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PubMed2005

Rapidly declining fine-scale spatial genetic structure in female red deer.

A growing literature now documents the presence of fine-scale genetic structure in wild vertebrate populations. Breeding population size, levels of dispersal and polygyny--all hypothesized to affect population genetic structure--are known to be influenced by ecological conditions experienced by populations. However the possibility of temporal or spatial variation in fine-scale genetic structure as a result of ecological change is rarely considered or explored. Here we investigate temporal variation in fine-scale genetic structure in a red deer population on the Isle or Rum, Scotland. We document extremely fine-scale spatial genetic structure (< 100 m) amongst females but not males across a 24-year study period during which resource competition has intensified and the population has reached habitat carrying capacity. Based on census data, adult deer were allocated to one of three subpopulations in each year of the study. Global F(ST) estimates for females generated using these subpopulations decreased over the study period, indicating a rapid decline in fine-scale genetic structure of the population. Global F(ST) estimates for males were not different from zero across the study period. Using census and genetic data, we illustrate that, as a consequence of a release from culling early in the study period, the number of breeding females has increased while levels of polygyny have decreased in this population. We found little evidence for increasing dispersal between subpopulations over time in either sex. We argue that both increasing female population size and decreasing polygyny could explain the decline in female population genetic structure.

Animals↗
PubMed1998

Replacement of massive blood loss.

Treatment of massive blood loss has experienced major changes during the recent decade. The transition towards pure component therapy has been the most significant issue, which has compelled the clinician to revise some of their basic strategies in treatment of massively bleeding patients. The importance of adequate volume resuscitation with crystalloids and colloids is still unrefutable, but the therapy of hemorrhagic derangements has changed. Plasma-poor red cells (RC) are now commonly used instead of whole blood (WB) or packed red blood cells (PRBC) to correct oxygen carrying capacity during massive blood loss. As the plasma content of RC is minimal, deficit of plasma and coagulation factors develops earlier than during transfusion of WB and PRBC. Hypofibrinogenemia develops first followed by other coagulation factor deficits and later by thrombocytopenia. Therefore the use of fresh frozen plasma (FFP) is the primary intervention to treat abnormal bleeding encountered in the replacement of massive blood loss with RC. As the development of thrombocytopenia is a highly individual phenomenon, the transfusion of platelets should be guided by repeatedly determined platelet counts.

Adult↗
PubMed1988

The effect of blood transfusion on cerebral blood-flow in preterm infants: a Doppler study.

Stable infants with anaemia needing a transfusion with adult red blood-cells were studied to elucidate changes in brain blood-flow velocity. Within 24 hours and at five to six days following transfusion a substantial mean flow velocity reduction was observed. Haemodynamic factors contributing to the reduction were an increase in cerebrovascular resistance and an increase in whole blood viscosity, as reflected by a raised pulsatility index. Transfusion with adult red blood-cells causes an elevation in haemoglobin concentration, thereby increasing the total oxygen-carrying capacity of arterial blood; however, this lowers the concentration of fetal haemoglobin which possesses a higher affinity for oxygen. Since cerebral oxygen transport is equal to the product of cerebral blood-flow and arterial oxygen content, this finding suggests the existence of a homeostatic mechanism for cerebral oxygen transport. The actual amount of cerebral oxygen transport was found to increase progressively as the percentage of fetal haemoglobin rose above 30 per cent. At higher fetal haemoglobin levels, appropriate elevations in cerebral blood-flow occurred, causing an increase in the supply of oxygen to the brain.

Blood Flow Velocity↗
PubMed1989

Cotransfection of nucleic acid segments by Sendai virus envelopes.

It is reported here that Sendai virus envelopes (SVE) can be used to transfect multiple copies of DNA segments of different varieties and size. This capability further increases the usefulness of SVE. In addition, the ability to simultaneously transfect multiple copies of different genome segments promises to be a powerful tool in the field of molecular biology. The simultaneous transfection of NEO gene and cytomegalovirus immediate early antigen gene was successfully done. Sendai virus envelopes (SVE)1 have been used successfully to study carcinogenesis of Epstein-Barr virus (1, 2). SVE have been shown to have a large carrying capacity (3) for the microinjection of macromolecules into target cells. SVE are hollow vesicles constructed from the viral proteins hemagglutinin HN and fusion factor F.

Antibodies, Monoclonal↗
PubMed2006

The interplay between climate variability and density dependence in the population viability of Chinook salmon.

The viability of populations is influenced by driving forces such as density dependence and climate variability, but most population viability analyses (PVAs) ignore these factors because of data limitations. Additionally, simplified PVAs produce limited measures of population viability such as annual population growth rate (lamda) or extinction risk. Here we developed a "mechanistic" PVA of threatened Chinook salmon (Oncorhynchus tshawytscha) in which, based on 40 years of detailed data, we related freshwater recruitment of juveniles to density of spawners, and third-year survival in the ocean to monthly indices of broad-scale ocean and climate conditions. Including climate variability in the model produced important effects: estimated population viability was very sensitive to assumptions of future climate conditions and the autocorrelation contained in the climate signal increased mean population abundance while increasing probability of quasi extinction. Because of the presence of density dependence in the model, however we could not distinguish among alternative climate scenarios through mean lamda values, emphasizing the importance of considering multiple measures to elucidate population viability. Our sensitivity analyses demonstrated that the importance of particular parameters varied across models and depended on which viability measure was the response variable. The density-dependent parameter associated with freshwater recruitment was consistently the most important, regardless of viability measure, suggesting that increasing juvenile carrying capacity is important for recovery.

Animals↗
PubMed2006

Using population viability analysis to predict the effects of climate change on the extinction risk of an endangered limestone endemic shrub, Arizona cliffrose.

The threat of global warming to rare species is a growing concern, yet few studies have predicted its effects on rare populations. Using demographic data gathered in both drought and nondrought years between 1996-2003 in central Arizona upper Sonoran Desert, we modeled population viability for the federally endangered Purshia subintegra (Kearney) Henrickson (Arizona cliffrose). We used deterministic matrix projection models and stochastic models simulating weather conditions during our study, given historical weather variation and under scenarios of increased aridity. Our models suggest that the P. subintegra population in Verde Valley is slowly declining and will be at greater risk of extinction with increased aridity. Across patches at a fine spatial scale, demographic performance was associated with environmental factors. Moist sites (patches with the highest soil moisture, lowest sand content, and most northern aspects) had the highest densities, highest seedling recruitment, and highest risk of extinction over the shortest time span. Extinction risk in moist sites was exacerbated by higher variance in recruitment and mortality. Dry sites had higher cumulative adult survival and lower extinction risk but negative growth rates. Steps necessary for the conservation of the species include introductions at more northern latitudes and in situ manipulations to enhance seedling recruitment and plant survival. We demonstrate that fine spatial-scale modeling is necessary to predict where patches with highest extinction risk or potential refugia for rare species may occur Because current climate projections for the 21st century imply range shifts at rates of 300 to 500 km/century, which are beyond even exceptional examples of shifts in the fossil record of 100-150 km, it is likely that preservation of many rare species will require human intervention and a long-term commitment. Global warming conditions are likely to reduce the carrying capacity of many rare species' habitats.

Arizona↗
PubMedDate not supplied

Boronated monoclonal antibody 225.28S for potential use in neutron capture therapy of malignant melanoma.

The concept of conjugating boron cluster compounds to monoclonal antibodies has been examined by several groups of research workers in boron neutron capture therapy (BNCT). The procedures reported to date for boronation of monoclonal antibodies resulted in either an inadequate level of boron incorporation, the precipitation of the conjugates, or a loss of immunological activity. The present report describes the conjugation of dicesium-mercapto-undecahydrododecaborate (Cs2B12H11SH) to 225.28S monoclonal antibody directed against high molecular weight melanoma-associated antigens (HMW-MAA), using poly-L-ornithine as a "bridge" to increase the carrying capacity of the antibody and to minimize change in the conformational structure of antibody. The method produces a boron content of 1,300 to 1,700 B atoms per molecule 225.28S while retaining the immunoreactivity. Characterization in terms of the homogeneity of the conjugation of the boron-monoclonal antibody conjugates has been studied by gel electrophoresis and ion-exchange HPLC.

Antibodies, Monoclonal↗
PubMed1975

Clinical and experimental studies on adenine, various nucleosides and their analogs in hematology.

In red blood cells as well as in platelets there appears to be a decrease in adenine nucleotides during storage under blood bank conditions. This can be decreased by use of anticoagulant preservatives with higher phosphate content than the standard ACD solution, through the addition of adenine and inosine. Maintenance of higher ATP levels appears to be related to longer circulating life span after transfusion into patients in the case of red blood cells but not platelets. Inosine and more alkaline preservative medium also contribute to the maintenance of 2,3-DPG levels in red blood cells, and with it to the maintenance of normal hemoglobin dissociation curves and thus oxygen-carrying capacity. Certain nucleoside analogs may contribute to the preservation of platelets and of whole blood by their platelet-aggregation inhibitory activity. Platelet-aggregation inhibitors may also be useful in preventing thromboembolic episodes with potentially greater safety than anticoagulants.

Adenine↗
PubMed1994

Artificial life extension. The epigenetic approach.

An epigenetic approach starts out from the direct (rather than the underlying genetic) causes. An epigenetic approach to aging has little chance of succeeding before a minimum amount of knowledge has been accumulated on the "genetic programming" that is currently believed to underlie aging. Two recent advances, one empirical and one theoretical, jointly brighten the prospect. The empirical one is the discovery that melatonin functions as an aging-controlling hormone in mammals. In 1979, Dilman and co-workers isolated a biologically active pineal extract (epithalamin) in rats which, as they later showed, stimulates melatonin production. Pierpaoli and co-workers in 1987 directly administered melatonin to mice. Both groups observed a surprising 25-percent increase of life span in conjunction with a postponed senescence. A similar effect was also achieved with an engraftment of young pineal tissue into the thymus of old mice by Pierpaoli's group. Beneficial effects of epithalamin in humans were reported by Dilman's group. The second advance is a deductive evolution-theoretical approach to aging discovered in 1988. In populations living in a niche with a fixed carrying capacity, any individual is in the long run replaced by a single successor. It follows that, as the expected cumulative number of adult progeny of the same sex approaches unity as a function of life time of the progenitor, the latter's survivability must approach zero if the sum is to remain unity. A physiological prediction follows: a centralized physicochemical clock--like a sedimentation process--must exist somewhere in the organism controlling a secreted substance that reaches all cells. In this way, the pineal coacervates and the pineal's hormonal product melatonin were arrived at on an independent route again. While melatonin as a drug has been used on human volunteers for decades, its anti-aging effect has yet to be proved. Detailed hormone profiles in different age groups and under different life styles have to be performed. A modified Hayflick in vitro experiment is also needed to elucidate the mechanism by which melatonin works in cells.

Aging↗
PubMed1980

A survey concerning cattle tick control in Queensland. 4. Use of resistant cattle and pasture spelling.

The results of a survey on tick control carried out in 1977-78 indicate that tick resistant cattle have been introduced for their heat and drought tolerance and their ability to grow more rapidly than European cattle, especially in the extensive grazing country of Northern and Central Queensland. In South-eastern Queensland acceptance of tick resistant cattle has been slower because producers believe they are more difficult to manage than European cattle. A need for more publicity to be given to the different handling methods required by these animals was shown. Some producers cull their less resistant crossbred Zebu cattle and others could be encouraged to do so. Pasture spelling appears to be quite common especially in the Costal North; it is being carried out for pasture management rather than as a tick control measure. Producers in Central and South-eastern Queensland, who do not spell pastures, feel that it reduces the carrying capacity.

Animals↗
PubMed1985

The occurrence, cost and control of sawfly larval (Lophyrotoma interrupta) poisoning of cattle in Queensland 1972-81.

A postal survey of cattle producers in the Maranoa, Warrego and Leichhardt districts of Queensland where poisoning of cattle by larvae of the sawfly (Lophyrotoma interrupta) occurs was carried out in 1982 with 179 replies (64% of those contacted). During 1972-81, 50 farms with 84,300 cattle experienced deaths (5254 on 37 farms) during July to September. The worst years were 1975 (955 deaths) and 1979 (1895 deaths). Heavy losses occurred on 9% of farms. These were where the silver-leaved iron bark (Eucalyptus melanophloia) was most common. To prevent the disease, 37 graziers moved cattle from dangerous areas and 52 partly removed E. melanophloia from their farms. 31 fed supplements to try to prevent the pica thought to cause cattle to eat larvae. 53 who had suffered sporadic or no deaths took no action. The survey results indicated that cattle should not be returned to dangerous areas until early October. The estimated total yearly cost from reduced carrying capacity, control measures and deaths was $1,100,000 (1981 values). Improved control by advice on property management and a better knowledge of the population dynamics of the sawfly was suggested. The use of antidotes or toxoids was thought inappropriate.

Animals↗
PubMedDate not supplied

Evaluation of citrate-phosphate-dextrose-adenine as a storage medium for packed canine erythrocytes.

Packed canine red blood cells (RBCs) stored in the anticoagulant-preservative solution citrate-phosphate-dextrose-adenine (CPDA-1) were studied at 1, 10, 20, 30, and 40 days. The extracellular concentrations of potassium and sodium, erythrocyte mean corpuscular volume, and osmotic fragility increased during storage (P less than 0.05). There was a decrease in the pH, plasma concentration of glucose, and erythrocyte concentrations of 2,3-diphosphoglycerate (2,3-DPG) and adenosine-5'-triphosphate (P less than 0.05). Erythrocyte 2,3-DPG concentration decreased by 54% within the first 24 hours of storage (P less than 0.001). Posttransfusion viability (PTV) decreased from 90% on day 1 to 46% on day 40 (P less than 0.05). The PTV of the RBCs stored for 10 and 20 days complied with the Food and Drug Administration (FDA) standard. Although there are marked biochemical and hematologic changes in stored packed red blood cells (pRBCs), 20-day-old units may be expected to be of acceptable quality. The sharp decrease in 2,3-DPG concentration suggests a reduction in oxygen carrying capacity in erythrocytes stored as pRBCs. Hyperkalemia occurs during storage of pRBCs and does not appear to be associated with high intraerythrocytic potassium concentrations.

Adenine↗
PubMed1970

Cardiovascular function in young lambs during summit metabolism.

1. Cardiac output in lambs less than 3 days old was 50-100% higher during summit metabolism than during exposure to thermoneutral conditions.2. The Fick method, based on oxygen consumption, and the dye dilution method for determination of cardiac output, gave qualitatively similar results, but there were considerable quantitative discrepancies.3. The thermogenic tissues, muscle and brown fat, extracted some 80% of the oxygen from the blood perfusing them during summit metabolism.4. Significant right to left shunts through the foramen ovale were detected in about half of the lambs during the first few days of life; the size and incidence of shunts decreased with advancing age but were apparently independent of environmental conditions.5. During exposure to extreme cold, left to right shunts through the ductus arteriosus were detected in a high proportion of lambs, < 12 hr old, with detectable foramen ovale shunts. Pressure measurements in pulmonary and systemic arteries in very young lambs indicated that right to left shunting via the ductus was unlikely to occur; none was detected.6. Summit metabolism was poorly related to oxygen carrying capacity of blood, but significant correlations of summit metabolism with cardiac output (positive) and with oxygen saturation of mixed venous blood (negative) were observed, though not consistently.7. It is concluded that the great variability of summit metabolism between lambs older than 6 hr is not readily explained in terms of cardiovascular phenomena, but that the quantity and efficiency of thermogenic tissues probably play an important role in limiting summit metabolism.

Adipose Tissue, Brown↗
PubMed1989

Effect of catecholamines on deformability of red cells from trout: relative roles of cyclic AMP and cell volume.

1. In the presence of catecholamine the nucleated red blood cells of trout show a large increase in cell volume as a result of an accumulation of sodium and chloride due to activation of an amiloride-sensitive, cyclic AMP-dependent Na+-H+ exchanger allowing Na+ to enter in exchange for internal H+. 2. The activation of this cyclic AMP-dependent Na+-H+ exchange is considered to be involved in an adaptive response to hypoxia by increasing the oxygen-carrying capacity of erythrocytes. But cell swelling could increase resistance to blood flow and thus impair the expected physiological advantages for oxygen transport. The effect of catecholamine on the deformability properties of the red blood cells has been studied by measuring the rate at which blood flows through a Nucleopore filter (5 microM). 3. The results show that stimulation by catecholamine in fact increases the erythrocyte deformability, a response which must favour the supply of oxygen at the tissue level. 4. Hormonal stimulation increases the cellular cyclic AMP content (and cyclic AMP-dependent phosphorylation of cytoskeleton proteins could influence cell deformability) and the cell volume. It has been shown that when cellular cyclic AMP content is increased under conditions where the cell cannot swell, the erythrocyte becomes more rigid and not more deformable. Conversely the results show a systematic coincidence between cell swelling and deformability increase. The precise way in which volume change and deformability are interrelated needs more study.

Amiloride↗
PubMed1992

Fetal breathing, sleep state and cardiovascular adaptations to anaemia in sheep.

1. In unanaesthetized fetal sheep (greater than 0.8 term) prolonged anaemia initially reduced the incidences of low-voltage electrocortical activity, rapid eye movements and breathing activity; but the incidence of each returned to normal within 4-7 h. 2. Anaemia induced a persistent rise in fetal heart rate and plasma concentrations of adrenaline, noradrenaline and cortisol. 3. After 16 h the fetal haematocrit was returned to normal. Isocapnic hypoxia induced less than 1 h later also inhibited eye and breathing activity. 4. After 1 h fetal arterial PO2 (Pa,O2) was returned to normal. This rise in O2 tension was associated with an elevation in the incidence of low-voltage electrocortical activity, eye movements and breathing. Breathing movements also occurred during high-voltage electrocortical activity. 5. It is concluded that the brain PO2 set-point for hypoxic inhibition adapts rapidly to alterations in O2-carrying capacity and is probably due to changes in the concentration and/or receptor affinity of a central neuromodulator. Secondly, a rise in brain PO2 at birth may contribute to the onset of continuous breathing.

Adaptation, Physiological↗
PubMed1995

Cervical vertebral strain measurements under axial and eccentric loading.

The mid to lower cervical spine is a common site for compression related injury. In the present study, we determined the patterns of localized strain distribution in the anterior aspect of the vertebral body and in the lateral masses of lower cervical three-segment units. Miniature strain gages were mounted to human cadaveric vertebrae. Each preparation was line-loaded using a knife-edge oriented in the coronal plane that was moved incrementally from anterior to posterior to induce compression-flexion or compression-extension loading. Uniform compressive loading and failure runs were also conducted. Failure tests indicated strain shifting to "restabilize" the preparation after failure of a component. Under these various compressive loading vectors, the location which resulted in the least amount of deformation for a given force application (i.e., stiffest axis) was quantified to be in the region between 0.5- 1.0 cm anterior to the posterior longitudinal ligament. The location in which line-loading produced no rotation (i.e., balance point) was in this region; it was also close to where the vertebral body strains change from compressive to tensile. Strain values from line loading in this region produced similar strains as recorded under uniform compressive loading, and this was also the region of minimum strain. The region of minimum strain was also more pronounced under higher magnitudes of loading, suggesting that as the maximum load carrying capacity is reached the stiffest axis becomes more well defined.

Aged↗
PubMedDate not supplied

Noninvasive monitoring of red blood cell transfusion in very low birthweight infants using diffuse optical spectroscopy.

Red blood cell (RBC) transfusion guidelines are designed to maintain adequate tissue oxygenation by increasing blood oxygen-carrying capacity. However, since tissue oxygenation is not measured, RBC transfusion guidelines are mostly subjective. Clinical evidence of oxygen transport/consumption mismatches in infants is often unclear and confounded by multiple factors. Invasive hemoglobin measurements can contribute further to anemia if performed too frequently. Diffuse optical spectroscopy (DOS) is a noninvasive quantitative method to measure the tissue oxy, deoxy, and total hemoglobin concentrations (ctO2Hb, ctHb, ctTHb), as well as mixed arterial-venous tissue hemoglobin saturation (stO2). Our objective is to determine if DOS can assess changes in tissue oxygenation in very low birth weight (VLBW) infants undergoing RBC transfusions. DOS measurements of ctO2Hb and ctHb are performed on 10 VLBW infants before and within 24 h after RBC transfusion. Seven nontransfused infants are studied to evaluate hemodynamic variations independent of RBC transfusion. Tissue near-infrared absorption and scattering values are measured using a four-wavelength (690, 750, 810, and 830 nm) frequency-domain tissue oximeter (OxiplexTS, ISS, Champaign, Illinois). In transfused subjects, DOS demonstrates significant increases in ctO2Hb (48+/-13 versus 74+/-20 microM, p<0.002), ctTHb (87+/-17 versus 107+/-24 microM, p=0.004), and stO2 (54+/-8 versus 68+/-6%, p<0.004) post-transfusion. DOS measurements correlate with mean hemoglobin increases for all infants (r=0.83, p<0.0001). No significant DOS changes occurred in the nontransfused group. Calculations of the differential path length for these transfused subjects show high variability (approximately 20%). DOS may serve as a noninvasive bedside tool to assess tissue oxygenation in infants and provide a functionally based transfusion trigger.

Anemia, Neonatal↗
PubMed2004

Neutral and anionic liposome-encapsulated hemoglobin: effect of postinserted poly(ethylene glycol)-distearoylphosphatidylethanolamine on distribution and circulation kinetics.

To prepare long-circulating liposomes, poly(ethylene glycol) (PEG)-lipid is usually mixed with other lipid components before vesicle formation. PEG-lipids can also be postinserted in the outer layer of liposomes after the preparation. In this study, PEG-distearoylphosphatidylethanolamine was incorporated by postinsertion technique into liposome-encapsulated hemoglobin (LEH) carrying neutral or negative charge. Postinsertion technique improved the encapsulation efficiency of hemoglobin from about 0.0017 to 0.017 (hemoglobin/phospholipid, molar ratio) for a similar lipid composition. Thus, neutral, anionic, PEG-neutral, and PEG-anionic LEHs were made and labeled with technetium-99m to follow their biodistribution. A small dose of LEH (approximately 15 mg of phospholipid) was injected intravenously in rabbits, and its distribution was monitored by blood sampling, gamma camera imaging, and tissue radioactivity counting on necropsy. The 24-h blood levels of neutral, PEG-neutral, anionic, and PEG-anionic LEHs were 14, 40.3, 13.1, and 35.7% of injected dose, respectively; calculated T(1/2) values of circulation were 8.9, 19.3, 9.6, and 16.5 h, respectively. PEGylation also influenced accumulation of LEH in the reticuloendothelial system. Liver uptake of neutral LEH dropped from 52.1 to 19.1%, whereas that of anionic LEH came down from 35.3 to 11.5% on PEGylation. In contrast, PEGylation increased the spleen uptake by 8.5- and 2.5-fold for neutral and anionic LEH, respectively. The results demonstrate that PEGylation by postinsertion not only improves the circulation t1/2 of LEH but also enhances hemoglobin content inside the vesicles for better oxygen-carrying capacity.

Animals↗