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Biomedical subjects

O Nilsson

Publications and source records attributed to O Nilsson.

At least 145 records · Page 8Linked to original sources
PubMed1995

Anoplocephala perfoliata in horses in Sweden: prevalence, infection levels and intestinal lesions.

Distal ileum, caecum and proximal colon of 470 horses were examined for helminths during 1 year at an abattoir in central Sweden. The infection levels of the horse tapeworm Anoplocephala perfoliata, their stage of development, site of attachment and gross pathological lesions caused by the worm were recorded. Faecal samples from 395 of the horses were examined specifically for tapeworm segments and eggs in order to correlate these findings with the numbers in the alimentary canal. In total 65% of the horses were infected with A. perfoliata and the mean intensity of infection was 79 worms per infected horse with a maximum of 912. The level of infection was significantly higher in (1) 3rd and 4th than in 1st and 2nd quarter of the year; (2) older horses than in yearlings; (3) females than in males and geldings; (4) thoroughbred and cold-blooded horses than in Swedish standard breeds and ponies. The level of infection was unaffected by the usage of anthelminthics against nematodes. Of the horses examined 51% had 1-100 worms whereas 14% were infected with more than 100 worms. Of the tapeworm positive horses 72% had mixed infections with both adult and juvenile worms, 20% solely juveniles, and 8% solely adults. The severity of intestinal lesions exacerbated by increasing numbers of A. perfoliata. About 11% of the intestines examined had severe lesions, but there was no history of acute abdominal distress in any of the horses included in this study. Although the number of detectable eggs was significantly higher for horses heavily infected with A. perfoliata, the egg recovery among infected horses was only 35%. An additional field survey comprising 218 horses on 88 premises in central and southern parts of Sweden showed that the prevalence of A. perfoliata egg positive horses was the same as found on faecal examination during the abattoir survey.

Animals↗
PubMed1995

Indium-111 activity concentration in tissue samples after intravenous injection of indium-111-DTPA-D-Phe-1-octreotide.

METHODS: Indium-111 activity concentrations in human tumor and normal tissue samples were determined at 24, 48 and 120 hr after i.v. injection of 111In-DTPA-D-Phe-1-octreotide. Fourteen patients were included in the study. Seven patients had medullary thyroid carcinoma, four had midgut carcinoid tumors, two had endocrine pancreatic tumors and one had chronic pancreatitis. RESULTS: For midgut carcinoids, the tumor-to-blood ratio was 51:220, for medullary thyroid carcinoma 4:39, and for two endocrine pancreatic tumors 6 and 1500. Tumor-to-muscle ratios varied between 1 and 1200 and tumor-to-fat between 2 and 1500 depending on tumor type. CONCLUSION: The sometimes extremely high tumor-to-normal tissue ratios present the possibility for use of radiolabeled octreotide for radiation therapy of somatostatin receptor positive tumors.

Abdominal Neoplasms↗
PubMed1994

Clinical efficacy of octreotide scintigraphy in patients with midgut carcinoid tumours and evaluation of intraoperative scintillation detection.

111In-diethylenetriamine penta-acetate-D-Phe1-octreotide scintigraphy was evaluated in a group of 27 patients with disseminated midgut carcinoid tumour. Additional information gained by the intraoperative use of a scintillation detector was studied in five patients with midgut carcinoid tumours and in two with endocrine pancreatic tumours. In 19 patients tumours not recognized by non-invasive radiological methods were visualized in 27 locations, most commonly in liver and para-aortic lymph nodes. Three false-negative tumour locations were noted (ovarian and peritoneal). With guidance from scintigraphic findings, nine patients underwent surgical tumour reduction, leading to complete remission in three. Clinically suspect tumour lesions were measured by the detector in situ, and ex vivo after excision. After excision the tissue:blood activity concentration ratios were calculated. In situ measurements were helpful in the localization of tumours and in the control of adequate clearance of tumour tissue. High tissue:blood activity concentration ratios at 1, 2 and 5 days in the five patients with midgut carcinoid tumour indicate a potential role for radiation therapy with radiolabelled octreotide in patients with somatostatin receptor-positive tumours.

Carcinoid Tumor↗
PubMed1994

Histamine as an intermediate growth factor in genesis of gastric ECLomas associated with hypergastrinemia in mastomys.

Profound and sustained inhibition of gastric acid secretion has been associated with development of carcinoid tumors of the fundic enterochromaffin-like (ECL) cells in rodents. While ECL cell hyperplasia has been recognized in humans, the development of carcinoid tumors is rare and often confined to patients under treatment for gastrinoma related to the multiple endocrine neoplasia type I (MEN1) syndrome. The Mastomys was utilized as a model for the rapid induction of ECLomas by insurmountable acid secretory blockade induced by the pharmacologically irreversible H2-receptor antagonist, loxtidine. Loxtidine-induced ECL cell hyperplasia and neoplasia were compared in the absence of presence of cyproheptadine (0.5 mg/kg), an H1-receptor antagonist. Loxtidine administration resulted in a significant increase in ECL cell hyperplasia and neoplasia as well as an increase in ECL cell number, mucosal thickness, plasma gastrin levels, and stomach weight. Cyproheptadine ameliorated loxtidine-induced ECL cell hyperplasia and neoplasia and significantly decreased loxtidine-stimulated increases in ECL cell number. Nevertheless, cyproheptadine failed to alter the loxtidine-induced increase in plasma gastrin, stomach weight or mucosal height. The results indicate that cyproheptadine, an H1-receptor antagonist, inhibits loxtidine-induced ECL cell hyperplasia independent of any effects on serum gastrin.

Animals↗
PubMed1994

On the stability and plastic properties of the interior L3 loop in R. capsulatus porin. A molecular dynamics study.

Structural properties of Rhodobacter capsulatus porin are studied by molecular dynamics simulation using the GROMOS force field. Unconstrained simulations of the trimer and monomer show the trimer to be more stable than the isolated monomer. Simulations of the L3 loop inside the pore are used to assess its stability and plastic properties. Simulated annealing shows that the conformational space available to the L3 loop inside the pore is very large. Simulations at different temperatures show that the energy hypersurface around the open state is complex and flat. These studies also indicate four zones that are more flexible than the rest of the loop. Two of these are stabilized by the addition of the detergent molecule present in the X-ray structure. It is possible that the two remaining flexible zones, situated in the half of the loop facing the extracellular end of the porin molecule, residues Asp93-Gly98 and Arg110-Leu111, are involved in a mechanism for opening and closing of the pore.

Amino Acid Sequence↗
PubMed1994

Clinical management of gastric carcinoid tumors.

Four types of gastric carcinoids have been identified: (1) multiple small body-fundus carcinoids associated with chronic atrophic gastritis type A (A-CAG); (2) sporadic solitary lesions without specific pathogenetic background (non-A-CAG); (3) carcinoidosis associated with Zollinger-Ellison/MEN 1 syndrome, and (4) rare tumors, e.g. gastrin cell tumors, neuroendocrine carcinomas and mixed endocrine-exocrine tumors. In a retrospective study of 15 patients with gastric carcinoids (11 A-CAG, 3 non-A-CAG and 1 gastrin cell tumor) over a 10-year period, the histopathological and clinical features were assessed. The A-CAG-type carcinoids were clinically silent with lymph node metastases in 2/11 cases but no hepatic metastases. The non-A-CAG-type carcinoids were malignant with disseminated disease, hormonal symptoms and increased urinary excretion of the main histamine metabolite, MeImAA. Five patients with A-CAG tumors were subjected to antrectomy to remove hypergastrinemia, which is thought to be of pathogenetic importance for these tumors. During the observation period (1.5-8 years) 1 patient developed recurrent tumors, while the other 4 showed persistent argyrophil cell hyperplasia. A prospective treatment protocol of these tumors is suggested with endoscopic removal of less numerous, small lesions as first-step therapy, followed by antrectomy at recurrence. Larger lesions should be excised in combination with antrectomy. Gastrectomy is reserved for the rare cases of invasive tumors with lymph node metastases. As evident from the outcome of patients with non-A-CAG tumors radical surgery should be performed whenever practicable.

Carcinoid Tumor↗
PubMed1993

Discrimination of MUC1 mucins from other sialyl-Le(a)-carrying glycoproteins produced by colon carcinoma cells using a novel monoclonal antibody.

Earlier studies (Baeckström et al., J. Biol. Chem., 266: 21537-21547, 1991) have revealed that the colon carcinoma cell line COLO 205 produces two different proteins carrying the carcinoma-associated sialyl-Le(a) carbohydrate epitope. One is the MUC1 mucin apoprotein, and the other protein is smaller and has not been characterized in detail. This paper describes a comparison of COLO 205 with three other colon carcinoma cell lines, aided by the use of a novel MUC1-reactive monoclonal antibody, Ma552. Ma552 reacted with H-CanAg, the MUC1 mucin purified from COLO 205, the binding increasing greatly upon partial deglycosylation of H-CanAg with trifluoromethanesulfonic acid. This pattern of reactivity was in contrast with that of the MUC1-reactive monoclonal antibody HMFG-2, which did not recognize H-CanAg without prior deglycosylation. The nature of the epitope of Ma552 was further investigated using a synthetic peptide corresponding to the tandem-repeat sequence of the MUC1 protein. When the peptide was used as an inhibitor of antibody binding to immobilized, partially deglycosylated H-CanAg mucin, Ma552 was inhibited, as was HMFG-2. Using short, immobilized synthetic peptides identical to parts of the MUC1 tandem repeat, the reactivity of Ma552 was mapped to the hexapeptide TRPAPG. Ma552 and C50, a monoclonal antibody reactive with sialyl-Le(a), were used in immunofluorometric assays to analyze gel filtration fractions of extracts and spent media from the colorectal carcinoma cell lines COLO 205, SW1116, LoVo, and LS 174T. Using C50 in a homologous assay, all sialyl-Le(a)-carrying glycoproteins were detected. Among these, mucins based on the MUC1 apoprotein were identified using Ma552 and C50 in a combination assay. The results showed that sialyl-Le(a) was present on more than one glycoprotein not only in COLO 205 but also in SW1116 and LoVo. The Ma552/Eu-C50 assay revealed the presence of sialyl-Le(a)-carrying MUC1 in COLO 205 as expected, as well as in SW1116. The presence of MUC1 in Ma552-reactive fractions was confirmed by deglycosylation followed by assaying with the monoclonal antibody HMFG-2. Furthermore, Northern blots revealed the presence of MUC1 mRNA only in the two Ma552-positive cell lines.

Amino Acid Sequence↗
PubMed1993

Comparison of demineralized allogeneic bone matrix grafting (the Urist procedure) and the Ilizarov procedure in large diaphyseal defects in sheep.

The bone inductive capability of the Urist and Ilizarov procedures was compared in the repair of large diaphyseal defects in sheep. In 30 animals, a 4 cm segmental defect was created in the middle portion of the right femur and was stabilized with an external fixator. The sheep were divided into four groups according to the type of reconstruction of the defect. In group 1, a demineralized allogeneic bone matrix (DABM) cylinder was used; in group 2, DABM chips; and in group 3, gradual transport of a piece of bone detached from the proximal femoral fragment was used to fill the defect. Group 4 served as a control (the defect was left empty). New bone formation was assessed by serial radiographs until the time of death at 2 or 4 months. Postmortem specimens were analyzed with respect to bone mineral content, uptake of isotopes (45Ca and 3H-proline), and histology. The first signs of new bone formation were radiographically evident at 4 weeks. In the two groups in which reconstruction involved DABM (Urist procedures), new bone failed to form in eight of the 13 animals. Full bridging of the defect was observed at 8 weeks in one animal with a DABM cylinder and two with DABM chips. No decisive difference in bone yield could be demonstrated between the two Urist procedures. In the group treated with the Ilizarov procedure, new bone formation consistently occurred at a high rate; full bridging of the defect was observed in seven of the eight animals. Bone mineral scanning and histologic analysis essentially confirmed the radiographic results. Uptake of isotopes was selectively analyzed in two sheep from each experimental group in which new bone formation was exhibited in the defect; new bone formation was increased compared with that in the contralateral femur but was equal among the three experimental groups. Our study shows that gradual transport of a detached piece of autogeneic bone (Ilizarov procedure) is more effective than implantation of DABM (Urist procedure) in eliciting new bone formation in large diaphyseal defects in sheep. The variable bone induction by DABM may be explained by differences in host immune responses to the implants.

Animals↗
PubMed1993

Response to repeated inoculations with Ascaris suum eggs in pigs during the fattening period. II. Specific IgA, IgG, and IgM antibodies determined by enzyme-linked immunosorbent assay.

Experimental trickle inoculations of pigs with low doses (2 x 25 eggs/week) and high doses (2 x 500 eggs/week) of Ascaris suum were followed by enzyme-linked immunosorbent assay (ELISA) during a 14-week period. Three antigens were employed for coating: hatching fluid of embryonated eggs, excretory/secretory antigens from in vitro-cultivated infective larvae (L2/L3-ES), and adult body fluid. Seroconversion times (week 2 for the high-dose group and week 4 for the low-dose group) were essentially identical for the three antigens. The assay employing L2/L3-ES, however, produced significantly higher readings. Specific serum antibody in the IgA and IgG classes showed very similar time courses in both groups. A weak and transient, specific IgM response was recorded in the high-dose group. Mean ELISA responses to L2/L3-ES did not differ significantly between the groups at the termination of the experiment. Specific antibody correlated weakly with the number of liver milk spots recorded at slaughter.

Animals↗
PubMed1993

Global characterization of protein secondary structures. Analysis of computer-modeled protein unfolding.

Analyses of structural and molecular shape changes undergone by a protein during an unfolding process are presented. The procedure, based on a spherical shape map method, provides a topological description of a three-dimensional macromolecular structure. Local properties of the backbone are used to derive a global characterization of its fold. A spherical shape map of backbone crossings is associated with a given macromolecular conformation. The map is built by classifying each point on the sphere according to the crossing pattern obtained when the backbone is observed along a direction defined by the center of the sphere and the chosen point. The surface of the sphere can be divided in equivalence classes. All the points within a given class correspond to directions from which the backbone has the same overcrossing pattern. Automatic computation and display of these equivalence classes is discussed, as is the implementation of the technique on a computer graphics workstation. The graphical manipulation simplifies the analysis of these maps when following a change in the conformation of the backbone. The procedure is illustrated with the results of a molecular dynamics computer simulation of the unfolding of the bacteriophage T4 glutaredoxin protein (in the form of its polyglycine model). The method gives a novel description of the differential structural stability for the characteristic secondary structural elements (alpha-helices and beta-sheets) present in the protein. Recognition of the persistence of structural elements over the simulation time is performed in an unbiased manner.

Algorithms↗
PubMed1993

Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer.

Prostate specific antigen (PSA) in serum has recently been shown to occur in complex with alpha 1-antichymotrypsin and as an approximately 30 kDa. noncomplexed molecular form. We characterized PSA by 3 different assays in samples from 144 patients with benign prostatic hyperplasia (BPH) and 121 with carcinoma of the prostate. One of these noncompetitive assays measured total PSA by detecting PSA complexed to serine proteinase inhibitors and the noncomplexed molecular form, a second measured only PSA in complex with alpha 1-antichymotrypsin, whereas a third detected the noncomplexed form. PSA in complex with alpha 1-antichymotrypsin was the predominant form in all patient sera. Noncomplexed PSA constituted a minor fraction that was significantly smaller in patients with untreated prostate cancer than in those with BPH (p < 0.0001). The proportion of noncomplexed PSA does not correlate to the serum concentration of PSA or that of alpha 1-antichymotrypsin. In men with a serum PSA concentration of less than 10 micrograms./l. the combination of assays measuring total PSA immunoreactivity, the noncomplexed molecular form and PSA in complex with alpha 1-antichymotrypsin may facilitate discrimination between prostate cancer and BPH.

Biomarkers, Tumor↗
PubMed1993

Practical aspects of 3,4-diaminopyridine treatment of the Lambert-Eaton myasthenic syndrome.

3,4-Diaminopyridine (3,4-DAP) given alone or combined with pyridostigmine is the recommended basic therapy in the Lambert-Eaton myasthenic syndrome (LEMS). We present and exemplify our routine test protocol for monitoring drug introduction and treatment regimen of cholinergic drugs in LEMS. The individual drug responses vary and no recommended standard doses exist. Routine electrophysiological repetitive nerve stimulation studies recording amplitude of initial compound muscle action potential (CMAP) in thenar muscles correlate excellently with clinical myasthenic muscle power tests in clinically affected muscle groups. Therefore repetitive clinical muscle power tests, that often are complicated by painful myalgia and activation potentiation, can be replaced by recordings of CMAP in the introduction and clinical follow up of cholinergic drug treatment in LEMS. Also, adverse effects and other treatment problems from the experience of continuous treatment of 19 LEMS patients with 3,4-DAP for up to 10 years are presented.

4-Aminopyridine↗
PubMed1993

Growth factors and carcinoid tumours.

The presence of growth factors and their receptors in human midgut carcinoids and in gastric carcinoids of Mastomys have been investigated. Human midgut carcinoid tumours produce IGF-I as demonstrated by immunocytochemistry and radioimmunoassay. IGF-I receptors were detectable in half of the tumours and stimulation of cultured tumour cells with IGF-I enhanced DNA synthesis. IGF-I may therefore act as an autocrine stimulator of carcinoid tumour growth. Expression of TGF-alpha and EGF-receptors could also be demonstrated in midgut carcinoids by immunocytochemistry and Northern analysis, suggesting that TGF-alpha participates in the autocrine modulation of carcinoid growth. Co-culture of human midgut carcinoid tumours and rat fetal cholinergic neurons demonstrated secretion of a potent neuronotrophic factor by cultured tumour cells. IGF-I and TGF-alpha may account for these neuronotrophic effects, but carcinoid tumours may also secrete an as yet unidentified growth factor. Gastric (ECL cell) carcinoids developed rapidly in Mastomys during hypergastrinemia due to histamine2-receptor blockade, suggesting that gastrin is an essential growth factor for these carcinoids.

Animals↗
PubMed1993

Embolisation therapy in the midgut carcinoid syndrome: just tumour ischaemia?

Forty-eight patients with midgut carcinoid tumours and disseminated disease were treated at our unit 1986-1991. All patients underwent primary surgery with optimal tumour reduction. Twenty-seven patients with bilobar liver metastases had subsequent embolizations of the hepatic arteries to further reduce the functional tumour mass and were thereafter treated with a low dose of octreotide. The response to this treatment was evaluated by CT at 3 months postembolization. The patients could then be divided into 13 responders (no visible hepatic tumours or more than 50% reduction, group I) and 14 non-responders (less than 50 reduction or progression, group II). When these patients were studied biochemically and in terms of prognosis, the reduction of 5-HIAA levels postembolization was much more pronounced in group I (80 +/- 3%) then in group II (28 +/- 12%). The biochemical and radiological responses were long-lasting in group I, none of the patients needed further ischaemic treatment. Of specific interest were 3 patients with bilobar disease, who after selective unilobar embolisation normalised their 5-HIAA levels and had bilateral tumour regression. These findings indicate involvement of systemic effects in addition to tumour ischaemia alone. The initial biochemical response with marked decrease of 5-HIAA levels in combination with tumour regression may thus serve as an indicator of good prognosis.

Adult↗