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Biomedical subjects

I Larsson

Publications and source records attributed to I Larsson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Orlistat (Ro 18-0647), a lipase inhibitor, in the treatment of human obesity: a multiple dose study.

OBJECTIVE: To evaluate efficacy and tolerability of the lipase inhibitor Orlistat (Ro 18-0647) in doses of 10, 60 and 120 mg three times a day in addition to a mild hypocaloric diet containing 30% of calories as fat. DESIGN: 4 week single-blind placebo run-in period of diet alone followed by a 12 week double-blind, placebo-controlled, randomized treatment period. SETTINGS: Five European outpatient clinics specializing in endocrinology and/or the treatment of obesity, one central laboratory. SUBJECTS: Of 237 healthy obese subjects meeting the inclusion criteria, 188 showed compliance to the diet during the run-in period and were randomized for the treatment period. MAIN OUTCOME MEASURES: Primary efficacy criterion was the difference in weight loss after 12 weeks of treatment between the Orlistat treated groups and the diet alone group. Secondary efficacy criteria were changes in serum total, HDL- and LDL-cholesterol. RESULTS: Compared to placebo a mean (+/- s.e.) additional weight loss of 0.63 +/- 0.54 kg with 30 mg a day (P = 0.246), 0.71 +/- 0.55 kg with 180 mg a day (P = 0.190) and 1.75 +/- 0.54 kg with 360 mg a day was seen (P = 0.001) or Orlistat was observed. Overall data indicated dose-dependency. Small decreases were seen in total and LDL-cholesterol (significant in the 180 and 360 mg a day groups) and LDL- to HDL-cholesterol ratio (significant in the 360 mg a day group only). Mild, mostly gastrointestinal side effects were observed more frequently in the Orlistat groups and caused premature withdrawal from the study in only four patients. No marked laboratory abnormalities were shown, including the lipid-soluble vitamins A, D and E. CONCLUSION: Orlistat, in an apparently dose-dependent manner, leads to additional weight loss compared to diet alone and overall, is well tolerated.

Adult↗
PubMed1994

Genomic organization of mouse and human Bruton's agammaglobulinemia tyrosine kinase (Btk) loci.

Btk is a cytoplasmic protein tyrosine kinase (PTK) that has been directly implicated in the pathogenesis of X-linked agammaglobulinaemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. We have isolated phage and cosmid clones that allowed us to deduce the genomic structure of mouse and human Btk loci. The mouse and human genes are contained within genomic regions that span approximately 43.5 kb and 37.5 kb, respectively. Both loci contain 18 coding exons ranging between 55 and 560 bp in size with introns ranging in size from 164 bp to approximately 9 kb. The 5'-untranslated regions are encoded by single exons located approximately 9 kb upstream of the first coding exon. Exon 18 encodes for the last 23 carboxyl-terminal amino acids and the entire 3'-untranslated region. The location of intron/exon boundaries in the catalytic domains of the mouse and human Btk loci differs from that found in other described sub-families of intracellular PTKs, namely that of Src, Fes/Fer, Csk, and Abl/Arg. This observation is consistent with the classification of Btk together with the recently characterized kinases, Tec and Itk, into a separate sub-family of cytoplasmic PTKs. Putative transcription initiation sites in the mouse and human Btk loci have been determined by using the rapid amplification of cDNA ends assay. Similar to many other PTK specific genes, the putative Btk promoters lack obvious TATAA and CAAAT motifs. Putative initiator elements and potential binding sites for Ets (PEA-3), zeste, and PuF transcription factors are located within the 300 bp which are located upstream of the major transcription start site in both species. These sequences can mediate promoter activity when placed upstream of a promotorless chloramphenicol acetyl transferase reporter gene in an orientation-dependent manner. The present analysis will significantly facilitate the mutational analyses of patients with XLA and the further characterization of the function and regulation of the Btk molecule.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1993

Effects of certain inflammatory mediators on bovine neutrophil migration in vivo and in vitro.

Migration of bovine neutrophils towards endotoxin, recombinant bovine interleukin-1 beta (rBoIL-1 beta), recombinant human tumor necrosis factor-alpha (rhTNF-alpha), platelet-activating factor (PAF), complement factor C5a, leukotriene B4 (LTB4), and recombinant human interleukin-8 (rhIL-8) was studied in vivo, using the teat cistern model, and in vitro using the modified Boyden chamber method. Infusion of endotoxin, rBoIL-1 beta, rhTNF-alpha, PAF, or C5a into the teat cistern induced significant accumulation of leukocytes, mainly neutrophils, during the sampling period. Endotoxin was, on a molar basis, the most potent inducer of cell accumulation in vivo, followed by rBoIL-1 beta, while C5a, PAF and rhTNF-alpha were less potent. No significant cell accumulation was observed after infusion of LTB4 or rhIL-8. A significant migration of cells into the teat cistern was first observed 2 h after the infusion of endotoxin or rBoIL-1 beta, the rBoIL-1 beta-induced response started somewhat earlier. The first significant cell accumulation after infusion of PAF or C5a was observed already 1.5 h post infusion. The largest numbers of cells were reached 2.5-4.5 h after the infusion of endotoxin, rBoIL-1 beta, rhTNF-alpha, PAF or C5a. In vitro, significant migration of bovine blood neutrophils was observed towards C5a or rhIL-8, and to a lower extent towards LTB4, while no chemotactic response to endotoxin, rBoIL-1 beta, rhTNF-alpha, and PAF was observed. Possible roles of the different substances as inducers of neutrophil migration into the bovine teat are discussed.

Animals↗
PubMed1992

Kinetic characterization of the substrate reaction between a complex of antithrombin with a synthetic reactive-bond loop tetradecapeptide and four target proteinases of the inhibitor.

A tetradecapeptide corresponding to the P1 to P14 region of the reactive-bond loop of antithrombin (AT) binds to the inhibitor, presumably as a middle strand of the A beta-sheet, thereby converting AT from an inhibitor to a substrate of thrombin (Björk, I., Ylinenjärvi, K., Olson, S.T., and Bock, P. E. (1992) J. Biol. Chem. 267, 1976-1982). The kinetics of cleavage of the AT reactive bond in the AT-peptide complex by four target proteinases were quantified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and densitometry. The kcat/Km values for thrombin and factor IXa were indistinguishable from the second-order rate constants for AT inhibition of these enzymes, whereas the values for factor Xa and plasmin were 10-17-fold higher than the inhibition rate constants. Heparin with high affinity for AT accelerated the substrate reaction with thrombin to an extent consistent with the reduced heparin affinity of the AT-peptide complex. These data show that blocking by the peptide of the putative intramolecular association of the P1 to P14 region of the AT reactive-bond loop with the A beta-sheet leads to AT functioning as a substrate of its target enzymes with an efficiency that equals or exceeds the action of uncomplexed AT as an inhibitor and with the expected heparin activation. The results thus suggest that a substrate-like attack of the proteinase on the inhibitor reactive bond in an exposed loop initiates the inhibition reaction. This attack presumably induces the subsequent trapping of the enzyme by the insertion of the reactive-bond loop into the A beta-sheet.

Amino Acid Sequence↗
PubMed1992

Bovine neutrophils recruited by endotoxin to a teat cistern continuously produce oxygen radicals and show increased phagocytosis and extracellular chemiluminescence.

Bovine neutrophils were harvested from a teat cistern following endotoxin infusion and were compared with blood neutrophils by measurements of chemiluminescent and phagocytic activity towards C3- and IgG-opsonized and unopsonized yeast particles. Both phagocytosis and luminol-dependent chemiluminescence elicited by all three particles were enhanced in the teat cells. The increase in the luminol-dependent chemiluminescence towards C3- and IgG-opsonized particles was due to an enhanced extracellular release of myeloperoxidase. The observed increase in phagocytosis of unopsonized yeast was shown to reflect the interaction between up-regulated CR3 receptors on the surface of the teat neutrophils and the yeast particles. A high chemiluminescent activity of the teat neutrophils in both the luminol- and lucigenin-dependent systems in the absence of a phagocytic prey indicated that the NADPH oxidase was permanently active and that myeloperoxidase was continuously released by the cells. Treatment of neutrophils with cytochalasin B showed that the chemiluminescence and phagocytosis of teat neutrophils were less sensitive to this drug than that of blood neutrophils. These results indicate that the teat neutrophils have up-regulated their receptors for IgG- and C3-opsonized and unopsonized yeast on the cell surface by the action of actin. The cells also have a permanently active NADPH oxidase dependent on the association with actin and show a higher tendency than blood neutrophils to secrete the content of their primary granules during phagocytosis.

Actins↗
PubMed1992

Ventilation of the paranasal sinuses studied with dynamic emission computer tomography.

This investigation's aim was to study a noninvasive method for determining the ventilation of the nasal sinuses. For this purpose, different insufflation techniques using xenon 133 were tried, along with different scintillation camera techniques. Xenon 133 gas was used for insufflation in the nose and sinuses, and the half-time of the washout curves was determined with the aid of digital scintillation cameras, one of which was capable of dynamic tomography. The tomographic procedure was superior because it made it possible to study the washout from the ethmoidal/sphenoidal sinuses as well. The washout was followed for up to 150 minutes. Great variations in washout were found between different sinuses and also in the same sinus over time. The single photon emission computed tomography (SPECT) technique, which is easy to perform and gives a limited absorbed dose to the patient, seems promising for the future evaluation of sinus ventilation and ostial function.

Absorption↗
PubMed1991

A new method for quantification of image distortion due to pile-up in scintillation cameras.

Characterization of the count-rate performance of scintillation cameras should include not only the specification of count losses. At high count rates, there is also an image distortion due to the mispositioning of pile-up events. In this paper a simple and clinically relevant procedure to quantify this distortion is presented. The images of a square uniform technetium-99m phantom at high and low count rates are used. The fraction of the total counts being correctly positioned is determined as the peripheral count density divided by the total average count density. This ratio, corrected for the camera non-uniformity at low count rates, is called the 'positioning ability'. According to the National Electrical Manufacturers' Association (NEMA), the 'system count rate performance with scatter' should be reported as the measured count rate giving 20% count losses. In this paper it is suggested that this measure be complemented by a measure of the fraction correct positioned events at this count rate. This fraction, the 'high count rate positioning ability', can be easily and accurately measured using our method. The method has been tested on two different scintillation cameras. For one of them the high count rate positioning ability was determined as 91% at a measured count rate of 30,000 s-1 with 20% count losses. For the other camera, the corresponding figures were 88% at 59,000 s-1 and close to 100% at 38,000 s-1, before and after the installation of a new pile-up rejection circuit, respectively.

Gamma Cameras↗
PubMed1991

A periodate-sensitive anti-phagocytic surface structure, induced by growth in milk whey, on Staphylococcus aureus isolated from bovine mastitis.

The phagocytic and chemiluminescent activity of purified bovine neutrophils in response to two Staphylococcus aureus strains isolated from mastitic bovine milk and grown in milk whey was studied. The activity was significantly reduced compared with the response elicited by the same strains grown in tryptic soy broth (TSB). A mild periodate treatment of the milk whey-grown strains resulted in a significant increase of both chemiluminescence and phagocytosis, whereas trypsin, subtilisin or papain treatment had no effect. The decreased binding of complement factor C3 to milk-whey-grown bacteria was restored to the level of TSB-grown homologous organisms by periodate treatment. Moreover, this treatment, but not treatment with trypsin, increased the surface hydrophobicity of milk-whey-grown bacteria. The chemiluminescent activity was as high towards heat-killed as towards live bacteria. Also, incubation of heat-killed TSB-grown bacteria in milk whey did not alter the chemiluminescent response, indicating that the reduced neutrophil activity towards milk-whey-grown bacteria was not due to binding of milk components to the microorganisms. These results strongly suggest that bovine mastitis S. aureus strains grown in milk whey produce an anti-phagocytic surface structure. This structure is heat- and protease-resistant and renders the bacterial surface hydrophilic. The anti-phagocytic material is altered or, more likely, released from the bacterial surface on periodate treatment and is probably of carbohydrate nature.

Animals↗
PubMed1990

Transport of serotonin from the rat jejunal lumen into mesenteric veins in vivo.

The transport of labelled (hot) and non-labelled (cold) serotonin (5-HT) into the mesenteric venous circulation was studied after instillation of test solutions into an isolated jejunal loop of anaesthetized rats. After instillation of [3H]H2O and [14C]5-HT there was an almost parallel appearance of the isotopes in mesenteric venous blood. After instillation of 5-HT a marked early increase of the total amounts of cold 5-HT was observed in mesenteric veins compared with animals instilled with saline only. In a third type of experiment the label was detected in mesenteric venous whole blood after instillation of [3H]5-HT into the gut lumen. After hydrolysis of blood cells and protein precipitation the samples were fractionated and determined for 5-HT and metabolites. Only 5-HT was detected in these fractions. The label was present within 5-HT peaks in three out of eight animals. The experiments indicate rapid transport of 5-HT (or metabolites) across the rat jejunal mucosa. These substances may be bound to a binding protein in platelets since the isotope was detected in whole blood but more seldom in supernatants after hydrolysis and precipitation.

Animals↗
PubMed1985

Radioimmunoassay of human sex hormone binding globulin: improved radioiodination procedure.

Sex hormone binding globulin (SHBG), purified by affinity chromatography from retroplacental blood plasma, was reacted with 3-(p-hydroxyphenyl) propionic acid N-hydroxysuccinimidyl ester (PHPPS, Bolton-Hunter reagent). The derivative of SHBG obtained (parahydroxyphenylpropionyl-SHBG; PHPP-SHBG) was stable and could, in contrast to underived SHBG, be efficiently 125I-iodinated with a lactoperoxidase technique. The PHPP-SHBG labelled with 125I had good antiserum binding and stability properties and was used for radioimmunoassay (RIA) of SHBG in serum. The RIA requires a total incubation time of 3 h. It has been standardized with purified SHBG and has a sensitivity of 5 micrograms/l, giving a lowest detectable concentration in the routine procedure (samples diluted 1:40) of about 0.2 mg/l. Variation within and between assay was 4.1% and 7.2%, respectively, for samples with values within the normal range. Values obtained by this RIA procedure correlate well with those obtained by a dihydrotestosterone binding method and by an electroimmunoassay technique. The mean serum concentration of SHBG in healthy, regularly menstruating women (n = 42) was 3.7 +/- 1.0 (SD, standard deviation) mg/l and in healthy men (n = 100) 2.0 +/- 0.9 mg/l.

Dihydrotestosterone↗
PubMed1985

Resectional operations and long-term results in carcinoma of the esophagus.

The 5 year survival rate after resectional operations for carcinoma of the esophagus is still very low. Many factors have been identified as contributing to these poor long-term results. The main factor found in this study, comprising 102 patients undergoing resection out of 125 patients operated upon during a 10 year period, was nonradical resection. The main cause of nonradical resection was invasion of the tumor into the mediastinum, which was observed in 80% of the patients. In 43 of the 102 patients undergoing resection, the penetration of the carcinoma into the tissue surrounding the esophagus was observed only histologically. Thirty-three of the 38 hospital survivors in this group died within 2 years of the operation of recurrence of carcinoma. Fourteen of 17 survivors after resectional operations in whom the tumor growth was still limited to the esophagus were alive from 2 to 9 years (mean 6 years) after the operation, without evidence of recurrence.

Adult↗
PubMed1984

Quantitative assessment of individual renal function. A comparison between creatinine excretion and a radionuclide method.

Individual renal function was evaluated in 21 patients. Two methods were used in each case, namely gamma camera renography and measurement of creatinine excretion in urine collected via a nephrostomy. The scintigraphic technique utilized measurement of renal parenchymal radionuclide uptake in an early phase. Good agreement was found between the results from both methods in most patients. Gamma camera renography was found to be clinically useful for assessing the function of individual kidneys.

Adult↗
PubMed1984

Lung expansion in premature newborn rabbits treated with emulsified synthetic surfactant; principles for experimental evaluation of synthetic substitutes for pulmonary surfactant.

This paper presents a sequence of tests for experimental evaluation of potential substitutes for pulmonary surfactant. Differential thermal analysis and the pulsating bubble technique were applied to identify an emulsified mixture of synthetic lipids with properties similar to those of natural surfactant. Instilled into the airways of premature newborn rabbits, this emulsion improved pulmonary pressure-volume characteristics and enhanced lung-thorax compliance during artificial ventilation. However, the in vivo effect was inferior to that of natural surfactant, especially as the emulsion failed to prevent the development of bronchiolar epithelial lesions.

Animals↗
PubMed1984

Purification and storage of thyroglobulin. Two important factors influencing the radioimmunoassay for thyroglobulin.

The effect upon the assay of the quality of the thyroglobulin (Tg) used as standard and tracer was evaluated by comparison of two preparations, one purified with protease inhibitors added (Tg-PI) and the other without (Tg-O). Tg-PI proved more stable than Tg-O. After freezing in phosphate-buffered saline almost all 125I-Tg-O was found to have dissociated into 12 S Tg, while only about half the 125I-Tg-PI had done so. Storage in glycerol, 500 g/l, at -20 degrees C or freezing in goat serum improved the quality of the 125I-Tg markedly, but Tg-PI still remained more stable than Tg-O. In addition, the two antisera tested gave different results in the radioimmunoassay with Tg-PI and Tg-O. With one antiserum a gradual loss of Tg immunoreactivity occurred parallel to the dissociation of Tg, while no such effect was noted with the other antiserum. This difference is believed to depend on varying proportions of conformational antibodies in the antisera, the binding sites for the conformational antibodies being distorted by the dissociation of the Tg molecule, while the binding sites for the sequential antibodies remain intact.

Chromatography, Gel↗
PubMed1984

A new sensitive immunosorbent radioassay for the detection of circulating antibodies to polypeptide hormones and proteins.

A solid-phase immunosorbent radioassay for the detection of circulating antibodies to protein hormones is described. The assay is based on the binding of the homologous 125I-labelled antigen to the antibodies which are then bound to anti-IgG antibodies covalently coupled to Sepharose. It can easily be applied as a complement to any radioimmunoassay for the detection of circulating antibodies to the ligand measured. The assay system avoids falsely elevated values due to interference of high serum concentrations of the antigen. The assay was applied to measure antibodies to FSH, LH, TSH, GH, prolactin, insulin and thyroglobulin (Tg). Among patients with chronic thyroiditis Tg antibodies were found in 100% of the sera. In diffuse toxic goitre 73% of the patients had detectable Tg antibodies. Insulin antibodies were present in 82% of the sera from patients with insulin treated diabetes. No antibodies were found against the other protein hormones tested.

Adolescent↗
PubMed1984

Renal function after urinary diversion. A study of continent caecal reservoir, ileal conduit and colonic conduit.

Total and separate renal function, renal parenchymal thickness and dilatation of the upper urinary tract were studied in 40 patients preoperatively and 24 to 67 months after urinary diversion, using 51Cr-EDTA clearance test, scintillation camera renography and urography. In ten patients a continent caecal reservoir was used for diversion. In the other patients, an ileal or a colonic conduit (15 patients with each method) was used, one ureter being implanted with an anti-reflux method and the other with direct technique. Renal function following urinary diversion showed little or no deterioration in most patients. The functional outcome was not related to the method of diversion or, in the conduit groups, to the mode of ureteral implantation. Serum creatinine tests and urography were not adequate for determining loss of renal function. Radionuclide studies proved to be valuable for assessing renal function after urinary diversion.

Adult↗