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Biomedical subjects

E Nilsson

Publications and source records attributed to E Nilsson.

At least 127 records · Page 7Linked to original sources
PubMed1989

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↗
PubMed1989

Calpain and calpastatin levels in different organs of the rabbit.

1. The levels of Ca-independent and Ca-dependent proteolytic activity as well as the activities of calpains and calpastatin in different organs of the rabbit was examined at various developmental stages. 2. Calpain and calpastatin levels were highest in the lung and in the kidney. 3. In all organs examined except the thymus the total level of calpain was higher than that of calpastatin. 4. In the thymus the levels of calpains and calpastatin decreased markedly with age.

Aging↗
PubMed1989

Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline.

The effect of the monoamine oxidase inhibitor selegiline on tyramine metabolism and intravenous and oral tyramine pressor sensitivity was studied in healthy subjects. After oral doses of tyramine, which caused systolic blood pressure to increase by 30 mm Hg, we determined plasma concentrations of p-hydroxyphenylacetic acid (HPAA) and of conjugated and unconjugated tyramine. When 20 mg/day of selegiline was administered, the AUCspec of HPAA decreased from 86% to 64% and the AUCspec of conjugated tyramine increased from 13% to 35% of the sum of total tyramine and HPAA. Pressor sensitivity was enhanced more with oral administration of tyramine than with intravenous administration of tyramine. After the drug was discontinued, initial values were reached within 4 days (one subject) and 2 weeks (two subjects). Fifty-five percent of the selegiline dose was eliminated in urine as amphetamine and methamphetamine. The findings support the assumption that selegiline does not selectively inhibit monoamine oxidase-B (MAO-B) when administered in doses of 20 mg/day and higher.

Administration, Oral↗
PubMed1989

Monoamine oxidase inhibition by phenelzine and brofaromine in healthy volunteers.

The two monoamine oxidase (MAO) inhibitors phenelzine and brofaromine given for 2 to 3 weeks were compared in six volunteers. Blood pressure sensitivity to intravenous tyramine increased 2.6-fold during phenelzine (60 mg/day) and 4.8-fold during brofaromine, whereas sensitivity to oral tyramine increased more during phenelzine (15.7-fold vs 8.5-fold). After withdrawal of phenelzine, pressor sensitivity to oral tyramine returned to control values within 2 and for more than 8 weeks. Relative bioavailability of conjugated tyramine was elevated sixfold by brofaromine and 11.6-fold by phenelzine. Urinary elimination of tryptamine increased during phenelzine and brofaromine to 12.7-fold and threefold, respectively. 3-Methoxy-4-hydroxyphenylglycol (MHPG) and 3-methoxy-4-hydroxymandelic acid (VMA) excretion decreased during brofaromine significantly by 72% and 49%, respectively. The nonsignificant decrease of MHPG excretion and the increase of intravenous tyramine pressor sensitivity caused by phenelzine are significantly related. The data suggest that the selective reversible MAO-A inhibitor brofaromine has a larger therapeutic safety than phenelzine.

Adult↗
PubMed1989

Halothane-induced variability in the neuromuscular transmission of patients with myasthenia gravis.

The purpose of the present clinical study was to explore the skeletal muscle mechano (MMG)- and electromyographic (EMG) responses during halothane/oxygen/air anaesthesia in patients with myasthenia gravis (MG) compared with patients with normal neuromuscular transmission. The majority of MG-patients had a significant decremental response of the evoked muscle action potentials to a train-of-four (TOF) stimulation during halothane exposure (mean decrease of train-of-four ratio was 33% during the highest mean halothane concentration of 1.9 MAC). An excellent correlation was found between MMG- and EMG-measurements (r2 = 0.878, P less than 0.001). However, marked individual variations in the neuromuscular response to halothane were seen. Neither preoperative muscle fatigability nor acetylcholine receptor antibodies predicted the decremental muscle responses produced by halothane among MG-patients. The increased presence of HLA-B8 among myasthenics with halothane-suppressed muscle responses after TOF stimulation could be demonstrated (P less than 0.01).

Adolescent↗
PubMed1989

Isolation and characterization of a tumor necrosis factor binding protein from urine.

Tumor necrosis factor (TNF)/cachectin can produce both beneficial and harmful manifestations. Mechanisms may operate to counteract potentially harmful effects such as shock and cachexia. The TNF binding protein (TNF-BP), which is found at increased levels in serum and urine of patients with chronic renal failure, may play such a role. TNF-BP was purified 1,000,000-fold to homogeneity from urine of patients with chronic renal failure by use of ion exchange chromatography, affinity chromatography on TNF-Sepharose and reverse phase chromatography. The purified protein contained only one chain with an apparent Mr on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 30,000. The aminoterminal amino acid sequence D-S-V-X-P-Q-G-K-Y-I-H-P-Q-V-N-S-I-X-K-T revealed no significant homologies with previously described protein sequences. TNF-BP may act as a regulator of the bioactivities of TNF/cachectin.

Amino Acid Sequence↗
PubMed1989

Characterization of the receptor for lymphotoxin; a spontaneous internalization without recycling and ligand-induced downregulation in HL-60 cells.

The receptor system for lymphotoxin (LT) was investigated by use of the human promyelocytic HL-60 cell line. Utilizing subcellular fractionation, internalization of cell surface bound recombinant LT (rLT) and transfer to lysosomes followed by degradation was demonstrated. Binding of rLT to its cell surface receptor induced a downregulation of the receptor which was persistent for at least 6 h. Downregulation of the receptors from the cell surface by activation of protein kinase C with the diacylglycerol OAG was completely reversible but the recovery of the binding capacity was dependent on protein synthesis as it was inhibited by cycloheximide. Treatment with cycloheximide alone resulted in a loss of binding capacity with a half life of approximately 2 h, suggesting a spontaneous consumption of receptors. Affinity cross-linking revealed three ligand-receptor complexes with Mr of 85, 105 and 125 kDa. Because of a strong tendency for ligand polymerization these results suggest oligomer binding of the ligand to a single receptor molecule with an apparent Mr of 70 kDa. N-linked glycosylation constituted 4 to 5 kDa of the total molecular weight. In conclusion, we demonstrated a spontaneous internalization of the receptor for LT without recycling, and that ligand binding resulted in an irreversible downregulation of the receptor.

Asparagine↗
PubMed1988

Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma.

Expression of the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNA 1 to 6) and membrane-associated protein (LMP) was investigated by immunoblotting in 83 nasopharyngeal carcinoma (NPC) biopsies and 25 other tumor and normal tissue specimens from the head and neck region. Fifty-eight of the 83 NPC biopsies were large enough to yield parallel data on virus DNA and viral expression. All 16 cases of clinically diagnosed and histologically confirmed NPCs from North Africa contained EBV DNA and expressed EBNA-1. Of 31 clinically diagnosed NPCs from China, 29 contained EBV DNA and 25 of these expressed EBNA-1. One control tissue biopsy from the oropharynx of NPC patients contained EBV DNA, but none expressed EBNA-1. The latent membrane protein (LMP) was detected in 22/31 of the Chinese and in 10/16 of the North African NPC biopsies. None of the NPC biopsies or control tissues expressed detectable amounts of EBNA 2 or any of the other 4 nuclear antigens which are invariably expressed in EBV-transformed B cells. A smaller number of tumors from Malaysia and East Africa exhibited a similar pattern of expression. EBV was rescued from a nude-mouse-passaged North African NPC tumor by co-cultivation of the tumor cells with umbilical cord blood lymphocytes. The tumor expressed EBNA 1 and LMP, but not EBNA 2 or the other 4 EBNAs. The resulting LCLs expressed all 6 nuclear antigens, EBNA 1 to 6 and LMP. Our data suggest that expression of the EBV genome is regulated in a tissue-specific fashion.

Animals↗
PubMed1988

Effects of ethanol on mechanisms for secretory and aggregatory responses of human granulocytes.

Since the mechanisms for inhibitory effects of ethanol on polymorphonuclear (PMN) leukocyte function are largely unknown we studied secretory and aggregatory responses after in vitro treatment of PMN with ethanol. Oxidative metabolism (assessed by chemiluminescence, superoxide ion production and oxygen consumption) and aggregation were reduced dose-dependently in the presence of ethanol when elicited by stimuli binding to surface receptors or other structures (fMLP and ConA). Similar results were obtained with non-receptor-dependent stimuli, as NaF and the calcium ionophore A23187. In contrast, phorbol myristate acetate peak responses were not affected. FMLP induced changes in Fura-2AM fluorescence (as a probe for fast intracellular calcium concentration changes) were, however, not influenced by ethanol. Neither were membrane potential changes [assessed by di-O-C5(3) fluorescence]. Thus, it is suggested that ethanol may impair a step of the stimulus-response-coupling in PMNs distal to the initial intracellular calcium mobilization.

Calcium↗
PubMed1988

Leukotriene B4 triggers highly characteristic and specific functional responses in neutrophils: studies of stimulus specific mechanisms.

By using human neutrophils we studied the on-off phenomenon for leukotriene B4 (LTB4) -induced functional responses compared with fMetLeuPhe (fMLP). LTB4 induced rapidly appearing and disappearing neutrophil chemiluminescent (CL), superoxide anion formation, aggregatory and membrane depolarizing responses, whereas fMLP responses were slower both in onset and termination. Increases of intracellular calcium concentrations (as reflected by quin2 and fura-2 fluorescence) were of similar magnitude for both stimuli; however, LTB4 responses were more rapidly terminated and fMLP responses were biphasic. When intracellular calcium fluxes, calmodulin or protein kinase C activities were inhibited by quin2, trifluoperazine, verapamil or 3,4,5-trimethoxybenzoic acid 8-diethylamino)octyl ester (TMB-8), profound changes were noted for chemiluminescent and aggregation kinetics induced by fMLP, whereas kinetics of LTB4 responses were less affected. When drugs were used to modulate cAMP levels, or to inhibit cyclo- and lipoxygenase metabolites of arachidonic acid, no effects on response kinetics were observed. Cytochalasin B both amplified and delayed responses although chemiluminescent responses to fMLP were amplified more than those to LTB4. Despite those effects cytochalasin B did not enhance peak fura-2 or quin2 responses to either fMLP or LTB4. Thus, LTB4 rapidly initiates functional responses in neutrophils, and stimulus-specific response patterns are already discernable during the mobilization of calcium, and can be modulated by interference with calcium-dependent reactions.

Aminoquinolines↗
PubMed1988

Carcinoma of the colon and rectum. Tumors missed by radiologic examination in 61 patients.

Radiologic examinations preceding the diagnosis of colorectal carcinomas were retrospectively scrutinized in 708 patients with 731 carcinomas that were radiographically investigated 741 times. Sixty-four lesions were missed 74 times, giving a 90% sensitivity of the radiographic methods used. Of the errors, 82% were perceptive, and 3% were interpretative. Eleven examinations in nine patients revealed no lesions, although the examinations were done within 2 years of the diagnosis of a carcinoma. Missed lesions were more common than expected in the cecum and the ascending colon (P less than 0.001), and 18% of the patients had multiple tumors (expected incidence 3.6%, P less than 0.001). The median delay in diagnosis was 20 months, and patients whose diagnosis was delayed for a long time tended to have more advanced carcinomas at diagnosis. As a lesion was identified either at the initial examination or retrospectively 730 of 741 times, the potential sensitivity of the radiographic methods used was 99%. It is concluded that barium enema is still an excellent method for the detection of colorectal carcinoma provided that perceptive errors can be minimized.

Barium Sulfate↗
PubMed1988

Phosphorylation of glucokinase from rat liver in vitro by protein kinase A with a concomitant decrease of its activity.

Glucokinase, purified from rat liver, was phosphorylated to an extent of 1 mol [32P]-phosphate/mol of enzyme when incubated with [32P]ATP and protein kinase A from pig or rabbit muscle. The phosphate was bound to serine residues. K0.5 increased and Vmax decreased upon phosphorylation. The phosphate group was removed during incubation of the phosphorylated glucokinase with alkaline phosphatase. Enzymatically inactive glucokinase was not phosphorylated by the protein kinase.

Animals↗
PubMed1988

Bambuterol: uptake and metabolism in guinea pig isolated lungs.

The lung uptake and biotransformation of 3H-bambuterol, a prodrug to terbutaline, were studied using isolated perfused and ventilated guinea pig lungs. 14C-Sucrose was used as an extracellular marker. The lung uptake of bambuterol was significantly (0.05 greater than or equal to P greater than or equal to 0.001) higher than that found for sucrose in single-pass perfusion experiments. High-performance liquid chromatographic (HPLC) analysis showed that 95.6 +/- 3.6% of the effluent 3H radioactivity was attributable to bambuterol. In recirculating experiments (120 min) the lung biotransformation of 3H-bambuterol (8.5 pmol/ml) was studied. Both oxidative and hydrolytic metabolism took place. The dominating metabolites were hydroxylated bambuterol and the monocarbamate derivative which is a product of hydrolysis of bambuterol. Traces of terbutaline were also formed. The results show that bambuterol has a certain affinity to lung tissue and that the drug is, to some extent, biotransformed in the guinea pig lung.

Animals↗
PubMed1987

Characterization of a relationship between the T-lymphocyte derived differentiation inducing factor (DIF) and lymphotoxin: a common receptor system for DIF, lymphotoxin and tumor necrosis factor downregulated by phorbol diesters.

Here we describe results which show that recombinant lymphotoxin (rLT), like the T-lymphocyte derived differentiation inducing factor (DIF), inhibited the clonogenic growth of some myeloid leukemia cell lines by concentrations of 1 to 30 pmol/l. Wild type HL-60 cells were resistant at these concentrations but responded with differentiation into monocyte-like cells at higher concentrations. An antigenic relationship between DIF and LT was indicated because a neutralizing monoclonal anti-LT antibody bound to and neutralized both differentiation and growth inhibitory effects of DIF. An activity, which cochromatographed with DIF during all purification steps, competed with binding of both rLT and recombinant tumor necrosis factor (rTNF) to HL-60 cells. By use of radioiodinated ligand, 2100 binding sites for rLT were detected on HL-60 cells with a Kd of 330 pmol/l. At 37 degrees C bound ligand was transferred to lysosomes, followed by degradation. rTNF and rLT were shown to compete for binding sites on HL-60 cells. Receptors for both rLT and rTNF were downregulated by activators of protein kinase C such as phorbol diester or diacylglycerol; the number of cell surface receptors decreased while the Kd remained unchanged. Our observations demonstrate a functional and antigenic relationship between DIF and LT and indicate that TNF, LT and DIF share binding sites on myeloid leukemia cells that are downregulated by activation of protein kinase-C.

Binding Sites↗
PubMed1987

The prevalence of renal amyloidosis of the AA-type in a series of 1,158 consecutive autopsies.

To determine the prevalence of renal amyloidosis of the AA-type in a defined population, formalin-fixed specimens from the kidneys of all the cases autopsied in 1983 at The General Hospital of Malmö, Sweden, were investigated using immunohistochemical techniques. Amyloid deposits of protein AA were found in 10 of 1,158 investigated cases and the calculated prevalence was 0.86 per cent. The mean age at death of the individuals with the AA-type of amyloidosis was 79 years. Six of the cases with amyloidosis had rheumatoid arthritis. The avidin-biotin-peroxidase complex technique was found to be superior to the immunofluorescence method and a high sensitivity and specificity was achieved when sequence-specific antibodies against a synthetized nonapeptide corresponding to a hydrophilic segment of the polypeptide chain of protein AA were used in the assay. Nine cases with other types of amyloid deposits in the kidneys were also detected. None of these cases showed any AA immunoreactivity but all of them demonstrated Congophilic deposits which were immunohistochemically stained by antibodies against the amyloid P-component. The prevalence of renal amyloidosis comprising all types of amyloid protein deposits was 1.64 per cent.

Aged↗
PubMed1986

Results of surgical treatment for iliofemoral venous thrombosis.

The long-term results after venous thrombectomy combined with a temporary arteriovenous fistula were evaluated in 19 patients. Clinical status, isotope phlebography, venous occlusion plethysmography and foot volumetry were performed after a mean follow-up time of 38 months (range 13-75). The primary operation was successful in 17 of the 19 patients; the 2 remaining had chronic occlusions of their iliac veins. At the time of closure of the arteriovenous fistula, i.e. 3 months after thrombectomy, 14 patients had a patent iliac vein. At follow-up eight patients were considered to have a patent iliac vein, eight had a partial restitution and three had an occluded iliac vein. The group as a whole had no impaired venous emptying of the leg, but the small group of patients with occlusion at follow-up according to isotope phlebography seemed to have an impaired venous emptying. Foot volumetry showed only minor signs of valvular insufficiency, mainly in limbs with distal extension of the initial thrombus or only partial restitution of venous patency. A good long-term result can be expected after venous thrombectomy with a temporary arteriovenous fistula particularly in younger patients where the thrombosis is limited to the iliofemoral segment. This emphasizes the importance of early operation before distal extension of the thrombus occurs.

Adolescent↗