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Biomedical subjects

I Beck

Publications and source records attributed to I Beck.

At least 19 recordsLinked to original sources
PubMed2006

Human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis: viral load and muscle tone are correlated.

Human T-lymphotropic virus type 1 (HTLV-1) infections are associated with varying degrees of HTLV-1 viral load and spasticity. Increased viral load is associated with higher risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The authors performed a cross-sectional study of 24 people with HAM/TSP in Lima, Perú, to determine if higher HTLV-1 viral load was correlated with increased muscle tone, measured with a device providing quantitative spasticity assessment (QSA). Median HTLV-1 viral load was 17.0 copies/100 peripheral blood mononuclear cells and QSA value was 39.9 Newton-meters/radian. HTLV-1 viral load was significantly correlated with QSA value (Spearman rho = .48, P = .02), suggesting viral load may play a role in expression of symptomatic neurologic disease. Longitudinal studies are needed to determine if treatments that reduce viral load will reduce muscle tone.

Cross-Sectional Studies↗
PubMed2003

Undesirable reactions of domestic pigeons to vaccination against paramyxovirus type 1.

Subcutaneous vaccination of fancy and racing pigeons with inactivated oil-based vaccines protects against all clinical manifestations caused by the Paramyxovirus type 1. Correct application of the vaccine may occasionally result in the development of granulomas or abscess-like lesions on the site of vaccine application. Although protected against disease as proven by challenge experiments, a variable proportion of vaccinated pigeons do not react with the formation of detectable serum antibodies. The pathogenesis of granuloma and abscess-like lesion developments and the failure to form humoral antibodies are presently not understood. Questions relating to legal liability of vaccinating veterinarians are briefly discussed.

Abscess↗
PubMed2000

Development of a blocking enzyme-linked immunosorbent assay for the detection of avian polyomavirus-specific antibodies.

Avian polyomavirus, described originally as budgerigar fledgling disease virus, has been associated with devastating contagious disease outbreaks in budgerigar aviaries. At present, this virus affects a wide range of psittacine and non-psittacine birds worldwide, and the serum neutralisation test is used for the serodiagnosis of avian polyomavirus infections. A blocking enzyme-linked immunosorbent assay was developed for the screening of large numbers of sera collected from various avian species. The assay employs a monoclonal antibody directed against the major structural protein VP1 as a blocking antibody in a sandwich blocking procedure. Either purified avian polyomavirus particles or avian polyomavirus VP1 expressed in recombinant baculovirus-infected Sf9 cells were used as antigen. The specificity of the blocking enzyme-linked immunosorbent assay was evaluated by testing sera directed against mammalian polyomaviruses. Using sera obtained from chicken infected experimentally with avian polyomavirus and a collection of psittacine field-origin sera, a good correlation was observed between the results of the blocking enzyme-linked immunosorbent assay and the serum neutralisation test. However, the blocking enzyme-linked immunosorbent assay is more rapid and more economic. Both, avian polyomavirus particles and VP1 produced by recombinant DNA technology proved to be suitable antigens.

Animals↗
PubMed1997

In vivo structure-function analysis of Drosophila Hairless.

Hairless plays an important role as the major antagonist in the Notch signalling pathway in Drosophila. It appears to be a direct inhibitor of the signal transducer Su(H). Hairless encodes a pioneer protein which was dissected in a structure-function analysis; a series of deletion constructs was tested for wild type and gain of function activity in the fly as well as for Su(H) binding. Thereby, the Hairless protein was subdivided into the absolutely essential Su(H)-binding domain, similarly important N- and C-terminal domains and a central antimorphic domain. Therefore, Hairless protein might have additional functions apart from Su(H) binding and may antagonize Notch mediated cell-cell communication in a more complex way than currently anticipated.

Animals↗
PubMed1997

Health economics of gastroesophageal reflux disease.

The present study provides an overview of the current state of health economics studies of gastroesophageal reflux disease (GERD). It indicates the strengths and weaknesses of individual studies, and the state of health economics analysis in general as they apply to GERD. Specifically, this study adopts a pharmacoeconomic perspective, which is a subsection of health economics analytical methods, to provide a comparative analysis of alternative courses of action based on cost and consequence. The pharmacoeconomic outlook is most effective when it considers a comprehensive societal perspective, with special consideration given to other relevant viewpoints, such as the payer, the primary provider and, most important, the patient. Pharmacoeconomics provides several specific analytical techniques for GERD-related health economics analysis. The Canadian Association of Gastroenterology consensus conference on GERD in 1996 thought that a cost effective analysis was the most appropriate technique to assess the pharmacoeconomics of GERD. Six previous studies on GERD health economics have been performed comparing omeprazole with H2 receptor antagonists. These studies vary in cost data collected and in analytical techniques. In general, the existing outcome measurements of these previous health economics studies are not ideal. Namely, they combine various GERD grades, use randomized controls, are endoscopically based, assess pharmaceutical therapy only and are short term. More appropriate health economic trials in GERD, which focus on GERD management strategies and therapeutic treatment of GERD, need to be designed and conducted. These economic assessments, however, should not replace detailed thinking, careful observation, good judgement and common sense.

Canada↗
PubMed1996

Absolute requirement of aryl hydrocarbon receptor nuclear translocator protein for gene activation by hypoxia.

Hypoxia-inducible factor 1 (HIF-1) is a DNA-binding heterodimeric protein complex originally described in the transcriptional activation of the erythropoietin gene by hypoxia. This protein complex is composed of two subunits, HIF-1alpha and -1beta (aryl hydrocarbon receptor nuclear translocator, ARNT). In this study, we used ARNT-deficient cells, derived from the mouse hepatoma cell line Hepa1c1c7, to further characterize HIF-1 complex formation and its relationship with gene activation by hypoxia and desferrioxamine (Df). Gel shift assays revealed that ARNT is absolutely required for the formation of the HIF-1 DNA-binding complex. Results from RNase protection assays and Northern blots showed that the lack of functional HIF-1 complex completely abrogated the response to hypoxia of vascular endothelial growth factor (VEGF) and the glycolytic enzymes aldolase A (ALDA) and phosphoglycerate kinase 1 (PGK-1), genes known to be upregulated by low oxygen tension. Desferrioxamine induction of VEGF and PGK-1 genes was reduced in the ARNT-deficient cells, but at difference with hypoxia, it was not completely suppressed. These results suggest that Df is able to activate gene transcription through HIF-1-independent mechanisms. Exposure to hypoxia or Df did not induce any changes in HIF-1alpha and -1beta mRNA levels, suggesting that posttranscriptional mechanisms are involved in HIF-1 complex activation.

Actins↗
PubMed1996

N,N'-bis-(3,4,5-trimethoxybenzyl) ethylenediamine N,N'-diacetic acid as a new iron chelator with potential medicinal applications against oxidative stress.

N,N'-bis-(3,4,5-trimethoxybenzyl) ethylenediamine N,N,-diacetic acid dihydrochloride (OR10141) is a member of a recently described series of "oxidative stress activatable iron chelators." These chelators have a relatively low affinity for iron but can be site-specifically oxidized, in situations mimicking oxidative stress in vitro, into species with strong iron-binding capacity. It is hoped that this local activation process will minimise toxicity compared to strong iron chelators that may interfere with iron metabolism. The present paper describes the results of experiments aimed at characterising oxidative reactions between iron-OR10141 complexes and hydrogen peroxide. Incubation of ascorbate and hydrogen peroxide with the ferric chelate of OR10141 in neutral aqueous solution yields a purple solution with a chromophore at 560 nm, which is consistent with an o-hydroxylation of one of the trimethoxybenzyl rings. Oxidation of OR10141 also takes place, although more slowly, by incubating hydrogen peroxide with ferric OR10141 complex in the absence of reductant. HPLC analysis shows that OR10141 is consumed during the reaction and transformed principally into N-(2-hydroxy 3,4,5-trimethoxybenzyl) N'-(3,4,5-trimethoxybenzyl) ethylenediamine N,N'-diacetic acid. Minor products are also formed, some of which were identified by mass spectrometry. The protective effect of OR10141 in vitro against DNA single strand breaks, protein damage, and lipid peroxidation induced by Fenton chemistry suggests that this compound is able to compete for iron with biological molecules and, thus, that this strategy of protection against oxidative stress is feasible. In addition, preliminary results showing protective effects of OR10141 dimethyl ester against toxicity induced by hydrogen peroxide in cell culture are described. It is concluded that OR10141 and related prodrugs might be useful in vivo in chronic situations involving oxidative stress.

Ascorbic Acid↗
PubMed1995

N,N'-bis-dibenzyl ethylenediaminediacetic acid (DBED): a site-specific hydroxyl radical scavenger acting as an "oxidative stress activatable" iron chelator in vitro.

During oxidative stress, iron traces are supposed to be released from normal storage sites and to catalyse oxidative damage by Fenton-type reactions. This type of damage is difficult to prevent in vivo except by the use of strong iron chelators such as deferoxamine (affinity constant for Fe(III): log K = 30.8). However, strong iron chelating agents are also suspected to mobilize iron from various storage and transport proteins thereby leading to toxic effects. In contrast, N,N'-bis-dibenzyl ethylenediaminediacetic acid (DBED) is an iron chelator with relatively low affinity for iron (affinity constant for Fe(III): log K < 15). In the present paper, we show that, in situations mimicking oxidative stress in vitro, DBED is site-specifically oxidized into new species with strong iron binding capacity. Indeed, in the presence of ascorbate as a reductant, the iron chelate of DBED reacts with H2O2 in aqueous solution to yield a purple chromophore with minor release of free HO. in the medium, as measured by aromatic hydroxylation assay. The formation of these purple species is not suppressed by the presence of HO. scavengers at high concentration. The visible spectrum of these species is consistent with a charge transfer band from a phenolate ligand to iron. N-2-hydroxybenzyl N'-benzyl ethylenediaminediacetic acid (HBBED) was identified in the medium as one of the oxidation products of DBED. Therefore, these results suggest that the iron chelate of DBED undergoes an intramolecular aromatic hydroxylation by HO. leading to 2-OH derivatives and hence that DBED is a site-specific HO. scavenger. Moreover, since the measured affinity for Fe(III) of HBBED (log K = 28) is at least 13 orders of magnitude higher than that of DBED and since ferric HBBED chelate is not a catalyst of Fenton chemistry, DBED may be looked as an "oxidative stress activatable" iron chelator, e.g. which increase in affinity for iron is triggered in the presence of H2O2 and an electron donor. Therefore it is proposed that DBED and related derivatives may be interesting as protective compounds against oxygen radicals toxicity, especially for chronic use.

Ascorbic Acid↗
PubMed1993

Characterization of hypoxia-responsive enhancer in the human erythropoietin gene shows presence of hypoxia-inducible 120-Kd nuclear DNA-binding protein in erythropoietin-producing and nonproducing cells.

Erythropoietin (Epo) production in response to hypoxia or cobalt is primarily mediated by activation of transcription of the Epo gene. Recently an hypoxia responsive enhancer was identified in the 3' flanking region of the mouse and human Epo genes. Using functional analysis in Hep 3B cells we define here the minimal enhancer element as a 29-bp segment starting at the Apa1 site in the 3' flanking region of the human Epo gene. Mutagenesis studies of the minimal element identified three different areas that are necessary for full enhancer activity. Electrophoretic mobility shift assays show the presence of hypoxia- and/or cobalt-inducible nuclear DNA-binding proteins that bind to one of the active sites of the enhancer. Induction of hypoxia-binding activity was abolished by Anisomycin, a potent protein synthesis inhibitor, suggesting that de novo protein synthesis is necessary for the activation process. Further characterization of DNA-binding proteins by use of UV light crosslinking identified a protein of molecular weight of approximately 120-Kd that was present only in hypoxic extracts. This protein was found to be present in hypoxic nuclear extracts from both Epo-producing and non-Epo-producing cells, suggesting that it may be involved in a more generalized mechanism of cellular response to hypoxia.

Base Sequence↗
PubMed1993

Antioxidant activity of flavonoids: efficiency of singlet oxygen (1 delta g) quenching.

Flavonoids, polyphenolic pigments widely present in plants, have been reported to act as scavengers of various oxidizing species. However, most often an overall antioxidant effect was measured. In this paper we report the results of a systematic study of the reactivity of 13 selected flavonoids (from the flavonol, flavone, flavanone and flavane families) with singlet oxygen (1O2(1 delta g)) in order to establish a structure-activity relationship. The rate constants of the chemical reaction of these flavonoids with 1O2(k r) and their rate constants of 1O2 physical quenching (kq) have been determined by kinetic measurements and near-IR singlet oxygen luminescence. The efficiency of the physical quenching is mainly controlled by the presence of a catechol moiety on ring B, whereas the structure of ring C (particularly the presence of a hydroxyl group activating the double bond) is the main factor determining the efficiency of the chemical reactivity of these compounds with 1O2. The total reactivity factor determining the efficiency of the chemical reactivity of these compounds with 1O2. The total reactivity scale is dominated by kq, which is in general higher than kr. (+)-Catechin is the most efficient quencher of the series.

Antioxidants↗
PubMed1991

Enhancer element at the 3'-flanking region controls transcriptional response to hypoxia in the human erythropoietin gene.

Erythropoietin gene expression is greatly stimulated under conditions of hypoxia. The activation of the erythropoietin gene appears regulated primarily at the level of gene transcription. To study cis-acting elements involved in the response to hypoxia a mini-gene was constructed by an internal deletion from exon II to V of the human erythropoietin gene and used in transient transfection assays in the erythropoietin producing Hep 3B cell line. It was initially found that hypoxia responsiveness was present in an erythropoietin fragment containing 400 base pairs (bp) of 5'-flanking and 600 bp of 3'-flanking regions. Deletion analysis showed no significant effect on the response to hypoxia when highly conserved regions of 5'-flanking sequence, exon and intron I, and exon V were removed from the mini-gene construct. However, removal of a fragment containing the 3' end of the gene and 3'-flanking sequences completely eliminated hypoxia responsiveness. Reinsertion of the above fragment upstream of the 5' end of the mini-gene restored the response to hypoxia. Further analysis using hybrid erythropoietin-chloramphenicol-acetyltransferase constructs allowed the localization of enhancer-like element(s) in the 3'-flanking region, approximately 120 bp downstream of the polyadenylation site of the human erythropoietin gene. Activation by these sequences were position- and orientation-independent and stimulated 15-fold transcription of the erythropoietin gene in response to hypoxia.

Cells, Cultured↗