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T Andersson

Publications and source records attributed to T Andersson.

At least 199 records · Page 11Linked to original sources
PubMed1990

Corresponding oscillations in neutrophil shape and filamentous actin content.

Human neutrophils pretreated with 17-hydroxywortmannin responded to the chemotactic agonist formyl-Met-Leu-Phe with a transient doubling in filamentous actin content which was characterized by prominent oscillations. These oscillations closely matched transient oscillations in suspension turbidity measured in parallel. The experimental data could be simulated using A----B----C stochastic series kinetic models with an oscillating intermediate species (B), allowing quantitative comparison of the frequencies of the oscillations (0.092 +/- 0.006 and 0.094 +/- 0.004 Hz) and the overall reaction rate constants for actin mobilization and turbidity changes (0.11 +/- 0.02 and 0.14 +/- 0.03 s-1, respectively). The total cell volume remained constant, indicating that stimulus-induced extension of lamellipods reduces the body volume by an amount proportional to the mass displaced outward. Light scattering theory predicts that a decrease in body size decreases the turbidity and that fluctuations in body size due to lamellipod extension and retraction cycles like those exhibited by crawling neutrophils result in turbidity oscillations (lamellipods scatter very little by comparison to the cell body, and both aggregation and degranulation were absent). The experiments thus suggest that the cyclic variations in F-actin content are correlated with periodic fluctuations in lamellipod size. The available evidence appears to be consistent with the hypothesis that actin polymerization provides the main driving force for lamellipod extension and that depolymerization causes lamellipod retraction.

Actins↗
PubMed1990

Pharmacokinetics of various single intravenous and oral doses of omeprazole.

The influence of dose on the kinetics of omeprazole and two of its metabolites, hydroxyomeprazole and the sulphone, has been studied. Ten healthy subjects were given omeprazole 10 and 40 mg iv and 10, 40 and 90 mg orally. No significant dose-related difference in any parameter calculated from the iv experiments was detected. Following the oral solutions, however, there was a dose-dependent increase in systemic availability, probably due to saturable first-pass elimination. The AUC of the sulphone also seemed to increase non-linearly with increasing dose, and that of the hydroxyomeprazole increased in proportion to dose. The slight dose-dependency of the bioavailability of the solution is considered to be of no or limited clinical relevance. Furthermore, since omeprazole is given orally as slowly absorbed enteric coated granules in the dose of 20 mg o.d., the potential for dose-dependent kinetics in clinical practice would be much less than in the present study.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

Effect of omeprazole and cimetidine on plasma diazepam levels.

The effects of steady state dosing with omeprazole and cimetidine on plasma diazepam levels have been studied in 12 healthy males. Single doses of diazepam (0.1 mg.kg-1 i.v.) were administered after one week of treatment with omeprazole 20 mg once daily, cimetidine 400 mg b.d. or placebo, and the treatment was continued for a further 5 days. Blood was collected for 120 h after the dose of diazepam for the measurement of diazepam and its major metabolite desmethyl diazepam. The mean clearance of diazepam was decreased by 27% and 38% and its half-life was increased by 36% and 39% after omeprazole and cimetidine, respectively. Neither drug had any apparent effect on the volume of distribution of diazepam. Desmethyldiazepam appeared more slowly after both omeprazole and cimetidine. It is concluded that the decrease in diazepam clearance was associated with inhibition of hepatic metabolism both by omeprazole and cimetidine. However, since diazepam has a wide therapeutic range, it is unlikely that concomitant treatment with therapeutically recommended doses of either omeprazole or cimetidine will result in a clinically significant interaction with diazepam.

Adult↗
PubMed1990

Progesterone metabolism in the microsomal fraction of the testis, head kidney, and trunk kidney from the rainbow trout.

In the present study on male rainbow trout, well-defined microsomal fractions from gonad, trunk kidney, and head kidney were used to study enzymes active on progesterone. The metabolites produced were identified by mass spectrometric analysis. In the testis the main metabolite was 17 alpha-hydroxyprogesterone which is an intermediate in the steroid biosynthetic pathway. 17 alpha-Hydroxyprogesterone was also identified in incubations from head and trunk kidney. The 17 alpha-hydroxylase activity was higher in the head kidney than in the trunk kidney which probably reflects the presence of steroid producing interrenal cells in this part of the kidney. The conversion of progesterone to 17 alpha-hydroxylated products in the testis and head kidney was NADPH dependent and inhibited by carbon monoxide, indicating the participation of cytochrome P450 monooxygenase in this reaction. NADH supported the reaction to some extent (27% of the NADPH-dependent activity) in the testis but not in the head kidney. In addition to 17 alpha-hydroxyprogesterone the head and trunk kidney microsomes gave rise to 16 alpha- and 6 beta-hydroxyprogesterone. These activities were low or absent in testis microsomes. Progesterone 5 alpha-reductase activity was only detected in trunk kidney microsomes.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Effect of omeprazole treatment on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole.

The effect of omeprazole treatment on diazepam plasma levels was studied in four slow and six rapid metabolizers of omeprazole. Single intravenous doses of diazepam (0.1 mg/kg) were administered after 1 week of oral treatment with omeprazole (20 mg) and placebo. This was a double-blind crossover study with randomized placebo and omeprazole treatments. Blood was collected up to 120 hours after diazepam dosing (still during one-daily omeprazole and placebo administration) for measurement of diazepam and its major metabolite desmethyldiazepam. The slow metabolizers of omeprazole also metabolized diazepam slowly, exhibiting only half the diazepam plasma clearance of the others. The mean clearance of diazepam was decreased 26% after omeprazole in the rapid metabolizers, whereas the slow group showed no apparent interaction. The mean plasma concentrations of desmethyldiazepam showed a more rapid formation in the rapid compared with the slow metabolizers, which is a logical consequence of the rate of diazepam metabolism.

Adult↗
PubMed1990

Tumor necrosis factor-induced degranulation in adherent human neutrophils is dependent on CD11b/CD18-integrin-triggered oscillations of cytosolic free Ca2+.

We have recently been able to correlate closely the "spontaneous" oscillatory activity of cytosolic free Ca2+ in adherent human neutrophils with the ability of tumor necrosis factor (TNF) to induce secretion of granule proteins from these cells. In the present work we show with a single-cell technique that preincubation of human neutrophils with antibodies to CD18, the common beta chain of leukocyte adhesion proteins, inhibits TNF-induced secretion of lactoferrin in a time- and concentration-dependent manner. Similar effects of CD18 antibodies were found on chemotactic factor (fMet-Leu-Phe)- but not on phorbol 12-myristate 13-acetate-induced secretion, suggesting that cell-surface-receptor-mediated secretion is dependent on integrin-associated signals. Similarly, antibodies to CD11b (alpha chain of macrophage 1) also inhibited TNF- and fMet-Leu-Phe- but not phorbol 12-myristate 13-acetate-stimulated release of lactoferrin. Antibodies to CD11a (alpha chain of lymphocyte function-associated antigen 1) or CD11c (alpha chain of p150,95) had only a minimal effect on agonist-induced secretion. Data obtained in several laboratories, including our own, made us suspect that integrin interaction with the surface is responsible for the oscillatory activity of cytosolic free Ca2+ in adherent cells. Indeed, preincubation with antibodies to either CD18 or CD11b, but not to CD11c, inhibited the oscillations of cytosolic free Ca2+ in adherent neutrophils. This inhibitory effect was evident both as a reduction of the number of responding cells and as a reduction of the oscillatory activity in the cells. In conclusion, the oscillatory activity of cytosolic free Ca2+ in adherent neutrophils is mediated through the CD18/CD11b integrins. The generation of this Ca2+ signal may explain how adherence, by way of the integrins, changes the functional properties of the cell and enables TNF to induce secretion.

Antibodies, Monoclonal↗
PubMed1990

Involvement of GTP-binding proteins in actin polymerization in human neutrophils.

The motility of human neutrophils, which is of vital importance for the role of these cells in host defense, is based on rapid and dynamic changes of the filamentous actin F-actin) network. Consequently, to understand how neutrophils move and ingest particles, we need to know how polymerization and depolymerization of actin are regulated. Previous studies by several investigators have, based on indirect evidence obtained with pertussis toxin, suggested a role for GTP-binding protein(s) (G protein) in chemotaxis-induced, but not phagocytosis-induced, reorganization of the F-actin network. The aim of the present investigation was to study the effects of directly activated G proteins (i.e., without prior ligand-receptor complex formation) on the F-actin content in human neutrophils. AlF4- induced a pronounced and sustained increase in F-actin in intact neutrophils. This effect coincided with an increase in cytosolic free Ca2+, indicating that phospholipase C and the subsequent transduction mechanism were also activated. Inhibition of phospholipase C activity by extensive depression of the cytosolic free Ca2+ level (less than 20 nM) only marginally affected the AlF4(-)-induced rise in F-actin content. The major part of the AlF4(-)-induced rise in F-actin content was also resistant to pertussis toxin, suggesting that pertussis toxin-insensitive G proteins in neutrophils are also able to trigger actin polymerization. The specificity of AlF4- in activating G proteins was also tested in permeabilized cells. In this case the effect was more rapid and could be totally abolished by guanosine 5'-[beta-thio]diphosphate. In analogy, in permeabilized cells guanosine 5'-[gamma-thio]triphosphate mimicked the effect of AlF4- on actin polymerization, and the effect induced by this nonhydrolyzable GTP analogue could also be totally abolished by guanosine 5'-[beta-thio]diphosphate. In summary, the present data support our previous hypothesis that G proteins are intimately linked to actin polymerization in human neutrophils.

Actins↗
PubMed1990

The pharmacokinetics of omeprazole in humans--a study of single intravenous and oral doses.

The pharmacokinetics of omeprazole, hydroxyomeprazole, omeprazolesulfone, and "remaining metabolites" have been studied in eight young healthy subjects following an acute i.v. and oral dose of 10 and 20 mg of 14C-labeled drug, respectively. The oral dose was given as a buffered solution. Two subjects exhibited essentially higher and more sustained plasma levels of omeprazole than the others. This was due to a higher bioavailability, lower clearance, and longer t1/2 of omeprazole in these two subjects. Maximum concentration (0.7-4.6 mumol/L) was reached between 10 and 25 min after oral dosing. The median bioavailability was 39% (25-117%) and the median systemic plasma clearance was 624 ml/min (range of 59-828 ml/min). The corresponding t1/2 for the i.v. dose was 35 min (16-150 min) and 39 min (14-186 min) after oral administration. The drug was rapidly distributed to extravascular sites (mean t1/2 lambda 1 = 3.0 +/- 0.8 min). Mean Vss was 0.23 +/- 0.04 L/kg. Low systemic clearance of omeprazole was associated with a decreased formation rate of hydroxyomepraxole and "remaining metabolites" while omeprazolesulfone formation seemed to be less affected. However, there was a clear-cut correlation between the t1/2 of omeprazole and of its omeprazolesulfone metabolite, indicating that the elimination of these two compounds is mediated by the same isoenzyme. The mean urinary recovery of the radioactive dose during 96 h was 78.3 +/- 2.3 and 75.7 +/- 2.6% for the i.v. and oral dose, respectively. Insignificant amounts were due to unchanged drug and omeprazolesulfone. The excretion of hydroxyomeprazole during the first 12 h varied between 4.6 to 15.5% of a given dose. The mean recovery of radioactivity in the feces was 19.3 +/- 3.1% of a given i.v. dose and 18.2 +/- 2.3% when given orally. It is concluded that omeprazole is mainly eliminated metabolically and that there is a substantial interindividual variation in the rate of formation of primary and secondary metabolites. This variation in omeprazole disposition is probably of limited clinical importance. The half-life, with a maximum of approximately 3 h, is too short to cause accumulation when the drug is administered in a once-daily regimen.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

A study of the interaction between omeprazole and phenytoin in epileptic patients.

This study was performed to determine the effect of omeprazole, given in therapeutically recommended doses, on the steady-state plasma levels of phenytoin in epileptic patients. Five men and three women of median age 34 years participated in the study. Steady-state plasma levels of phenytoin were measured once a week for 2 weeks before and after, respectively, and during 3 weeks of concomitant omeprazole treatment with 20 mg daily. Urinary excretion of phenytoin and its metabolite [5-(p-hydroxyphenyl)-5-phenyl-hydantoin] were determined before and at the end of the omeprazole treatment period. The steady-state plasma phenytoin levels as well as urinary excretion of phenytoin and its main metabolite were unchanged during omeprazole treatment. The results from this study suggest that concomitant omeprazole treatment in therapeutically recommended doses (20 mg daily) will not significantly affect the steady-state plasma levels of phenytoin in epileptic patients.

Adult↗
PubMed1990

Pharmacokinetics and bioavailability of omeprazole after single and repeated oral administration in healthy subjects.

1. Ten healthy subjects were given 20 mg omeprazole EC (enteric coated) granules once daily for 8 days. An i.v. tracer dose of [14C]-omeprazole was given simultaneously with the first and last oral doses and blood sampling was performed thereafter. In order to study the extent of absorption at minimal acid exposure, a single dose of 20 mg omeprazole was also given as a buffered solution, before and after the treatment with EC granules. 2. Kinetic parameters of omeprazole after the i.v. tracer dose were unchanged on repeated dosing while AUC increased by approximately 40% for the solution and 60% for the EC granules. 3. The increased AUC is caused by an increased systemic availability, which may be explained by a decreased first-pass elimination during repeated treatment and/or by a reduced degradation of omeprazole in the stomach secondary to the profound decrease in intragastric acidity caused by the drug. 4. The implication of these findings is that the antisecretory effect of therapeutic doses of omeprazole must be studied during repeated administration and not judged from studies using single doses only.

Adult↗
PubMed1990

Biopsy of the pancreas with a biopsy gun.

Cutting-needle biopsy under ultrasonic guidance was performed in 47 patients with suspected pancreatic carcinoma. The final diagnosis as revealed by autopsy, surgery, or radiologic/clinical follow-up was pancreatic malignancy in 39 patients and benign disease in eight. A correct diagnosis with the aid of biopsy findings was obtained in 44 of the 47 patients (94%). In three patients with carcinoma of the pancreas, the correct diagnosis was not obtained with use of results from the first biopsy. In two of these three patients, simultaneous biopsy of a liver metastasis revealed the presence of a malignant tumor growth. After the biopsy, two patients had a vasovagal reaction, and two experienced mild pain. No case of biopsy-induced pancreatitis occurred, although in one patient a transient rise in the serum amylase level was seen. The present results show that cut biopsy of the pancreas is a useful, reliable, and nontraumatic method in the diagnosis of pancreatic malignancy.

Adenoma, Islet Cell↗
PubMed1990

Sex differences in cytochrome P-450-dependent xenobiotic and steroid metabolism in the mature rainbow trout kidney.

The rainbow trout kidney during the late reproductive stages was found to exhibit a profound sex-related difference in its capacity to metabolize both xenobiotic model substrates and endogenous steroids. The cytochrome P-450 content of trunk kidney microsomes was 28-fold higher in males than in females. In trunk kidney microsomes, the dealkylation of various 7-alkoxycoumarins was 22- to 38-fold higher in males than in females, whereas ethylmorphine-N-demethylase (EMND) and 7-ethoxyresorufin-O-deethylase (EROD) activities were only slightly higher in males than in females. In contrast to the alkoxycoumarin- and EROD activities, the EMND activity showed considerable activity in the head kidney microsomes and the level was found to be higher in females than in males. Progesterone and androstenedione 16- and 6 beta-hydroxylase activities were present mainly in the male trunk kidney microsomes. On the contrary, the oestradiol 2-hydroxylase was distributed along the whole kidney and showed a 2.8-fold higher activity in the female head kidney than in the male head kidney. The catalytic analysis indicated a differential regulation of trout renal P-450 isoenzymes during sexual maturation. Furthermore, the data presented indicate that the high level of the hemoprotein in male trunk kidney was not a general increased level of the protein, but rather an increase of certain cytochrome P-450 isoenzymes.

Androstenedione↗
PubMed1989

Properties, in theory and practice, of novel gel filtration media for standard liquid chromatography.

The influence of experimental parameters on the separation result in gel filtration may readily be predicted from a few basic equations, as demonstrated with the aid of experimental observations on Sephacryl HR. Excellent agreement between the predicted resolution and that determined experimentally was found for parameters such as temperature, particle size, column length, flow velocity, sample volume and gel porosity. The theoretical prediction of an optimum sample volume for a constant processing rate was also experimentally verified. An exhaustive investigation of the physical, chemical and functional properties of Sephacryl HR was undertaken to facilitate the interpretation of experimental observations.

Acrylic Resins↗
PubMed1989

Effect of tumor necrosis factor and granulocyte/macrophage colony-stimulating factor on neutrophil degranulation.

Both TNF and and granulocyte/macrophage CSF (GM-CSF) can activate neutrophils. The aim of this work was to determine the effect of these cytokines on neutrophil degranulation. The secretion of lactoferrin of secondary granules and myeloperoxidase (MPO) of primary granules from single adherent human neutrophils was assayed by use of a reverse hemolytic plaque assay. Both rTNF and rGM-CSF caused secretion of lactoferrin in a dose-dependent manner. Both agents also caused secretion of MPO, but only in the presence of cytochalasin B. Preincubation with pertussis toxin inhibited rGM-CSF-induced secretion of both lactoferrin and MPO. rTNF-induced MPO secretion was also blocked by pertussis toxin, whereas lactoferrin secretion was only slightly affected. Neither rTNF nor rGM-CSF caused any detectable changes in the concentration of cytoplasmic free Ca2+ in fura-2-loaded cells. However, when neutrophils were loaded with increasing concentrations of quin-2 to buffer any local, not detectable, changes in the concentration of cytoplasmic Ca2+, both rTNF- and rGM-CSF-induced secretion of lactoferrin and MPO were almost totally abolished at a relatively low quin-2 concentration. These results suggest a role of a regulatory G-protein and minute local changes in the concentration of cytoplasmic Ca2+ in TNF- and GM-CSF-induced neutrophil degranulation.

Buffers↗
PubMed1989

Cortisol induction of metallothionein in primary culture of rainbow trout hepatocytes.

In the present experiment, metabolically active primary cultures of rainbow trout hepatocytes were utilized to study the inducibility of metallothionein after cortisol treatment. Glucocorticoid induction of metallothionein has previously only been demonstrated in mammalian systems. We now demonstrate the inducibility of rainbow trout metallothionein by cortisol treatment of primary hepatocytes. A 90% elevation above control levels was achieved within 8 days of treatment. Zinc treatment was performed to evaluate the system, and 100 microns zinc in the culture medium resulted in a 350% increase of the metallothionein levels. We conclude that primary culture of rainbow trout hepatocytes constitutes an efficient system for studies of MT induction kinetics.

Animals↗