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Biomedical subjects

L Boquist

Publications and source records attributed to L Boquist.

At least 37 records · Page 2Linked to original sources
PubMed1987

NADP-linked dismutation and concentrations of citrate, cytosolic free Ca2+ and phosphoenolpyruvate in islet B-cells stimulated with glucose.

B-cells stimulated with glucose showed enhanced activities of NADP-isocitrate dehydrogenase, aconitase, ATP-citrate lyase and phosphoenolpyruvate carboxy-kinase, elevated cytosolic [NADPH]/[NADP+] ratio, and increased concentrations of glucose 6-phosphate, 6-phosphogluconate, citrate, phosphoenolpyruvate and cytosolic free Ca2+. Phosphoenolpyruvate induced release of Ca2+ accumulated in isolated mitochondria. Glucose is suggested to stimulate a cytosolic NADP-linked dismutation and synthesis of citrate, associated with increased cytosolic free Ca2+ concentration. Subsequent breakdown of cytosolic citrate may yield Pi (possibly related to the "phosphate flush") and phosphoenolpyruvate which potentiates the release of Ca2+ accumulated in the B-cell mitochondria.

Animals↗
PubMed1987

Long-term effects of surgery for normocalcaemic hyperparathyroidism.

A retrospective study of the long-term effects of surgery for normocalcaemic hyperparathyroidism in 82 patients is presented. The median postoperative follow-up time was 96 months. In most of the patients recurrent renal calculi had been the main preoperative symptom, and intermittent peaks of hypercalcaemia were recognized in more than 50% of them. Of the 19 patients with severe tendency to calculus formation, 12 appeared to have been cured by parathyroidectomy. These cured patients were found at operation to have parathyroid adenoma or hyperplasia, or even normal glands. Preoperatively depressed renal function normalized in about 50% of cases, as assessed by the desmopressin test. No patient had paralysis of the recurrent laryngeal nerve, and all were normocalcaemic during follow-up. Parathyroid surgery should be considered for this category of patients, although it is very difficult to distinguish between those who stand to benefit and those who do not.

Adult↗
PubMed1986

Inhibition by streptozotocin of the activity of succinyl-CoA synthetase in vitro and in vivo.

The activity of succinyl-CoA synthetase from mouse liver and kidney was inhibited by streptozotocin in vitro. Streptozotocin behaved essentially as a non-competitive inhibitor, and the following kinetic values were obtained (in the presence of 10 nM streptozotocin): apparent Km 1.7 mM, apparent Ki 10 nM, and kcat 440 nkat X kg-1. Compared with non-diabetic control mice, the succinyl-CoA synthetase activity was significantly decreased in the islets and kidneys of mice with early (1 h) and manifest (greater than or equal to 2 days) streptozotocin diabetes, whereas the activity in the liver was not significantly altered. Inhibited succinyl-CoA synthetase activity is believed to play a prominent role in the cellular effects of streptozotocin.

Animals↗
PubMed1986

Persistent hypercalcemia after neck exploration--an analysis of 34 cases.

A retrospective analysis of 34 patients undergoing 45 re-explorations for persistent hypercalcemia is presented. Thirteen out of the 20 enlarged parathyroid glands were found at reoperation to be normally located, indicating that the initial exploration had been incomplete. A follow-up study of the reoperated patients showed that 25 (74%) were normocalcaemic. Three patients had permanent unilateral recurrent laryngeal nerve damage and 2 patients required calcium and/or vitamin D therapy. Ultrasonography was effective in the diagnosis and localisation of residual parathyroid adenoma in patients with persistent postoperative hyperparathyroidism.

Adenoma↗
PubMed1986

Ca2+ transport in isolated mouse liver mitochondria; role of reductive carboxylation and citrate?

The uptake of Ca2+ in isolated mouse liver mitochondria respiring on succinate in the presence of rotenone and added Pi, was inhibited by dibucaine, fluorocitrate, p-hydroxymercuribenzoate (PMB), malonate, palmitoyl-CoA, succinyl-CoA and trifluoroperazine. The release of accumulated Ca2+ was stimulated by arsenite, malonate, PMB, palmitoyl-CoA and succinyl-CoA, whereas the release was inhibited by dibucaine, fluorocitrate, trifluoroperazine, and by oligomycin, especially in the presence of ADP. The pyridine nucleotides were oxidized in mitochondria incubated with PMB. The observations suggest a possible contributory role of reductive carboxylation for the uptake of Ca2+, and a possible role of citrate for the retention of Ca2+ in isolated mouse liver mitochondria.

Animals↗
PubMed1986

Osteopenia in mice with genetic diabetes.

Bone mass and growth were studied in mice with genetic diabetes (db/db) characterized by obesity, hyperinsulinemia and hyperglycemia, in their lean litter mates (db/+) and in non-diabetic mice of the same strain (+/+). No significant difference was observed between db/+ and +/+ mice. The length, bone mass, bone mineral mass, bone mineral density and content of moisture of the tibia of the db/db mice were significantly decreased compared with the db/+ and +/+ mice. Microradiographs of the distal femur diaphysis of the db/db mice showed a significant reduction of the spongious bone area and of the number and thickness of bone trabeculae with a normal mineralization. The amount of osteoid was significantly increased in the db/db mice. The area of cortical bone of the tibia epiphysis of the db/db mice was significantly decreased compared with the db/+ and +/+ mice. The data suggest the occurrence of osteopenia due to decreased mineralization in mice with genetic diabetes.

Animals↗
PubMed1986

Factors affecting Ca2+ transport in mouse islet and kidney mitochondria.

The transport of Ca2+ in islet and kidney mitochondria respiring on succinate was inhibited by atractylate and fluorocitrate, and stimulated by pyruvate, isocitrate, alpha-ketoglutarate, dibutyryl cAMP, oligomycin and bongkrekate, and by in vivo administration of glucagon, glyceraldehyde or glucose. The kidney [beta-hydroxybutyrate]/[acetoacetate] ratio was increased in glyceraldehyde treated mice. The data suggest a relationship, which might be influenced by cAMP, between activity of pyruvate, isocitrate and alpha-ketoglutarate dehydrogenases and transport of Ca2+ in islet and kidney mitochondria. A contributory role of reductive carboxylation for Ca2+ uptake, and a role of citrate for Ca2+ retention are discussed.

Animals↗
PubMed1985

Alterations in mitochondrial aconitase activity and respiration, and in concentration of citrate in some organs of mice with experimental or genetic diabetes.

Mouse islets (not used for respiration), kidneys and liver were studied in early and manifest alloxan diabetes, and in genetic diabetes. In these organs the mitochondrial aconitase activity was lower, state 3 respiration with citrate or pyruvate plus malate (but not with succinate) was decreased, and the concentration of citrate was increased, compared with non-diabetic control mice. The alterations suggest a role of lowered activity of mitochondrial aconitase in alloxan diabetes, and probably also in genetic diabetes.

Aconitate Hydratase↗
PubMed1985

Quantitative morphological assessment of parathyroid activity in response to variations in calcium concentration in vitro.

Isolated parathyroid glands from gerbils incubated at low (0.5 mM), normal (1.25 mM) or high (3 mM) calcium concentration for 1 or 6 h were studied with regard to the following stereological parameters: the volume densities of the nucleus, mitochondria, endoplasmic reticulum, Golgi zone, lipid bodies, lysosomes, secretory granules and storage granules, and the surface densities of the cell membrane and endoplasmic reticulum. In glands incubated for 1 h no significant differences were seen between the experimental groups in any of the parameters investigated, however, the volume density of the Golgi zone and the surface density of the cell membrane were significantly increased in glands incubated for 6 h at low calcium concentration, compared with those incubated at high calcium concentration. The enlargement of the Golgi zone in stimulated glands was also evident when the two glands from the same animal incubated at different calcium concentrations were compared. The data suggest that the early response of parathyroid glands to altered concentration of extracellular calcium includes functional activities associated with the Golgi zone.

Animals↗
PubMed1985

Alloxan effects on mitochondria in vitro, studied with regard to inhibition of mitochondrial aconitase.

The recently observed inhibition by alloxan of mitochondrial aconitase was studied with regard to oxygen consumption, accumulated Ca2+ and volume of isolated mitochondria from mouse islets (not used for respiratory experiments), liver and kidneys. Altered respiration, efflux of Ca2+ and volume increase were induced in a manner dependent on the concentration of alloxan, the energetic state of the mitochondria, the addition of Ca2+ and reductant, and the type and concentration of substrate used. State 3 and, less pronounced, state 4 respiration were inhibited, accumulated Ca2+ was released, and the mitochondrial volume was increased at a minimum concentration of alloxan of 10-100 microM when pyruvate, citrate or cis-aconitate were substrates. The alloxan effects were less marked or absent when other substrates were used. The efflux of Ca2+ induced by alloxan in mitochondria respiring on pyruvate, citrate or cis-aconitate was inhibited or reversed by isocitrate. Potentiation of the alloxan effects was seen on increasing the concentration of alloxan, decreasing the concentration of substrate, addition of low concentrations of Ca2+ or reductant, and addition of alloxan before the substrate (non-energized state). The data support the finding of inhibition by alloxan of mitochondrial aconitase.

Aconitate Hydratase↗
PubMed1984

Inhibition by alloxan of mitochondrial aconitase and other enzymes associated with the citric acid cycle.

Considerable variations were found in the in vitro effect of alloxan on mouse liver enzymes associated with the citric acid cycle. The following approximative alloxan concentrations induced 50% inhibition of enzyme activity: 10(-6)M for aconitase, 10(-4)M for NAD-linked isocitrate dehydrogenase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase and fumarase, and 10(-3)M for citrate synthase and NADP-linked isocitrate dehydrogenase. Pyruvate dehydrogenase, succinate dehydrogenase and malate dehydrogenase were not inhibited by 10(-3)M alloxan. The inhibition of aconitase was competitive both when using mouse liver and purified porcine heart enzyme. The Ki values for the purified enzyme in the presence of 5 microM alloxan were 0.22 microM with citrate, 4.0 microM with cis-aconitate and 0.62 microM with isocitrate as substrate. The high sensitivity of aconitase for inhibition by alloxan probably plays a prominent role for the toxic effects of alloxan.

Aconitate Hydratase↗
PubMed1984

Structure of the parathyroid glands, as revealed by different methods of fixation. A quantitative light- and electron-microscopic study in untreated Mongolian gerbils.

Stereology and semi-automatic image analysis were used with the aim of comparing the structure of parathyroid glands from untreated adult Mongolian gerbils fixed by immersion with those fixed by perfusion. Subclassification of the chief cells based upon the staining affinity or electron density of the cytoplasm was readily performed only in glands fixed by immersion, and so-called atrophic cells were observed only in these glands. The atrophic cells were often surrounded by "light" chief cells. In glands fixed by perfusion, "light" chief cells were only rarely encountered. A significant difference between glands fixed by immersion and those fixed by perfusion was found only with regard to the form of cells and nuclei, those fixed by perfusion being more spherical. When comparing individual cells within glands fixed by immersion, "light" chief cells were more spherical and had a significantly larger nuclear and cellular size, and a lower mitochondrial volume density than the "intermediate"/"dark" chief cells. Otherwise there were no significant differences in any of the parameters investigated. These data indicate that occurrence of so-called "light" chief cells and atrophic cells is a result of improper fixation. The results of this study do not favour the concept of a functional cycle with a simultaneous occurrence of active and inactive cells within parathyroid glands.

Animals↗
PubMed1984

Alloxan effects on mitochondria: study of oxygen consumption, fluxes of Mg2+, Ca2+, K+ and adenine nucleotides, membrane potential and volume change in vitro.

Isolated mouse liver mitochondria incubated with alloxan showed stimulated resting (state 4) respiration with succinate, and inhibited resting respiration with pyridine-linked substrates, whereas active (state 3) respiration was decreased with both kinds of substrates. The effects were dependent on the concentration of alloxan, on the energy state, and on transport of inorganic phosphate and uptake of Ca2+. Using succinate as substrate, the effects of alloxan on endogenous Mg2+, K+ and adenine nucleotides, uptake of K+, accumulated Ca2+, membrane potential and volume were studied in liver mitochondria, and in addition efflux of endogenous K+ and accumulated Ca2+ were investigated in mouse islet mitochondria. High concentrations of alloxan (greater than or equal to 3 mmol/l) induced efflux of endogenous Mg2+, K+ and adenine nucleotides, efflux of accumulated Ca2+, inhibition of uptake of K+, loss of membrane potential, and swelling. Low concentrations of alloxan (less than 3 mmol/l) had similar effects only in the presence of added Ca2+ and inorganic phosphate. The influence of potentially protective agents was studied mainly with regard to alloxan induced swelling. Complete or partial protection was offered by antimycin A, malonate, La3+, Ni2+, ruthenium red, mersalyl and N-ethylmaleimide, suggesting requirement for energized transport of Ca2+ and uptake of inorganic phosphate. The start of the respiratory changes, decrease of membrane potential and loss of Mg2+ preceded the release of accumulated Ca2+, which occurred in parallel with efflux of K+ and swelling. The loss of Ca2+ in association with swelling agrees with data previously obtained using qualitative and quantitative electron microscopy and X-ray microanalysis of islet beta cells from alloxan-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1984

The normal parathyroid glands of the Mongolian gerbil. A quantitative structural study.

The parathyroid glands of the normal Mongolian gerbil were studied by light and electron microscopy, using stereology and semi-automatic image analysis. Basic quantitative data are presented for various nuclear parameters, and for mitochondria, endoplasmic reticulum, Golgi complex, secretory granules, storage granules, lysosomes and lipoid bodies. Chief cells predominate in the normal gland. Atrophic cells are only rarely encountered. The chief cells can be qualitatively subclassified into light, dark and intermediate variants, but quantitatively there is no difference among these variants with regard to the volume densities of mitochondria, lamellar rough endoplasmic reticulum, Golgi complex, secretory granules and storage granules, suggesting that the subclassification of the chief cells plays no functional role. A statistically significant correlation between volume densities of Golgi complex and secretory granules was found. Compared with the chief cells, the atrophic cells exhibit significantly less lamellar rough endoplasmic reticulum and secretory granules, whereas the content of vesicular rough endoplasmic reticulum is increased. The atrophic cells are suggested to be a degenerative variant of the chief cells.

Animals↗
PubMed1984

Quantitative parathyroid morphology is unaltered in prolonged hypocalcemia. A quantitative electron microscopic study in the Mongolian gerbil.

Hypocalcemia was induced in adult Mongolian gerbils by a combination of a calcium deficient diet and repeated injections of ethylene-diamine-tetra-acetate (EDTA). This treatment caused tetany and death in some of the animals. Laboratory analyses on the eight experimental day disclosed significantly decreased concentrations of serum calcium and significantly increased concentrations of serum phosphate. Stereological methods and semi-automatic image analysis were used for ultrastructural study of the parathyroid glands with the aim of disclosing if any quantitative alterations occur in prolonged hypocalcemia. Compared with normocalcemic animals no significant change was observed in the hypocalcemic gerbils with regard to the nuclear profile area, the volume densities of nucleus, mitochondria, endoplasmic reticulum, Golgi complex, lysosomes, secretory granules and storage granules, or the surface density of the cell membrane. The only significant change in the hypocalcemic animals was a slight increase in the volume density of lipoid bodies and a similarly slight decrease in the surface density of the endoplasmic reticulum, changes which at present are difficult to explain. The data demonstrate that hypocalcemic stimulation in vivo does not give rise to quantitative morphological changes in parathyroid chief cells, and thus do not support the idea of a functional adaptation of the chief cells to variations in the ambient calcium concentration.

Animals↗
PubMed1984

Inhibition by dithioerythritol of alloxan induced efflux of Ca2+ and accompanying alterations in isolated liver mitochondria.

Isolated mouse liver mitochondria respiring on succinate released Ca2+ when incubated with alloxan, accompanied by decreased membrane potential, stimulated state 4 respiration and swelling. All these effects of alloxan were inhibited by equimolar or higher concentrations of dithioerythritol (DTE), and in presence of added ATP a carboxyatractyloside-sensitive reuptake of Ca2+ was observed. The process of release and uptake of Ca2+ could be repeated by additional administrations of higher concentrations of alloxan and DTE plus ATP, respectively. The data suggest that the mitochondrial action of alloxan involves oxidation of membrane thiol groups.

Alloxan↗
PubMed1984

Alloxan effects on mitochondria in vitro: correlation between endogenous adenine nucleotides and efflux of Ca2+.

The efflux of Ca2+ induced by alloxan in isolated mouse liver mitochondria was potentiated by atractylate, and by depletion of the organelles in adenine nucleotides, whereas bongkrekate, and added ATP or ADP, but not AMP, inhibited the alloxan effect. The data suggest that the Ca2+ releasing action of alloxan is dependent on the intramitochondrial pool of adenine nucleotides.

Adenine Nucleotides↗