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Biomedical subjects

R E Weber

Publications and source records attributed to R E Weber.

At least 55 records · Page 3Linked to original sources
PubMed1989

Gas exchange in fish gills with parallel inhomogeneities.

Using a mathematical model, the effects of water and blood flow inequality on gas exchange in the fish gill were investigated. The results show that O2 exchange is more sensitive to flow inequalities than CO2 exchange. Oxygen exchange is most sensitive to blood flow inequality, whereas carbon dioxide exchange is equally sensitive to inequalities in water and blood flow. Furthermore, it is shown that the effects of flow inequalities cannot be abolished by matching the two flows exactly. The results suggest that the greatest potential for regulation of gas exchange lies on the blood side of the exchanger, and that adjustments in flow distributions to maintain homeostasis in oxygen exchange in the face of changing environmental conditions and/or changing organismic demands, most likely will be accompanied by a change in the acid-base status of the animal.

Animals↗
PubMed1989

Deposition of cigarette smoke particles in the rat.

The fractional deposition of cigarette smoke particles in the respiratory tracts of rats was studied. Male and female rats were conditioned in nose-only exposure tubes 25 min/day for 2 days, exposed to cigarette smoke at mass concentrations of 95 or 341 mg/m3, 25 min/day for 3 days, and then exposed to smoke at mass concentrations of 212 and 657 mg/m3, 25 min/day for 5 days. Mainstream cigarette smoke was generated by a modified Walton smoking machine from two 1R3 research cigarettes burned sequentially for each exposure. Deposition studies were conducted by placing the rats in plethysmograph tubes to allow respiratory minute volume measurements during exposure, then exposing them to [14C]dotriacontane-labeled cigarette smoke at mass concentrations of 202 or 624 mg/m3 for 25 min, using the same smoking machine. Size distribution, real-time concentration, and 14C activity of the smoke particles were determined using a multijet Mercer impactor, a real-time aerosol monitor, and filter samples, respectively. Immediately after the exposure, the rats were terminated to determine the distribution of the 14C. Individual lung lobes, trachea and lobar bronchi, head, larynx, kidneys, liver, gastrointestinal (GI) tract, blood, and depleted carcass of each rat were analyzed for 14C content. Results showed that the GI tract contained 16-31% of the total activity, indicating significant clearance from the large airways and nose to the GI tract during the exposure and during the 10-15 min between the cessation of the exposure and the removal of the organs. Total deposition of the inhaled 14C activity was 20.1 +/- 1.6% for both exposure concentrations. The intrapulmonary deposition fractions (lung lobes plus airways below the lobar bronchi) were 12.4 +/- 0.9 and 15.9 +/- 1.4% for concentrations of 202 and 624 mg/m3, respectively, suggesting a slight enhancement in upper airway deposition for animals exposed to the higher smoke concentration.

Alkanes↗
PubMed1989

Continuous cardiac output determination using transtracheal Doppler: initial results in humans.

Transtracheal Doppler, a procedure developed in the authors' laboratory, provides an estimate of cardiac output in endotracheally intubated dogs. The present study reports initial results in humans with a Doppler probe incorporated into an endotracheal tube. The system was first calibrated by empirically determining phi, the angle of the ultrasound beam with respect to the blood velocity vector. For a best least squares fit for phi, aortic diameters can be calibrated over a range of 22-37 mm. The calibration was then tested in a separate group of patients using the same empirically derived angle to calculate cardiac outputs. The transtracheal Doppler cardiac outputs show good correlation with those obtained by thermodilution over a range of cardiac outputs, 2.69-8.62 1/min, R2 = 0.835.

Adolescent↗
PubMed1989

Amino-acid sequences and functional differentiation of hemoglobins A and D from swift (Apus apus, Apodiformes).

The blood of the adult swift contains one major (HbA = alpha 2A beta 2) and two minor components (HbD = alpha 2D beta 2 and HbD'). The components were separated by FPLC with a TSK SP-5 PW-column in phosphate buffers, and were eluted with a linear NaCl gradient. HbD' could be detected only in freshly prepared hemolysates with the sensitive FPLC separation method. The globin chains were separated on a cation exchanger (CM-cellulose), the tryptic peptides by HPLC with a RP-2 LiChrosorb column. Their amino-acid sequences were determined by automatic Edman degradation with the film- or gas-phase method. For the alpha A-, alpha D- and beta-chains, peptide alignment was achieved by homologous comparison with the corresponding chains of the greylag goose (Anser anser). The structural significance of the substitutions was examined with the aid of molecular graphics. The oxygen-binding properties of the stripped hemolysate and of HbA and HbD and their dependence on pH, temperature and inositol polyphosphate are presented and discussed with reference to molecular structures and hypothermy that occurs during torpidity.

Amino Acid Sequence↗
PubMed1989

High-altitude respiration of falconiformes. The primary structures and functional properties of the major and minor hemoglobin components of the adult White-Headed Vulture (Trigonoceps occipitalis, Aegypiinae).

The primary structures of the hemoglobin components Hb A and Hb D of White-Headed Vulture (Trigonoceps occipitalis) are presented. The globin chains were separated on CM-Cellulose in 8M urea buffer, the components by FPLC in phosphate buffers. The amino-acid sequences were established by automatic Edman degradation of the globin chains and of the tryptic peptides in liquid phase and gas-phase sequenators. The sequences differ from those of European Black Vulture by only one mutation in the alpha A-chains (alpha 137). The alpha D-chains and the beta-chains are identical. This means that for the first time identical minor components in birds have been found. An updated list of identical globin chains is presented. Hb D exhibited a higher oxygen affinity than Hb A. At pH 7.5 and 38 degrees C P50 values of 0.80 and 0.64 kPa (6.0 and 4.8 mm Hg), respectively. Both hemoglobins showed similar Bohr factors displayed a pronounced sensitivity to inositol hexakis(phosphate), which increased P50 values of Hbs A and D to 4.0 and 3.6 kPa (30 and 26 mm Hg), respectively. The molecular and physiological significance of the findings is discussed with special reference to oxygen transport by hemoglobin at high altitude.

Altitude↗
PubMed1989

Allosteric transition in hemoglobin (alpha 2A beta 2I) from the rhynchocephalian reptile relict Sphenodon punctatus.

The major hemoglobin component Hb A of the tuatara, Sphenodon punctatus, a relict of the rhynochocephalian reptiles that lived 200 million years ago, was investigated in the light of the apparent contradiction inherent in an effect of organic phosphate cofactors on the oxygen affinity of hemoglobins exhibiting hyperbolic oxygen equilibrium curves. The heterotropic allosteric effect of ATP, the major erythrocytic cofactor in the tuatara, is shown to be correlated with distinct homotropic interactions (Hill's cooperativity coefficient at half-saturation, n50, attaining 1.3-1.5 above pH 7.5), and with free energies of heme-heme interaction (4.7 kJ.mole-1 at pH 7.2) which resemble those in other vertebrate hemoglobins that exhibit higher n50 values. Curiously, chloride ions increase hemoglobin-oxygen affinity below pH +/- 7.2. The possible mechanisms underlying the effects of ATP and chloride are discussed.

Adenosine Triphosphate↗
PubMed1989

Transtracheal Doppler: a new procedure for continuous cardiac output measurement.

An endotracheal tube with a 5 mm diameter ultrasonic transducer incorporated into its distal end was inserted into the tracheas of six anesthetized dogs. The device provides for ultrasound measurement of aortic diameter and blood velocity in the ascending aorta to obtain cardiac outputs. Because measurements are made proximal to the origins of the aortic arch vessels, total cardiac output is obtained. Procedures for measurement of aortic diameter, aortic blood velocity, and cardiac output are discussed. The resulting data were used to empirically determine the angle of incidence of the ultrasound beam that gave the best least squares fit over a range of thermodilution cardiac outputs. For an angle of incidence of 62.3 degrees, the relationship between cardiac output determined by thermal dilution and by transtracheal Doppler was transtracheal Doppler cardiac output = -.69 + 1.19 thermal dilution cardiac output. R2 = .82. The results from this preliminary assessment of the feasibility of measuring cardiac output in dogs using transtracheal Doppler suggest that additional studies should be pursued. Additional issues that require investigation include confirmation of constancy of human anatomy and demonstration of lack of tracheal trauma from the Doppler equipped endotracheal tube.

Animals↗
PubMed1988

Functional characterization of fetal and adult yak hemoglobins: an oxygen binding cascade and its molecular basis.

In contrast to most other mammals, the yak, which is native to high altitudes, has two major fetal and two or four major adult hemoglobin (Hb) components. We report the oxygen affinities and sensitivities to pH and 2,3-diphosphoglycerate of the two fetal and two adult Hbs commonly found in calves, compared to those of adult cow Hb A, and relate these findings to their primary structures and to placental maternal-fetal oxygen transfer at altitude. Arranged in order of decreasing oxygen affinity the Hbs are F1 (alpha I2 gamma 2), F2 (alpha II2 gamma 2), A1 (alpha II2 beta II2), and cow Hb A. The higher affinity of the fetal than the adult yak Hbs correlates with the beta 15Trp----Phe substitution, whereas the higher affinity in yak than in cow Hb correlates with the beta 135Ala----Val substitution. The difference in oxygen affinities between yak Hbs A1 and A2, which have identical beta chains, suggests the existence of yet unknown mechanisms determining oxygen affinity. The larger Bohr effects of F2 than F1 and of A2 than A1 are attributable to alpha-chain differences, most probably the alpha I50Glu----alpha II50His substitution.

Altitude↗
PubMed1988

High-altitude respiration of birds. Structural adaptations in the major and minor hemoglobin components of adult Rüppell's Griffon (Gyps rueppellii, Aegypiinae): a new molecular pattern for hypoxic tolerance.

The primary structures of the hemoglobins Hb A, Hb A', Hb D and Hb D' of Rüppell's Griffon (Gyps rueppellii), which can fly as high as 11,300 m, are presented. The globin chains were separated on CM-Cellulose in 8M urea buffers, the four hemoglobin components by FPLC in phosphate buffers. The amino-acid sequences of five globin chains were established by automatic Edman degradation of the globin chains and of the tryptic peptides in liquid-phase and gas-phase sequenators. The sequences are compared with those of other Falconiformes. A new molecular pattern for survival at extreme altitudes is presented. For the first time four hemoglobins are found in blood of a bird; they show identical beta-chains and differ in the alpha A- and alpha D-chains by only one replacement. These four hemoglobins cause a gradient in oxygen affinities. The two main components Hb A and Hb A' differ at position alpha 34 Thr/Ile. In case of Ile as found in Hb A' an alpha 1 beta 1-interface is interrupted raising oxygen affinity compared to Hb A. In addition the hemoglobins of the A- and D-groups differ at position alpha 38 Pro or Gln/Thr (alpha 1 beta 2-interface). Expression of Gln in Hb D/D' raises the oxygen affinity of these components compared to Hb A/A' by destabilization of the deoxy-structure. The physiological advantage lies in the functional interplay of four hemoglobin components. Three levels of affinity are predicted: low affinity Hb A, Hb A' of intermediate affinity, and high affinity Hb D/D'. This cascade tallies exactly with oxygen affinities measured in the isolated components and predicts oxygen transport by the composite hemoglobins over an extended range of oxygen affinities. It is contended that the mechanisms of duplication of the alpha-genome (creating four hemoglobins) and of nucleotide replacements (creating different functional properties) are responsible for this remarkable hypoxic tolerance to 11,300 m. Based on this pattern the hypoxic tolerances of other vultures are predicted.

Acclimatization↗
PubMed1988

High altitude and hemoglobin function in the vultures Gyps rueppellii and Aegypius monachus.

Functional characteristics of the stripped composite hemoglobins (Hbs) of the vultures Gyps rueppellii and Aegypius monachus that can fly at extremely high altitudes, and of component Hbs of G. rueppellii are reported, in relation to influences of pH, temperature and inositol hexaphosphate. G. rueppellii Hbs A, A' and D represent a sequence of increasing oxygen affinity, which is opposite to earlier results on avian Hb components, but correlates with two alpha-chain substitutions that predictably affect oxygen affinity. The homo- and heterotropic interactions in oxygen binding are related to primary structures of the constituent polypeptide chains to trace molecular adaptations to high-altitude respiration, and to physiological factors (pulmonary hypoxia and hypocapnia, body temperature shifts, and lung and nasal gas and heat exchange) to discern their possible survival value at altitudes of 11,300 m.

Acclimatization↗
PubMed1987

Thermodynamic analysis of precisely measured oxygen equilibria of tench (Tinca tinca) hemoglobin and their dependence on ATP and protons.

Precise oxygen equilibria including extreme, high and low saturation values were determined for hemoglobin (Hb) from the freshwater teleost Tinca tinca at three temperatures, each at two pH levels and in the presence and absence of the erythrocytic cofactor ATP, at twofold molar excess over Hb. Analysis of the data in terms of Adair's successive oxygenation theory shows that in the absence of ATP, each of the four oxygenation steps are exothermic, but that net heat release decreases as pH falls from 8.2 to 7.4. ATP greatly depresses the temperature sensitivity of oxygenation particularly at physiological erythrocytic pH, where endothermic cofactor dissociation finds expression in a reverse temperature sensitivity for binding of the 3rd oxygen molecule to the tetrameric Hb. Enthalpy (delta Hi) and entropy (delta Si) changes of oxygenation vary with oxygenation step, i, as well as with pH and ATP addition, but the variations of delta Hi are similar to those of delta Si reflecting enthalpy-entropy compensation. The data show that the cooperative effects in tench Hb can be dominated either by entropic or enthalpic contributions, depending on the experimental condition and the oxygenation step.

Adenosine Triphosphate↗
PubMed1987

Analysis of teleost hemoglobin by Adair and Monod-Wyman-Changeux models. Effects of nucleoside triphosphates and pH on oxygenation of tench hemoglobin.

The allosteric effects of the erythrocytic nucleoside triphosphates (NTP) and of proton concentrations were investigated by precise measurement of Hb-O2 equilibria of tench hemoglobin (including extreme, high and low saturation ranges) and analysed in terms of the MWC two state model and the Adair four step oxygenation theory. At low concentrations (NTP/Hb ratio = 1.0, and pH greater than 7.3) ATP, GTP and protons decrease Hb-O2 affinity by increasing the allosteric constant L and reducing KT, the association constant of the deoxy, tense state of the Hb, without significantly affecting that (KR) of the oxy state, increasing the free energy of cooperativity (delta G). High concentrations of these effectors, however, also reduce KR. The greater sensitivity of the half-saturation O2 tension (P50) of the Hb to GTP than to ATP at the same concentration, correlates with greater effects of GTP on both KT and KR. The pH and NTP dependence of the four Adair association constants and the calculated fractional populations of Hb molecules in different stages of oxygenation show that the autochthonous NTP effectors and protons stabilize the T structure and postpone the T----R transition basic to cooperativity in fish Hb. The possible implications of the findings for aquatic respiration are discussed.

Animals↗
PubMed1987

The effect of shape and position of the oxygen equilibrium curve on extraction and ventilation requirement in fishes.

The effects of haemoglobin-oxygen affinity and of cooperativity in oxygen binding on the oxygen extraction and ventilation requirement in fish are analysed using the mathematical model of Malte and Weber (1985). It is shown that a high affinity may allow a substantial reduction in ventilatory requirement and that optimal O2 uptake depends on a delicate balance between affinity and cooperativity. Using P50 and nH values from the literature, the oxygen extraction values predicted by the model for carp and rainbow trout coincide neatly with the values found for these species, indicating that the differences in oxygen extraction are a direct result of different blood oxygen binding properties.

Animals↗
PubMed1987

Embryonic pig hemoglobins Gower I (zeta 2 epsilon 2), Gower II (alpha 2 epsilon 2), Heide I (zeta 2 theta 2) and Heide II (alpha 2 theta 2): oxygen-binding functions related to structure and embryonic oxygen supply.

The common pig lacks a fetal hemoglobin but has four embryonic hemoglobins: Gower I (zeta 2 epsilon 2), Gower II (alpha 2 epsilon 2), Heide I (zeta 2 theta 2) and Heide II (alpha 2 theta 2) as well as adult Hb A (alpha 2 beta 2) and the amino acid sequence for each of the five constituent polypeptide chains has been established. The oxygenation characteristics of the five components, measured in relation to pH, temperature and the erythrocytic ligand 2,3-diphosphoglycerate (DPG), together with the changes in their relative concentrations during early embryonic life, are given. The findings indicate a progressive decrease in maternal-fetal oxygen affinity difference and thus in oxygen transfer efficacy at a given diffusion gradient that correlates with the development of the gas exchange structures. The functional properties of the individual hemoglobins are additionally discussed in relation to molecular structure.

2,3-Diphosphoglycerate↗
PubMed1987

Molecular basis for ATP/2,3-bisphosphoglycerate control switch-over (poikilotherm/homeotherm) an intermediate amino-acid sequence in the hemoglobin of the great Indian rhinoceros (Rhinoceros unicornis, Perissodactyla).

The complete primary structure of the two hemoglobin components of the Great Indian Rhinoceros (Rhinoceros unicornis) is presented. The ratio for the two components B(alpha 2 beta I2): A(alpha 2 beta II2) is 6:4. Polypeptide subunits were separated by chromatography on CM-cellulose in a buffer containing 8M urea. The sequence was studied by degradation of the tryptic and hydrolytic cleavage products in a liquid phase sequencer. At position beta NA2 component B has Asp, whereas component A has Glu, an ATP-binding site in fish and reptilian hemoglobins. The other phosphate binding sites i.e. beta NA1 Val, beta EF6 Lys and beta H21 His are identical with 2,3-bisphosphoglycerate-(DPG)binding sites in mammalian hemoglobins, whereby rhinoceros hemoglobin resembles both ATP-sensitive poikilotherm hemoglobin and DPG-sensitive mammalian hemoglobin. The two components (beta I/beta II) additionally differ by exchange of Glu----Gly at position beta A3 and Gln----Lys at position beta GH3. The significance of these changes is discussed. Oxygenation properties of the two hemoglobins components and their dependence on ATP and DPG are given. The structure and function of Rhinoceros hemoglobin may give an insight into the evolution of the organic phosphate binding in vertebrate hemoglobins.

2,3-Diphosphoglycerate↗
PubMed1987

Primary structure and functional properties of the hemoglobin from the free-tailed bat Tadarida brasiliensis (Chiroptera). Small effect of carbon dioxide on oxygen affinity.

The hemoglobin of the Free-Tailed Bat Tadarida brasiliensis (Microchiroptera) comprises two components (Hb I and Hb II) in nearly equal amounts. Both hemoglobins have identical beta-chains, whereas the alpha-chains differ in having glycine (Hb I) or aspartic acid (Hb II) in position 115 (GH3). The components could be isolated by DEAE-Sephacel chromatography and separated into the globin chains by chromatography on carboxymethyl-cellulose CM-52. The sequences have been determined by Edman degradation with the film technique or the gas phase method (the alpha I-chains with the latter method only), using the native chains and tryptic peptides, as well as the C-terminal prolyl-peptide obtained by acid hydrolysis of the Asp-Pro bond in the beta-chains. The comparison with human hemoglobin showed 18 substitutions in the alpha-chains and 24 in the beta-chains. In the alpha-chains one amino-acid exchange involves an alpha 1/beta 1-contact. In the beta-chains one heme contact, three alpha 1/beta 1- and one alpha 1/beta 2-contacts are substituted. A comparison with other chiropteran hemoglobin sequences shows similar distances to Micro- and Megachiroptera. The oxygenation characteristics of the composite hemolysate and the two components, measured in relation to pH, Cl-, and 2,3-bis-phosphoglycerate, are described. The effect of carbon dioxide on oxygen affinity is considerably smaller than that observed in human hemoglobin, which might be an adaptation to life under hypercapnic conditions.

Amino Acid Sequence↗
PubMed1986

Oxygen binding functions of blood and hemoglobin from the Chinese pangolin, Manis pentadactyla: possible implications of burrowing and low body temperature.

We measured O2 equilibria of adult blood and of 'stripped' (cofactor-free) hemolysates from adult and newborn Manis pentadactyla, in order to assess the implications of the burrowing habit and the low deep-core temperature in pangolins, and to discern the mechanisms for maternal-fetal O2 transfer. At pH 7.4 and body temperature (33 degrees C) the blood O2 affinity was significantly higher than in similarly sized non-burrowing, 'normothermic' mammals (P50 = 21 and 33 mm Hg, respectively) indicating an adaptation to hypoxic burrow conditions. This difference is not attributable to a higher intrinsic O2 affinity in the pangolin Hb or to significant differences in its sensitivity to temperature and erythrocytic 2,3 diphosphoglycerate (DPG), but tallies with lower DPG/Hb ratios than generally found in mammals. Stripped adult and newborn hemolysates show similar O2 affinities and pH and DPG sensitivities, but reveal a specific adult Hb that develops after birth, in sharp contrast with the ontogenetic changes in other mammals where specific fetal Hbs are lost after birth.

2,3-Diphosphoglycerate↗