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A method for separating according to mass a mixture of macromolecules or small particles suspended in a fluid. II. Experiments in a gravitational field.

Berg, H C; Purcell, E M; Stewart, W W
Tipo: text
Publicado em /10/1967 Português
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Pathophysiological concentrations of glucose promote oxidative modification of low density lipoprotein by a superoxide-dependent pathway.

Kawamura, M; Heinecke, J W; Chait, A
Tipo: text
Publicado em /08/1994 Português
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Oxidized lipoproteins may be important in the pathogenesis of atherosclerosis. Because diabetic subjects are particularly prone to vascular disease, and glucose autoxidation and protein glycation generate reactive oxygen species, we explored the role of glucose in lipoprotein oxidation. Glucose enhanced low density lipoprotein (LDL) oxidation at concentrations seen in the diabetic state. Conjugated dienes, thiobarbituric acid reactive substances, electrophoretic mobility, and degradation by macrophages were increased when LDL was modified in the presence of glucose. In contrast, free lysine groups and fibroblast degradation were reduced. Although loss of reactive lysine groups could be due to either oxidative modification or nonenzymatic glycation of apolipoprotein B-100, inhibition of lipid peroxidation by the metal chelator, diethylenetriamine pentaacetic acid, blocked the changes in free lysines. Thus, glycation of lysine residues is unlikely to account for the alterations in macrophage and fibroblast uptake of LDL modified in the presence of glucose. Glucose-mediated enhancement of LDL oxidation was partially blocked by superoxide dismutase and nearly completely inhibited by butylated hydroxytoluene. These findings indicate that glucose enhances LDL lipid peroxidation by an oxidative pathway involving superoxide and raise the possibility that the chronic hyperglycemia of diabetes accelerates lipoprotein oxidation...

A membrane-embedded glutamate is required for ligand binding to the multidrug transporter EmrE

Muth, T.R.; Schuldiner, S.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: text
Publicado em 17/01/2000 Português
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EmrE is an Escherichia coli multidrug transporter that confers resistance to a variety of toxins by removing them in exchange for hydrogen ions. The detergent-solubilized protein binds tetraphenylphosphonium (TPP+) with a KD of 10 nM. One mole of ligand is bound per ?3 mol of EmrE, suggesting that there is one binding site per trimer. The steep pH dependence of binding suggests that one or more residues, with an apparent pK of ?7.5, release protons prior to ligand binding. A conservative Asp replacement (E14D) at position 14 of the only membrane-embedded charged residue shows little transport activity, but binds TPP+ at levels similar to those of the wild-type protein. The apparent pK of the Asp shifts to

Oxidative Activity of Cytoplasmic Particles of Apples: Electron Transfer Chain

Lieberman, Morris
Tipo: text
Publicado em /11/1960 Português
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In vitro guinea pig leukocyte reactions to Rickettsia rickettsii.

Kenyon, R H; Ascher, M S; Kishimoto, R A; Pedersen, C E
Tipo: text
Publicado em /12/1977 Português
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The presence of cell-mediated immunity in Rocky Mountain spotted fever-infected guinea pigs was determined by two in vitro assays: whole blood lymphocyte transformation (LT) and macrophage migration inhibition. Increased LT was detected as early as 1 week in guinea pigs infected with Rickettsia rickettsii and treated with oxytetracycline and was detected by two weeks in infected but untreated guinea pigs. Elevated LT was still detectable at 10 weeks postinfection. Guinea pigs vaccinated with killed rickettsiae failed to develop lymphocyte responsiveness; however, there was a rapid lymphocyte response after challenge with live organisms, suggesting potentiation by the vaccine. Vaccinated guinea pigs that were challenged and then treated with antibiotic failed to develop LT, suggesting that infection is necessary for the observed response. Macrophage migration inhibition was detected in both infected and vaccinated guinea pigs by 1 week after infection, but this response was no longer detected 4 to 5 weeks later. Antibody appeared at 2 to 3 weeks postinfection and was present at low levels through week 10. Antibody-treated rickettsiae were phagocytized and destroyed by guinea pig peritoneal macrophages, whereas normal serum-treated rickettsiae replicated and eventually destroyed the phagocytes.

High-Resolution Structure of the Histidine-Containing Phosphocarrier Protein (HPr) from Staphylococcus aureus and Characterization of Its Interaction with the Bifunctional HPr Kinase/Phosphorylase

Maurer, Till; Meier, Sebastian; Kachel, Norman; Munte, Claudia Elisabeth; Hasenbein, Sonja; Koch, Brigitte; Hengstenberg, Wolfgang; Kalbitzer, Hans Robert
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: text
Publicado em /09/2004 Português
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A high-resolution structure of the histidine-containing phosphocarrier protein (HPr) from Staphylococcus aureus was obtained by heteronuclear multidimensional nuclear magnetic resonance (NMR) spectroscopy on the basis of 1,766 structural restraints. Twenty-three hydrogen bonds in HPr could be directly detected by polarization transfer from the amide nitrogen to the carbonyl carbon involved in the hydrogen bond. Differential line broadening was used to characterize the interaction of HPr with the HPr kinase/phosphorylase (HPrK/P) of Staphylococcus xylosus, which is responsible for phosphorylation-dephosphorylation of the hydroxyl group of the regulatory serine residue at position 46. The dissociation constant Kd was determined to be 0.10 ± 0.02 mM at 303 K from the NMR data, assuming independent binding. The data are consistent with a stoichiometry of 1 HPr molecule per HPrK/P monomer in solution. Using transversal relaxation optimized spectroscopy-heteronuclear single quantum correlation, we mapped the interaction site of the two proteins in the 330-kDa complex. As expected, it covers the region around Ser46 and the small helix b following this residue. In addition, HPrK/P also binds to the second phosphorylation site of HPr at position 15. This interaction may be essential for the recognition of the phosphorylation state of His15 and the phosphorylation-dependent regulation of the kinase/phosphorylase activity. In accordance with this observation...

Kawasaki syndrome in office pediatrics.

Stein, M T
Tipo: text
Publicado em /10/1984 Português
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Inhibitory synaptic currents in rat cerebellar Purkinje cells: modulation by postsynaptic depolarization.

Vincent, P; Armstrong, C M; Marty, A
Tipo: text
Publicado em /10/1992 Português
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1. Synaptic currents were recorded in voltage-clamped cerebellar Purkinje cells using the tight-seal whole-cell recording technique. Cells were dialysed with a CsCl solution and were held at -60 or -70 mV. Inhibitory interneurones (basket and stellate cells) were stimulated using an extracellular pipette positioned in the molecular layer. Blockers of excitatory glutamatergic synapses were included in the bath solution. 2. Evoked synaptic currents were observed after a latency of 3-4 ms. The time course of synaptic currents could in most cases be fitted to a biexponential curve, with a rise time constant, tau on, of 1-3 ms and a decay time constant, tau off, of 7-13 ms. These currents were blocked by bicuculline. 3. The mean amplitude of evoked synaptic currents increased in discrete steps when the voltage applied to the stimulating pipette was increased. At each level, very prominent fluctuations of the amplitude were observed among trials. 4. Complex synaptic currents corresponding to repetitive activity of the presynaptic interneurone were occasionally observed, particularly with high intensity presynaptic stimulation. This repetitive activity could lead to bursts of synaptic currents lasting for several seconds. 5. Following a depolarizing voltage train in the postsynaptic Purkinje cell...

Suppression of a Lethal Trisomic Phenotype in Drosophila Melanogaster by Increased Dosage of an Unlinked Locus

Dorer, D. R.; Cadden, M. A.; Gordesky-Gold, B.; Harries, G.; Christensen, A. C.
Tipo: text
Publicado em /05/1993 Português
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One of the most extreme examples of gene dosage sensitivity is the Triplo-lethal locus (Tpl) on the third chromosome of Drosophila melanogaster, which is lethal when present in either one or three copies. Increased dosage of an unlinked locus, Isis, suppresses the triplo-lethal phenotype of Tpl, but not the haplo-lethal phenotype. We have mapped Isis to the X chromosome region 7E3-8A5, and shown that the suppression is a gene dosage effect. Altered dosage of Isis in the presence of two copies of Tpl has no obvious effects. By examining the interactions between Isis dosage and Tpl we suggest that Isis does not directly repress Tpl expression, but acts downstream on the triplo-lethal phenotype of Tpl.

AUTHOR INDEX: V-Z

Tipo: text
Publicado em /12/1984 Português
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Highly nonlinear photodamage in two-photon fluorescence microscopy.

Hopt, A; Neher, E
Tipo: text
Publicado em /04/2001 Português
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Two-photon fluorescence excitation is being increasingly used in laser scan microscopy due to very low photodamage induced by this technique under normal operation. However, excitation intensity has to be kept low, because nonlinear photodamage sets in when laser power is increased above a certain threshold. We studied this kind of damage in bovine adrenal chromaffin cells, using two different indicators of damage: changes in resting [Ca(2+)] level and the degranulation reaction. In agreement with previous studies, we found that, for both criteria, damage is proportional to the integral (over space and time) of light intensity raised to a power approximately 2.5. Thus, widening the laser pulse shape at constant average intensity both in time and in focal volume is beneficial for avoiding this kind of damage. Both measures, of course, reduce the two-photon fluorescence excitation. However, loss of signal can be compensated by increasing excitation power, such that, at constant damaging potential, signals may be even larger with long pulses and large focal volumes, because the exponent of the power law of damage is higher (mu approximately 2.5) than that of the two-photon signal (mu approximately 2).

Cholecystokinin antagonists in gastroenterology

Calam, J
Tipo: text
Publicado em /06/1993 Português
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Discussion

Tipo: text
Publicado em /10/1971 Português
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TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 26, 1927

Tipo: text
Publicado em /02/1928 Português
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Indicators for Treatment Strategies of Colorectal Liver Metastases

Ueno, Hideki; Mochizuki, Hidetaka; Hatsuse, Kazuo; Hase, Kazuo; Yamamoto, Tetsuhisa
Tipo: text
Publicado em /01/2000 Português
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Modulation of sensory neuron mechanotransduction by PKC- and nerve growth factor-dependent pathways

Di Castro, Amalia; Drew, Liam J.; Wood, John N.; Cesare, Paolo
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: text
Português
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Many sensations of pain are evoked by mechanical stimuli, and in inflammatory conditions, sensitivity to such stimuli is commonly increased. Here we used cultured sensory neurons as a model of the peripheral terminal to investigate the effects of inflammatory signaling pathways on mechanosensitive ion channels. Activation of two of these pathways enhanced transduction in a major population of nociceptors. The proinflammatory neurotrophin nerve growth factor caused an up-regulation of mechanically activated currents via a transcriptional mechanism. Activators of PKC, given in vitro and in vivo, also caused an increase in mechanically activated membrane current and behavioral sensitization to mechanical stimulation, respectively. The effect of activating PKC was inhibited by tetanus toxin, suggesting that insertion of new channels into the cell membrane is involved in sensitization. These results reveal previously undescribed mechanisms by which PKC and nerve growth factor synergistically enhance the response of nociceptors to mechanical stimuli, suggesting possible targets for pain treatment.

Action of chlorothiazide on the distribution, excretion and hypotensive effect of pempidine in man

Dollery, C. T.; Emslie-Smith, D.; Muggleton, D. F.
Tipo: text
Publicado em /12/1961 Português
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When chlorothiazide is given to hypertensive patients who are receiving pempidine a rise in plasma pempidine concentration occurs and this is proportionately greater than the additional fall in blood pressure. After pempidine has been added to human whole blood in vitro or in vivo the ratio of the pempidine concentration in the red cells to that in the plasma falls in the course of 1 hr from an initial value greater than 2 to about 1.2. If chlorothiazide is present also, however, the ratio remains constant at 0.7. Changes in the plasma pempidine concentration in vivo probably result from the binding of pempidine to plasma protein in the presence of chlorothiazide. This has been observed in vitro by a dialysis technique.

Worksite smoking cessation programs: a potential for national impact.

Stachnik, T; Stoffelmayr, B
Tipo: text
Publicado em /12/1983 Português
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Data from three pilot studies of small worksite smoking cessation programs demonstrate that programs which appeal to all smokers in an organization, not just those who have stated an interest in achieving cessation, will attract a high per cent of smokers and assist an unusually high per cent of them to achieve and maintain abstinence.

An Introduction to Pharmaceutical Formulation

Ecobichon, D. J.
Tipo: text
Publicado em /08/1966 Português
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Henry Currey FRIBA (1820–1900): leading Victorian hospital architect, and early exponent of the "pavilion principle"

Cook, G
Fonte: BMJ Group Publicador: BMJ Group
Tipo: text
Publicado em /06/2002 Português
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