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Results for “knowledge accumulation”

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PubMed2000

Two novel intrinsic annexins accumulate in wheat membranes in response to low temperature.

Four immunologically related proteins that belong to the annexin family were identified in cold acclimated wheat (Triticum aestivum). Two soluble forms with molecular masses of 34 and 36 kDa were found to bind phospholipid membranes in a calcium-dependent manner. These two forms are similar to the previously reported doublet in several plant species. The other two forms, with molecular masses of 39 and 22.5 kDa, were found associated with the microsomal fraction. Biochemical analysis showed that both forms are intrinsic membrane proteins and their association with the membrane is calcium independent. This is, to our knowledge, the first report of the presence of these annexin forms in plants. Membrane purification by two phase partitioning demonstrated that the p39 form is localized to the plasma membrane. Immunoblot analysis showed that the protein level of both p39 and p22.5 increases gradually reaching a maximum level after one day of low temperature exposure. The protein accumulation was similar in both hardy and less hardy cultivars, suggesting that the accumulation is not correlated with freezing tolerance. The results are discussed with respect to the possible role of these new intrinsic membrane annexins in low temperature signal transduction pathway.

Annexins↗

PubMed1987

Accumulation pattern of amino acid substitutions in protein evolution.

A simple method for the evolutionary analysis of amino acid sequence data is presented and used to examine whether the number of variable sites (NVS) of a protein is constant during its evolution. The NVSs for hemoglobin and for mitochondrial cytochrome c are each found to be almost constant, and the ratio between the NVSs is close to the ratio between the unit evolutionary periods. This indicates that the substitution rate per variable site is almost uniform for these proteins, as the neutral theory claims. An advantage of the present analysis is that it can be done without knowledge of paleontological divergence times and can be extended to bacterial proteins such as bacterial c-type cytochromes. It is suggested that the NVS of cytochrome c has been almost constant even over the long period (ca. 3.0 billion years) of bacterial evolution but that at least two different substitution rates are necessary to describe the accumulated changes in the sequence. This "two clock" interpretation is consistent with fossil evidence for the appearance times of photosynthetic bacteria and eukaryotes.

Amino Acid Sequence↗

PubMed2006

Prevention and early detection of oral and pharyngeal cancer in veterans.

OBJECTIVES: To assess knowledge of oral and pharyngeal cancer (OPC) clinical signs and risk factors, the association between the risk factors and OPC, and the experience with OPC screening between newly diagnosed OPC patients and controls among a population of veterans in North Carolina. STUDY DESIGN: A case-control study with 31 OPC cases and 30 frequency-matched controls recruited from 2003 to 2004. Bivariate analysis using chi-square statistics and multivariate logistic regression was implemented to estimate the association with OPC. RESULTS: Only 34% of respondents knew 1 clinical sign and 4 or 5 risk factors for OPC. The lifetime accumulation of tobacco had a significant relationship with OPC (>20 pack-years; OR, 3.2; 95% CI, 1.01-10.3). Many respondents had not had an oral cancer examination within 3 years, mostly through ignorance. Most VA OPC patients were diagnosed by physicians, rather than by dentists. CONCLUSIONS: A considerable knowledge deficit on OPC was found among North Carolina veterans. Use of tobacco was a risk factor for OPC in this population.

Age Factors↗

PubMed1984

Fatty acyl-CoA dehydrogenase deficiency: enzyme measurement and studies on alternative metabolism.

Fatty acyl-CoA dehydrogenase deficiencies are defined as disorders of the metabolism of straight chain acyl-CoA esters at the level of short chain acyl-CoA, general (medium chain) acyl-CoA and long chain acyl-CoA dehydrogenases. Patients with proven or indicated defects in either general (medium chain) or long chain acyl-CoA dehydrogenase have been reported. In recent years assays for the enzymatic diagnosis in cells, especially cultured skin fibroblasts, from such patients have been developed. The different methods are reviewed. The urinary excretion profile of organic acids from patients with fatty acyl-CoA dehydrogenase deficiencies are characterized by the presence of different compounds originating from the primary accumulated acyl-CoA ester(s). The most important biochemical processes involved in the formation of these compounds are glycine conjugation and omega/omega-1 oxidation. The biochemistry of these pathways is discussed and the knowledge gained from in vitro and in vivo studies is used to explain the excretion pattern in some of the patients with general (medium chain) acyl-CoA dehydrogenase deficiency.

Acids↗

PubMed2005

A case of idiopathic sclerosing mediastinitis in a 7-year-old Japanese boy.

UNLABELLED: Sclerosing mediastinitis is a very rare benign disorder characterised by the development of dense fibrous tissue within the mediastinum. Affected patients are typically young adults with infant cases being uncommon especially in areas without endemic histoplasmosis. We report a Japanese boy with markedly elevated serum inflammatory markers for more than 1 year in the absence of any clinical manifestations. 67Ga-scintigraphy demonstrated an accumulation in the mediastinal region and an open biopsy revealed a hard fibrous mass in the anteriosuperior mediastinum. Thus, a diagnosis of idiopathic sclerosing mediastinitis was made. CONCLUSION: To the best of our knowledge, this case is the youngest patient reported with this disorder. In patients with mediastinal mass lesions the diagnosis of sclerosing mediastinitis should be considered as well as infectious, autoimmune or neoplastic disease even in children.

Anemia↗

PubMed1977

Metallobiochemistry of heavy metal pollution: nuclear and radiochemical techniques for long term--low level exposure (LLE) experiments.

The chronic exposure of man to increasing amounts of heavy metals as a consequence of environmental pollution, requires accurate knowledge of how much the homeostatic control of trace elements can stand increased exposure to abnormal amounts of metal pollutants without alteration of the biochemical functions. This topic includes the study of the accumulation of metal pollutants in the body with the identification of metal biocomplexes under long term-low level exposure (LLE) conditions. Extremely sensitive analytical techniques are required for experimentation at the heavy metal levels which are typical of a polluted environment in order to assess the limits of physiological homeostatic controls. The possiblity of applying nuclear and radiochemical techniques, such as neutron activation analysis, multiple tracing, high resolution gamma-ray spectrometry and Cerenkov counting, coupled with biochemical techniques, such as gel filtration, ion-exchange chromatography, polyacrylamide gel electrophoresis and differential centrifugation, has been demonstrated in various typical applications in metallobiochemistry. The subject of the first part of this paper is the development and improvement of the techniques, dealing with potential metal binding components, such as metalloenzymes and nucleic acids chosen as models. The developments refer to: preparation of labelled metal pollutants with very high specific activity to label in vivo nanogram or subnanogram amounts of pollutant metals; neutron activation analysis of enzymes and nucleic acids with the aim of analyzing concentrations of many metal pollutants in the identified metal binding components of the microsamples; radiochemical methods including radiobiochemical techniques for multielement tracer experiments and for studying the interaction of heavy metas and metal binding components; development of complementary counting techniques. The in vivo applications are centered on biochemical studies on cadmium, in particular on the long term-low exposure experiment, which is under investigation at present, with the identification of both critical organs of accumulation and of the cadmium binding components. Results are given for biochemical mechanisms involving cadmium such as the stimulation of the "de novo" biosynthesis of rat liver and intestine cadmium binding proteins (CdBP) and on the systematic study of the interaction of metal pollutants and rat liver cadmium binding proteins itself. Preliminary data are also given for short term experiments dealing with the identification of cellular metal binding components for V, Se, Cd and Pb.

Alkaline Phosphatase↗

PubMed1985

Immunological and microbiological factors in the pathogenesis of atherosclerosis.

Among the several pathological events that lead to the formation of an atheromatous lesion, endothelial cell damage, smooth muscle cell proliferation, and foam cell formation, are considered as particularly significant. In this review we summarize data suggesting that immunological and microbial factors may cause, directly or indirectly, these pathological events. Binding of immunocomplexes to endothelial cells, phagocytic cells, platelets, or erythrocytes could be the starting point for a variety of circuits leading to endothelial cell cytotoxicity and to the release of a variety of mediators, including cell proliferative factors. Endothelial cell toxicity could also be induced, directly or indirectly, by endotoxin; however, the possibility that endotoxin and other microbial factors may induce abnormalities in lipid metabolism at the monocyte/macrophage level which eventually result in intracellular accumulation of cholesterol (particularly if cholesterol levels are elevated) is specially attractive as a potential pathogenic mechanism. The various pathologic pathways discussed in this review appear plausible on the basis of our current knowledge and point to the need to investigate the potential role of infectious processes, autoimmune reactions, and administration of antigenic compounds as possible risk factors for the development of atherosclerosis.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2004

Mitochondrial dysfunction in chronic ischemia and peripheral vascular disease.

In peripheral vascular disease, impaired muscle energy metabolism is assumed to be due mainly to defective vascular O2 supply, the resulting cellular hypoxia inhibiting oxidative ATP synthesis. Older work suggested a compensatory increase in muscle aerobic enzymes, but more recent studies suggest a relative decrease in some mitochondrial components and an accumulation of damage in mitochondrial DNA, perhaps due to reactive oxygen species. However, to establish whether in vivo muscle mitochondria suffer from anything other than a low concentration of O2 will require more knowledge of the mitochondrial behaviour at low PO2, and the actual cell PO2 during exercise.

Journal Article↗

PubMed2006

The anion channel blocker, 4,4'-dinitrostilbene-2,2'-disulfonic acid prevents neuronal death and excitatory amino acid release during glycolysis inhibition in the hippocampus in vivo.

Neuronal death associated with cerebral ischemia and hypoglycemia is related to increased release of excitatory amino acids (EAA) and energy failure. The intrahippocampal administration of the glycolysis inhibitor, iodoacetate (IOA), induces the accumulation of EAA and neuronal death. We have investigated by microdialysis the role of exocytosis, glutamate transporters and volume-sensitive organic anion channel (VSOAC) on IOA-induced EAA release. Results show that the early component of EAA release is inhibited by riluzole, a voltage-dependent sodium channel blocker, and by the VSOAC blocker, tamoxifen, while the early and late components are blocked by the glutamate transport inhibitors, L-trans-pyrrolidine 2,4-dicarboxylate (PDC) and DL-threo-beta-benzyloxyaspartate (DL-TBOA); and by the VSOAC blocker 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS). Riluzole, DL-TBOA and tamoxifen did not prevent IOA-induced neuronal death, while PDC and DNDS did. The VSOAC blockers 5-nitro-2-(3-phenylpropyl-amino) benzoic acid (NPPB) and phloretin had no effect either on EAA efflux or neuronal damage. Results suggest that acute inhibition of glycolytic metabolism promotes the accumulation of EAA by exocytosis, impairment or reverse action of glutamate transporters and activation of a DNDS-sensitive mechanism. The latest is substantially involved in the triggering of neuronal death. To our knowledge, this is the first study to show protection of neuronal death by DNDS in an in vivo model of neuronal damage, associated with deficient energy metabolism and EAA release, two conditions involved in some pathological states such as ischemia and hypoglycemia.

Animals↗

PubMed2000

Peripheral pathogenesis of prion diseases.

Prions are infectious pathogens that cause a group of neurodegenerative diseases characterized by spongiform degeneration of the central nervous system. Prions appear to lack any informational nucleic acid. The most notable prion diseases include bovine spongiform encephalopathy, scrapie in sheep and Creutzfeldt-Jakob disease of humans. Transmission is thought to be achieved through conversion of a normal host protein into a pathological isoform. Although the main pathological changes during the course of the disease occur in the brain, the infectious agent accumulates early in lymphoid tissue. The subsequent development of clinical disease depends on the presence of an intact immune system including mature B-cells. In this article we review the state of knowledge on the routes of neuroinvasion used by the infectious agent in order to gain access to the central nervous system upon entry into extracerebral sites.

Animals↗

PubMed2001

Cancer genetics in oncology practice.

Cancer is a genetic disease caused by the progressive accumulation of mutations in critical genes that control cell growth and differentiation. Completion of the Human Genome Project promises to revolutionize the practice of Medicine, especially Oncology care. The tremendous gains in the knowledge of the structure and function of human genes will surely impact the diagnosis, prognosis and treatment of cancer. Moreover, it will lead to more effective cancer control through the use of genetics to quantify individual cancer risks. This article reviews the current status of genetic testing and counseling for cancer risk assessment and will suggest a framework for integrating such counseling into oncology practice.

Adenomatous Polyposis Coli↗

PubMed2000

Serotonin in mania and in the mechanism of action of mood stabilizers: a review of clinical studies.

OBJECTIVES: Serotonin (5-hydroxytryptamine, 5-HT) was implicated in the pathophysiology of manic-depressive illness as early as 1958. Although extensive evidence has accumulated since then to support 5-HT's role in depression, relatively fewer studies examined its role in mania. The purpose of this paper was to review and summarize the current state of knowledge on the role of 5-HT in mania and its treatment. METHODS: We systemically reviewed clinical studies of 1) 5-HT function in mania and 2) 5-HT in the mechanism of action of mood stabilizers, including lithium and anticonvulsants. RESULTS: Review showed that cerebrospinal fluid, postmortem, platelet, neuroendocrine challenge, and tryptophan depletion studies provided some evidence to support the hypothesis that a 5-HT deficit is involved in mania and that enhancement of 5-HT neurotransmission exerts a mood-stabilizing effect. CONCLUSIONS: There is some evidence from clinical studies for the contribution of 5-HT in mania and in the mechanism of action of mood stabilizers. However, it is very likely that other neurotransmitters also play important roles. Future directions for research include 1) in vivo study of 5-HT receptor subtypes using positron emission tomography, 2) investigation of the interaction between 5-HT and other neurotransmitter systems, and 3) determination of the relationships between diagnostic subtypes of mania and 5-HT function and other neurotransmitter systems.

Anticonvulsants↗

PubMed2003

Mechanisms of resistance to topoisomerase I-targeting drugs.

DNA topoisomerases are a class of enzymes that alter the topology of DNA and are targets of several anticancer drugs. Camptothecins (CPTs) are a relatively new family of compounds that specifically target topoisomerase I (Top1). These compounds "poison" Top1 by binding to the Top1-DNA complex in a manner that prevents the religation of DNA. Topotecan and irinotecan are two CPTs that are approved for the treatment of a variety of malignancies, including colorectal, ovarian, and small cell lung cancers, as well as myeloid malignancies. Although CPTs have proven to be effective anticancer drugs, resistance is still a critical clinical problem. The mechanisms underlying de novo and acquired clinical resistance to CPTs and the newer classes of Top1 poisons are unclear. However, based on preclinical studies, it is likely that clinical resistance to these drugs is the result of: (1) inadequate accumulation of drug in the tumor, (2) resistance-conferring alterations in Top1, or (3) alterations in the cellular response to the Top1-CPT interaction. This review will focus on the current knowledge regarding mechanisms of resistance to CPTs and other Top1-targeting drugs.

Antineoplastic Agents↗

PubMed2002

Novel collagen glomerulopathy in a homotrimeric type I collagen mouse (oim).

BACKGROUND: Oim/oim mice [osteogenesis imperfecta model; homozygous null for the proalpha2(I) collagen gene] synthesize exclusively the homotrimeric type I collagen isotype, alpha1(I)3, and are unable to synthesize the normal heterotrimeric type I collagen isotype, alpha1(I)2alpha2(I). Previous studies of the oim/oim mouse have focused on the musculoskeletal system, with no systematic evaluation of other organ systems. METHODS: Multiple tissues from oim/oim, oim/+ (heterozygous) and +/+ (wild-type) mice were examined for gross and histological abnormalities. Tissues were stained with (1) hematoxylin and eosin (to assess lesion formation), (2) picrosirius red (collagen content), and (3) periodic acid methenamine silver (basement membrane). Kidneys were further evaluated ultrastructurally by electron microscopy and immunohistochemically with anti-alpha1(I) and anti-alpha1(III) collagen antibodies. RESULTS: Histological analyses revealed accumulations of picrosirius red-positive material, consistent with collagen, in glomeruli of 28/29 oim/oim mice, with no evidence of mesangial cell proliferation. Only the most severely affected animals had evidence of increased capillary basement membrane thickening or mild inflammation around the affected glomeruli. Electron microscopy confirmed the presence of fibrillar collagen. Immunohistochemistry with anti-alpha1(I) collagen antibodies confirmed accumulation of type I collagen in the oim/oim glomeruli. The +/+ and oim/+ kidneys had normal mesangium with no evidence of infiltration of collagenous material. CONCLUSIONS: This study demonstrates the first evidence, to our knowledge, of abnormal glomerular collagen deposition associated with a type I collagen defect. Further in vivo and in vitro studies are necessary to elucidate the mechanistic, functional, and pathological significance of the oim/oim collagen glomerulopathy.

Animals↗

PubMed1998

Cell apoptosis and granulomatous lung diseases.

Apoptosis, also known as activation-induced cell death or programmed cell death, is an active suicide mechanism that is involved in normal tissue turnover during embryogenesis and adult life. There are many examples of apoptosis in the immune system, including programmed cell death of T cells during negative intrathymic selection of the TCR repertoire and, in the postthymic phase, death of responsive T cells upon specific activation of the TCR/CD3 complex. Induction of apoptosis assures rapid disappearance of the immune response upon antigenic clearance, avoiding the metabolic costs involved in sustaining a large number of effector cells. The knowledge that failure of immune cells to die is the cause of a number of immune-mediated disorders has opened intriguing new avenues of exploration into the pathogenetic events leading to the accumulation of immunoinflammatory cells at sites of ongoing inflammation in granulomatous disorders, including granulomas initiated by infectious agents, such as Mycobacterium tuberculosis, or in sarcoidosis. In this paper we review recent results obtained in experimental animal models and patients with immune granuloma suggesting that the positive induction by ligands binding to membrane receptors or the induction or loss of intracellular suppressor signals regulates immunoregulatory mechanisms that drive the progressive development of the granulomatous structure. The great advances in understanding how mechanisms for the activation or downregulation of apoptosis have a pathogenetic role in the outcome of granulomatous disorders are also briefly considered.

Adult↗

PubMed2006

Multimodality stroke prevention.

BACKGROUND: Prevention harbors the greatest potential for reducing the societal burden from stroke. As evidence accumulates on the multifactorial pathogenesis of vascular disease and the impact of novel combination therapies targeted at reducing recurrent vascular events, a new paradigm is emerging, which is that of multimodality vascular prevention. Knowledge of the evidence behind this strategy and the effective means for implementing it could be useful to the practicing neurologist taking care of stroke patients. REVIEW SUMMARY: Our review presents the evidence behind the broadening therapeutic options for recurrent vascular event prevention in ischemic stroke patients whose underlying stroke pathophysiologic mechanism is either presumed to be due to atherosclerosis or who have prior evidence of systemic atherosclerosis. We elaborate on conventional and novel vascular risk factors, as well as risk factor prediction models. Therapies discussed include antithrombotics, statins, antihypertensives, surgical/endovascular treatments, and lifestyle modification. Basis for evidence (or the lack thereof), national guideline recommendations, areas of controversy, and avenues of future focus for these treatments are also discussed in this paper. Furthermore, the knowledge-treatment gap as it pertains to optimal vascular risk-factor control and appropriate initiation and maintenance of evidence-based preventive therapies is explored, and an effective hospital-based intervention involving the in-hospital initiation of these treatments prior to discharge, that may help bridge this gap, is detailed. CONCLUSIONS: Neurologists should be aware that a timely, systematic, evidence-based multimodal preventive approach to atherothrombotic disease in stroke patients that transcends the continuum of care across points of service will likely increase treatment rates and improve clinical outcomes.

Cardiovascular Agents↗

PubMed2006

Latency and reactivation of human cytomegalovirus.

Human cytomegalovirus (HCMV) persists as a subclinical, lifelong infection in the normal human host, maintained at least in part by its carriage in the absence of detectable infectious virus--the hallmark of latent infection. Reactivation from latency in immunocompromised individuals, in contrast, often results in serious disease. Latency and reactivation are defining characteristics of the herpesviruses and key to understanding their biology. However, the precise cellular sites in which HCMV is carried and the mechanisms regulating its latency and reactivation during natural infection remain poorly understood. This review will detail our current knowledge of where HCMV is carried in healthy individuals, which viral genes are expressed upon carriage of the virus and what effect this has on cellular gene expression. It will also address the accumulating evidence suggesting that reactivation of HCMV from latency appears to be linked intrinsically to the differentiation status of the myeloid cell, and how the cellular mechanisms that normally control host gene expression play a critical role in the differential regulation of viral gene expression during latency and reactivation.

Carrier State↗

PubMed1998

Lipases and carboxylesterases: possible roles in the hepatic metabolism of retinol.

The formation of hydrolysis of retinyl esters are key processes in the metabolism of the fat-soluble micronutrient vitamin A. Long-chain acyl esters of retinol are the major chemical form of vitamin A (retinoid) stored in the body. Retinyl esters are found in a variety of tissues and cell types, but most of the total body retinoid is accounted for by the retinyl esters stored in the liver. Thus, these esters represent the major endogenous source of retinoid that can be delivered to peripheral tissues for conversion to biologically active forms. This review summarizes current knowledge about the identity, function, and regulation of the hepatic enzymes potentially involved in catalyzing the hydrolysis of retinyl esters. These enzymes include several known and characterized lipases and carboxylesterases. Although there is accumulating evidence that these enzymes function as retinyl ester hydrolases in vitro, it is not clear which play important physiological roles in hepatic retinyl ester metabolism.

Animals↗