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PubMed1991

[Superoxide anion generation of human polymorphonuclear leukocytes in urine].

In order to clarify the role of polymorphonuclear leukocytes (PMNs) in the defence mechanism of the urinary tract, we investigated the superoxide anion (O2-) generation of PMNs in the urine. We tested urines mixing concentrated urine with diluted ones in various ratios. Peripheral blood derived PMNs were stimulated in tested urines or phosphate buffer solution (1M, pH 7.0) with phorbol-myristate acetate and O2- generation of PMNs was measured by means of chemiluminescence (CL) method. The CL values of PMNs in tested urines were 1/30 that of phosphate buffer solution. However, PMNs generated O2- at maximum levels when the urine osmolarity was 300-400 mOsm/kg. Furthermore, PMNs did not generate O2- when the urine osmolarity was more than 600 mOsm/kg, or less than 200 mOsm/kg. We also investigated the influence of urea and creatinine on O2- generation of PMNs. The O2- generation of PMNs decreased when the urea concentration rose. However, there was no influence of creatinine on O2- generation of PMNs. From these results, it was elucidated that PMNs generated O2- when the urine osmolarity was 300-400 mOsm/kg. Therefore, urine osmolarity of the patients with urinary tract infection should be kept at 300-400 mOsm/kg, and diuresis might be important for the patients with urinary tract infection.

Creatinine↗
PubMed1989

Phorbol myristate acetate modulates calcium ion-dependent superoxide anion generation induced by a monoclonal antibody raised against polymorphonuclear leukocytes.

We used a monoclonal antibody, YI 51, raised against human polymorphonuclear leukocytes (PMN) to induce superoxide anion (O2-) generation in cells. Although YI 51 alone played only a small part in inducing O2- generation in PMN, the amount of O2- generation induced in 5 X 10(5) PMN was 3.7 to 5.5 nmol/min when F(ab')2 fragments of rabbit anti-mouse immunoglobulin antibody were added as a cross-linking agent. This O2- -inducing activity was high compared with that of wheat germ agglutinin (WGA), insoluble immunoglobulin G immune complexes (IC), or phorbol myristate acetate (PMA). The binding of YI 51 and soluble immunoglobulin G IC to PMN was not reciprocally inhibitory, indicating that YI 51 does not interfere with ligand binding to the Fc receptor-binding site. In the absence of calcium ion (Ca2+), O2- generation induced by YI 51 decreased to 10 to 20% of that in the presence of Ca2+. In contrast, O2- generation in response to WGA, IC, or PMA under Ca2+-free conditions was not affected. When PMN were pretreated with low concentrations of PMA (10(-10) to 10(-9) M), the amount of O2- generation by the cells in response to YI 51 in Ca2+-free buffer was enhanced in a concentration-dependent manner. It also equaled the O2- generated by the cells in buffer containing Ca2+. In cells pretreated with PMA, the amount of O2- induced by WGA was enhanced two- to threefold over that in untreated cells. In contrast, there was no augmentation over untreated cells with stimulation by IC. These results suggest that YI 51, IC, and WGA induce O2- generation in human PMN in different manners.

Animals↗
PubMed1981

Effect of long generation times on growth of Bacteroides thetaiotaomicron in carbohydrate-induced continuous culture.

We investigated the ability of Bacteroides thetaiotaomicron, an obligate anaerobe from human colonic microflora, to grow in a carbohydrate-limited continuous culture at generation times ranging from 3.5 to 28 h per division. Four carbohydrates were tested: glucose, N-acetylglucosamine, glucuronic acid, and glucosamine. At a generation time of 3.5 h per division, the growth yields for bacteria growing on glucose, N-acetylglucosamine, and glucuronic acid were 76, 68, and 50 g of cells (dry weight) per mol of substrate, respectively. Growth yields at 28 h per division were 61, 52, and 37 g/mol of substrate, respectively. When glucosamine was the carbohydrate source, a stable population of bacteria was attainable only at generation times longer than 12 h per division. Growth yields at 15 and 32 h per division were 11 and 33 g/mol of substrate, respectively. There was no significant variation with increasing generation times in the specific activities of selected glycolytic enzymes, of disaccharidases such as alpha- and beta-glucosidases and alpha- and beta-galactosidases, or of the polysaccharidase chondroitin sulfate lyase. By contrast, the pattern of fermentation products varied with both the generation time and the carbon source. At a generation time of 3.5 h per division, the main products from the fermentation of glucose were acetate and succinate, with a trace of propionate. At 28 h per division, propionate concentrations were higher and succinate concentrations were lower than at 3.5 h per division. The products from the fermentation of glucosamine were the same as those from glucose fermentation. However, when N-acetylglucosamine was fermented, the concentration of acetate was much higher at all generation times than when glucose was the carbon source. When glucuronic acid was the carbon source, acetate was the main fermentation product, and only traces of propionate and succinate were detected. Another characteristic that varied with the growth rate was the ability of B. thetaiotaomicron to produce the inducible enzyme alpha-glucosidase when exposed to maltose. The ability of the organism to produce this enzyme declined with increasing generation times.

Acetylglucosamine↗
PubMed1976

Factors involved in the generation and replication of rhabdovirus defective T particles.

Previous indications that cloned B virions might be genetically predisposed to generate a particular defective T particle are shown to be inaccurate. T particle generation was found to be a much more random process than was previously believed. We show that the previously observed generation of particular sizes of T particles by B virion pools is due to the random generation of T particles during preparation of first-passage pools of cloned B virions, and these breed true during the additional passages needed to produce visible quantities of T particles. It is also shown that different host cell lines selectively amplify different T particles, suggesting a strong role of host cell factors in T particle replication. Surprisingly, our line of HeLa cells did not generate or replicate detectable T particles of vesicular stomatitis virus (VSV) Indiana after either serial undiluted passage or direct addition of T particles, even though the added T particles strongly interfered with B virion replication. In contrast to VSV, rabies virus generates large amounts of T particles during the first passage of cloned B virions, and every rabies-infected baby hamster kidney-21 cell culture evolves into a persistent carrier state. We find that T particle RNA is biologically inactive although T particle nucleocapsid ribonucleoprotein replicates and interferes in cells coinfected with B virions. Efforts to study the mechanism of T particle generation by in vitro attempts to generate T particles or modify their size (using sheared ribonucleoprotein or chemical or UV mutagenesis) were unsuccessful. The kinetics of UV and nitrous acid inactivation of T particles indicate a smaller target size relative to B virions, even after correcting for lengths of RNA molecules. The intercalating dye proflavine does not photosensitize VSV B virions or T particles when present during replication, indicating that there is little or no RNA base pairing in the helical nucleocapsids of either.

Cell Line↗
PubMed1981

Suppression of vesicular stomatitis virus defective intefering particle generation by a function(s) associated with human chromosome 16.

Human-mouse somatic cell hybrids were made between adenine phosphoribosyltransferase-deficient mouse L cells and a strain of human primary fibroblasts and selected in medium containing alanosine and adenine (J. A. Tischfield and F. H. Ruddle, Proc. Natl. Acad. Sci. U.S.A. 71:45-49, 1974). These hybrids were tested for the generation of defective interfering (DI) particles of vesicular stomatitis virus to determine whether or not a host gene controls the induction of DI particles. None of the seven independently arising hybrid clones tested generated detectable DI particles during 13 successive undiluted passages. In addition, the parental human cells also failed to generate DI particles. In contrast, the parental mouse cells generated a detectable level of DI particles during continuous passage. Thus, failure to generate DI particles appears to act in a dominant fashion in these hybrids. Human chromosome 16 and adenine phosphoribosyltransferase were present, as a direct consequence of the selection system, in all of the hybrid clones that failed to generate DI particles. It was the only human chromosome observed in the cells of every hybrid clone. This was verified by both isozyme and karyotype analyses. After hybrids were back-selected (with 2,6-diaminopurine) for loss of human adenine phosphoribosyltransferase and chromosome 16, they gained the ability to generate DI particles. Replication of DI particles already present in virus stocks, however, was normal in all of the hybrid clones and the parental human cells. This suggests that the induction, but not the replication, of DI particles is affected by the human genome and that a factor on human chromosome 16 seems to selectively suppress the mouse cell's ability to generate DI particles in the hybrids. These results support the idea that the induction of DI particles is controlled in part by host cell function(s), as suggested previously (C. Y. Kang and R. Allen, J. Virol. 25:202-206, 1978).

Animals↗
PubMed1993

Effect of quartz and alumina dust on generation of superoxide radicals and hydrogen peroxide by alveolar macrophages, granulocytes, and monocytes.

Phagocytosis of quartz particles by rabbit alveolar macrophages and monocytes and human granulocytes and monocytes was accompanied by stimulation of substrate free reduction of nitroblue tetrazolium to formazan. This reflects activation of an oxygen dependent bactericidal system of phagocytes and total (exogenic and endogenic) generation of active oxygen species. Low fibrogenic and cytotoxic alumina dust tended to increase formazan production by comparison with quartz dust. During phagocytosis of quartz dust by alveolar macrophages and monocytes there was no exogenic generation of superoxide radicals and hydrogen peroxide by these cells. By contrast, incubation of human granulocytes with quartz dust caused a significant increase in exogenic generation of superoxide radicals and hydrogen peroxide. Under such conditions, low fibrogenic alumina dust had no effect on hydrogen peroxide generation and substantially decreased the level of superoxide radical generation by human granulocytes. During incubation of rabbit granulocytes with quartz dust, an increase in the level of superoxide radical generation was also detected. It is considered that the differences between alveolar macrophages and granulocytes in their response to quartz dust are important from a physiological point of view. Alveolar macrophages are permanently present in pulmonary alveolae in large quantities; therefore their uncontrolled generation of superoxide radicals and hydrogen peroxide might immediately cause damage to pulmonary parenchyma. At the same time, destruction products from alveolar macrophages that died during phagocytosis of quartz particles contain a factor attracting granulocytes. Presence of a significant number of granulocytes in bronchopulmonary lavage fluid in cases of silicosis indicates development of a pathological process. This agrees well with the data obtained on exogenic generation of superoxide radicals and hydrogen peroxide by granulocytes, and on stimulation of this process due to phagocytosis of the quartz dust.

Aluminum Oxide↗
PubMed2003

Generating Quitline calls during Australia's National Tobacco Campaign: effects of television advertisement execution and programme placement.

OBJECTIVE: The study sought to measure the relative efficiency of different television advertisements and types of television programmes in which advertisements were placed, in generating calls to Australia's national Quitline. DESIGN: The study entailed an analysis of the number of calls generated to the Quitline relative to the weight of advertising exposure (in target audience rating points (TARPs) for particular television advertisements and for placement of these advertisements in particular types of television programmes. A total of 238 television advertisement placements and 1769 calls to the Quitline were analysed in Sydney and Melbourne. RESULTS: The more graphic "eye" advertisement conveying new information about the association between smoking and macular degeneration leading to blindness was more efficient in generating quitline calls than the "tar" advertisement, which reinforced the message of tar in a smoker's lungs. Combining the health effects advertisements with a quitline modelling advertisement tended to increase the efficiency of generating Quitline calls. Placing advertisements in lower involvement programmes appears to provide greater efficiency in generating Quitline calls than in higher involvement programmes. CONCLUSIONS: Tobacco control campaign planners can increase the number of calls to telephone quitlines by assessing the efficiency of particular advertisements to generate such calls. Pairing of health effect and quitline modelling advertisements can increase efficiency in generating calls. Placement of advertisements in lower involvement programme types may increase efficiency in generating Quitline calls.

Adolescent↗
PubMed2006

Species- and tissue-specific relationships between mitochondrial permeability transition and generation of ROS in brain and liver mitochondria of rats and mice.

In animal models of neurodegenerative diseases pathological changes vary with the type of organ and species of the animals. We studied differences in the mitochondrial permeability transition (mPT) and reactive oxygen species (ROS) generation in the liver (LM) and brain (BM) of Sprague-Dawley rats and C57Bl mice. In the presence of ADP mouse LM and rat LM required three times less Ca(2+) to initiate mPT than the corresponding BM. Mouse LM and BM sequestered 70% and 50% more Ca(2+) phosphate than the rat LM and BM. MBM generated 50% more ROS with glutamate than the RBM, but not with succinate. With the NAD substrates, generation of ROS do not depend on the energy state of the BM. Organization of the respiratory complexes into the respirasome is a possible mechanism to prevent ROS generation in the BM. With BM oxidizing succinate, 80% of ROS generation was energy dependent. Induction of mPT does not affect ROS generation with NAD substrates and inhibit with succinate as a substrate. The relative insensitivity of the liver to systemic insults is associated with its high regenerative capacity. Neuronal cells with low regenerative capacity and a long life span protect themselves by minimizing ROS generation and by the ability to withstand very large Ca(2+) insults. We suggest that additional factors, such as oxidative stress, are required to initiate neurodegeneration. Thus the observed differences in the Ca(2+)-induced mPT and ROS generation may underlie both the organ-specific and species-specific variability in the animal models of neurodegenerative diseases.

Animals↗
PubMed1980

Mechanisms underlying pattern generation in lobster stomatogastric ganglion as determined by selective inactivation of identified neurons. I. Pyloric system.

1. Four factors contribute to pattern generation in the pyloric network of the lobster stomatogastric ganglion. These are: a) endogenously oscillating neurons; b) synaptic network properties; c) nonlinear cellular properties, including the generation of plateau potentials; and d) excitatory input from the commissural ganglia. The roles and relative importance of these factors were investigated with a new technique for inactivating single specific identified neurons. 2. In stomatogastric ganglia in which the excitatory input is left intact, a) pattern generation continues when any cell or pair of cells other than the endogenous bursters are inactivated, b) pattern generation also continues when the endogenous bursters are inactivated, c) pattern generation ceases when the endogenous bursters plus one other particular cell are inactivated. This cell, although not an endogenous burster, displays a strong tendency to generate plateau potentials. 3. In stomatogastric ganglia that have been isolated from excitatory input, a) pattern generation continues when any cell or pair of cells other than the endogenous bursters are inactivated, b) pattern generation ceases when the endogenous bursters are inactivated. 4. Some of the inputs to the stomatogastric ganglion normally fire in bursts. However, their potentiation and acceleration of the output pattern are also produced by tonic stimulation of the nerve. The effect of one of those inputs is mimicked by bath application of dopamine to the stomatogastric ganglion. 5. The roles and importance of the three most important factors were qualitatively summarized in a chart specifying the activity of the network as a function of its intactness.

Action Potentials↗
PubMed1986

Generator potentials and spike initiation in auditory fibers of goldfish.

Responses were recorded extra- or intracellularly from single, small afferent fibers of the goldfish saccule, that is, S2 fibers, to clarify how the spontaneous and sound-evoked firings in these fibers are initiated from generator potentials. Spontaneously active units randomly selected from the saccular nerve of five goldfish (total 78 units) were classified by the coefficient of variation (CV) of interspike intervals into irregular (59 units; CV greater than 0.3), intermediate (10 units), and regular types (9 units; CV less than 0.23). The irregular type showed a burst (38 units) or random (21 units) pattern of firing in spontaneous activity. In cases where a clear generator potential could be recorded in response to each sound wave, spontaneous generator potentials could also be observed in the absence of stimulus sound. These spontaneous potentials were irregular in amplitude and time course, and often contained components much slower than the sound-evoked generator potentials. The sound-evoked generator potentials in S2 fibers were produced with a delay of 0.4-0.85 ms following each sound wave, and had a time course comparable to the sound-evoked excitatory postsynaptic potentials (EPSPs) of large S1 fibers. They also shared other properties such as adaptive decline in amplitude, incremental and decremental responses, and off-suppression. The mean amplitude of the sound-evoked generator potentials in S2 fibers was linearly related to the rate of afferent firing. There was no apparent difference in the action potential threshold amplitude for spontaneous and sound-evoked generator potentials. It may be concluded that the generator potentials that underlie the spontaneous and sound-evoked firing of S2 fibers are produced by the release of transmitter by hair cells.

Adaptation, Physiological↗
PubMed1992

Mechanisms of gastric rhythm generation in the isolated stomatogastric ganglion of spiny lobsters: bursting pacemaker potentials, synaptic interactions, and muscarinic modulation.

1. The gastric central pattern generator (CPG), located in the stomatogastric ganglion (STG) of the spiny lobster (Panulirus interruptus), is nonrhythmic when deprived of neuromodulatory inputs from anterior ganglia. Leaving these inputs intact in vitro can sustain a gastric rhythm but also introduces numerous, uncontrolled and largely unknown modulatory and synaptic influences that greatly complicate analysis of this CPG. 2. Here we induced gastric rhythms in the isolated STG, by superfusing a specific modulator, the muscarinic agonist, pilocarpine. Muscarinic agents sustain vigorous gastric rhythms in the isolated STG. Our aim was to analyze the pattern-generating functions of the restricted gastric circuit, free of complicating influences from other ganglia, and under specific (muscarinic) modulation. 3. We used combinations of multiple cell hyperpolarizations, photodeletions, and synaptic blockade by picrotoxin to assess the pattern-generating role of individual gastric neurons and to study the activity of subcircuits. 4. Four identified gastric neurons [lateral gastric (LG), dorsal gastric (DG), 2 electrically coupled lateral posterior gastric (2LPGs)] acted as pattern-generating cells. They showed bursting pacemaker potentials (BPPs), i.e., plateau (or driver) potentials that underlay bursts of axonal spikes and slow, interburst depolarizing potentials that underlay repetitive burst activity. LG and DG, at least, became conditional bursters, able to burst repetitively because of intrinsic oscillations. The other gastric neurons behaved mainly as follower cells and derived their rhythmic bursting from synaptic coupling to the pattern-generator cells and from their own intrinsic (but nonoscillatory) properties. 5. The pattern-generating neurons form a novel "kernel" circuit that works by the cooperative interaction of cellular properties and synaptic connectivity. 6. This study constitutes the first complete and fully consistent analysis of pattern generation in the gastric network of the isolated STG. These mechanisms pertain to muscarinic rhythms in particular but also, we suggest, to gastric rhythm generation and CPG function in general. We suggest that 1) rhythmicity normally depends on the induction of bursty membrane properties in at least some component neurons; 2) different subcircuits can produce rhythmic patterns and may be activated by different modulators; and 3) the gastric network shares several important "building blocks" with CPGs that have been analyzed in other systems. 7. Muscarinic inputs are implicated as an important gastric regulator. We compare these responses with the reported modulatory actions of the anterior pyloric modulator (AMP), an identified, putatively cholinergic input interneuron that may act via muscarinic mechanisms.

Animals↗
PubMed1998

Role of cyclic adenosine monophosphate in reducing superoxide anion generation in guinea pig alveolar macrophages.

Aveolar macrophages (AM) may contribute to airway inflammation via release of superoxide anion (O2-). Elevation of intracellular cyclic adenosine monophosphate (cAMP) levels has been shown to suppress O2- generation, although the exact mechanism is uncertain. To examine the inhibitory effect of cAMP against different stimuli for O2- generation, we compared the effect of cAMP on O2- generation caused by phorbol myristate acetate (PMA), a direct protein kinase C activator, and N-formyl-methionyl-leucyl-phenylalanine (FMLP), which couples its membrane receptor and stimulates guanosine triphosphate binding protein, in guinea pig AM. Cyclic nucleotide phosphodiesterase (PDE) isoenzyme inhibitors or CPT-cAMP, a cAMP analogue, were used in order to increase intracellular cAMP levels. The O2- generation caused by either PMA or FMLP was reduced by cilostazol (PDE 3 inhibitor) and Ro20-1724 (PDE 4 inhibitor), but not by zaprinast (PDE 5 inhibitor). The degree of reduction in O2- generation was not different between PMA and FMLP. Furthermore, CPT-cAMP also reduced PMA- or FMLP-induced O2- generation to a similar degree, although only high concentrations (10(-5) or 10(-4) mol/l) of this agent were effective in producing significant inhibition. A remarkable elevation of the cAMP level is required to produce the inhibitory effect on O2- generation in guinea pig AM. An elevation of cAMP may suppress O2- generation by inhibiting plural sites of the intracellular signaling pathways.

Animals↗
PubMed2006

Lysophosphatidic acid induces thrombogenic activity through phosphatidylserine exposure and procoagulant microvesicle generation in human erythrocytes.

OBJECTIVE: Although erythrocytes have been suggested to play a role in blood clotting, mediated through phosphatidylserine (PS) exposure and/or PS-bearing microvesicle generation, an endogenous substance that triggers the membrane alterations leading to a procoagulant activity in erythrocytes has not been reported. We now demonstrated that lysophosphatidic acid (LPA), an important lipid mediator in various pathophysiological processes, induces PS exposure and procoagulant microvesicle generation in erythrocytes, which represent a biological significance resulting in induction of thrombogenic activity. METHODS AND RESULTS: In human erythrocytes, LPA treatment resulted in PS exposure on remnant cells and PS-bearing microvesicle generation in a concentration-dependent manner. Consistent with the microvesicle generation, scanning electron microscopic study revealed that LPA treatment induced surface changes, alteration of normal discocytic shape into echinocytes followed by spherocytes. Surprisingly, chelation of intracellular calcium did not affect LPA-induced PS exposure and microvesicle generation. On the other hand, protein kinase C (PKC) inhibitors significantly reduced PS exposure and microvesicle generation induced by LPA, reflecting the role of calcium-independent PKC. Activation of PKC was confirmed by Western blot analysis showing translocation of calcium-independent isoform, PKCzeta, to erythrocyte membrane. The activity of flippase, which is important in the maintenance of membrane asymmetry, was also inhibited by LPA. Furthermore, LPA-exposed erythrocytes actually potentiated the thrombin generation as determined by prothrombinase assay and accelerated the coagulation process initiated by recombinant human tissue factor in plasma. The adherence of erythrocytes to endothelial cells, another important feature of thrombogenic process, was also stimulated by LPA treatment. CONCLUSIONS: These results suggested that LPA-exposed erythrocytes could make an important contribution to thrombosis mediated through PS exposure and procoagulant microvesicle generation.

Adolescent↗
PubMed2006

Effects on coagulation and fibrinolysis induced by influenza in mice with a reduced capacity to generate activated protein C and a deficiency in plasminogen activator inhibitor type 1.

Influenza infections increase the risk of diseases associated with a prothrombotic state, such as venous thrombosis and atherothrombotic diseases. However, it is unclear whether influenza leads to a prothrombotic state in vivo. To determine whether influenza activates coagulation, we measured coagulation and fibrinolysis in influenza-infected C57BL/6 mice. We found that influenza increased thrombin generation, fibrin deposition, and fibrinolysis. In addition, we used various anti- and prothrombotic models to study pathways involved in the influenza-induced prothrombotic state. A reduced capacity to generate activated protein C in TM(pro/pro) mice increased thrombin generation and fibrinolysis, whereas treatment with heparin decreased thrombin generation in influenza-infected C57Bl/6 mice. Thrombin generation was not changed in hyperfibrinolytic mice, deficient in plasminogen activator inhibitor type-1 (PAI-1(-/-)); however, increased fibrin degradation was seen. Treatment with tranexamic acid reduced fibrinolysis, but thrombin generation was unchanged. We conclude that influenza infection generates thrombin, increased by reduced levels of protein C and decreased by heparin. The fibrinolytic system appears not to be important for thrombin generation. These findings suggest that influenza leads to a prothrombotic state by coagulation activation. Heparin treatment reduces the influenza induced prothrombotic state.

Animals↗
PubMed2005

Movement generation with circuits of spiking neurons.

How can complex movements that take hundreds of milliseconds be generated by stereotypical neural microcircuits consisting of spiking neurons with a much faster dynamics? We show that linear readouts from generic neural microcircuit models can be trained to generate basic arm movements. Such movement generation is independent of the arm model used and the type of feedback that the circuit receives. We demonstrate this by considering two different models of a two-jointed arm, a standard model from robotics and a standard model from biology, that each generates different kinds of feedback. Feedback that arrives with biologically realistic delays of 50 to 280 ms turns out to give rise to the best performance. If a feedback with such desirable delay is not available, the neural microcircuit model also achieves good performance if it uses internally generated estimates of such feedback. Existing methods for movement generation in robotics that take the particular dynamics of sensors and actuators into account (embodiment of motor systems) are taken one step further with this approach, which provides methods for also using the embodiment of motion generation circuitry, that is, the inherent dynamics and spatial structure of neural circuits, for the generation of movement.

Action Potentials↗
PubMed2005

The apple does not fall far from the tree: attachment styles and personality vulnerabilities to depression in three generations of women.

The intergenerational transmission of attachment insecurity was examined in a community sample of 300 participants consisting of 100 three-generation triads of women. It was hypothesized that personality vulnerabilities mediate the association between attachment insecurity and depression within each generation. Findings show significant intergenerational congruence of trait vulnerabilities and attachment styles. Moreover, the second generation's attachment dimensions and personality vulnerabilities were found to mediate the association between first- and third-generation scores on attachment and vulnerability variables. Findings supported the following hypothesized within- and between-generation paths: Within generations, self-criticism was found to mediate the association between attachment insecurity and depression; between generations, depression, but not self-criticism, mediated the association between assessments of attachment insecurity in mothers and their daughters. This study constitutes a first approach to the delineation of the role played by self-criticism in the association between negative models of the self and depression across generations.

Adult↗
PubMed2001

Hydroxyl radical generation: the effect of bicarbonate, dioxygen and buffer concentration on pH-dependent chemiluminescence.

Enhanced chemiluminescence (CL) induced by HO* was detected using the primary enhancers luminol (Lum), isoluminol (ILum) and lucigenin (Luc), in the absence of HCO3-, at pH 9.5, 10.0 and 10.5 but not between pH 4.0 and 9.0. This was confirmed using nine different HO* generators. FeCl3/NTA/H2O2 was the only HO* generator that was able to generate singular HO* which was obtained entirely from the Fenton reaction. However, this was so only at pH 10.0 since at all other pHs multiple ROS were produced. This was confirmed by the chemical detection of the fluorescent hydroxylated product of terephthalic acid in the absence of O2. No HO* Lum-CL pH optima coincided with the O2*- mediated Lum-CL optima found at pH 8.0 and 9.0. Bicarbonate had an enhancing effect on Lum-CL which was 70-2700% at pH 10.0 for the different HO* generators. This was due to the conversion of the radical-electron from HO* to CO3*-, making CL detection more efficient since less HO* were lost initially before detection. Methyl-cypridine-luciferin analogue (MCLA) elicited CL in the pH range 4.0-10.0 with the same set of generators in the absence of HCO3-. The iron-containing generators had their different MCLA-CL optima at pH 4.5, 5.0 or 6.0, excluding those overlapping with the O2(*-)-mediated CL optima. The two copper-containing generators had optima at the same pHs, viz, 7.0 and 10.5. Again, FeCl3/NTA/H2O2 was the only HO* generator able to produce singular HO* by the Fenton reaction. However, whereas Lum-CL was able to detect singular HO* only at pH 10.0, MCLA-CL detected it at pH 5.0 and 5.5. Therefore, MCLA is the most suitable CL enhancer for physiological assessments since it is the most sensitive enhancer and has HO* CL optima nearer to physiological pH than the other probes. The HCO3- enhancement of MCLA-CL was even greater than that of Lum-CL, since increases of 114-fold and 37-fold, respectively, were obtained at these HO*-specific pH optima for FeCl3/NTA/H2O2. Therefore, bicarbonate concentration is as important a parameter as pH when the enhanced CL of a non-cellular system is determined. Hydrogen peroxide was not able to elicit CL directly but, due to trace metal contamination, it produced artifactual CL due to HO* formation. High H2O2 levels, which prevent spontaneous O2*- dismutation, helped to establish the overlapping pH optima of CL mediated by O2*- and HO* which were artifactually produced either by O2*- via H2O2 and trace metals or by perferryl intermediates, respectively. Due to spontaneous dismutation to H2O2, only 22% of the O2*- produced by HX/XO could be detected by enhanced CL.

Acridines↗
PubMed2004

Patients with severe sepsis vary markedly in their ability to generate activated protein C.

Activated protein C (APC) supplementation significantly reduces mortality in patients with severe sepsis, presumably by down-regulating coagulation, inflammation, and apoptosis. In vivo, endogenous APC is generated from protein C (PC) "on demand" in response to elevated thrombin levels. Thrombomodulin and endothelial cell protein C receptor are endothelial receptors required to generate APC endogenously. Since these receptors may be down-regulated in sepsis, we measured plasma markers of APC generation in 32 patients with severe sepsis to determine whether APC generation is impaired and whether markers of APC generation correlate with 28-day mortality. Relative to normals, all patients had elevated F1 + 2 and thrombin-antithrombin complex (TAT) levels (markers of thrombin generation and inhibition, respectively), and 28 of 32 patients had reduced PC levels. In 20 patients, APC levels paralleled elevated F1 + 2 levels, whereas 12 patients had low APC levels despite elevated F1 + 2 levels, suggesting that APC generation is impaired in the latter. No significant differences exist between survivors and nonsurvivors with respect to baseline PC levels, F1 + 2 levels, and APACHE II (acute physiology and chronic health evaluation) scores. Baseline APC levels were higher in survivors (P = .024), and baseline F1 + 2/APC ratios were lower in survivors (P = .047). Larger studies are warranted to establish whether APC generation profiles aid in managing sepsis.

APACHE↗