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PubMed1995

Learning and evolution: a quantitative genetics approach.

Recent models of the interactions between learning and evolution show that learning increases the rate at which populations find optima in fixed environments. However, learning ability is only advantageous in variable environments. In this study, quantitative genetics models are used to investigate the effects of individual learning on evolution. Two models of populations of learning individuals are constructed and analyzed. In the first model, the effect of learning is represented as an increase in the variance of selection. Dynamical equations and equilibrium conditions are derived for a population of learning individuals under fixed and variable environmental selection. In the second model, the amount of individual learning effort is regulated by a second gene specifying the duration of a critical learning period. The second model includes a model of the learning process to determine the individual fitness costs and benefits accrued during the learning period. Individuals are then selected for the optimal learning investment. The similarities of the results from these two models suggest that the net effects of learning on evolution are relatively independent of the mechanisms underlying the learning process.

Animals↗
PubMed1992

Does frequency-dependent selection optimize fitness?

In evolutionary biology, the axiom that natural selection tends ideally to maximize inclusive fitness of the individual or some other suitable quantity is often advanced (Cody, 1974; Maynard Smith, 1978; Krebs & McCleery, 1984; Houston et al., 1988). Moreover, the evolutionists generally distinguish two situations (Dawkins, 1980; Maynard Smith, 1982): one in which fitness is independent of the frequency of the phenotypes present in the population (frequency-independent selection), and one in which it does depend on this frequency (frequency-dependent selection). This led some authors such as Parker (1984), and more recently Parker & Maynard Smith (1990), to consider "a 2-speed optimization": frequency-independent selection should lead to a "simple optimum" at the end of the selective process, since all the individuals should have the same strategy and the mean fitness of the population should be maximized; frequency-dependent selection, formulated in terms of the theory of games, should lead to a "competitive optimum" even though the "evolutionary stable strategy" (or "ESS"; Maynard Smith & Price, 1973) characterizing the equilibrium "is not the strategy that maximizes fitness in a population sense" (Parker & Maynard Smith, 1990: 30). Our aim in this short communication is to criticize the concept of "competitive optimum" by Parker & Maynard Smith, as well as the general ability of natural selection to "maximize fitness", even in "phenotypic models" (Lloyd, 1977). These models, devoid of genetic constraints since each strategist is assumed to reproduce its own kind, are especially suitable for examining the ideal effect of natural selection.

Animals↗
PubMed1984

A specific mutation abolishing Na+/H+ antiport activity in hamster fibroblasts precludes growth at neutral and acidic pH.

A H+-suicide technique based on the reversibility of Na+/H+ antiport was developed for the selection of mutants deficient in this membrane-bound activity. The strategy was to use the Na+/H+ antiporter as a H+-vector killing device. Chinese hamster lung fibroblasts (CCL39) were loaded with LiCl and incubated in Na+-, Li+-free choline Cl saline solution (pH 5.5). Under these conditions, intracellular pH dropped in 5 min from 7.1 to 4.8, leading to a rapid loss of cell viability (less than 0.1% survival after 30 min). Cytoplasmic acidification and cell death were prevented by treatment with 5-N,N-dimethylamiloride, a potent inhibitor of Na+/H+ antiport. Of the H+-suicide resistant clones that survived two cycles of selection, 90% were found deficient in Na+/H+ antiport activity. One class of mutants (PS10, PS12) fully resistant to the H+-suicide test, does not acidify the cell interior in response to an outward-directed Li+ gradient and has no detectable amiloride-sensitive Na+ influx measured either in Li+- or H+-loaded cells. Growth of these fibroblast clones lacking Na+/H+ antiport was found to be pH conditional in HCO3(-)-free medium. Whereas wild-type cells can grow over a wide range of external pHs (6.6-8.2), PS mutants cannot grow at neutral and acidic pHs (pH less than 7.2); their optimal growth occurs at alkaline pH values (pH 8-8.3). These findings strongly suggest that the Na+/H+ antiport activity through regulation of intracellular pH plays a crucial role in growth control.

Acid-Base Equilibrium↗
PubMed1988

Colonization of the Krakatau Islands by vertebrates: equilibrium, succession, and possible delayed extinction.

MacArthur and Wilson [MacArthur, R. H. & Wilson, E. O. (1967) The Theory of Island Biogeography (Princeton Univ. Press, Princeton, NJ)] used the rate of recolonization of the Krakatau Islands (sterilized in the cataclysmic 1883 eruption) by birds and vascular plants to test their equilibrium model of immigration and extinction processes on islands. Working with data only up to 1933, they concluded that the number of resident land bird species had approached equilibrium by 1908-1919, 25-36 years after the eruption, when the number of vascular plant species was still increasing. Recent surveys of vertebrates on the archipelago show continuing colonization, as well as species turnover. Nonmigrant nonmarine birds and reptiles are only now approaching equilibrium species numbers; archipelago acquisition rates for these groups are lower than in the 40 years following the 1883 eruption. Apparent (minimal) annual extinction rates are an order of magnitude lower than those calculated for equilibrium by MacArthur and Wilson. The active volcano Anak Krakatau emerged in 1930 and suffered an eruption in 1952 that destroyed the vegetation. It is still at an early stage of succession and on the threshold of major vegetational change. This island and a physically dynamic, ever-young spit on Sertung I, also held at an early successional stage, may provide (i) ecological refuges for some species whose optimal habitat on the older islands is being extirpated by vegetational succession and (ii) ecological "windows" through which such species may still establish from the mainland, thus postponing their extinction on the archipelago.

Animals↗
PubMed2004

Bacterial energetics, stoichiometry, and kinetic modeling of 2,4-dinitrotoluene biodegradation in a batch respirometer.

A stoichiometric equation and kinetic model were developed and validated using experimental data from batch respirometer studies on the biodegradation of 2,4-dinitrotoluene (DNT). The stoichiometric equation integrates bacterial energetics and is revised from that in a previous study by including the mass balance of phosphorus (P) in the biomass. Stoichiometric results on O2 consumption, CO2 evolution, and nitrite evolution are in good agreement with respirometer data. However, the optimal P requirement is significantly higher than the stoichiometrically derived P, implying potentially limited bioavailability of P and the need for buffering capacity in the media to mitigate the adverse pH effect for optimal growth of DNT-degrading bacteria. An array of models was evaluated to fit the O2/CO2 data acquired experimentally and the DNT depletion data calculated from derived stoichiometric coefficients and cell yield. The deterministic, integrated Monod model provides the goodness of fit to the test data on DNT depletion, and the Monod model parameters (Ks, X0, mumax, and Y) were estimated by nonlinear regression. Further analyses with an equilibrium model (MINTEQ) indicate the interrelated nature of medium chemical compositions in controlling the rate and extent of DNT biodegradation. Results from the present batch respirometer study help to unravel some key factors in controlling DNT biodegradation in complex remediation systems, in particular the interactions between acidogenic DNT bacteria and various parameters, including pH and P, the latter of which could serve as a nutrient, a buffer, and a controlling factor on the bioavailable fractions of minerals (Ca, Fe, Zn, and Mo) in the medium.

Aerobiosis↗
PubMed2005

Biodiversity and agro-ecology in field margins.

This multidisciplinary study investigates agro-ecological functions (nature conservation, agriculture, environment) and implications of newly created, mown sown and unsown field margin strips installed on ex-arable land to increase biodiversity. From conservational concern, the development of species rich field margin strips was not strongly affected by the installed type of margin strip since species diversity converged over time, whether strips were sown or not. Convergence between unsown and sown margin strips occurred also in terms of species composition: unsown and sown strips became similar over time. Mowing without removal of cuttings significantly reduced species richness, yielded more grassy margin strips and delayed similarity in species composition between sown and unsown margin strips. Species richness on the longer term was not significantly affected by light regime nor by disturbance despite significant temporary effects shortly after the disturbance event. On the contrary vegetation composition in terms of importance of functional groups changed after disturbance: the share of spontaneous species within functional groups increased resulting in higher similarity between the sown and unsown vegetation. Furthermore risk of invasion was highest in the disturbed unsown community on the unshaded side of a tree lane. A positive effect of botanical diversity on insect number and diversity was found. However the effects of botanical diversity on insect number was mediated by light regime. At high light availability differences between plant communities were more pronounced compared to low light availablilty. The abundance of some insect families was dependent on the vegetation composition. Furthermore light availability significantly influenced insect diversity as well as the spatial distribution of families. From agricultural concern, installing margin strips by sowing a species mixture and a mowing regime with removal of cuttings are good practices to diminish the risk of species ingrowth into adjacent crops by creeping roots and rhizomes. Seed dispersal was only problematic one year after the installation of the field margin strips particularly nearby the unsown margin strip and wind-borne seeds were dispersed over limited distances, mainly within 4 m of field margins. Annual herbage yield was not affected by mowing management. DM yield of sown/unsown communities converged over time. Compared to herbage from an intensively managed fertilized grassland, field margin herbage revealed a low feeding value, owing to a low crude protein content, a low digestibility and a high crude fibre content. The unsown community had a higher forage quality than communities sown to bred commercially available grass varieties. Both digestibility and crude protein content decreased over time irrespective of plant community or location. Mid June cuts were more productive than mid September cuts but digestibility and crude protein content was lower. The use of herbage from field margins as hay for horses or as a component in farmland compost are good alternatives. A strong relation was found between the distribution of pest insects and their antagonist families along field margin strips indicating a status of biological equilibrium. From environmental concern, field margin strips buffered boundary vegetation and watercourses against cropped areas loaded with high levels of mineral nitrogen. Margin strips reduced the mineral nitrogen content of the soil in the margin and mineral nitrogen loss during wintermonths. Mineral nitrogen loss was not affected by field margin type but by distance from the field crop. A minimal width of 5 m is necessary to reach an optimal reduction in mineral soil N and N losses.

Agriculture↗
PubMed1989

Construction and use of a RIA-gram.

All equilibrium protein binding assays, as exemplified by radioimmunoassays (RIA) are governed by the law of mass action. If the reactants are homogenous, then the reaction is characterized by a simple apparent dissociation constant (Kd). We have calculated a set of binding curves, a RIA-gram, in which all concentrations are expressed with Kd as unit. This RIA-gram can be generally employed to optimise equilibrium protein binding assays. Using the RIA-gram we illustrate three points. First, the sensitivity of a given assay is related to either the Kd or the concentration of the labeled ligand, whichever is the larger. Second, if Kd determines the sensitivity of the assay, one can not improve the sensitivity by decreasing the concentration of the labeled ligand below 0.1Kd. Finally, in order to obtain an optimal assay the fraction of ligand bound when only labeled ligand is present depends on the concentration of labeled ligand and on the concentration for which one wants the highest sensitivity of the assay.

Humans↗
PubMed1996

Effect of different buffers on the biocompatibility of CAPD solutions.

Commercially available solutions for continuous ambulatory peritoneal dialysis (CAPD) affect the viability and function of the cells in the peritoneal cavity. The low biocompatibility of the solutions may be caused by a low pH, hyperosmolality, high glucose content, and lack of potassium, glutamine, and other components essential for normal cellular functions. The nature of the buffer employed is also important for the cytotoxicity of the solutions. Lactate, the most frequently used buffer, has been shown to inhibit cellular functions important for the peritoneal defense system including phagocytosis, bacterial killing, and secretion of cytokines. It is generally believed that the cytotoxicity of lactate is caused by lowering of intracellular pH and impairment of metabolism due to changed redox potentials. However, the cytotoxicity of lactate is highly dependent upon the pH of the solutions, indicating that passive or active diffusion across the cell membrane is determining the effects of lactate. Bicarbonate has been heavily advocated as an alternative buffer because it is the most important naturally occurring buffer in plasma and it enables a pH of approximately 7.4 in the solutions. However, due to sedimentation of calcium carbonate (CaCO3) and production of toxic glucose metabolites it is difficult to prepare and store bicarbonate-based solutions. Moreover, investigations have revealed that even bicarbonate-based solutions are not optimal regarding biocompatibility, presumably due to a paradoxical intracellular acidification caused by influx of carbon dioxide (CO2). More recently, the effect of other buffers such as pyruvate and histidine have been examined. Especially pyruvate is a promising new buffer candidate.

Acid-Base Equilibrium↗
PubMed1995

Many combinations of amino acid sequences in a conserved region of the D1 protein satisfy photosystem II function.

The putative de helix of the D1 protein is located at the acceptor side of photosystem II (PS II) and serves as an indispensable part of a niche that binds the secondary plastoquinone QB. Combinatorial mutagenesis was applied to a stretch of four residues in a highly conserved region of this putative helix in order to reveal amino acid combinations that are able to support PS II function. An obligate photoheterotrophic mutant of the cyanobacterium Synechocystis sp. PCC 6803, missing four residues (delta YFGR254-7) in the de helix, was transformed with a D1-coding sequence carrying fully degenerate combinations of codons at the site of the deletion. Upon selection for photoautotrophy, 25 mutants with functional PS II were isolated. All mutants showed different codon combinations at positions 254 to 257; none was identical to the wild-type sequence, and none of the conserved residues was found to be mandatory for PS II function. However, 24 of the mutants contained Tyr of Phe at position 254 while at the other three positions many different amino acid combinations could be functionally accommodated. Most sequences maintained an amphiphilic arrangement of the helix that may align Tyr254 facing the QB binding pocket. This residue is proposed to be functionally analogous to Phe216 of the L subunit in purple bacteria which contributes to binding of QB. Most of the PS II properties were similar in the mutants compared to wild-type. Noticeable modifications in the mutants concerned the semiquinone equilibrium of electron transfer between QA and QB, and the affinity of PS II inhibitors. Differential effects on the semiquinone equilibrium were observed between two distinct quinones occupying the QB site (plastoquinone versus 2,5-dichloro-p-benzo- quinone), implying that residues in this domain are involved, directly or indirectly, with different binding determinants of the quinones. Even though many different combinations of amino acids in positions 254 to 257 of the D1 protein may satisfy the primary function of PS II, complex requirements need to be combined for optimized performance of the QB binding niche.

Amino Acid Sequence↗
PubMed1995

Receptor-ligand interactions measured by an improved spun column chromatography technique. A high efficiency and high throughput size separation method.

Size exclusion chromatography may under the right circumstances be an easy and powerful way to measure in solution the interaction between a receptor an dits ligand. Spun column chromatography is a fast size exclusion technique of increasing popularity, however, little information exists on the method development essential to obtain efficient separation in particular when used for analytical purposes. In this paper we describe a systematic approach to select the optimal parameters for spun column separation including a simple modification of the technique whereby the spun columns are eluted by high-speed gradient centrifugation. This modification is easy to implement and it considerably improves spun column performance. We hypothesize that the high-speed centrifugation step leads to the release of additional buffer which assists in the complete elution of excluded molecules while the gradient centrifugation helps to achieve equilibrium across the gel matrix during the elution. The new method has been used successfully for several different receptor-ligand interactions, and this paper describes a general approach on how to develop new applications of the technique.

Amino Acid Sequence↗
PubMed2004

High-level production and optimization of monodispersity of 11beta-hydroxysteroid dehydrogenase type 1.

11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an intraluminally oriented, endoplasmic reticulum (ER)-bound enzyme catalyzing the interconversion between inactive cortisone and hormonally active cortisol. Heterologous production of 11beta-HSD1, devoid of its N-terminal transmembrane segment, is possible but yields only small amounts of soluble protein. Here we show that the soluble portion of recombinant 11beta-HSD1 produced in E. coli is found mainly as multimeric aggregates in the absence of detergent, and to a large extent associated with the endogenous chaperonin GroEL and other E. coli proteins. By co-overexpressing GroEL/ES and adding an 11beta-HSD1 inhibitor during protein synthesis, we have increased the accumulation of soluble 11beta-HSD1 by more than one order of magnitude. Using monodispersity as a screening criterion, we have also optimized the purification process by evaluating various solubilizing systems for the chromatographic steps, finally obtaining stable monodisperse preparations of both human and guinea pig 11beta-HSD1. By analytical ultracentrifugation, we could demonstrate that 11beta-HSD1 mainly exists as a dimer in the solubilized state. Moreover, active site titration of human 11beta-HSD1 revealed that at least 75% of the protein in a typical preparation represents active enzyme. Equilibrium unfolding experiments indicate that addition of inhibitor and the cofactor NADP(H) can stabilize the conformational stability of this enzyme in an additive manner. The outlined procedure may provide a general method for preparing similar proteins to oligomeric homogeneity and with retained biological activity.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2006

The development of a computer model for a fixed bed gasifier and its use for optimization and control.

The development of a mathematical model of a fixed-bed gasifier is described. The model was used for studies of the stationary performance of the gasifier and the results were compared to experimental results. The model was also used in an effort to identify an efficient control strategy for the operation during load changes. The resulting strategy was very simple and has been implemented in an unmanned, automatically controlled, power plant that was operated for over 3000h. The mathematical model was based on conservation of mass and energy in a simple one-dimensional flow, chemical equilibrium in the gas phase, and a Langmuir-Hinshelwood correlation describing the reaction kinetics in the char. The results of the thermo-gravimetric analysis experiments required to determine the reactivity for char of beech as a function of temperature, gas composition and conversion ratio of the char are presented.

Carbon↗
PubMed2006

A two stage batch adsorber design for methylene blue removal to minimize contact time.

The adsorption of methylene blue onto bentonite in a batch adsorber has been studied. Three kinetic models, the intraparticle diffusion equation and the pseudo first and second order equations, were selected to follow the adsorption process. Kinetic parameters, rate constants, equilibrium adsorption capacities and related correlation coefficients for each kinetic model were calculated and discussed. It was shown that the adsorption of methylene blue onto bentonite could be described by the pseudo second order equation. Adsorption of methylene blue onto bentonite followed the Langmuir isotherm. A model has been developed for the design of a two stage batch adsorber based on pseudo second order adsorption kinetics. The model has been optimized with respect to operating time in order to minimize total contact time to achieve a specified amount of methylene blue removal using a fixed mass of adsorbent. The results of two stage batch adsorber design studies showed that the required times for specified amounts of methylene blue removal significantly decreased. This design is particularly suitable for low-cost adsorbents/adsorption systems when minimising contact time is a major operational and design criterion and a significant volume of effluent needs to be treated in the minimum amount of time.

Adsorption↗
PubMed2002

Extraction of anthocyanins and other phenolics from black currants with sulfured water.

Health benefits of fruits, vegetables, and red wine are attributed to anthocyanins and other phytochemicals. In this research, the extraction of phenolics from black currants was optimized using different SO(2) concentrations (28, 300, 700, 1100, and 1372 ppm), temperatures (6, 20, 40, 60, and 74 degrees C), and solvent to solid ratios (S/S) (6, 20, 40, 60, and 74 mL/g). Surface response methodology was used to optimize yields of anthocyanins and total phenolics, as well as their antiradical and antioxidant activities. The extraction of phenolics varied with the SO(2) concentration, S/S, and temperature. Maximum yields of total phenolics and anthocyanins were obtained at an SO(2) concentration of 1000-1200 ppm and 19 L of solvent/kg of milled frozen berries. The increase of extraction temperature increased the rate of extraction and, thus, times to reach equilibrium for the extraction of total phenolics and anthocyanins were reduced. However, for the extraction of anthocyanins it is recommended that temperatures of 30-35 degrees C be used, as higher temperatures will degrade these compounds. Antioxidant activity was affected by all three experimental variables evaluated; however, the main variable affecting it was S/S. The higher the S/S, the lower the antioxidant index.

Anthocyanins↗
PubMed1997

Trade-off-invariant rules for evolutionarily stable life histories.

Optimization models have been widely and successfully used in evolutionary ecology to predict the attributes of organisms. Most such models maximize darwinian fitness in the face of trade-offs and constraints; the numerical results usually depend on the exact form of the trade-offs or constraints. But not always: for example, earlier work predicted that the optimal range in offspring size ought to show a - 1 scaling with small litter size, independent of most details of the underlying offspring-survival/ offspring-size trade-off relation. Here I report that in non-growing (stationary), age-structured populations, three major life-history attributes (age at first breeding, size of an offspring in large litters, and reproductive effort) are likely to evolve to equilibrium values that satisfy a universal numerical rule; the underlying trade-off will have a slope of - 1 at the optimum, independent of most other aspects of the trade-off. Each of these three attributes can be viewed as an allocation problem between just two alternatives; the trade-off is then between having more of one alternative and less of the other. The slope of the trade-off is simply the slope of the curve of allowed combinations of the two alternatives. The theory predicts that natural selection will push to an equilibrium where the slope is always - 1. The economic structure is the same as that which underlies evolution of the sex ratio where the two alternatives are sons and daughters.

Aging↗
PubMed1975

Purification and properties of isoenzymes of cinnamyl-alcohol dehydrogenase from soybean-cell-suspension cultures.

Two isoenzymes of an NADP+ -dependent cinnamyl alcohol dehydrogenase and an NAD+ - dependent aliphatic alcohol dehydrogenase were extracted from cell suspension cultures of soybean (Glycine max L., var. Mandarin) which form lignin during growth. These enzymes could be separated from each other by chromatography on DEAE-cellulose and hydroxyapatite. The cinnamyl alcohol dehydrogenase isoenzymes were partially purified by (NH4)2SO4 fractionation, and column chromatography on DEAE-cellulose, Sephadex G-100, and hydroxyapatite. The molecular weight of the enzymes were estimated by the elution volumes from a Sephadex G-100 column and were found to be about 43,000 (isoenzyme 1) and 69,000 (isoenzyme 2). Maximum rates of reaction were observed in the case of coniferyl alcohol oxidation at pH 9.2 (Isoenzyme 1) and pH 8.8 (isoenzyme 2); in the reverse reaction pH 6.5 was optimal for isoenzyme 2. Whereas isoenzyme 1 is specific for coniferyl alcohol, isoenzyme 2 can also oxidize cinnamyl alcohol and a number of substituted cinnamyl alcohols, Km values for substituted cinnamaldehydes are 3-11 times lower than for the corresponding alcohols. Neither isoenzyme reacted with benzyl alcohol, anisic alcohol or ethanol. Substrate inhibition for the forward and reverse reaction was found with isoenzyme 2 but not with isoenzyme 1. The equilibrium constant was determined to be about 10(9) in favour of coniferaldehyde reduction. The possible role of the cinnamyl alcohol dehydrogenase in lignin biosynthesis is discussed.

Alcohol Oxidoreductases↗
PubMed1990

Solubilisation of the 5-hydroxytryptamine3 receptor from pooled rat cortical and hippocampal membranes.

5-Hydroxytryptamine3 (5-HT3) receptors have been identified in the rat brain using the radioligand [3H]Q ICS 205-930. We report here that these sites have been solubilised from membranes prepared from pooled rat cerebral cortex and hippocampus using various detergents. Of the six detergents tested (1% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulphonate, 0.5% deoxycholate, 1% Lubrol, 0.5% digitonin, 1% Triton X-100, and 1% octyl glucoside), deoxycholate (0.5%) yielded the best solubilisation (54.6 +/- 6% of receptor, 70.5 +/- 4% of protein; n = 3). However, most detergents inhibited binding of [3H]Q ICS 205-930 in solution. Binding was found to be optimal after the receptor had been exchanged by gel filtration through Sephadex G-25 into the detergent Lubrol PX (0.05%). Binding of [3H]Q ICS 205-930 to these soluble sites was saturable and specific (Bmax = 46.1 +/- 6 fmol/mg of protein; KD = 0.33 +/- 0.09 nM; n = 4) and was similar to that observed in membranes. Kinetic studies of [3H]Q ICS 205-930 binding demonstrated it to be rapid, with equilibrium being achieved within 15 min at 4 degrees C. The KD determined from the rates of association and dissociation (0.38 nM) agreed well with that determined by saturation analysis. Various antagonists completed for the soluble receptors with a rank order of potency typical for binding at a 5-HT3 receptor site: zacopride (Ki = 0.26 nM) greater than quipazine (0.37 nM) = Q ICS 205-930 (0.33 nM) greater than ICS 205-930 (0.93 nM) greater than GR 38032F (2.2 nM) greater than BRL 24924 (4.1 nM) greater than MDL 72222 (23.4 nM) greater than ketanserin (6,000 nM). The agonists 5-HT and 2-methyl-5-HT also competed for [3H]Q ICS 205-930 binding with high affinity (39.6 and 55.6 nM, respectively). Therefore, we conclude that the 5-HT3 receptor of rat brain has been successfully solubilised, and this should provide a good starting point for purification of the receptor.

Animals↗
PubMedDate not supplied

Dialysis leukopenia and hypoxemia in a patient without measurable complement activity.

We have studied complement activity, total leukocyte counts, PO2 and acid-base balance during a single hemodialysis with cuprophan membranes in a patient with hereditary angioedema and C3NeF-positive chronic membranoproliferative glomerulonephritis. Before, during and after the dialytic procedure plasma complement activity (total hemolytic complement, classical and alternative pathway activities) was not detectable and no C3-conversion occurred, while profound leukopenia (from 8,500 to 1,800 leukocytes/microliter) and hypoxemia (from 101.8 to 86 mmHg PO2) were found within 20 min from the initiation of hemodialysis. Similar results were obtained by studying the same parameters during two additional hemodialytic procedures. In vitro experiments showed that the patient's C3 could not be converted, either by cuprophan or zymosan, a specific and potent complement activator, even under optimal experimental conditions. Our data demonstrate that complement activation is not the only possible mechanism responsible for early leukopenia (as well as hypoxemia) during dialysis with cuprophan membranes.

Acid-Base Equilibrium↗