[Skaraborg's formula with high staff flexibility: feelings are high].
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Biomedical subjects
Publications and source records attributed to G Johansson.
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The interaction of human serum albumin with fatty acids has been determined using the method of affinity partitioning in aqueous biphasic systems containing dextran, poly(ethylene glycol) and esters of dicarboxylic acids with poly(ethylene glycol). The difference in the partition of albumin in phase systems with and without the poly(ethylene glycol)-bound fatty acid group provides a measure of the interaction of fatty acids with the protein. The relative contribution of the polar and non-polar interaction to the binding of fatty acids to albumin has been estimated by comparing the present data with that obtained earlier using poly(ethylene glycol)-bound straight chain aliphatic hydrocarbons. In both cases, the aliphatic chain should contain a minimum of 8 carbon atoms to affect the partition of albumin and that the maximum effect is obtained with chains containing 16 carbon atoms. The effect of the polymer-bound fatty acid group is higher than the corresponding hydrocarbon only when the number of carbon atoms in it exceeds 12. The relative effect of polymer-bound 16-carbon chains, with and without a carboxyl group in the terminal position is independent of pH in the range 5--9.
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Forty-four patients with recurrent formation of calcium-containing renal stones were treated with bendroflumethiazide for at least 2 years. Prior to treatment each patient had formed, on average, one stone per year for 8 years; during treatment only 4 patients formed new stones. A reduction in urinary calcium excretion was seen in almost all patients irrespective of their initial urinary calcium level. The apparent clinical benefit was not related to pre-treatment urinary electrolyte levels. Side effects were slight: one patient developed symptomatic hyperuricaemia and in one case sustained hypercalcaemia was found. Long-term treatment with thiazides appears to be a safe and effective method for the prevention of recurrent calcium stones.
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Magnesium metabolism was studied in 106 apparently healthy subjects aged between 15 and 80 years. The serum magnesium values had a gaussian distribution with a narrow range and with no age or sex dependence. The basal, urinary magnesium excretion was greater in men than in women at all ages and decreased with age. The magnesium and calcium excretions were closely correlated in both sexes. The fractional, gastrointestinal absorption of magnesium, assessed by a newly developed technique using the radionuclide 28Mg, compared favourably with that in earlier balance and tracer studies. The intracellular magnesium content, estimated in muscle specimens obtained by percutaneous biopsies, was not correlated to age or sex. A magnesium-loading test was performed, and the normal range for magnesium retention was calculated. No correlation was demonstrated between different magnesium parameters within the normal range in these subjects.
The partition of phosphorfructokinase (EC 2.7.1.11) from baker's yeast between the liquid phases of an aqueous biphasic systeem changes drastically in the pH interval 7-8, in contrast to other proteins. This abnormal behaviour is correlated to changes in sedimentation coefficient and binding capacity of the enzyme in this pH region. Since the molecular weight of phosphofructokinase does not change, these findings must reflect conformational changes in the enzyme molecule.
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Two biphasic systems, both consisting of water, dextran and poly(ethylene glycol) but differing in the molecular weight of the latter polymer, Mr = 35 000 (systems A) and 6000 (systems B), have been studied. The phase diagrams for the two systems at 20 degrees are compared. The partition of proteins influenced by salts and the viscosity of the phases are direct functions of the difference in composition between the upper and the lower phase as measured by the lengths of the tie-lines found for the systems in the phase diagram. The solubility of gamma-globulin is 1.5-2 times larger in an A system than in a B system with corresponding tie-line. In both systems, poly(ethylene glycol) palmitate has less effect on the partition of serum albumin than would be predicted from the distribution of poly(ethylene glycol) and reflects the non-ideality of simple equilibrium models.
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In aqueous two-phase system, the partition of bacteria and lipopolysaccharide from a rough (R) strain (Rd-mutant) of Salmonella typhimurium is influenced by polymers with covalently linked hydrophobic groups indicating hydrophobic structures accessible at the cell surface. Furthermore, the partition of the R bacteria is influenced by a number of inorganic positive and negative ions, presumably as a consequence of interaction with negatively charged surface structures. In contrast, smooth (S) bacteria and lipopolysaccharide from the parent strain do not seem to participate in either hydrophobic or charge interaction indicating extensive hydrophilicity without charge. Thus, the S-specific polysaccharide side chain of S. typhimurium might serve the purpose of blindfolding aspecific host defence mechanisms dependent on hydrophobicity and charge. On the contrary, the R bacteria and R lipopolysaccharide have physico-chemical properties which predispose to interaction with several types of cells, organelles and molecules.
A model for the partition of charged molecules in aqueous multiphase systems has been developed. The partition coefficient of one component, or the overall partition coefficient of a number of components, between two arbitrary phases is expressed in terms of the difference in electrical potential between the phases (due to electrolytes present in the system), the net charges of the partitioned components and their partition coefficients in a (sometimes hypothetical) uncharged state. The fraction of material in one phase has also been described as a function of the net charges of the partitioned components. The model fits well to experimental data for partition of chromate, pyridine, ribonuclease A, two types of CO-hemoglobin and an enzyme mixture (yeast lysate) in three-phase systems consisting of poly(ethylene glycol), dextran, Ficoll and water. Minor deviations from the model are construed to be a pH-dependent uptake of ions. The data have also been used to detect differences in solvation of similar proteins, as well as the presence of several forms of some glycolytic enzymes present in yeast lysate.
The activities of liver microsomal enzymes were studied in preparations from unanesthetized rats and rats anesthetized for one hour with nitrous oxide, diethyl ether, halothane or chloroform. Most of the enzymes studied were cytochrome P-450-dependent oxygenases that hydroxylate endogenous substrates. The other microsomal enzymes, assayed for comparison, included the cytochrome P-450-dependent aminopyrine demethylase, glucose-6-phosphatase, a dehydrogenase, and NADPH-cytochrome P-450 reductase. No anesthetic was associated with a significant change in activity of any enzyme studied. In rats pretreated with phenobarbital no anesthetic except chloroform changed enzymic activity. All hydroxylations were inhibited markedly by chloroform, as were a microsomal dehydrogenation, hydrolysis of glucose-6-phosphate, and NADPH-cytochrome P-450 reductase activity. Administration of alpha-tocopherol did not prevent the inhibition associated with chloroform in phenobarbital-induced animals. It is concluded that cytochrome P-450-dependent hydroxylations involved in metabolic processes normally proceeding in the endoplasmic reticulum of the liver are not permanently affected by the anesthetics used in this study. The inhibitory effect of chloroform after pretreatment with phenobarbital is unspecific and affects a large number of different microsomal enzymes. Evidence that mechanisms other than lipid peroxidation may be responsible for the toxic effects of chloroform in the liver is presented.
The effect of membrane stabilizing drugs on cation induced pinocytosis was studied in Amoeba proteus. Initially the presence of local anesthetic drugs during a pinocytosis cycle had a stimulating effect on channel formation, however, the capacity to develop pinocytotic channels was reversibly inhibited after a period of treatment with these drugs. Imipramine, vinblastine and the phenothiazines had effects similar to local anaesthetics. The local anesthetics inhibited pinocytosis in the following order: dibucaine greater than tetracaine greater than bupivacaine greater than lidocaine greater than procaine, and the phenothiazines: thioridazine greater than prochlorperazine greater chlorpromazine greater than prometazine. Pinocytosis, when induced by Na+ or tris, was more affected by the drugs and by calcium binding agents than pinocytosis induced by K+. After pretreatment with inhibitory concentration of dibucaine (3 x 10(-4) M) the depolarization of the membrane and the conductance increase during pinocytosis were normal, while the increase of oxygen uptake during the pincoytosis cycle was abolished. Addition of Ca++ before, during or after dibucaine treatment decreased the effect of the drug. Conversely, in dibucaine-treated cells, cation induced pinocytosis was less inhibited by Ca++ than pinocytosis in normal cells. Addition of EGTA to the inducing solutions potentiated the inhibitory effect of the drug. It is suggested that these drugs release Ca++ from the cell surface and at higher concentration or after prolonged incubation time interfere with a Ca++ mechanism which couples the membrane and contractile systems in the cytoplasm.