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Biomedical subjects

M Nuutinen

Publications and source records attributed to M Nuutinen.

At least 55 records · Page 3Linked to original sources

Oxygen transport in the blood of arctic mammals: adaptation to local heterothermia.

The oxygen binding of whole blood from humans and two arctic mammals, reindeer and muskox, has been studied as a function of carbon dioxide and temperature. All bloods display a marked Bohr effect with Bohr coefficients in the range -0.44- -0.73. The Bohr effect is more pronounced at 20 degrees C. The temperature sensitivity of reindeer and muskox blood expressed by the apparent heat of oxygenation, delta H, is almost three times lower than that of human HbA under the same experimental conditions. This thermodynamic difference gives special benefits to arctic mammals with large heterothermy by safeguarding oxygen unloading at very low ambient temperatures.

Acclimatization↗

The chloride shift may facilitate oxygen loading and unloading to/from the hemoglobin from the brown bear (Ursus arctos L.).

1. The oxygen binding properties of hemolyzed bear blood were studied in 0.1 M Tris and 0.1 M Hepes buffer with respect to the possible effects of temperature, pH, pCO2, 2,3-DPG, and chloride ions. 2. There was a significant Bohr shift with a Bohr factor (delta log P50/delta pH) of the magnitude of -0.5. The temperature sensitivity expressed by the apparent heat of oxygenation minus the heat of oxygen in solution was about -8.1 kcal/mol at pH 7.4. 3. Chloride ions decreased the oxygen affinity in the concentration range 50-200 mM, and there was a marked increase in the co-operativity of oxygenation up to a chloride concentration of about 200 mM. 4. There were no effects of pCO2 and 2,3-DPG in the presence of 200 mM Cl-, while in the absence of Cl-, 2,3-DPG had the same effect as 200 mM Cl- at 37 degrees C and pH 7.4. 5. Our results suggests at least two different binding sites for the chloride ion, one high affinity site which may also bind 2,3-DPG in the absence of chloride, and one or more low affinity sites, which only binds chloride. 6. The results further show, that a chloride shift of about 33 mM may account for as much as a 40% increase in O2 unloading, without taking into account the additional effect of the Bohr shift.

2,3-Diphosphoglycerate↗

Oxygen radical injury and loss of high-energy compounds in anoxic and reperfused rat heart: prevention by exogenous fructose-1,6-bisphosphate.

Isolated Langendorff-perfused rat hearts after 10 minutes preperfusion, were subjected to a substrate-free anoxic perfusion (20 minutes) followed by 20 minutes reperfusion with a glucose-containing oxygen-balanced medium. Under the same perfusion conditions, the effect of exogenous 5mM fructose-1,6-bisphosphate has been investigated. The xanthine dehydrogenase to xanthine oxidase ratio, concentrations of high-energy phosphates and of TBA-reactive material (TBARS) were determined at the end of each perfusion period in both control and fructose-1,6-bisphosphate-treated hearts. Results indicate that anoxia induces the irreversible transformation of xanthine dehydrogenase into oxidase as a consequence of the sharp decrease of the myocardial energy metabolism. This finding is supported by the protective effect exerted by exogenous fructose-1,6-bisphosphate which is able to maintain the correct xanthine dehydrogenase/oxidase ratio by preventing the depletion of phosphorylated compounds during anoxia. Moreover, in control hearts, the release of lactate dehydrogenase during reperfusion, is paralleled by a 50% increase in the concentration of tissue TBARS. On the contrary, in fructose-1,6-bisphosphate-treated hearts this concentration does not significantly change after reoxygenation, while a slight but significant increase of lactate dehydrogenase activity in the perfusates is observed. On the whole these data indicate a direct contribution of oxygen-derived free radicals to the worsening of post-anoxic hearts. A hypothesis on the mechanism of action of fructose-1,6-bisphosphate in anoxic and reperfused rat heart and its possible application in the clinical therapy of myocardial infarction are presented.

Animals↗

Arctic adaptation in reindeer. The energy saving of a hemoglobin.

Previous results [(1988) Arct. Med. Res. 47, 83-88] have shown that hemoglobin from reindeer is characterized by a low overall heat of oxygenation. This particular aspect has been investigated further in a series of precise oxygen equilibrium experiments. The results obtained show a peculiar dependence of the temperature effect on the fractional saturation of hemoglobin with oxygen, which could be regarded as a very interesting case of molecular adaptation to extreme environmental conditions.

2,3-Diphosphoglycerate↗

A method for preparing freeze-clamped tissue samples for metabolite analyses.

A rapid and simple method for preparing freeze-clamped tissue samples for metabolite determinations is described. Freeze-clamped rat heart tissue samples weighing from 0.8 to 1.0 g were homogenized directly in an Ultra-Turrax homogenizer for 60 s in 3.5 ml of ice-cold 0.6 M HClO4 without pulverizing them in liquid nitrogen. After centrifugation, the pellet was rehomogenized in the Ultra-Turrax homogenizer for 30 s in 1.5 ml of HClO4. Following a further centrifugation the extracts were combined and the pH was adjusted to 7.0 by adding 5 M K2CO3. The neutralized supernatant was used for the desired assays. The analyses of the tissue extracts obtained from isolated perfused rat hearts by the present method give similar results for different kinds of metabolites than those processed according to the previous classical method. Moreover, the values of the various parameters determined from the tissue extracts prepared according to the method described here are similar to the data reported in literature. The method can be readily applied to any other freeze-clamped tissue. The greatest improvement obtained is that the homogenization procedure can be accomplished easily and conveniently in about one-tenth of the time required for the earlier classical method without the time-consuming and unpleasant tissue grinding in liquid nitrogen.

Adenosine Triphosphate↗

Arctic life adaptation--I. The function of reindeer hemoglobin.

1. The functional properties of hemoglobin from the reindeer (Rangifer tarandus tarandus L.) are characterized as a function of pH, temperature and organic phosphate concentration. 2. Alongside overall similarities shared with most vertebrate hemoglobins, hemoglobin from the reindeer shows significant differences with respect to the effect of both organic phosphates and chloride anions. 3. The limited effect of temperature on oxygen binding (delta H = -4 kcal/mol O2) could be regarded as an interesting case of molecular adaptation to extreme environmental conditions.

Adaptation, Physiological↗

Long-term outcome for children with congenital heart defects. A study from 1 year birth cohort born in 1966 in northern Finland.

The incidence of congenital heart defects (CHD) in a birth cohort of 12,058 live births born in Northern Finland in 1966 was 4.15/1000 with a mortality due to CHD 1.41/1000 up to 14 years of age. The long-term social and educational outcome for CHD children was significantly poorer than for normal children of the same age when evaluated on the basis of school and army service records, and the incidence of cerebral palsy, epilepsy and mental retardation was significantly higher. 15.4% of the Down's syndrome cases in the cohort also had CHD. The CHD boys were significantly lighter in weight than the controls even as adolescents (14 years of age). The only difference between the operated and non-operated group was the higher weight of the boys at the age of 18 years in the former.

Adolescent↗

Epidemiology of symptomatic infections of the urinary tract in children.

The epidemiology of symptomatic infections of the urinary tract in children and the factors that may alter the risk of infection are not well known. Numbers of children aged under 15 discharged from hospitals because of symptomatic infections of the urinary tract during 1978-84 were obtained from the database kept by the Finnish National Board of Health. Information on continuous treatment for recurrent urinary tract infections was obtained from records kept by the Social Insurance Institution on patients receiving free medicines. The yearly rate of attacks of symptomatic infections/1000 girls decreased significantly from 2.67 (95% confidence interval 2.52 to 2.82) in 1978 to 1.88 (1.76 to 2.01) in 1984. In boys the rate also decreased significantly, from 0.85 (0.77 to 0.93) in 1978 to 0.59 (0.52 to 0.66) in 1984. The period prevalence of free treatment/1000 girls decreased significantly from 7.80 (7.55 to 8.05) in 1978 to 5.30 (5.10 to 5.51) in 1984 but did not change significantly in boys. Although the findings may partly have been caused by changes in policies of admission to hospital, they suggest a decreasing trend in symptomatic urinary tract infections in childhood, which may be associated with changes in the care of infants.

Adolescent↗

The stimulation of a casein kinase II from yeast by polyamines occurs with endogenous substrates at cytosolic salt levels.

A casein kinase II that is tightly bound to yeast ribosomes was partially purified and used to phosphorylate YL 44 and an unidentified 36 kDa protein in purified ribosomes. At typical cytosolic salt concentrations the phosphorylation was strongly stimulated by moderate concentrations (200 microM) of spermine or spermidine. The lowest effective concentration of spermine (20 microM, causing less than 50% stimulation) was close to that of total spermine reported in nongrowing yeast. Increases in free polyamines accompanying the 10-fold increase in total spermine and spermidine in growing yeast may therefore significantly stimulate this phosphorylation.

Casein Kinases↗

Ca2+/calmodulin-dependent protein kinase in Saccharomyces cerevisiae.

Ca2+-dependent chromatography of soluble cytosolic proteins on calmodulin-Sepharose gave a fraction that exhibited Ca2+- and calmodulin-dependent phosphorylation of several polypeptides, including 60, 56 and 45 kDa species. At 0.2 microM beef calmodulin the phosphorylation was optimal at 3 microM free Ca2+, and at 80 microM free Ca2+ it was half-maximal at about 0.1 microM beef calmodulin. It is concluded that the fraction contains calmodulin-dependent protein kinase(s) which is (are) autophosphorylated or associated with substrates.

Chromatography↗

Suppression of in vivo antibody responses by suppressor factors induced by human myeloma proteins.

Suppressor factors induced in vitro, using purified human IgG and IgA myeloma proteins, were shown to efficiently suppress murine antibody production in vivo. The suppression was not isotype specific, viz. IgG and IgA suppressor factors suppressed the production of IgM and IgG antibody. Neither the suppressor factors (SF) nor the inducing proteins suppressed the proliferative responses to concanavalin A and purified protein derivative (PPD). The results are compared to the in vitro findings and discussed in the context of isotype regulation, hypogammaglobulinemia and immunotherapy.

Animals↗

Suppressor factors generated from human mononuclear cells by means of purified myeloma proteins.

Peripheral blood mononuclear cells (PBMC) from normal human donors were cultured in Marbrook flasks in the presence of purified IgG or IgA myeloma proteins. The culture supernatants were tested for their ability to suppress pokeweed mitogen (PWM)- or Epstein-Barr virus (EBV)-driven Ig synthesis by normal PBMC. Two supernatants from PBMC cultured with IgG and one from PBMC cultured with IgA were tested and suppressed PWM-driven Ig synthesis as measured by a reverse haemolytic plaque assay and by quantitation of the Ig secreted into the culture medium of the PWM-driven cells. This suppression was not restricted to the Ig isotype of the 'inducing' myeloma protein, but was extended to IgG, IgA, and IgM. The suppressive effect could be absorbed out with human IgG.

Antibody Formation↗

Plasma membrane phosphate transport and extracellular phosphate concentration in the regulation of cellular respiration in isolated perfused rat heart.

The role of extracellular Pi and transmembrane fluxes across the sarcolemma in the regulation of cellular respiration was studied in isolated Langendorff-perfused rat hearts. Extracellular phosphate did not significantly affect the oxygen consumption or cellular phosphorylation potential of the myocardium. K+-induced arrest was used to change the mechanical work load of the heart. Arresting the heart caused a rapid decrease in the unidirectional efflux of phosphate determined by in vitro prelabelling of the intracellular phosphate compounds with 32P and determining the specific radioactivity of the gamma-P of ATP, and the label appearance into the perfusion medium. At normal or elevated perfusate phosphate concentration there was a fairly slow net uptake of phosphate. The decrease in phosphate fluxes upon the K+-induced arrest was probably not due to a decrease in the transmembrane Na+ or K+ gradients because a further increase in the perfusate K+ concentration caused an increase in the K+ efflux to the levels observed in contracting hearts. The use of higher than normal concentrations of phosphate necessitated a lowering of the extracellular Ca2+ concentration, which caused a diminution of the oxygen consumption, accompanied by mitochondrial flavoprotein in the heart. This finding suggested that the extracellular Ca2+ concentration may be involved in the substrate level regulation of mitochondrial metabolism.

Animals↗