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Biomedical subjects

T Andersson

Publications and source records attributed to T Andersson.

At least 217 records · Page 12Linked to original sources

Antiandrogenic treatment of benign prostatic hyperplasia: a placebo controlled trial.

In a randomized triple-blind multicentre study, injections with the anti-androgenic agent oxendolone were compared with placebo in the treatment of benign prostatic hyperplasia. Thirty patients were treated with weekly injections of oxendolone 200 mg during a 3 months' period, and 30 patients were allocated to placebo treatment. During oxendolone treatment the maximum urinary flow rate increased statistically significantly (from 6.8 ml/s to 8.2 ml/s). However compared to placebo, the oxendolone effect was statistically insignificant. A slight but statistically significant improvement of the symptoms "sensation of retention", "urgency" and "frequency", was observed following oxendolone treatment, but an almost identical effect was seen in the placebo group. Following either treatment no change was observed in the residual urine volumes, in prostatic volume as measured by transrectal ultrasonotomography, or in any other therapeutic parameters. Conservative treatment of benign prostatic hyperplasia with the antiandrogen oxendolone in a dose of 200 mg a week cannot be recommended for clinical use.

Aged↗

Phorbol ester-induced activation of protein kinase C leads to increased formation of diacylglycerol in human neutrophils.

Human neutrophils stimulated with a phorbol ester (phorbol 12-myristrate 13-acetate or phorbol 12,13-dibutyrate) responded with an increase in diacylglycerol, considered the natural activator of protein kinase C. The amounts of diacylglycerol formed were considerable, reaching 700-900% of basal after 20 min. In contrast, 4-alpha-phorbol 12-myristate 13-acetate did not induce any detectable formation of diacylglycerol. Simultaneously, phorbol 12-myristate 13-acetate exposure caused increased breakdown of both phosphatidylcholine and phosphatidylinositol 4,5-bisphosphate. These results suggest that once activated, protein kinase C can positively modulate its own activity by inducing additional formation of diacylglycerol from at least two different sources.

Calcium↗

Visual evoked potential--a tool in the diagnosis of hepatic encephalopathy?

Visual evoked potentials (VEP) have been suggested to be of value in the diagnosis of subclinical and mild hepatic encephalopathy. In the present study, a comparison between VEP and four psychometric tests (number connection test A and B, digit symbol and word memory test) was performed in 42 cirrhotic patients, 17 of whom had clinical signs of encephalopathy. The results were compared to sex- and age-matched healthy controls. The VEP latencies for P2 (the second positive wave) and N3 (the third negative wave) were 11% and 26% longer (P less than 0.01-0.001) in the patients than in the controls. Moreover, the latencies for N2 (the second negative wave) and P2 were longer in the encephalopathic as compared to the non-encephalopathic patients (P less than 0.05). There was a significant correlation between the latencies for N2 and number connection tests A and B and digit symbol test. However, of the patients with clinical encephalopathy, less than half had VEP latencies longer than the mean +/- 2 S.D. above those for the controls. In contrast, none of the encephalopathic patients had normal results on the psychometric tests. This study demonstrates that although statistically significant differences exist between groups of cirrhotic patients and controls, VEP is not a reliable tool for the diagnosis of encephalopathy in the individual patient.

Adult↗

Caesium-137 in Perch in Swedish Lakes after Chernobyl-present situation, relationships and trends.

The Chernobyl accident, and the general acidification of Swedish water systems, form the base for this project. The aims of the work have been to present results on the linkage between the concentration of Cs-137 in fish, lake load of Cs and lake characteristics, to give a preliminary prognosis on the recovery, and to put the results within a wider framework of environmental hazard analysis. A broad set of data on limnology, morphometry and drainage area conditions from 41 lakes were collected during 1986 and 1987. Cs-137 was determined in 1 + perch (Cs-pe, 1-year-old perch), water, material collected by sediment traps and from surficial sediments. The main results are as follows. The average value of Cs-pe for all lakes has dropped from 9800 Bq kg(-1) (wet) to 5040 between the 2 years. Generally, the decrease is between 5 and 90%. We have tested if any factor(s) could be specifically linked to this decrease-no such factors have been found. The concentrations of Cs in sediment traps have, on average, decreased by 80%. Very high correlations exist between Cs-pe and the caesium load as determined from the sediment traps. Between 1 and 10% (mean 3.9%) of the initial fall-out deposition to the drainage area was transported from land to water during June to August 1986. The variation in initial fall-out deposition explains 65-69% of the variability in Cs-pe; the degree of explanation (= coefficient of determination, r2) increases to about 85% if one also takes into account the lake water hardness and totP. A map showing with lakes likely to have 1 + perch with higher mean Cs-concentrations than 1500 Bq kg(-1) wet is presented. Between 4000 and 7000 lakes in Sweden appear to have Cs-pe higher than 1500 Bq kg(-1) wet, figures which emphasize the serious impact of the Chernobyl accident on the environmental conditions in Sweden.

Journal Article↗

Characterization of cytochrome P-450-dependent activities in hagfish, dogfish, perch and spectacle caiman.

1. Owing to interest in the original function and evolution of cytochrome P-450 this enzyme system was studied in four species each at different levels on the phylogenetic tree, representing Agnatha, Selachi, Teleostei, and Reptilia. 2. All species contained considerable amounts of hepatic microsomal cytochrome P-450. The content in dogfish, perch and spectacle caiman was 0.2-0.3 while in the dogfish it was 0.6 nmol per mg protein. 3. Hepatic microsomal cytochrome P-450 dependent ethylmorphine demethylase, benzo(a)pyrene hydroxylase, 7-ethoxycoumarin-O-deethylase and 7-ethoxyresorufin-O-deethylase activities have been measured and the assays were carefully characterized with respect to pH-, protein content-, incubation time- and temperature-activity relationships. 4. The study revealed species-dependent differences in the liver microsomal cytochrome P-450 enzyme system, which could be due to differences in cytochrome P-450 composition or in the microenvironment around the enzyme.

7-Alkoxycoumarin O-Dealkylase↗

Association of ligand-receptor complexes with actin filaments in human neutrophils: a possible regulatory role for a G-protein.

Most ligand-receptor interactions result in an immediate generation of various second messengers and a subsequent association of the ligand-receptor complex to the cytoskeleton. Depending on the receptor involved, this linkage to the cytoskeleton has been suggested to play a role in the termination of second messenger generation and/or the endocytic process whereby the ligand-receptor complex is internalized. We have studied how the binding of chemotactic peptide-receptor complexes to the cytoskeleton of human neutrophils is accomplished. As much as 76% of the tritiated formylmethionyl-leucyl-phenylalanine (fMet-Leu-[3H]Phe) specifically bound to intact cells, obtained by a 30-s stimulation with 20 nM fMet-Leu-[3H]Phe, still remained after Triton X-100 extraction. Preincubating intact cells with dihydrocytochalasin B (dhCB) or washing the cytoskeletal preparation with a high concentration of potassium, reduced the binding of ligand-receptor complexes to the cytoskeleton by 46% or more. Inhibition of fMet-Leu-Phe-induced generation of second messengers by ADP-ribosylating the alpha-subunit of the receptor-coupled G-protein with pertussis toxin, did not reduce the binding of ligand-receptor complexes to the cytoskeleton. However, using guanosine-5'-O-(2-thiodiphosphate) (GDP beta S) to prevent the dissociation of the fMet-Leu-Phe-associated G-protein within electrically permeabilized cells, led to a pronounced reduction (62%) of the binding between ligand-receptor complexes and the cytoskeleton. In summary, in human neutrophils the rapid association between chemotactic peptide-receptor complexes and the cytoskeleton is dependent on filamentous actin. This association is most likely regulated by the activation and dissociation of the fMet-Leu-Phe-associated G-protein.

Actins↗

Receptor-mediated phagocytosis in human neutrophils is associated with increased formation of inositol phosphates and diacylglycerol. Elevation in cytosolic free calcium and formation of inositol phosphates can be dissociated from accumulation of diacylglycerol.

Phagocytosis of C3bi- or IgG-opsonized yeast particles in human neutrophils was found to be associated with an increased formation of inositol phosphates and diacylglycerol. Pertussis toxin only marginally affected phagocytosis of IgG- and C3bi-opsonized particles and the associated formation of second messengers. Forskolin, which induced a threefold rise of cellular cAMP, however, markedly inhibited both C3bi- and IgG-mediated phagocytosis as well as the particle-induced formation of inositol phosphates and diacylglycerol. These observations are in contrast to what was found to occur with chemotactic factors and indicate that chemotactic and phagocytic signaling can be regulated independently in human neutrophils. Since C3bi-mediated phagocytosis has been shown to occur at vanishingly low cytosolic free calcium levels, calcium-depleted cells were used to study the importance of the inositol cycle for the engulfment of C3bi-opsonized particles. Despite a total lack of receptor-induced formation of inositol phosphates, a significantly increased accumulation of diacylglycerol accompanied the ingestion of C3bi-opsonized particles. These data show that the engulfment of C3bi-opsonized particles can occur independently of both a calcium transient and an increased inositol phosphate production. However, the observed accumulation of diacylglycerol, not derived from phosphoinositides, suggests that this second messenger play a role in the control of the engulfment process.

Antigens, Differentiation↗

Relative proton density and relaxation times in liver metastases during interferon treatment.

Relaxation times and relative proton densities were calculated from magnetic resonance examinations of the liver in eight patients with liver metastases from neuroendocrine tumours. Single, spin-echo sequences with eight different repetition times and a four-echo sequence were used to calculate T1 and T2 in tumour and normal liver, and the proton density tumour-liver quotient, before and during treatment with interferon. Changes over time of these parameters were compared with variations in tumour marker levels and changes in size and number of the metastases. During therapy, six out of eight cases showed a decrease in tumour T1, five responding to therapy and one with stationary disease, while the two patients with progressive disease showed unchanged tumour T1. The proton density quotient also decreased in a corresponding way, indicating a change in water content in tumours responding to interferon therapy. No significant change in liver T1, tumour T2 or liver T2 occurred in any patient. It is thus possible to perform reliable measurements of relaxation parameters over time, which may be valuable in follow-up of tumour treatment.

Adult↗

Omeprazole: pharmacokinetics and metabolism in man.

Omeprazole is acid labile and, therefore, has to be protected from exposure to the acidic gastric juice when given orally. Following a single oral dose of buffered suspension, omeprazole is rapidly absorbed with peak plasma concentrations within 0.5 hours. The volume of distribution is 0.3 litres/kg corresponding to the volume of extracellular water. In contrast to the long duration of antisecretory action, omeprazole is rapidly eliminated from plasma. The half-life is less than 1 hour, and omeprazole is almost entirely cleared from plasma within 3-4 hours. Omeprazole is completely metabolized in the liver. The two major plasma metabolites are the sulphone and hydroxyomeprazole, neither of which contributes to the antisecretory activity. About 80% of a given dose is excreted in the urine, and the remainder via the bile. The absorption of the coated granule formulation dispensed in hard gelatine capsules is slower, with peak concentrations 1-3 hours after dose. Bioavailability after a single dose is 35% and increases during repeated once-daily dosing to 60%. Omeprazole can potentially interact with the hepatic microsomal cytochrome P-450 enzymes. Studies show that the clearance of both diazepam and phenytoin are decreased and their terminal half-lives are increased during concomitant omeprazole treatment, both interactions being attributable to inhibition of hepatic metabolism. No interaction with propranolol or theophylline has been noted.

Administration, Oral↗

Nuclear DNA distribution in neuroendocrine gastroenteropancreatic tumors before and during treatment.

The nuclear DNA contents of tumor cells in 73 patients with endocrine gastrointestinal tumors, 19 patients with endocrine pancreatic tumors (EPT) and 54 patients with malignant carcinoid tumors were determined before and after treatment. The DNA profiles were divided into diploid and aneuploid. In untreated patients, 9 out of 10 (90%) primary EPT and all 9 primary malignant carcinoid tumors (100%) were diploid. Tumor cell imprints from liver metastases of patients with untreated EPT showed aneuploidy in 5 of 11 cases, but only in 7 out of 46 DNA records from patients with untreated carcinoid liver metastases. DNA alteration from diploid to aneuploid profiles occurred in 2 patients with endocrine pancreatic tumors who had received chemotherapy. A change from diploid to aneuploid records was also seen in 7/23 (30%) carcinoid tumors after treatment. The DNA patterns before and after treatment did not show any correlation with survival or treatment response.

Adenoma, Islet Cell↗

Increased breakdown of phosphatidylinositol 4,5-bisphosphate is not an initiating factor for actin assembly in human neutrophils.

The present study examined the possible role of increased phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) breakdown in the regulation of actin assembly in human neutrophils. Tetracaine, a local anesthetic, was used since it has recently been proposed to inhibit the phosphorylation of phosphatidylinositol 4-phosphate to form PtdIns(4,5)P2. Surprisingly, it was found that incubation with tetracaine alone increased the breakdown of PtdIns(4,5)P2, measured as total inositol trisphosphate formation. This occurred without any rise above basal in the cellular content of filamentous actin. However, in the presence of formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe), tetracaine potentiated the chemotactic-induced increase of both inositol trisphosphate formation and actin polymerization. To further explore the relationship between increased PtdIns(4,5)P2 breakdown and actin polymerization, the activity of phospholipase C was depressed by lowering the cytosolic free calcium ion level or by incubating the cells with ionomycin. In these cells, fMet-Leu-Phe stimulation still raised the cellular content of filamentous actin to a level similar to levels in nontreated cells, despite the absence of PtdIns(4,5)P2 hydrolysis. Consequently, increased breakdown of PtdIns(4,5)P2 alone is not enough to initiate actin polymerization, nor is the polymerization of actin dependent on an increased PtdIns(4,5)P2 breakdown. However, we cannot exclude the possibility that increased turnover of phosphoinositides might act as a modulator of actin assembly.

Actins↗

Does protein kinase C control receptor-mediated phagocytosis in human neutrophils?

It was previously demonstrated that C3bi- but not IgG-mediated phagocytosis in human neutrophils is a Ca2+-independent process [(1985) Nature 315, 509-511]. The objective of this study was to elucidate the nature of an additional messenger signal(s) that may be involved in receptor-mediated phagocytosis in these cells. The C3bi- and IgG-mediated phagocytic ability of neutrophils was inhibited by forskolin, a potent activator of adenylate cyclase. It was found that forskolin induced a 3-fold increase in cAMP levels and simultaneously reduced the uptake of both C3bi- and IgG-opsonized particles by 65%. This inhibition was reversed by exposure to either phorbol myristate acetate (PMA) or diacylglycerol (OAG), which are both activators of protein kinase C, but not by the inactive analog 4 alpha-PMA. PMA could also restore the phagocytic ability of neutrophils with an experimentally impaired calcium response. These results suggest that activation of protein kinase C might be an important transducing signal controlling receptor-mediated phagocytosis in human neutrophils.

Cyclic AMP↗

Regulation of receptor-mediated calcium influx across the plasma membrane in a human leukemic T-cell line: evidence of its dependence on an initial calcium mobilization from intracellular stores.

It has been repeatedly shown that stimulation of a human leukemic T-cell line, JURKAT, by lectins such as phytohaemagglutinin and anti-T3 antibody (OKT3) leads to an elevation in the concentration of cytosolic free Ca2. This Ca2+ transient results from both an intracellular mobilization and an influx of Ca2+ through specific membrane channels. The objective of this study was to investigate the mechanism by which receptor-mediated influx of Ca2+ is regulated in JURKAT cells, which demonstrably lack 'voltage-dependent calcium channels'. It was found that upon increased loading with quin2 or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) there was a pronounced decline of both phytohaemagglutinin-stimulated and OKT3-stimulated influx of 45Ca2+. Using 15 microM quin2/AM or 30 microM BAPTA/AM, agonist-stimulated 45Ca2+ influx was almost totally abolished. At these concentrations of both quin2/AM or BAPTA/AM, phytohaemagglutinin and OKT3 could still induce a rise of cytosolic free Ca2+ above 200 nM. In the presence of La3+ (200 microM), which completely inhibited the agonist-induced 45Ca2+ influx, both phytohaemagglutinin and OKT3 were able to raise the concentrations of cytosolic free Ca2+ to well above 200 nM by merely mobilizing Ca2+ from intracellular stores alone. The data suggest that an agonist-induced increase in the concentration of cytosolic free Ca2+, due to mobilization from intracellular stores, could either directly or indirectly, initiate receptor-mediated Ca2+ influx across the plasma membrane in JURKAT cells.

Aminoquinolines↗

The 5' flanking region of the gene for the Epstein-Barr virus-encoded nuclear antigen 2 contains a cell type specific cis-acting regulatory element that activates transcription in transfected B-cells.

We have recently identified the promoter that positions the initiation (cap) site for RNA encoding the Epstein-Barr virus (EBV) determined nuclear antigen 2 (EBNA2) in transfected COS-1 cells. The cells were transfected with recombinant vectors that contained the BamHI WYH region of the EBV genome. In order to delineate regulatory DNA sequences required for the expression of EBNA2 the 5' flanking region of the gene was linked to reporter genes in expression vectors and transfected into EBV genome-negative lymphoid DG75 cells. We demonstrate that several cis-acting elements contribute to a transcriptional enhancer activity found in the region between nucleotides-553 and -86 relative to the cap site. The enhancer was active in lymphoid DG75 cells but not in HeLa cells and stimulated transcription also from the heterologous thymidine kinase (TK) and beta-globin promoters. Nuclear extracts of lymphoid cells contained protein factors that bound to the enhancer. The in vitro introduction of a mutation in the enhancer sequence that substantially reduced the transcription stimulatory activity concurrently blocked the binding of one of the factors.

Animals↗

Long-term effects of bleached kraft mill effluents on red and white blood cell status, ion balance, and vertebral structure in fish.

In a laboratory investigation fourhorn sculpin (Myoxocephalus quadricornis) were exposed for 5-9 months to wastewater from pine and birch lines from a bleached kraft pulp plant. This long-term exposure to bleached kraft mill effluent (BKME) affected the hematology, the ion balance, and the vertebral structure. Decreased values for hematocrit and hemoglobin and a reduced red blood cell count, as well as increased levels of methemoglobin, indicated disturbances in the red blood cell status. The white blood cell picture was not significantly affected by the BKME exposure. Decreased levels of potassium and chloride ions in the blood plasma in some of the exposed fish suggest an impaired ability to maintain ion homeostasis. Elevated frequencies of vertebral deformations in fish exposed to BKME confirm previous observations of vertebral damage in feral fourhorn sculpin caught in the receiving body of water of the same bleached kraft pulp industry. Many of the parameters analyzed in this investigation may be used as health indicators in future laboratory and field studies on fish exposed to BKME.

Animals↗

Mercury in fish in Swedish lakes.

The aim of this work has been to try to obtain a picture of the past, present and future mercury situation in fish in Swedish lakes, to make an estimate of the number of lakes threatened by 'blacklisting', and to see if the data can be used to reveal anything about the impact of liming on the Hg content in pike. The register contains a broad set of data from 1456 lakes. The main results are as follows. Trend analyses indicate that the Hg content in 1-kg pike seems to increase with time. This is interesting since there has been a significant decrease in mercury emissions from Swedish industries during the last two decades. High Hg contents in 1-kg pike appear in a very characteristic pattern, linked to specific sources of Hg emission. The data indicate that old Swedish 'sins' are still causing a lot of problems. The factors governing the leakage of Hg from soils to water ought to be a very important topic for further studies. The Hg content in pike shows the highest correlation with the following parameters: Hg in surficial sediments, pH, distance from point source and water hardness, lake water alkalinity and conductivity, water retention time, size of drainage area and lake surface. A formula which provides the best possible degree of explanation (r2 = 0.78) has been derived. At present there are about 250 lakes 'blacklisted' in Sweden due to high Hg content in fish. Our data show that there are at least 9400 lakes that ought to be 'blacklisted' today. A successful liming operation will alter the chemical conditions in lakes and also decrease the Hg content in fish.

Journal Article↗

Drinking habits and alcohol abuse among young men: a prospective longitudinal study.

The relationship between self-reported frequency of drunkenness at 14-16 years of age and registered alcohol abuse at age 15-25 was studied in a large and representative group of Swedish men. The results showed that the proportion of boys who had experienced drunkenness more than 10 times increased rapidly between ages 14-16. Before the age of 25, 17% of the boys were registered in governmental records (police, social authorities or psychiatric services) because of alcohol abuse. A high frequency of self-reported drunkenness at age 14-16 was found to be significantly related to registered alcohol abuse at age 18-24. At the same time, however, it was found that 70-80% of the adolescent boys with the greatest frequency of drunkenness were not registered for alcohol abuse in early adult years. Using self-reported frequency of drunkenness at age 14-16 as a basis for predicting registered alcohol abuse at age 18-24 allowed correct classification of only 6% more boys than would have been expected by using a random procedure. The present study indicated that initial drinking habits per se are of limited importance in the development of alcohol abuse in early adulthood. However, the results showed that the combination of high self-reported frequency of drunkenness and appearance in government registers as early as age 15-17 constitutes a serious indication of continuing alcohol abuse.

Adolescent↗