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Biomedical subjects

T Andersson

Publications and source records attributed to T Andersson.

At least 235 records · Page 13Linked to original sources

Treatment of malignant endocrine pancreatic tumors with a new long-acting somatostatin analogue, SMS 201-995.

Ten patients with malignant endocrine pancreatic tumors were treated with SMS 201-995 at doses of 50 micrograms twice daily, administered subcutaneously. Four out of 10 patients (40%)-1 patient with the Zollinger-Ellison syndrome and 3 of 6 with the watery diarrhea syndrome--responded objectively with more than 50% reduction of peptide levels, with a median duration of 15.5 months. All four patients improved symptomatically, with decreasing dyspeptic symptoms and decreasing diarrhoea. Three additional patients had a clear relief of symptoms without an effect on tumor-secreted peptides. The disease progressed in three patients during treatment. No reduction of tumor mass was seen in any of the patients. The main side effect noted was a slight but maintained increase in fasting blood glucose in four patients. In conclusion, SMS 201-995 had a beneficial effect in more than half of the patients and seems to be a valuable adjunct to other causal therapy in this patient category, especially in acute situations and weak patients because of its very few side effects.

Aged↗

Differences in the incidence of hip fracture. Comparison of an urban and a rural population in southern Sweden.

The incidence of hip fracture from 1981 to 1984 inclusive in the urban population of the city of Malmö was compared with three rural municipalities around the city of Ystad in southern Sweden. A higher incidence of hip fracture was found in the urban population, especially among women. Patients with a hip fracture in Malmö had a lower mean age. Women in Malmö lived more often alone or in institutions.

Aged↗

High-performance liquid chromatography of 2-mercaptopropionylglycine and its metabolite 2-mercaptopropionic acid in plasma and urine after treatment with thiopronine.

2-Mercaptopropionic acid has been identified as a normal metabolite of 2-mercaptopropionylglycine (thiopronine) when this drug was given to humans and dogs. A high-performance liquid chromatographic method was developed to resolve the derivatives of these two thiols and thus enable simultaneous determination of the two compounds in plasma and urine.

Amino Acids, Sulfur↗

Plasma membrane potential modulates chemotactic peptide-stimulated cytosolic free Ca2+ changes in human neutrophils.

The relationship between fMet-Leu-Phe-induced changes in the cytosolic free Ca2+ concentration [( Ca2+]i), plasma membrane potential depolarization, and metabolic responses was studied in human neutrophils. Receptor-activated depolarization occurred both at high and resting [Ca2+]i, but was inhibited at very low [Ca2+]i. Phorbol 12-myristate 13-acetate-induced plasma membrane depolarization, on the contrary, was independent of [Ca2+]i. The threshold fMet-Leu-Phe concentration for plasma membrane depolarization (10(-8) M) was at least 1 log unit higher than that for [Ca2+]i increases (5 X 10(-10) M) and coincident with that for NADPH oxidase activation. Nearly maximal [Ca2+]i increases were elicited by 3 X 10(-9) fMet-Leu-Phe in the absence of any significant plasma membrane potential change. This observation allowed us to investigate the effects of artificially induced plasma membrane depolarization and hyperpolarization at low fMet-Leu-Phe concentrations (10(-9) to 3 X 10(-9) M) which did not perturb plasma membrane potential. Depolarizing (gramicidin D at 10(-7) to 10(-6) M or KCl at 50 mM) and hyperpolarizing (valinomycin at 4 microM) treatments had little influence on unstimulated [Ca2+]i levels, whereas fMet-Leu-Phe-induced transients were significantly altered. Gramicidin D and KCl decreased the fMet-Leu-Phe-induced [Ca2+]i increases in Ca2+-containing or in Ca2+-free media. Valinomycin, on the contrary, increased receptor-stimulated [Ca2+]i increases, and the effect was larger in the presence of extracellular Ca2+. Valinomycin also strongly potentiated secretion. It is suggested that plasma membrane depolarization in human neutrophils is a physiological feedback mechanism inhibiting receptor-dependent [Ca2+]i changes.

Calcium↗

Subcellular localization and properties of cytochrome P-450 and UDP glucuronosyltransferase in the rainbow trout kidney.

Rainbow trout kidney was subfractionated by differential centrifugation to obtain preparations suitable for the study of xenobiotic metabolizing enzymes and to ascertain the distribution of these activities in the cell. The cytochrome P-450-dependent monooxygenase, NADPH-cytochrome c reductase, and UDP glucuronosyltransferase, which are enzymes important in the biotransformation of xenobiotics, were enriched in the microsomal fraction. Another xenobiotic-metabolizing enzyme, epoxide hydrolase, was enriched in the mitochondrial and microsomal fractions almost to the same extent. Cytochrome P-450-dependent monooxygenase and UDP glucuronosyltransferase activities were characterized in the trout kidney microsomes. The cytochrome P-450 deethylation of 7-ethoxycoumarin and 7-ethoxyresorufin as well as the glucuronidation of p-nitrophenol in the kidney were found to proceed at rates comparable to those occurring in the liver. The difference spectrum of the complex between carbon monoxide and reduced trout kidney microsomes showed a peak at 448.5 nm. Addition of 7-ethoxycoumarin to kidney microsomes produced an absorbance change in difference spectrum similar to the substrate binding spectrum found in rainbow trout liver and rat liver microsomes.

Animals↗

Chemotactic factor binding and functional capacity: a comparison between human granulocytes and differentiated HL-60 cells.

In the presence of dimethyl sulfoxide (DMSO), the leukemic promyelocytic cell line HL-60 will differentiate into mature polymorphonuclear granulocytes. In the present report, we compare chemotactic factor binding and function in HL-60 cells with that of normal human granulocytes using the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP) as ligand. The cellular response measured as CL was changed as a result of storage or conditioning of normal peripheral blood cells. With these cells, a conditioning procedure at room temperature resulted in a pronounced increase in the CL response. The increase of the CL response was probably a result of increased expression of cryptic receptors, since the changes of the oxidative response to FMLP was accompanied by increased binding of the peptide to the cell surface. Scatchard analysis revealed that the increased binding was due to an increased number of receptors. In differentiated HL-60 cells, conditioning neither led to increased production of oxidative metabolites, nor to any increased binding of the peptide. The data thus indicate that many FMLP receptors could reside in a cryptic site that is not accessible to extracellular ligands, and that conditioning results in an increased exposure of these receptors, followed by an increased oxidative response to the ligand in normal cells but not in mature HL-60 cells.

Cell Line↗

Thrombogenicity of pulmonary-artery catheters.

The thrombogenicity of heparin-bonded and non-heparin-bonded pulmonary-artery catheters was compared by means of pull-out phlebography in a prospective, randomized clinical study of 20 patients in an intensive care unit (ICU). The duration of catheterization averaged 47.4 +/- 4.1 h in the heparin-bonded group (10 patients) and 45.7 +/- 7.1 h in the non-heparin-bonded (10 patients). Age, clinical diagnosis, mean time required to obtain a stable wedge position, heparin dose administered and clotting indices were comparable between the groups. There was no statistically significant difference in the length of formed thrombi (2.3 +/- 1.89 vs 5.88 +/- 4.62 cm) or frequency of thrombus formation between the groups. The thrombi originated and propagated from the puncture site. They were mural proximally and formed sleeves in the superior vena cava. Several sleeves stripped off on withdrawal of the catheter. Protection from thrombosis offered by heparin bonding of pulmonary-artery catheters should, therefore, not be overestimated--at least not in long-term catheterization of ICU patients.

Aged↗

Species characteristics of the hepatic xenobiotic and steroid biotransformation systems of two teleost fish, Atlantic cod (Gadus morhua) and rainbow trout (Salmo gairdneri).

Groups of Atlantic cod and rainbow trout were treated (ip) with beta-naphthoflavone (BNF), phenobarbital, or peanut oil (controls), and properties of the hepatic xenobiotic and steroid metabolizing enzyme systems were evaluated. In both species, BNF treatment resulted in significant induction of microsomal 7-ethoxycoumarin O-deethylase, 7-ethoxyresorufin O-deethylase, biphenyl 4-hydroxylase, and phenanthrene oxidation, especially at the 1,2-position. Immunochemical studies with rabbit IgG prepared against the major BNF-inducible cytochrome P-450 in cod, P-450c, revealed increased amounts of immunoreactive protein in liver slices from both species after BNF treatment. The molecular weight of the induced protein was approximately 58,000 Da, as shown by Western blotting. When titrating biphenyl 4-hydroxylation, however, the antibodies distinguished between the two species, inhibiting the activity of BNF-induced cod 90% and that of rainbow trout 40% at 10 mg IgG/nmol P-450. Furthermore, cytochrome b5 content and UDP-glucuronyltransferase activity were significantly induced only in rainbow trout, whereas the specific content of cytochrome P-450 was significantly increased only in cod. Differences between the two species were observed in the levels of constitutive activities, the amount of induction, and in the regioselectivity of phenanthrene oxidation and androstenedione metabolism. Treatment with phenobarbital showed no effect on any of the parameters investigated in either species. The results show that although there are many common features of the hepatic xenobiotic and steroid biotransformation systems of the two teleosts, certain species characteristics exist in constitutive properties and induction responses.

7-Alkoxycoumarin O-Dealkylase↗

Comparison of xenobiotic biotransformation enzymes in kidney and liver of rainbow trout (Salmo gairdneri).

The microsomal cytochrome P-450 content in kidney of rainbow trout (Salmo gairdneri) was approximately 5-fold lower than the content in liver. The renal ethoxycoumarin- and ethoxyresorufin-O-deethylase activities calculated on a per-cytochrome P-450 basis were, however, found to be about 10-fold higher than the hepatic activities. The patterns of time-dependent increase and subsequent decrease of microsomal cytochrome P-450-dependent monooxygenase activities after a single injection of beta-naphthoflavone (BNF) were similar in the kidney and liver. The microsomal ethoxyresorufin- and ethoxycoumarin-O-deethylase activities were maximally induced in liver (120- and 10-fold, respectively) by a single BNF injection (50 mg/kg body wt), whereas in kidney the maximal levels of induction (135- and 21-fold, respectively) were reached after three injections with BNF. The induction of cytochrome P-450 systems was associated with synthesis of a new microsomal protein of 58,000 Da in both kidney and liver. UDP-glucuronosyl transferase activity toward p-nitrophenol was about 8-fold lower in kidney than in liver. A significant 2.5-fold elevation in microsomal UDP-glucuronosyltransferase activity was found in the kidney 14 days after a single injection with BNF (50 mg/kg). In the liver, a 2-fold increase of this activity was seen 3 days after the treatment. The results indicate that the rainbow trout kidney in addition to the liver is of great importance in biotransformation of lipophilic xenobiotics.

7-Alkoxycoumarin O-Dealkylase↗

Long-term effects of bleached kraft mill effluents on carbohydrate metabolism and hepatic xenobiotic biotransformation enzymes in fish.

In a laboratory investigation, fourhorn sculpin (Myoxocephalus quadricornis) were exposed for 5-9 months to waste water from pine and birch lines from a bleached kraft pulp plant. The bleached kraft mill effluents (BKME) affected both the carbohydrate metabolism and the xenobiotic metabolism. Thus, an elevated muscle glycogen content in fish exposed to effluent from the pine pulp line suggests a metabolic imbalance. A liver enlargement and a strong elevation of the hepatic cytochrome P-450-dependent ethoxyresorufin-O-deethylase activity after exposure to the bleached pine pulp effluents indicate the presence of cytochrome P-450-inducing agents in the BKME. The results also demonstrate that many physiological test parameters may be used as good indicators of sublethal disturbances in fish to BKME exposure.

Animals↗

Characterization of PHA and anti-T3 induced transduction mechanisms in a human T-cell leukaemia line.

Stimulation of the T-cell line JURKAT with PHA or anti-T3 antibody leads to a rapid and sustained rise of cytosolic free Ca2+, as determined by quin2 fluorescence measurements. Pertussis toxin and N-ethylmaleimide, substances known to inactivate a regulatory N-protein, caused partial to complete inhibition of the cytosolic free Ca2+ response induced both by anti-T3 or PHA. The high cytosolic free Ca2+ level induced by anti-T3 or PHA declined more rapidly after addition of phorbol ester, phorbol myristate acetate (PMA). PMA did not affect cytosolic free Ca2+ changes induced by ionomycin indicating that the effect of PMA is due to a direct inhibitory effect on a transduction mechanism and not to activation of Ca2+ extrusion. Our data suggest that a regulatory N-protein is involved in the transduction of the PHA and anti-T3 response into a rapid and sustained elevation of cytosolic free Ca2+. Activation of protein kinase C by PMA modulates the calcium response in JURKAT cells, suggesting that protein kinase C may be involved in feedback regulation of the transduction mechanism.

Calcium↗

Biliary excretion of intravenous [14C] omeprazole in humans.

We have studied the biliary excretion of [14C] omeprazole in humans. The study was performed in eight healthy subjects and the technique used was based on multiple marker dilution principles with double-lumen tubes placed in both the stomach and intestine. The results obtained show a 16% biliary excretion of [14C] omeprazole. These data suggest a minimal "spillover" of omeprazole from the gastric mucosa into the gastric lumen in humans. The results also agree with previous data of the fecal recovery of radiolabeled omeprazole that suggest that the fecal excretion of intravenous omeprazole in humans is entirely accounted for by biliary excretion.

Adult↗

Percutaneous ultrasonography-guided cutting biopsy from liver metastases of endocrine gastrointestinal tumors.

Ultrasonography-guided cutting needle biopsy of the liver was performed in 186 instances on 95 different patients with carcinoid and endocrine pancreatic tumors. In 171 cases, biopsy specimens were taken from liver metastases found on ultrasonography, and in 93% of these the obtained material was adequate for a correct diagnosis. In the 7% for which an incorrect diagnosis was made, all but one biopsy specimen contained normal liver tissue, indicating that the needle-guiding technique, and not the sampling technique, is the most critical part of the biopsy procedure. Tumor specimens were examined with silver stains and immunocytochemistry after application of monoclonal serotonin antibodies. The argyrophil silver stain of Grimelius could be applied on all specimens and had positive results in all but one case, demonstrating the neurohormonal endocrine origin of the metastases. The argentaffin reaction and/or serotonin immunoreactivity could be applied in 152 cases and had positive results in 115 of 122 (94%) of the mid-gut carcinoid tumors and negative results in 27 of 28 (96.4%) of the non-mid-gut carcinoid tumors and endocrine pancreatic tumors. Major complications occurred in 1.5%; none was lethal or required surgery. The results show that the technique used for tumor biopsy is very accurate and provides material sufficient for multiple histopathologic and immunocytochemical analyses without exposing the patients to high complication risks. It is further concluded that the staining techniques and immunocytochemical analyses applied on the biopsy specimens are valid for the prediction of the location of the primary endocrine tumor.

Adult↗

Mumps virus infection of dissociated rodent spinal ganglia in vitro. Expression and disappearance of viral structural proteins from neurons.

Cultured spinal ganglia and cord from mice and hamsters were infected with mumps virus or Sendai virus. Expression of five structural proteins, the haemagglutinin-neuraminidase, fusion, nucleocapsid (NP), phospho (P) and matrix proteins was examined with monoclonal antibodies to each protein. In Sendai virus-infected mouse neurons all five viral proteins were detected. In hamster neurons infected with mumps virus all viral proteins were also expressed, but in mouse neurons only the NP and P proteins were seen. This suggests a species-specific cellular restriction of viral protein synthesis in mumps virus-infected mouse neurons. There was no, or only a slight, reduction in the number of neurons between days 4 and 20 after infection of mouse cultures with mumps virus, but the proportion of infected neurons diminished from 68% to 15% during this time.

Animals↗

Cell surface expression of fMet-Leu-Phe receptors on human neutrophils. Correlation to changes in the cytosolic free Ca2+ level and action of phorbol myristate acetate.

We have studied how cytosolic free Ca2+ ([Ca2+]i) changes and phorbol myristate acetate (PMA) exposure affects ligand-independent cell surface expression of fMet-Leu-Phe receptors on human neutrophils. Mere incubation primed neutrophils to double their binding of fMet-Leu-Phe. This spontaneous increase of peptide binding was unaffected by changes in the extracellular calcium concentration. However, depression of the [Ca2+]i totally abolished the increased binding of fMet-Leu-Phe. Scatchard-Plot analysis revealed that the observed increase of peptide binding was due to an increased number of receptors. Normalization of the [Ca2+]i in cells where it was initially depressed resulted in a slow but progressive increase in fMet-Leu-Phe binding. The rate of receptor recruitment could be enhanced by rapidly increasing the [Ca2+]i by addition of ionomycin. Addition of PMA to cells with near maximal receptor expression led to a marked reduction of fMet-Leu-Phe binding without affecting [Ca2+]i. These observations suggest the existence of a dual regulatory mechanism for up- and down-regulation of fMet-Leu-Phe receptors on the cell surface of human neutrophils.

Aminoquinolines↗

Treatment of malignant endocrine pancreatic tumours with human leucocyte interferon.

22 patients with advanced malignant endocrine pancreatic tumours were treated with human leucocyte interferon 3-6 X 10(6) IU per day. Objective responses (more than 50% reduction in tumour markers or tumour size) were seen in 7/7 with watery diarrhoea/hypokalaemia/achlorhydria syndrome, 3/4 with the Zollinger-Ellison syndrome, 6/9 with "non-functioning" tumours, and 1 with a mixed tumour mainly producing somatostatin. The median duration of response was 8.5 months, and all responders improved clinically. Adverse effects seemed more tolerable than those of cytotoxic treatment.

Clinical Trials as Topic↗