molecules, less progress has been made in understanding the molecular basis of cytophilia. Our extensive studies of the structural and functional aspects of the interaction of IgG in monomeric form with human natural killer cells, via the type IIIA IgG Fc receptor (Fc gamma RIIIA), provide a focal point for revisiting this major pathway of direct and continuous communication between the humoral and cellular compartments of the immune system.

Animals↗
PubMed1998

Fruit development in trillium. Dependence On stem carbohydrate reserves

Leaves are the main source of carbon for fruit maturation in most species. However, in plants seeing contrasting light conditions such as some spring plants, carbon fixed during the spring could be used to support fruit development in the summer, when photosynthetic rates are low. We monitored carbohydrate content in the rhizome (a perennating organ) and the aboveground stem of trillium (Trillium erectum) over the entire growing season (May-November). At the beginning of the fruiting stage, stems carrying a developing fruit were harvested, their leaves were removed, and the leafless stems were maintained in aqueous solution under controlled conditions up to full fruit maturation. These experiments showed that stem carbohydrate content was sufficient to support fruit development in the absence of leaves and rhizome. This is the first reported case, to our knowledge, of complete fruit development sustained only by a temporary carbohydrate reservoir. This carbohydrate accumulation in the stem during the spring enables the plant to make better use of the high irradiances occurring at that time. Many other species might establish short-term carbohydrate reservoirs in response to seasonal changes in growing conditions.

Journal Article↗
PubMed1998

Platelet proteins as autoantibody targets in idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP), caused by autoantibodies directed against certain platelet antigens, is the most common entity of the immune thrombocytopenias. ITP is an acquired disorder and can affect both children and adults. However, the clinical syndromes of ITP are distinct between children and adults. Childhood (acute) ITP characteristically is acute in onset, occurs within 1-2 weeks of an infection, usually of viral origin, resolves spontaneously within 6 months. Adult (chronic) ITP has an insidious onset and rarely resolves spontaneously. Over the last decade considerable new information has accumulated as to the pathophysiological mechanisms of immune thrombocytopenias. In addition, most of the knowledge on this disorder has been obtained from studies of adult patients with chronic ITP. The present work gives an updated overview of the platelet autoantigens and the molecular immunological reactions in ITP.

Acute Disease↗
PubMed2000

Nondisjunction in trisomy 21: origin and mechanisms.

Chromosomal aneuploidy is a fundamental characteristic of the human species. In this review we summarize the knowledge about the origin and mechanisms of nondisjunction in human trisomy 21 that has accumulated during the last decade by using DNA polymorphism analysis. The first molecular correlate of nondisjunction in humans is altered recombination, meiosis I errors being associated with reduced recombination and maternal meiosis II errors with increased recombination between the nondisjoined chromosomes. Thus, virtually all maternal meiotic errors of chromosome 21 seem to be initiated in meiosis I. Advanced maternal age remains the only well documented risk factor for maternal meiotic nondisjunction, but there is, however, still a surprising lack of understanding of the basic mechanisms behind the maternal age effect.

Down Syndrome↗
PubMed1986

The implications and limitations of genetic models of alcoholism and other addictions.

The kind of clear-cut model of the genetic sources of alcoholism perceived by the public and presented in popular tracts does not accurately reflect the state of knowledge in this area. No persuasive genetic mechanism has been proposed to account for accumulated data about alcoholic behavior, social differences in alcoholism rates or the unfolding of the disease. Biological findings about the offspring of alcoholics have been inconsistent and grounds exist to challenge the notion of an enhanced genetic liability for alcoholism that has been accepted wisdom for the last decade. Genuine attempts to forge data and theory into genetic models have been limited to men alcoholics and to a minority of severely afflicted alcoholics with other special characteristics. However, several investigators dispute the idea of a special type of inherited alcoholism affecting only such groups. Even for these populations, balanced genetic models leave room for the substantial impact of environmental, social and individual factors (including personal values and intentions) so that drinking to excess can only be predicted within a complex, multivariate framework. The denial of this complexity in some quarters obscures what has been discovered through genetically oriented research and has dangerous consequences for prevention and treatment policies.

Alcohol Drinking↗
PubMed2006

Periodontal status in patients with gingival mucous membrane pemphigoid.

BACKGROUND: Mucous membrane pemphigoid (MMP) describes an autoimmune disease with a range of variants, including those with oral, ocular, and cutaneous lesions. Persistent oral lesions, lack of effective oral hygiene, and plaque accumulation may increase the risk of long-term periodontal disease. However, to our knowledge, no studies have evaluated the relationship between the presence of gingival MMP and periodontal health. The purpose of this study was to evaluate the possible impact of gingival pemphigoid lesions on the human periodontium. METHODS: Twenty patients with histologic confirmation of subepithelial separation with or without direct immunofluorescence testing were randomly chosen to participate in a study evaluating their periodontal status. Parameters evaluated included plaque score, gingival index, bleeding index, probing depths, recession, clinical attachment level, mobility, furcation involvement, number of missing teeth, and Machtei criteria, a previously defined criteria for periodontitis. Individuals matched with respect to age, gender, and smoking history were selected and evaluated for the same parameters. RESULTS: MMP patients had statistically significant larger mean gingival index scores than age, gender, and smoking history matched controls. Plaque scores, bleeding index, mobility, furcations, clinical attachment level, recession, and periodontal status did not show statistically significant differences between MMP and control patients. A statistically significant difference in plaque index was found when patients with MMP in treatment were compared to patients with MMP in remission. Among patients with MMP, those diagnosed >5 years in the past had statistically significantly greater Class I furcation involvement and recession on facial and lingual surfaces of teeth. CONCLUSIONS: A relationship was found to suggest that patients with MMP exhibit more gingival inflammation than a control population. Among patients with MMP, patients currently in treatment have higher plaque indices than those in remission and not receiving treatment. Furthermore, when comparing patients with MMP who received a diagnosis>5 years in the past to those with a diagnosis in the past 5 years, statistically significantly greater Class I furcation and facial and lingual recession were measured. Long-term follow-up in this population may provide additional information as to periodontal progression in MMP versus control patients.

Adult↗
PubMed2006

Cytokines and hormones in the regulation of hypoxia inducible factor-1alpha (HIF-1alpha).

Hypoxia inducible factor-1 (HIF-1) is a central component of the oxygen sensing system that coordinates cellular responses to conditions of decreased oxygen availability. The hypoxia inducible transcription factor HIF-1 is a heterodimer composed of the helix-loop-helix-Per-Arnt-Sim (bHLH-PAS) proteins HIF-1alpha and the aryl hydrocarbon nuclear translocator (ARNT) also known as HIF-1beta. Transactivation of HIF-1 transmits a hypoxic signal into patho-physiological responses such as angiogenesis, erythropoiesis, vasomotor control, an altered energy metabolism, as well as cell survival decisions by regulating a staidly growing number of target genes. Among recent advances are the discoveries that cytokines and growth factors make use of the 'hypoxic signaling system' under normoxia. Here we summarize current knowledge and existing concepts that help to understand how cytokines and hormones affect protein accumulation of HIF-1alpha and discuss potential implications of activating HIF-1 under normoxia. Considering the fundamental role of cytokines during inflammation may predict a role of HIF-1alpha in coordinating cellular responses to pathogens and point to the connection of cancer and inflammation. Moreover, we will address potential feed-back mechanisms showing an impact of HIF-1 on cytokine production. These considerations suggest an intimate signaling cross-talk between cytokines and the HIF-1 system.

Cytokines↗
PubMed1984

Endocrine regulation of fetal and postnatal meat animal growth.

Evidence is discussed which indicates that nutrient partitioning between muscle and adipose tissue can be altered by growth hormone administration in meat animals. In the limited number of studies conducted with meat animals, growth rate, feed efficiency and carcass composition were improved by growth hormone administration. When insulin was administered to normally growing swine no improvement in growth performance was observed. The mechanisms by which growth hormone affects growth performance are not clear but considerable data from rodent studies exist to indicate that many of the growth promoting effects of this hormone are due to somatomedins. However, few data are available for meat animals to indicate whether the growth promoting effects of growth hormone are mediated by somatomedins. Knowledge about the mechanisms that regulate growth hormone synthesis, secretion and biological action is accumulating. It is apparent that growth hormone administration induces an insulin-resistant state in rodents and meat animals. It is not clear whether chronic growth hormone administration in meat animals induces a growth hormone resistant state. Based on the available information, manipulation of systemic hormone concentrations and(or) tissue sensitivity to hormones involved in growth and differentiation may result in means to manipulate fetal and postnatal growth and development.

Adipose Tissue↗
PubMed2001

Cytokine and chemokine blockade as immunointervention strategy for the treatment of diffuse lung diseases.

Cytokines and chemokines are essential components for the pathophysiology of sarcoidosis. In the last decade, evidence has accumulated indicating that most of the events that lead to the alveolitis, granuloma formation and tissue injury are regulated by these mediators and their receptors. Recently, information on the possible pathogenetic role of cytokines has been translated into the development of potent cytokine antagonists which have proved to be powerful means of controlling disease activity in some inflammatory diseases. Molecules capable of neutralizing tumor necrosis factor-alpha (TNF-alpha) are currently used in the clinical setting of rheumatoid arthritis and active Crohn's disease. TNF-alpha is one of most important cytokines in the pathogenesis of sarcoidosis: not unexpectedly, data suggest the real possibility of using anti-TNF strategies to treat refractory sarcoidosis. These data are preliminary and should promote further clinical trials to confirm both the efficacy and tolerability of anti-TNF agents when used in patients with sarcoidosis and other interstitial lung diseases which are characterized by an up-regulation of TNF-alpha expression in the pulmonary milieu. Blockades of other inflammatory cytokines are also expected to be therapeutic in sarcoidosis and other T-cell mediated diffuse lung diseases. In particular, therapies directed at neutralizing chemokines and other molecules which control trafficking and accumulation of immunocompetent cells are potentially more selective and attractive but require a priori knowledge of precise pathways regulating the inflammation state involving the alveolar and interstitial structures.

Antibodies, Monoclonal↗
PubMedDate not supplied

Primary signet-ring cell carcinoma of the lung with histochemical characterization.

Signet-ring cell carcinoma (SRCC) is a unique sub-type of mucin-producing adenocarcinoma characterized by abundant intracellular mucin accumulation. Although SRCC has been found in various organs, to the best of our knowledge there have only been a few reports of primary SRCC of the lung. Furthermore, most of the reports describe the coexistence of SRCC with differentiated components, while only one case has been reported as pure SRCC. We report here on a patient with primary SRCC of the lung with histochemical characterization. In our case, the tumor cells were mostly composed of signet-ring cells. Although the patient achieved only a minor response after systemic chemotherapy, he has been doing well, without any further treatment, for 33 months after diagnosis.

Carcinoma, Signet Ring Cell↗
PubMed2005

MR imaging of cerebral cortical involvement in aceruloplasminemia.

Aceruloplasminemia is a rare autosomal recessive disorder. The lack of ceruloplasmin ferroxidase activity leads to parenchymal and reticuloendothelial iron overload, resulting in diabetes and progressive neurodegeneration with extrapyramidal disorders, ataxia, and dementia. We describe the MR imaging findings in a 40-year-old woman with hereditary aceruloplasminemia. The abnormal T2 hypointensities were more marked than those seen in any other condition, including degenerative disorders of the basal ganglia and Wilson disease, and they may be typical of aceruloplasminemia. To our knowledge, involvement of the cortex has not been described and suggests that brain iron accumulation in aceruloplasminemia is more extensive than previously believed, even in asymptomatic patients.

Adult↗
PubMed2005

Neurotrophin system activation in bronchoalveolar lavage fluid immune cells in pulmonary sarcoidosis.

BACKGROUND AND AIM OF THE STUDY: Pulmonary sarcoidosis is a chronic granulomatous disease characterized by macrophage and CD4+ T-cell accumulation at the site of inflammation. Analysis of the cytokine network has substantially improved knowledge on immunopathogenesis of sarcoidosis. We hypothesize that neurotrophins (NTs), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and NT-3, besides their importance in immune system activities, participate in chronic inflammatory disorders and in repair processes. METHODS: The expression of NTs and NT receptors was assessed in broncho alveolar lavage (BAL) macrophages, CD4 and CD8 T-cells, from 10 patients with pulmonary sarcoidosis, using molecular biology, Western blotting and immunocytochemistry. RESULTS: Increased levels of NTs and of high affinity NT receptor (Trks) transcripts and proteins in BAL macrophages, CD4+ and CD8+ T-cells from pulmonary sarcoidosis patients were demonstrated in comparison with healthy controls. Contrarily to healthy controls, in pulmonary sarcoidosis the expression of NGF was increased in alveolar macrophages as well as NGF and BDNF in CD4+ and CD8+ T-cells. An increased expression of TrkA, TrkB and TrkC receptors was also noticeable. Furthermore, BDNF expression in alveolar macrophages and NT-3 expression in the three different BAL immune cell populations investigated were induced during sarcoidosis. A significant correlation was observed between CD4:CD8 ratio, lymphocytosis, radiological stage and CD4 and CD8 NT expression. CONCLUSIONS: These findings suggest that NTs are exaggeratedly expressed in BAL immune cells in pulmonary sarcoidosis and may participate in the progression of disease modulating immune cell functions.

Adult↗
PubMed2006

The carotid atherosclerotic plaque and microembolisation during carotid stenting.

Microembolisation is an important issue in carotid artery stenting. During different phases in the stenting process, numerous emboli are dislodged from the atherosclerotic plaque. Embolisation can be measured as microembolic signals detected by transcranial Doppler (TCD) monitoring during the procedure or as new ischemic areas determined by magnetic resonance imaging. This article gives an overview of the principles of emboli detection methods, their clinical relevance, and risk factors associated with microembolisation. In addition, protection devices are discussed in relation to embolisation. Although they potentially protect the brain, particularly filter devices increase the amount of TCD-detected cerebral microemboli. Special attention is paid to the carotid artery plaque, which is subject to ongoing research that may yield important implications for clinical practice in the near future. Evidence is accumulating that unstable, vulnerable plaques are associated with increased microembolisation during carotid interventions. This knowledge of the vulnerable plaque can be translated to the clinical setting by plaque imaging. A first approach has been made by duplex imaging of carotid plaque morphology. More advanced methods such as molecular magnetic resonance imaging and optical coherence tomography could aid in optimal treatment selection based on plaque characteristics thus reducing microembolisation and associated cerebral adverse events.

Angioplasty↗
PubMed2006

[Cardiac hypertrophy: molecular and cellular events].

Cardiac hypertrophy is one of the main ways in which cardiomyocytes respond to mechanical and neurohormonal stimuli. It enables myocytes to increase their work output, which improves cardiac pump function. However, this compensatory mechanism can become overwhelmed by biomechanical stress, thereby resulting in heart failure, which is associated with high morbidity and mortality. The complex molecular processes that lead to cardiomyocyte growth involve membrane receptors, second messengers, and transcription factors. The common final pathway of all these intracellular substances is gene expression, whose variations are being revealed in increasing detail. The genetic response is characterized by the re-expression of fetal genes, an event which is regarded as the molecular marker of pathologic cardiac hypertrophy, and which is absent in normal physiologic cardiac growth. The possibility of stopping or reversing pathologic cardiac hypertrophy and, thereby, slowing the development of heart failure is a topic of considerable clinical interest and a large amount of relevant data has accumulated. The purpose of this review was to provide a schematic overview of current knowledge about the molecular pathogenesis of cardiomyocyte hypertrophy, with special emphasis on new research topics and investigations.

Cardiomegaly↗
PubMed1991

Clinical evaluation of an algorithm for the interpretation of hyperamylasemia.

Total amylase concentration in serum continues to be widely determined in the diagnosis of acute pancreatic disease. Accumulated experience has made clear, however, that this determination has distinct limitations. Consequently, the knowledge of the origin of hyperamylasemia may have an important influence on treatment, hospitalization, and extent of clinical investigations. We undertook a logical and systematic approach to the interpretation of hyperamylasemia through the use of an algorithm that can be applied in clinical situations without the need for the integration of radiologic procedures or clinical data. The proposed algorithm was tested for effectiveness in 97 consecutive hospitalized patients with hyperamylasemia (amylase level greater than twice the upper reference limit) for a 2-year period. The majority (52.5%) of these patients had acute pancreatitis. The algorithm assigned the correct diagnostic categories in 95.8% of cases, with a disagreement between patient diagnosis and algorithm-generated diagnosis in only four cases. These four patients (two with acute biliary disease, one with bacterial peritonitis, and one with chronic renal failure) had pancreatic lipase values greater than five times the upper reference limit, so that the algorithm classified their condition as acute pancreatitis. The clinical trial indicated that the proposed decision tree, which requires only knowledge of biochemical data that are readily available, is useful in the evaluation of elevated amylase activity and facilitates arrival at a definitive diagnosis.

Acute Disease↗
PubMedDate not supplied

[Autoantibodies in the diagnosis of autoimmune diseases of the liver].

In recent years a considerable knowledge concerning the use of autoantibodies as diagnostic markers in clinical hepatology, has been accumulated. The present article reviews the most important autoantibodies such as anti-smooth muscle, antimicrosomal of the liver and kidney, antimitochondria and antinuclear antibodies.

Animals↗