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PubMed1985

[Stability of 8 second or third generation cephalosporins in peritoneal dialysis fluid].

The main complication of chronic ambulatory peritoneal dialysis is peritoneal infection due to contamination while handling dialysate bags. For this reason antibiotics should be added to the dialysate to prevent infection. Some antibiotics are known to be unstable when dissolved in dialysate. We therefore studied the bactericidal activity of eight second or third generation cephalosporins against Escherichia coli and Staphylococcus aureus under conditions similar to in vivo situations. Comparison of killing curves shows that bactericidal activity is unchanged after 24 hours in the dialysis fluid at room temperature.

Bacterial Infections↗
PubMed1991

Polar axis fixation in Fucus zygotes: components of the cytoskeleton and extracellular matrix.

Polar axis formation and polar axis stabilization (or fixation) can be separated and analyzed in synchronously developing zygotes of the brown alga Fucus. Extensive experimental evidence points to a role for both the cytoskeleton and the extracellular matrix (ECM) in the process of axis fixation in Fucus. A structural complex composed of the cytoskeleton and the ECM has been postulated to stabilize membrane asymmetries generated as a result of axis-forming vectors. This axis stabilizing complex (ASC) may take the form of transmembrane connections between the cytoskeleton on the cytoplasmic face and the ECM on the external side of the plasma membrane, similar to focal contacts in animal cells. At present we know of two components in the proposed ASC of Fucus: an adhesive sulfated glycoprotein which is localized in the ECM, and an actin network which is localized on the adjoining cytoplasmic face. This preliminary report describes evidence for the presence of molecules in two-celled Fucus embryos that are similar to those found in focal contacts in animal cells, i.e. vinculin, integrin and vitronectin. However, their localization and interaction with each other relative to the polar axis has yet to be determined. These initial observations will provide the basis to pursue further an analysis of these components in the process of polar axis fixation.

Cell Polarity↗
PubMed1991

Methods for the assessment of the stability of tablet disintegrants.

To allow assessment of the long-term stability of tablet disintegrants, two mechanisms for their functionality (i.e., water uptake and swelling force generation) were monitored. Three disintegrants, alginic acid, sodium starch glycolate, and crospovidone, were used to establish the methodology. The water uptake and swelling force methodologies developed were reproducible, thus allowing for the evaluation of the effect of time, temperature, and humidity on these properties of disintegrants. The data obtained suggest that the process of water uptake and swelling force generation was essentially a two-step process. Initially, water entered the pore space in the powder bed; there was a definitive lag time before a swelling force was generated. In the stability evaluation of alginic acid and sodium starch glycolate, samples were stored for 1-year. Above 30 degrees C and 75% relative humidity, the swelling force performance of alginic acid was markedly affected. Changes seen with sodium starch glycolate were much less marked.

Alginates↗
PubMed1990

Comparison of the acid stability of azithromycin and erythromycin A.

In acidic aqueous media, erythromycin A is rapidly degraded via intramolecular dehydration to form erythromycin-6.9-hemiketal and then anhydroerythromycin, both of which possess little antimicrobial activity. Azithromycin, a new azalide antibiotic, has a methyl-substituted nitrogen in place of the carbonyl at the 9a position of the aglycone ring, thus blocking the internal dehydration pathway. As a result, azithromycin decomposition occurs primarily via acid-catalysed hydrolysis of the ether bond to the neutral cladinose sugar. Rate constants and the time for 10% decay (T1/10) were determined for both azithromycin and erythromycin A at pH2 using various levels of acetonitrile cosolvent and constant ionic strength. Semi-log plots of the decay rate constants versus the reciprocal of the solution dielectric constants were used to extrapolate to totally aqueous conditions. In solution at 37 degrees C and pH2 with ionic strength mu = 0.02, azithromycin was degraded with a T1/10 of 20.1 min while erythromycin underwent 10% decay in only 3.7 sec. The activation energy for hydrolysis of the ether bond connecting cladinose to azithromycin was 25.3 kcal/mol while the internal dehydration reaction of erythromycin had an activation energy of 15.6 kcal/mol. A solution stability profile was generated for azithromycin over the pH range of 1.0 to 4.1 at 30 degrees C. Stability was found to improve ten-fold for each unit increase in pH.

Acetonitriles↗
PubMed1986

Morphogenesis and the control of microtubule dynamics in cells.

Microtubules show unusual dynamic properties at steady state in vitro. While overall the polymer mass remains stable, individual polymers in the population are either growing or shrinking. This phenomenon called dynamic instability is best explained by the known coupling of polymerization to GTP hydrolysis, and the hypothesis that the stability or instability of the whole polymer is determined by whether GTP or GDP is bound to the terminal subunit. Similar unusual dynamics have now also been found in vivo. By visualizing new subunit assembly after injection of tubulin modified with biotin into living fibroblast cells, we can visualize new growth on individual microtubules with antibody to biotin. Microtubules grow in vivo at about 4 microns min-1 and after rapid and precessive depolymerization old microtubules are replaced by new growth from the centrosome. Some microtubules turn over much more slowly and these stable microtubules have a different spatial distribution from the majority of dynamic ones. The existence of both stable and dynamic microtubules in the same cell suggests a model for morphogenesis of the microtubule cytoskeleton. The rapid turnover of microtubules in the cell provides a complex population upon which selective factors can act. Stability can be generated at the end of the polymer and affects the entire microtubule. This model of selective stabilization at the microtubule ends is discussed in terms of recent experiments on the establishment of kinetochore-pole microtubules during mitosis.

Animals↗
PubMed1991

Characterization of a region of the Enterococcus faecalis plasmid pAM beta 1 which enhances the segregational stability of pAM beta 1-derived cloning vectors in Bacillus subtilis.

The nucleotide sequence of a 2.13-kb EcoRI-HindIII, pAM beta 1-derived fragment, isolated from the gram-positive cloning vector pHV1431, has been determined and shown to encode two ORFs. ORF H encodes for a protein of 23,930 Da which exhibits substantial homology to bacterial site-specific recombinases, particularly the resolvases of the gram-positive transposons Tn917 (30.3% identity) and Tn552 (31.6% identity) and the clostridial plasmid pIP404 (27.1% identity). The second ORF (I) is incomplete and encodes a polypeptide which has significant homology with Escherichia coli topoisomerase I (26.0% identity). Insertion of either the entire 2.13-kb EcoRI-HindIII fragment or a 0.73-kb EcoRI-DraI subfragment encoding only the resolvase into the pAM beta 1-based cloning vector pMTL500E causes a significant enhancement of segregational stability (from 6.5 X 10(-2) to 3.0-4.0 X 10(-3) plasmid loss per cell per generation). Improved segregational stability is mirrored by a reduction in plasmid polymerization. The introduction of a stop codon into the resolvase coding region negates its ability to promote segregational stability. It is proposed that the identified determinant stabilizes pAM beta 1-based vectors in Bacillus subtilis by maintaining the plasmid population in the monomeric state, thereby reducing the chances of producing plasmid-free segregants.

Amino Acid Sequence↗
PubMed1990

Prediction of rates of inbreeding in selected populations.

A method is presented for the prediction of rate of inbreeding for populations with discrete generations. The matrix of Wright's numerator relationships is partitioned into 'contribution' matrices which describe the contribution of the Mendelian sampling of genes of ancestors in a given generation to the relationship between individuals in later generations. These contributions stabilize with time and the value to which they stabilize is shown to be related to the asymptotic rate of inbreeding and therefore also the effective population size, Ne approximately 2N/(mu 2r + sigma 2r), where N is the number of individuals per generation and mu r and sigma 2r are the mean and variance of long-term relationships or long-term contributions. These stabilized values are then predicted using a recursive equation via the concept of selective advantage for populations with hierarchical mating structures undergoing mass selection. Account is taken of the change in genetic parameters as a consequence of selection and also the increasing 'competitiveness' of contemporaries as selection proceeds. Examples are given and predicted rates of inbreeding are compared to those calculated in simulations. For populations of 20 males and 20, 40, 100 or 200 females the rate of inbreeding was found to increase by as much as 75% over the rate of inbreeding in an unselected population depending on mating ratio, selection intensity and heritability of the selected trait. The prediction presented here estimated the rate of inbreeding usually within 5% of that calculated from simulation.

Animals↗
PubMed1992

Promoter methylation and progressive transgene inactivation in Arabidopsis.

Agrobacterium-transformed Arabidopsis plants were generated and the stability of their T-DNA-encoded resistance to kanamycin was examined. Of seven families, each homozygous for a single insertion event, two showed progressive inactivation of resistance over four generations of inbreeding. Loss of resistance was associated with methylation of an Sst II site in the nos promoter of the kanamycin resistance gene. Treatment of plant roots from inactive lines with the demethylating agent 5-azacytidine restored the ability of such lines to form callus on kanamycin-containing media. These observations are consistent with the view that methylation is a factor in the progressive inactivation of transgenes in Arabidopsis.

DNA, Bacterial↗
PubMed1985

Stability of atrial sensing and pacing after dual chamber pulse generator implantation.

The continued efficacy of dual chamber pacing is predicated on the stability of both atrial and ventricular electrodes. The introduction of the tined atrial J lead has decreased the incidence of atrial lead dislodgment, allowing for continued effective sensing and pacing. To study the evolution of atrial pacing and sensing threshold, 54 patients with identical pulse generators and atrial electrodes were evaluated for 58 +/- 29 weeks (mean +/- SD). Immediately after pacemaker implantation in 39 patients, the amplitude of the atrial signal was measured by programming the pulse generator to the lowest sensitivity that assured pacing in the atrial synchronous mode. Three levels of atrial sensing were possible: high (0.5 mV), intermediate (1.3 mV) and low (2.5 mV) sensitivity. Three patients had a high, 16 patients had a medium and 20 patients had a low atrial sensitivity. The P wave amplitude and slew rate measured on a physiologic recorder did not differ significantly between the latter two groups. The atrial charge threshold increased from 1.8 +/- 1.3 microcoulombs (microC) to a maximal value of 2.5 +/- 1.3 microC, 3 days to 1 week after implantation (p = 0.02). This remained elevated for 1 to 3 months (p = 0.05) and then decreased, remaining stable over the ensuing year. The atrial sensitivity for the group with noninvasive measurement did not change significantly, although there was considerable patient variation. For 54% of the patients, atrial sensing remained stable or improved. In 26% of the patients, further programming to higher sensitivity settings ws required. In the remaining 20% of the patients, the atrial sensitivity setting fluctuated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Age, period and cohort effects on the risk of major depression: results from five United States communities.

Rates of major depression are presented from the recently completed Epidemiologic Catchment Area (ECA) Study based on probability samples of over 18,000 adults, 18 years of age and older, living in five U.S. communities. These rates were analyzed to describe simultaneously the changes affecting successive birth cohorts and the changes associated with the period in which the onset of the disorder occurred, using age-period-cohort (APC) models. The non-identifiability problem inherent in all APC models was resolved by assuming that the linear period effect and linear cohort effect were non-negative. This assumption is consistent with our a priori substantive knowledge of the disease. Under this assumption, as the linear period effect varies from its minimum to its maximum values, a family of curves representing the possible effects of a factor was generated for each of the time factors--age, period and cohort. The results of the analysis showed a sharp increase in rates of major depression among both men and women in the birth cohort born during the years 1935-1945. The rates among females, however, seemed to have stabilized in the generations born since 1945, while the rates in males continued to rise sharply among the cohorts born in the following decade, after which, in 1955, they also levelled off. In contrast, the rates associated with period of onset of major depression continued to increase between the years 1960-1980 among both men and women of all ages studied. These findings are considered in light of the persistent concentration of depression in women and in biologically related members of families of affected individuals.

Adolescent↗
PubMed1986

Long-term maintenance of hepatocyte functional activity in co-culture: requirements for sinusoidal endothelial cells and dexamethasone.

Sinusoidal cells isolated from adult rat liver have been established in primary culture and in cell line. The presence of factor VIII R:Ag and peroxidatic/phagocytosis activities were the criteria used to distinguish in freshly isolated cells the endothelial cells from the Kupffer cells and suggested the endothelial origin of the cell line. Using a co-culture system, the effect of sinusoidal liver cells on hepatocyte functional activity was characterized. A plateau in which the state of differentiation was stabilized could be generated for co-cultured hepatocytes isolated from adult rat and a disappearance of the initial expression of alpha 1-fetoprotein (AFP) and the increase and/or maintenance of albumin secretion were measured with co-cultured hepatocytes isolated from suckling rat. The presence of dexamethasone was required for such beneficial effect. The hepatocyte-stabilizing activity was also produced by a pulmonary endothelial cell line.

Cell Communication↗
PubMed1985

[Stabilization of physostigmine salicylate injection solutions].

Aimed at the centralized manufacture of physostigmin salicylate injection solutions, the efficacy of different stabilizators has been studied under conditions of the thermic load. As for physostigmin sodium pyrosulphite is no antioxidant but a discolouration-protective agent. A decrease of the physostigmin content is not avoided. During the tests ascorbic acid proved to be the most efficient stabilizator, because its application resulted in the most favourable rates of storage stability and usability and at the same time in a pH stabilization to the optimum range of 3 necessary for the physostigmin keeping quality. An additionally stabilizing effect is obtained by a 5 min carbon dioxide gasing of the solutions. Moreover, ascorbic acid is as viewed in physiological perspective the most harmless one. A servicable stabilizing procedure for generation of 0.1% physostigmin salicylate injection solutions has been developed on this basis. These solutions had repeatedly and successfully been applied an antidote to intoxications with atropine syndrome, especially to intoxications with tricyclic anti-depressives and phenothiazines.

Ascorbic Acid↗
PubMedDate not supplied

Enhancing oxygen transfer in surface-aerated bioreactors by stable foams.

To enhance oxygen transfer in surface-aeration bioreactors, stabilized foams were generated to increase the gas-liquid interfacial area by slowly introducing coarse bubbles into media containing fetal bovine serum. The bubble sparging rates were so low (i.e., 20 and 50 mL/h) that the contribution to oxygen transfer from these bubbles was due to foaming instead of bubbling. Furthermore, no physical cell damage caused by bubble sparging was observed. Oxygen transfer coefficients, kLa, in the bioreactors were measured in cell-free media. Without the foam-stabilizing agent (i.e., serum), no appreciable change in kLa was observed due to the bubble sparging. On the other hand, with serum, kLa increased with increasing serum content and bubble sparging rate and corresponded well with the degree of foaming. With 10% fetal bovine serum and a bubble sparging rate of 50 mL/h, kLa increased approximately 90% compared with no foaming. The enhancing effect of foam on oxygen transfer in surface aeration bioreactors has been further demonstrated with hybridoma cultures simultaneously grown in three identical bioreactors with and without stabilized foams.

Aerobiosis↗
PubMed1988

Sensory interaction with central 'generators' during respiration in the dogfish.

The activity in sensory and motor nerves of the gills was recorded from selected branches of the vagus nerve in decerebrate dogfish, Scyliorhinus canicula. Vagal motoneuronal activity was observed at the start of the rapid pharyngeal contraction and was followed by sensory nerve activity which preceded the slow expansion phase. Rhythmical vagal motoneuronal activity was still present after all movements had been prevented by curare paralysis although the frequency of the rhythm was higher than in the ventilating fish. Electrical stimulation of vagal sensory fibres had 3 effects on the ventilatory movements. (1) It evoked a reflex contraction of several gill muscles after a latency of about 11 ms. (2) It could reset the respiratory cycle because a stimulus given during expansion delayed the onset of the subsequent contraction. (3) The stimulus could entrain the rhythm if it was given continuously at a frequency close to that of ventilation. The vagal motor rhythm was disrupted by trigeminal nerve stimulation in the paralyzed fish but not if the motor rhythm was being entrained by vagal nerve stimulation. Vagal sensory activity may be important, therefore, in maintaining the stability of the generating circuits.

Animals↗
PubMed1976

Rhythmic swimming activity in neurones of the isolated nerve cord of the leech.

1. Repeating bursts of motor neurone impulses have been recorded from the nerves of completely isolated nerve cords of the medicinal leech. The salient features of this burst rhythm are similar to those obtained in the semi-intact preparation during swimming. Hence the basic swimming rhythm is generated by a central oscillator. 2. Quantitative comparisons between the impulse patterns obtained from the isolated nerve cord and those obtained from a semi-intact preparation show that the variation in both dorsal to ventral motor neurone phasing and burst duration with swim cycle period differ in these two preparations. 3. The increase of intersegmental delay with period, which is a prominent feature of swimming behaviour of the intact animal, is not seen in either the semi-intact or isolated cord preparations. 4. In the semi-intact preparation, stretching the body wall or depolarizing an inhibitory motor neurone changes the burst duration of excitatory motor neurones in the same segment. In the isolated nerve cord, these manipulations also change the period of the swim cycle in the entire cord. 5. These comparisons suggest that sensory input stabilizes the centrally generated swimming rhythm, determines the phasing of the bursts of impulses from dorsal and ventral motor neurones, and matches the intersegmental delay to the cycle period so as to maintain a constant body shape at all rates of swimming.

Action Potentials↗