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PubMed2003

Evidence of a hybrid-zone in Atlantic cod (Gadus morhua) in the Baltic and the Danish Belt Sea revealed by individual admixture analysis.

The study of hybrid zones is central to our understanding of the genetic basis of reproductive isolation and speciation, yet very little is known about the extent and significance of hybrid zones in marine fishes. We examined the population structure of cod in the transition area between the North Sea and the Baltic Sea employing nine microsatellite loci. Genetic differentiation between the North Sea sample and the rest increased along a transect to the Baltic proper, with a large increase in level of differentiation occurring in the Western Baltic area. Our objective was to determine whether this pattern was caused purely by varying degrees of mechanical mixing of North Sea and Baltic Sea cod or by interbreeding and formation of a hybrid swarm. Simulation studies revealed that traditional Hardy-Weinberg analysis did not have sufficient power for detection of a Wahlund effect. However, using a model-based clustering method for individual admixture analysis, we were able to demonstrate the existence of intermediate genotypes in all samples from the transition area. Accordingly, our data were explained best by a model of a hybrid swarm flanked by pure nonadmixed populations in the North Sea and the Baltic Sea proper. Significant correlation of gene identities across loci (gametic phase disequilibrium) was found only in a sample from the Western Baltic, suggesting this area as the centre of the apparent hybrid zone. A hybrid zone for cod in the ecotone between the high-saline North Sea and the low-saline Baltic Sea is discussed in relation to its possible origin and maintenance, and in relation to a classical study of haemoglobin variation in cod from the Baltic Sea/Danish Belt Sea, suggesting mixing of two divergent populations without interbreeding.

Animals↗
PubMed2000

Human oesophageal adenocarcinoma cell lines JROECL 47 and JROECL 50 are admixtures of the human colon carcinoma cell line HCT 116.

In two recently described human oesophageal adenocarcinoma cell lines JROECL 47 and JROECL 50, derived from one tumour, we detected identical E-cadherin and beta-catenin gene mutations as in colon carcinoma cell line HCT 116. We demonstrate by HLA-typing, mutation analysis and microsatellite analysis that cell lines JROECL 47 and JROECL 50 are admixtures of the human colon adenocarcinoma cell line HCT 116.

Adenocarcinoma↗
PubMed1991

Drift, admixture, and selection in human evolution: a study with DNA polymorphisms.

Accuracy of evolutionary analysis of populations within a species requires the testing of a large number of genetic polymorphisms belonging to many loci. We report here a reconstruction of human differentiation based on 100 DNA polymorphisms tested in five populations from four continents. The results agree with earlier conclusions based on other classes of genetic markers but reveal that Europeans do not fit a simple model of independently evolving populations with equal evolutionary rates. Evolutionary models involving early admixture are compatible with the data. Taking one such model into account, we examined through simulation whether random genetic drift alone might explain the variation among gene frequencies across populations and genes. A measure of variation among populations was calculated for each polymorphism, and its distribution for the 100 polymorphisms was compared with that expected for a drift-only hypothesis. At least two-thirds of the polymorphisms appear to be selectively neutral, but there are significant deviations at the two ends of the observed distribution of the measure of variation: a slight excess of polymorphisms with low variation and a greater excess with high variation. This indicates that a few DNA polymorphisms are affected by natural selection, rarely heterotic, and more often disruptive, while most are selectively neutral.

Animals↗
PubMed1978

Carcinogens and analogs: trace analysis of thirteen compounds in admixture in wastewater and human urine.

A gas chromatographic method is described for determining traces of 13 carcinogens and related compounds (aromatic amines and estrogens) in admixture in wastewater and human urine. This method was developed for use in toxicological research for monitoring the safe disposal of wastewater and to signal any accidental exposure of personnel to hazardous test substances. Salient elements of the procedure are: extraction of phenolic and neutral residues from the acidified sample, liquid--liquid partitioning cleanup and separation of neutral from phenolic residues at pH 14 and 10.2, acid hydrolysis of the neutral component, subsequent alkalinization of the sample and extraction of the basic residues as the free amines, conversion of all residues to the corresponding pentafluoropropionyl (PFP) derivatives and quantification by electron-capture gas chromatography. Residues were detectable in wastewater and urine at the 0.1 and 1 ppb levels, respectively. Additional information is provided concerning partition values for all PFP derivatives in five solvent systems, structure verification of the derivatives by mass spectrometry and the adaption of this method to the monitoring of surfaces and air in potentially contaminated work areas.

Amines↗
PubMed1992

Emulsion stability in a total nutrient admixture for total parenteral nutrition.

A total parenteral nutrition solution containing lipid was tested up to 28 days at 4 degrees C followed by an additional 2 days at 22 degrees C (room temperature) for stability of the emulsion. The total nutrient admixture (TNA) contained 1000 ml 10% FreAmine, 1000 ml 50% dextrose, 500 ml 10% Soyacal, electrolytes, vitamins and trace elements. Stability was determined by direct observation, light and electron microscopy, Coulter counter, pH, osmolality, and fatty acid profile. Samples were tested when fresh at 0 hours, after 2 days at 22 degrees C, 14 days at 4 degrees followed by 2 days at 22 degrees C, and 28 days at 4 degrees C followed by 1 and 2 days at 22 degrees C. Light microscopy measured particles greater than 2 microns in diameter; 99% of these particles were less than 6 microns, with no increase with time. Electron microscopy found that lipid particle size increased slightly up to 30 days, at which time the mean diameter was 0.36 +/- 0.01 micron. Coulter counter studies found that lipid droplet diameter increased while at 22 degrees C; however, on day 30, 99% of the particles were less than 1.97 microns. Mean pH and osmolality were 6.35 +/- 0.04 and 1880 +/- 14.5 mOsm/kg, respectively, with no change over time. Analysis of fatty acids by gas chromatography showed that fatty acid profiles and amounts of triglyceride, phospholipid and total lipid did not change. Thus, the emulsion in the TNA was stable for 28 days refrigeration, followed by 2 days at room temperature.

Drug Stability↗
PubMed2000

Significant admixture linkage disequilibrium across 30 cM around the FY locus in African Americans.

Scientists, to understand the importance of allelic polymorphisms on phenotypes that are quantitative and environmentally interacting, are now turning to population-association screens, especially in instances in which pedigree analysis is difficult. Because association screens require linkage disequilibrium between markers and disease loci, maximizing the degree of linkage disequilibrium increases the chances of discovering functional gene-marker associations. One theoretically valid approach-mapping by admixture linkage disequilibrium (MALD), using recently admixed African Americans-is empirically evaluated here by measurement of marker associations with 15 short tandem repeats (STRs) and an insertion/deletion polymorphism of the AT3 locus in a 70-cM segment at 1q22-23, around the FY (Duffy) locus. The FY polymorphism (-46T-->C) disrupts the GATA promoter motif, specifically blocking FY erythroid expression and has a nearly fixed allele-frequency difference between European Americans and native Africans that is likely a consequence of a selective advantage of FY-/- in malaria infections. Analysis of linkage disequilibrium around the FY gene has indicated that there is strong and consistent linkage disequilibrium between FY and three flanking loci (D1S303, SPTA1, and D1S484) spanning 8 cM. We observed significant linkage-disequilibrium signals over a 30-cM region from -4.4 to 16.3 cM (from D1S2777 to D1S196) for STRs and at 26.4 cM (AT3), which provided quantitative estimates of centimorgan limits, by MALD assessment in African American population-association analyses, of 5-10 cM.

Africa↗
PubMed2006

Nebulized drug admixtures: effect on aerosol characteristics and albuterol output.

Although not recommended, co-administration of drugs separately prescribed for nebulization is done in real life. The impact of this practice on drug output and aerosol characteristics is poorly understood. We studied the effect of drug admixtures (DA) on aerosol characteristics and drug output of nebulized albuterol delivered by a continuous output (CONT) and a breath enhanced nebulizer (BEN). Albuterol was nebulized alone (ALB) and combined with cromolyn sodium (A+CRO), ipratropium bromide (A+IB), tobramycin (A+TOB), flunisolide (A+FLU), and n-acetylcysteine (A+NAC). A BEN (PARI LC Plus) and a CONT (Hudson T UP-DRAFT II) were tested at 8 liters per minute (Lpm) for 2 and 5 min, respectively. Albuterol output and aerosol characteristics were determined by impaction and chemical analysis. Mass median aerodynamic diameter (MMAD; microm) A+CRO reduced MMAD from 2.57 (ALB) to 1.29 with CONT. A+FLU increased MMAD from 2.71 (ALB) to 3.40 with BEN. Geometric standard deviation (GSD) A+CRO increased GSD from 2.66 (ALB) to 3.36 with CONT. GSD was 2.33 for ALB and was not changed by DA with BEN. BEN generated a smaller and less heterodisperse aerosol than CONT. Respirable fraction (RF%) was 74% for ALB and was not changed by DA with CON. A+TOB and A+FLU decreased RF% from 75%, to 70% and 67% (respectively) with BEN. Respirable mass (RM; microg) for ALB was 935 and was not changed by DA with CONT. A+IB and A+FLU increased RM from 917 (ALB) to 1172 and 1240, respectively, with BEN. Co-nebulization of albuterol with other drugs can affect its output and aerosol characteristics. In vivo data is needed to asses the clinical implications of our findings.

Adrenergic beta-Agonists↗
PubMed1985

Relationships between inspired oxygen concentration and venous admixture during nitrous oxide-oxygen-halothane anaesthesia.

The inspired oxygen concentration (F/O2) was changed on 43 occasions at about 30-min intervals in 13 patients during artificial ventilation with mixtures of nitrous oxide (N2O), oxygen and halothane. Ventilator settings remained unchanged for each patient and at the end of each period, samples of arterial and central venous blood (and, in six patients, pulmonary arterial blood) and inspired and expired gases were collected. Oxygen tension was measured with a dedicated electrode shown to be unaffected by N2O. Venous admixture (Qva/Qt) was calculated at each F/O2. There was a highly significant correlation between the direction of change of F/O2 and that of Qva/Qt, irrespective of whether F/O2 increased or decreased. In 10 patients, there was a progressive increase in Qva/Qt as F/O2 increased above 40%, and in all patients Qva/Qt on nearly 100% oxygen was greater than that measured at the next lowest concentration (60-80%). These results are at variance with the pattern of behaviour predicted from the "critical Va/Q" theory and support the concept of an oxygen-dependent redistribution of perfusion.

Adult↗
PubMed1986

Extradural morphine: influence of adrenaline admixture.

The influence of the addition of adrenaline on extradural morphine analgesia and pharmacokinetics was investigated in a double-blind study. Morphine 2 mg was administered to 14 patients undergoing thoracotomy. In addition, adrenaline 50 micrograms added to the extradural solution, was administered to half of the patients, selected randomly. Morphine concentrations in serial plasma and cerebrospinal fluid (CSF) samples were measured. Postoperative analgesia was estimated by determining the requirement for additional analgesics. Following extradural administration of plain morphine, the peak morphine concentrations in CSF were 22 +/- 5 (SEM) times those in plasma; during the elimination phase the CSF concentrations exceeded those in plasma by about 150 times. The area under the concentration v. time curve (AUC) was 162 +/- 27 (SEM) times larger in CSF than in plasma. The admixture of adrenaline with the extradural morphine increased the individual variability in CSF and plasma concentrations. However, compared with the plain morphine group, adrenaline did not significantly increase the concentrations of morphine in CSF, nor were the morphine concentrations in plasma significantly decreased. The duration of analgesia was related to the amount of morphine in CSF, that is AUC (P less than 0.05) and peak concentrations of morphine in CSF (P less than 0.05).

Aged↗
PubMed1995

Non-invasive estimation of venous admixture: validation of a new formula.

We have developed a computer program that estimates venous admixture (intra-pulmonary shunt) from four measurements: haemoglobin concentration, end-tidal carbon dioxide tension (PE'CO2), fractional inspired oxygen concentration (FIO2) and pulse oximetry (SpO2). The formula was tested on patients in an intensive therapy unit by using it to estimate shunt while it was measured simultaneously by a standard, invasive method. A total of 101 measurements were made in 29 patients. After correcting the systematic errors in the assumed differences between PE'CO2 and arterial PCO2, and between SpO2 and co-oximetrically measured SaO2, and correcting for a trend in the arteriovenous oxygen concentration difference (C(a-v))2) with shunt, the bias of the non-invasive minus invasive shunt differences was negligible, with no significant dependence on shunt. The limits of agreement were then +/- 16% shunt overall (+/- 13% within patients). When SaO2 was used instead of SpO2, the limits were +/- 11% (+/- 8% within patients).

Carbon Dioxide↗
PubMed1999

Population structure among African and derived populations of Drosophila simulans: evidence for ancient subdivision and recent admixture.

Previous studies based on allozyme variation have found little evidence for genetic differentiation in Drosophila simulans. On the basis of DNA sequence variation at two nuclear loci in four African populations of D. simulans, we show that there is significant structure to D. simulans populations within Africa. Variation at one of the loci, vermilion, appears to be neutral and supports an eastern African origin for European and American populations. Samples from the West Indies, Europe, and North America had a nucleotide diversity lower than that of African populations at vermilion and show nonequilibrium haplotype distributions at both vermilion and G6pd, consistent with a hypothesis of recent bottleneck and possibly also admixture in the history of these populations. Directional selection, previously documented at G6pd, appears to have occurred within the coalescence time of the species, obscuring deep population history.

Africa↗
PubMed2003

Effects of population structure and admixture on exact tests for association between Loci.

The probability of multilocus genotype counts conditional on allelic counts and on allelic independence provides a test statistic for independence within and between loci. As the number of loci increases and each sampled genotype becomes unique, the conditional probability becomes a function of total heterozygosity. In that case, it does not address between-locus dependence directly but only indirectly through detection of the Wahlund effect. Moreover, the test will reject the hypothesis of allelic independence only for small values of heterozygosity. Low heterozygosity is expected for population subdivision but not for population admixture. The test may therefore be inappropriate for admixed populations. If individuals with parents in two different populations are always considered to belong to one of the populations, then heterozygosity is increased in that population and the exact test should not be used for sparse data sets from that population. If such a case is suspected, then alternative testing strategies are suggested.

Data Interpretation, Statistical↗
PubMed2003

Genetic differentiation between American and European Drosophila melanogaster populations could be attributed to admixture of African alleles.

A total of 48 polymorphic microsatellite loci were characterized in 13 Drosophila melanogaster populations originating from Europe, America, and Africa. Consistent with previous results, the African D. melanogaster populations were the most differentiated populations and harbored most variation. Despite an overall similarity, American and European populations were significantly differentiated. Interestingly, genetic distances based on the proportion of shared alleles as well as FST values suggested that the American D. melanogaster populations are more closely related to the African populations than European ones are. We also detected a higher proportion of putative African alleles in the American populations, indicating recent admixture of African alleles on the American continent.

Africa↗
PubMed2001

Inferring admixture proportions from molecular data: extension to any number of parental populations.

The relative contribution of two parental populations to a hybrid group (the admixture proportions) can be estimated using not only the frequencies of different alleles, but also the degree of molecular divergence between them. In this paper, we extend this possibility to the case of any number of parental populations. The newly derived multiparental estimator is tested by Monte Carlo simulations and by generating artificial hybrid groups by pooling mtDNA samples from human populations. The general properties (including the variance) of the two-parental estimator seem to be retained by the multiparental estimator. When mixed human populations are considered and hypervariable single-locus data are analyzed (mtDNA control region), errors in the estimated contributions appear reasonably low only when highly differentiated parental populations are involved. Finally, the method applied to the hybrid Canary Island population points to a much lower female contribution from Spain than has previously been estimated.

DNA, Mitochondrial↗
PubMed1980

Changes in venous admixture with alterations of inspired oxygen concentration.

To assess the change in venous admixture during breathing of 100 per cent oxygen (FIO2 1.0), shunt fraction (Qs/Qt) was calculated at a maintenance FIO2 (FIO2m:0.27--0.70) and at FIO2 1.0 in 40 studies of 34 patients with acute respiratory failure. At FIO2 1.0 Qs/Qt increased in 26 studies, but did not increase in 14 studies. Patients in whom Qs/Qt increased during breathing of oxygen and mild respiratory failure, as indicated by low Qs/Qt values at FI02m and a low incidence of diffuse parenchymal infiltrates on chest roentgenograms. All patients who had recently had cardiovascular surgical procedures were in this group. Respiratory failure was more severe in those in whom Qs/Qt decreased with oxygen, as indicated by high Qs/Qt values at FIO2m, evidence of diffuse pulmonary disease by roentgenography, and signs of adult respiratory distress syndrome. The authors conclude that changes in Qs/Qt in response to FIO2 1.0 in acute respiratory failure are related to the severity of respiratory insufficiency.

Acute Disease↗
PubMed1985

Prostaglandin F2 alpha improves oxygen tension and reduces venous admixture during one-lung ventilation in anesthetized paralyzed dogs.

The authors investigated the effect of prostaglandin F2 alpha infused into the pulmonary artery of an acutely atelectatic lung in dogs. Seven dogs were anesthetized with piritramid and pentobarbital and intubated with a Kottmeier canine endobronchial tube. Cardiac output, pulmonary arterial, capillary wedge, and systemic arterial pressure were measured via indwelling catheters. Ventilating both lungs with 66% O2, PaO2 was 327 +/- 15 mmHg (mean +/- SD) and venous admixture (Qsp/Qt) was 11 +/- 3%. One-lung atelectasis reduced PaO2 to 91 +/- 12 mmHg and increased Qsp/Qt to 40 +/- 4%. Prostaglandin F2 alpha in doses of 0.4, 0.6, 1.2, and 1.8 micrograms X kg-1 X min-1 was infused into the pulmonary artery of the atelectatic lung through a second pulmonary artery catheter. Up to a dose of 1.2 micrograms X kg-1 X min-1 there was a dose-dependent reduction in Qsp/Qt to a minimum of 25 +/- 4% and an increase in PaO2 to 168 +/- 25 mmHg, which could be explained by enhanced pulmonary vasoconstriction in the atelectatic lung with increased blood flow diversion toward the ventilated lung. Infusion of 1.8 micrograms X kg-1 X min-1 decreased PaO2 to 156 +/- 32 mmHg and increased Qsp/Qt to 32 +/- 9%. Increased systemic effects of prostaglandin F2 alpha were observed and presumably were related to saturation of prostaglandin-dehydrogenase leading to vasoconstriction in both lungs and thus reduced blood flow diversion toward the ventilated lung.

Animals↗
PubMed1989

Physiologic dead space, venous admixture, and the arterial to end-tidal carbon dioxide difference in infants and children undergoing cardiac surgery.

End-tidal CO2 (PETCO2), arterial CO2 (PaCO2), mixed expired CO2 (PECO2), arterial and mixed venous oxygen contents were measured and the PaCO2 to PETCO2 difference (delta PCO2), physiologic dead space to tidal volume ratios (VD/VT) and venous admixture (Qs/Qt) were calculated in 41 anesthetized infants and children undergoing repair of congenital cardiac lesions. Eighteen children were acyanotic; 9 with normal pulmonary blood flow (PBF) and normal intracardiac anatomy (normal group); and 9 with increased PBF (acyanotic group). Twenty-three children were cyanotic; 14 with right to left intracardiac shunts and decreased PBF (cyanotic (D) group); and 9 with mixing lesions with normal or increased PBF (cyanotic (I) group). Correlations between PaCO2 and PETCO2 in the four groups of children were carried out and the relationship of delta PCO2 to VD/VT and Qs/Qt was determined. PETCO2 correlated closely with the PaCO2 in the normal and acyanotic groups (r2 = 0.97 and 0.91, respectively) and the lines of regression for the relationship between PaCO2 and PETCO2 for both groups did not differ from the line of identity (P less than or equal to 0.05). Mean +/- SD VD/VT for the normal and acyanotic groups were 0.35 +/- 0.17 and 0.39 +/- 0.19, respectively (NS). Corresponding values for the cyanotic (D) group and cyanotic (I) group were 0.38 +/- 0.16 and 0.55 +/- 0.16, respectively (NS), and were significantly greater than those from the normal and acyanotic groups (P less than 0.05). The relationship of delta PCO2 to VD/VT and Qs/Qt demonstrated that VD/VT was the most important determinant of delta PCO2, but in instances where Qs/Qt were large (e.g., cyanotic congenital heart disease) the percentage contribution of Qs/Qt to the delta PCO2 can be considerable.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide↗
PubMed1992

Mapping the spread of epidural phenol in cancer pain patients by radionuclide admixture and epidural scintigraphy.

This study used a radionuclide imaging technique to map the spread and density contours of phenol in glycerin injected into the epidural space of cancer patients. Correlations were made between phenol injectate volume, sequence of injection, position of patient, and resultant epidural spread and analgesic outcome. Fifteen patients with cancer pain (average age of 61 years) were treated with serial epidural phenol in glycerin injections. Phenol in glycerin is miscible with [99mTc]sulfur colloid. An assumption was made that the admixture injected epidurally was inseparable prior to absorption and the spread was recorded by continuous gamma camera observations with computer collection for 30 min postinjection. The spread of injectate volumes of 2, 3, and 4 ml were compared and further correlations made between observed spread and sequence of injections (first to fifth in series within each patient) and position of patient. Small volumes of phenol may spread extensively in the epidural space (3 ml spreads a mean 13.6 segments) with wide variation among patients. Initial phenol injections spread further than subsequent injections. Maximum spread is achieved by 15 min postinjection and epidural distribution is mostly uniform, independent of patient position. Good analgesia was obtained in 14 patients (93%). Epidural neurolysis using serial injections of small volumes of phenol in glycerin is an effective, safe technique for cancer pain relief. Injectate volumes larger than 3 ml may be unnecessary and potentially dangerous.

Adult↗