Search PubMed⌕ Search

Biomedical subjects

W Moll

Publications and source records attributed to W Moll.

At least 37 records · Page 2Linked to original sources
PubMed1985

Pressure-diameter curves of mesometrial arteries of guinea pigs demonstrate a non-muscular, oestrogen-inducible mechanism of lumen regulation.

Pressure-diameter curves were determined on mesometrial (uterine radial) arteries obtained from guinea pigs during different stages of ovarian cycle and pregnancy. In order to investigate changes in arterial diameter that are not caused by the vascular musculature, we studied excised arteries that were relaxed by papaverine (40 mg/l). The pressure-diameter curves were found to be shifted toward wider diameters when the arteries studied were obtained from pregnant, oestrous or oestrogen treated animals (oestradiol benzoate, 10 micrograms s.c.): the external diameter at 60 mm Hg transmural pressure on the 14th day of pregnancy exceeded the one during dioestrus by 50%. At term, there was a 7-fold increase. During oestrus and 24 h after oestrogen treatment the diameter was 30-40% wider than during dioestrus. Moreover, we found that the diameter measured on excised vessels in the presence of papaverine is the same as the one observed in situ. We conclude that the mesometrial arteries of guinea pigs possess a muscle-independent mechanism of lumen regulation. The mechanism operates in non-pregnant and pregnant animals. It may be induced by oestrogen and seems to be qualified for long-term lumen regulation during pregnancy. In contrast, dilation by smooth muscle relaxation appears to be of minor importance in mesometrial arteries.

Animals↗
PubMed1984

Drastic rise of intracellular adenosine(5')tetraphospho(5')adenosine correlates with onset of DNA synthesis in eukaryotic cells.

An assay of adenosine(5')tetraphospho(5')adenosine (Ap4A), based on the luciferin/luciferase method for ATP measurement, was developed, which allows one to determine picomolar amounts of unlabeled Ap4A in cellular extracts. In eukaryotic cells this method yielded levels of Ap4A varying from 0.01 microM to 13 microM depending on the growth, cell cycle, transformation, and differentiation state of cells. After mitogenic stimulation of G1-arrested mouse 3T3 and baby hamster kidney fibroblasts the Ap4A pools gradually increased 1000-fold during progression through the G1 phase reaching maximum Ap4A concentrations of about 10 microM in the S phase. Quiescent 3T3 cells reach a high level of Ap4A (1 microM) in a 'committed' but prereplicative state if exposed to an external mitogenic stimulant (excess of serum) and simultaneously to a synchronizer which inhibits entry into the S phase (hydroxyurea). When the block for DNA replication was removed at varying times after removal of the stimulant decay of commitment to DNA synthesis was found correlated with a shrinkage of the Ap4A pool. Cells lacking a defined G1 phase (V79 lung fibroblasts, Physarum) possess a constitutively high base level of Ap4A (about 0.3 microM) even during mitosis. From this high level, Ap4A concentration increases only about tenfold during the S phase. Temperature-down-shift experiments, using chick embryo cells infected with transformation-defective temperature-sensitive viral mutants(td-ts), have shown that the expression of the transformed state at 35 degrees C is accompanied by a tenfold increase of the cellular Ap4A pool. Treatment of exponentially growing human cells with interferon leads, concomitantly with an inhibition of DNA syntheses, to a tenfold decrease in intracellular Ap4A levels within 20 h. The possibility of Ap4A being a 'second messenger' of cell cycle and proliferation control is discussed in the light of these results and those reported previously demonstrating that Ap4A is a ligand of mammalian DNA polymerase alpha, triggers DNA replication in quiescent mammalian cells and is active in priming DNA synthesis.

Adenine Nucleotides↗
PubMed1984

Problems and pitfalls in estimating average pharmacokinetic parameters.

The problems of obtaining optimal average parameter estimates (APE) from experimental pharmacokinetic data are considered. Four different approaches, three parametric and one non-parametric tests, are compared, using selected individual alcohol concentration data. Pooling the raw data for estimating APE can obscure individual pharmacokinetic characteristics, whereas averaging individual parameter estimates (IPE) exposes unique statistical problems. Furthermore, careful consideration should be given to weighting procedures. The advantages and shortcomings of all four methods are discussed. It is concluded that none can be considered as a universally applicable statistical method in view of the purpose for which the information, derived from a set of data, e.g. an alcohol-kinetic study, is required.

Computers↗
PubMed1984

The pharmacokinetics of alcohol in human breath, venous and arterial blood after oral ingestion.

The concentration-time profile of ethanol in breath air (AAC), arterial (ABAC) and venous blood (VBAC) of human volunteers was studied after four different oral doses of absolute alcohol--0.5, 0.75, 1.0, and 1.25 g/kg body weight. Seventy-eight single dose experiments were carried out in 42 subjects. In all 78 studies AAC was measured and VBAC was estimated simultaneously in blood collected from a cubital vein of 36 volunteers. Arterial blood, too, was collected from 8 subjects from a catheter in a brachial artery. All blood alcohol concentrations were analysed independently by gas chromatography (GLC) and an enzymatic (ADH) method. A one-compartment open model with first order absorption and pseudo-zero-order elimination was employed to calculate the pharmacokinetic parameters. The average values for the first order absorption rate constant (ka) ranged from 2.2 to 3.1, from 2.4 to 2.6 and from 1.0 to 1.7 h-1 for ACC, ABAC and VBAC, respectively. The pseudo-zero-order elimination rate constant (beta) was 0.17 to 0.18, 0.21 to 0.22 and 0.26 to 0.27 g X 1(-1) X h-1, respectively. During absorption ABAC tended to be higher than VBAC, peaking at a higher level (Cmax) and with a shorter time to peak (tmax) until an arterio-venous concentration equilibrium was reached, whereafter VBAC remained above ABAC. Although there was a close relationship between AAC, ABAC and VBAC during elimination, AAC closely followed the pattern of ABAC during absorption and tended to deviate from VBAC. AAC, therefore, is a much better predictor of ABAC during absorption than VBAC.

Absorption↗
PubMed1984

Evidence for rotational contribution to protein-facilitated proton transport.

Two modes of molecular motion of carrier molecules can, in principle, lead to a facilitated transport of a substrate: translational and rotational diffusion. In the present study, which deals with the mechanism of the facilitated diffusion of H+ and O2 in solutions of earthworm hemoglobin, examples for both types of facilitation are presented. Only translational, not rotational, diffusion of earthworm hemoglobin appears to lead to a facilitated O2 flux. In contrast, substantial facilitated H+ fluxes of comparable size arise from rotational diffusion as well as from translational diffusion of this large protein. This is derived from measurements of facilitated H+ and O2 fluxes in earthworm hemoglobin solutions and determinations of the rotational and translational diffusion coefficients of earthworm hemoglobin with the help of a theoretical treatment of facilitated diffusion by rotational carrier diffusion. H+ transport by rotational protein diffusion appears to be a case where the often-postulated mechanism of facilitated transport by rotation of a carrier lends itself to experimental verification.

Biological Transport↗
PubMed1983

Blood circulation and oxygen transport in the fetal guinea pig.

Anaesthetized fetal guinea pigs near term were studied under conditions, where maternal placental flow of haemoglobin was maintained within the normal range. The rate of maternal fetal equilibration of intravenously injected 3H2O was found to be similar as in unanaesthetized animals (half time 4 min) indicating that fetal circulation was undisturbed under the present experimental conditions. Umbilical blood flow as determined by a modified 3H2O method was 0.13 ml . min-1 . g-1 of fetal body mass. Radioactive microspheres, injected into the fetal saphenous (jugular) vein, were distributed to the placenta, the lower body, the upper body and the lungs at a ratio of 31(47):27(39):30(6):12(8). From these data, cardiac output was calculated (0.38 ml . min-1 . g-1) and found to be almost equally distributed between the placenta, the lower body and the upper body. There was preferential streaming of the inferior vena caval blood to the upper body. There was no evidence for flow through a ductus venosus. The O2-saturation in the fetal carotid arterial blood was 59 +/- 4%. The O2-supply to the fetal tissues was estimated to be 3 times the oxygen consumption.

Animals↗
PubMed1981

High oxygen affinity of maternal blood reduces fetal weight in rats.

In order to obtain information on the physiological significance of the difference in oxygen affinity between maternal and fetal blood, we have examined the effect of an acute increase of the oxygen affinity of maternal blood in pregnant rats, on fetal body weight, fetal brain and liver weights, placental weight, and the hematocrit of fetal blood. The increase in oxygen affinity was produced by exchange-transfusing pregnant rats on day 19 of gestation with blood that had been treated previously with sodium cyanate. As a result of the exchange transfusion, the difference in oxygen affinity between maternal and fetal blood essentially disappeared. Pregnant rats exchanged with normal blood served as controls. On day 21 of gestation, the fetal body weight and the fetal liver weight were significantly smaller by 18% and 25% respectively, in the group where the oxygen affinity of the maternal blood was acutely raised when compared to the controls. Also, the hematocrit of the fetal blood was significantly higher in the group where mothers had the high blood oxygen affinity. Placental weight and fetal brain weight were not significantly altered. We infer, that the reduction of fetal weight is due to fetal hypoxia which is caused by the abolishment of the difference in oxygen affinity between maternal and fetal blood. Human infants, whose birth weight is too small for their gestational age have a significantly increased postnatal mortality compared to babies with normal weight. We suppose that the increased mortality of newborns who are too small for their gestational age, represents a selective pressure that has favoured the evolution of a high oxygen affinity of fetal in comparison with maternal blood.

Animals↗
PubMed1980

Facilitated diffusion of lactic acid in the guinea-pig placenta.

In the guinea-pig placenta which was artificially perfused on the fetal side while maternal placental blood flow was controlled, the placental transfer per mean transplacental concentration difference (the transfer coefficient TC) was determined for lactate. TC for L-lactate (TCLL) was compared to that for D-lactate (TCDL) and measured for various concentrations of L-lactate, bicarbonate, pyruvate and CO2. Applying a "closed circuit" perfusion technique, L-lactate and proton concentrations on both sides of the placenta were followed during infusion of HCl and sodium L-lactate into the fetal circulation. It was found that TCLL is 3 times TCDL. TCLL is depressed by increasing concentrations of L-lactate while TC for Cl-36 is not. TCLL is also depressed by 50 mmol.1-1 pyruvate. Concentration changes of glucose do not affect TCLL. TCLL rises with the proton concentration, independently of the concomitant changes of the bicarbonate concentration. Transplacental proton concentration gradients produce L-lactate concentration gradients and vice versa. It is concluded that (1) facilitated diffusion of L-lactate occurs in the placenta and that (2) L-lactate transfer is coupled with proton transfer. Beside the well-known placental transport system for glucose this is the second passive transport system found in a placenta.

Animals↗
PubMed1978

The flow resistance of the spiral artery and the related intervillous space in the rhesus monkey placenta.

Uteroplacental arteries of 4 rhesus monkeys were cannulated at their myometrical portions and perfused with dextran solutions and blood. Pressure-flow curves were obtained for the spiral artery and the related intervillous space, i.e. for the functional cotyledonary unit of the haemochorial villous placenta. For a flow of 3 ml.min-1, which is probably the normal rate of flow through the spiral artery, the pressure at the entry of the spiral artery was found to be 13--18 mm Hg (1.7--2.4kPa) during uterine relaxation (uterine diastole). There was a direct proportional relationship between the spiral artery flow and the pressure difference between the spiral artery and the amniotic fluid; the pressure difference per flow (the resistance of the cotyledonary unit) was found to be 1--3 mm Hg . ml-1 . min (8--24kPa . ml-1 . s). It is concluded that the spiral artery and the related intervillous space do not offer a limiting resistance to maternal blood flow in the absence of uterine contractions.

Animals↗
PubMed1978

Net charge and oxygen affinity of human hemoglobin are independent of hemoglobin concentration.

The dependence of net charge and oxygen affinity of human hemoglobin upon hemoglobin concentration was reinvestigated. In contrast to earlier reports from various laboratories, both functional properties of hemoglobin were found to be independent of hemoglobin concentration. Two findings indicate a concentration-independent net charge of carbonmonoxy hemoglobin at pH 6.6: (A) The pH value of a given carbonmonoty hemoglobin solution remains constant at 6.6 when the hemoglobin concentration is raised from 10 to 40 g/dl, indicating that there is no change in protonation of titratable groups of hemoglobin: (b) the net charge of carbonmonoxy hemoglobin as estimated from the Donnan distribution of 22Na+ shows no dependence on hemoglobin concentration in this concentration range. The oxygen affinity of human hemoglobin was determined from measurements of oxygen concentrations in equilibrated samples using a Lex-O2-Con apparatus (Lexington Instruments, Waltham, Mass.). P50 averaged 11.4 mm Hg at 37 degrees C, pH = 7.2, and ionic strength approximately 0.15. Neither P50 nor Hill's n showed any variation with hemoglobin concentrations increasing from 10 to 40 g/dl.

Electrophysiology↗
PubMed1977

The placental transfer of lactate and bicarbonate in the guinea-pig.

In order to study the lactic acid transfer in a hemochorial placenta, the placenta of the guinea-pig was perfused in situ through the umbilical circulation with a colloidal solution containing L(+)-lactate and bicarbonate in various concentrations. It was found that the transfer rates of lactate and bicarbonate were proportional to the respective materno-fetal arterial concentration differences. When the concentration gradients for lactate and bicarbonate were opposite to each other, an exchange of lactate for bicarbonate occurred which is equivalent to a lactic acid transfer. The placental permeability for lactate was found to be 25 micronmol(h - micronmol/ml) per g of placental weight (S.E. = 2). A similar value was obtained for bicarbonate (23 micronmol/(h - micronmol/ml) per g; S.E. = 1.3). It is calculated that fetal concentrations of lactate and bicarbonate follow maternal concentration changes with a half time of 23 min.

Animals↗
PubMed1977

Transfer of N2O, CO and HTO in the artificially perfused guinea-pig placenta.

The fetal vascular system of the guinea-pig placenta at term was perfused with a dextran solution at a rate of 3.6 and 9 ml/min, while the uteroplacental (maternal) blood flow was adjusted to 4-18 ml/min. N2O, CO, and tritiated water (HTO) were added to the perfusion fluid. The effectiveness of placental transfer of these substances, i.e. the actual transfer related to the maximum transfer occuring when the fetal vein equlibrates with the maternal artery, was calculated. It was found that the effectiveness of the CO transfer was 98% (SD = 2%). The effectiveness of the N2O transfer was about 90% (SD = 6%) when the maternofetal flow ratio was two and about 75% (SD = 13%) when the ratio was one. The effectiveness of the transfer was the same for HTO and N2O. It was concluded: (1) The vascular and diffusional shunts on the fetal side of the placenta are only 2%. (2) The placenta has the properties of a countercurrent system in which the effectiveness of gas transfer is decreased by about 25% at a flow ratio of one and by 10% at a flow ratio of two by inhomogeneity of the maternofetal flow ratio. (3) The diffusional resistance for HTO is unmeasurabbly small; its transfer is solely limited by blood flow.

Animals↗
PubMed1976

Proton transport by phosphate diffusion--a mechanism of facilitated CO2 transfer.

We have measured CO2 fluxes across phosphate solutions at different carbonic anhydrase concentrations, bicarbonate concentration gradients, phosphate concentrations, and mobilities. Temperature was 22-25 degrees C, the pH of the phosphate solutions was 7.0-7.3. We found that under physiological conditions of pH and pCO2 a facilitated diffusion of CO2 occurs in addition to free diffusion when (a) sufficient carbonic anhydrase is present, and (b) a concentration gradient of HCO3- is established along with a pCO2 gradient, and (c) the phosphate buffer has a mobility comparable to that of bicarbonate. When the phosphate was immobilized by attaching 0.25-mm-long cellulose particles, no facilitation of CO2 diffusion was detectable. A mechanism of facilitated CO2 diffusion in phosphate solutions analogous to that in albumin solutions was proposed on the basis of these findings: bicarbonate diffusion together with a facilitated proton transport by phosphate diffusion. A mathematical model of this mechanism was formulated. The CO2 fluxed predicted by the model agree quantitatively with the experimentally determined fluxes. It is concluded that a highly effective proton transport mechanism acts in solutions of mobile phosphate buffers. By this mechanism; CO2 transfer may be increased up to fivefold and proton transfer may be increased to 10,000-fold.

Carbon Dioxide↗
PubMed1976

The flow resistance of the maternal placental vascular bed of anesthetized guinea pigs.

In anesthetized guinea pigs, the maternal placental vascular bed (the spiral arteries and the trophoblastic lacunae with the draining veins) was perfused with blood via a tube connecting a carotid artery and a spiral artery. The placental blood flow and the blood pressures at the beginning of the perfused spiral artery, in the peripheral part of a nonperfused spiral artery and in the placental vein were measured. From these data the vascular resistance of the maternal vascular bed was calculated to be only 0.8 mm Hg min/ml. A driving pressure of about 10 mm Hg maintains the probably normal placental blood flow. The vascular resistance was found to be independent of the blood pressure and the blood flow.

Animals↗