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Biomedical subjects

O Nilsson

Publications and source records attributed to O Nilsson.

At least 19 recordsLinked to original sources
PubMed1992

Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth?

The presence of IGF-I and IGF-I receptors in human midgut carcinoid tumours has been investigated. Using immunocytochemistry, IGF-I-positive tumour cells were demonstrated in 11/11 tumour cases studied. Labelling of consecutive sections with antibodies against IGF-I and proliferating cell nuclear antigen (PCNA)/cyclin demonstrated a co-distribution of the 2 antigens in carcinoid tumours. Extracts of tumour tissues were subjected to radioimmunoassay and shown to contain significant amounts of IGF-I. Reverse-phase HPLC of tumour extracts demonstrated a major IGF-I-immunoreactive component eluting in the position of rhIGF-I, but also 2 other more hydrophobic forms. Conditioned serum-free media from primary cultures of carcinoid tumors contained detectable amounts of IGF-I, indicating a spontaneous release of IGF-I from tumour cells into the culture medium. Levels of IGF-I in media were reduced (19%) after incubation of cultures with a somatostatin analogue for 4 days. IGF-I receptors were observed on tumour cells in 4/10 tumours by immunocytochemistry. Tumour cells with immunoreactive IGF-I receptors could be stimulated to enhanced growth, measured as an increase in DNA contents, by exogenous administration of IGF-I every 3-4 days for 2 weeks. The results show that cultured human midgut carcinoid tumours secrete IGF-I and that some of the tumours also have IGF-I receptors. We therefore suggest that IGF-I may act as an autocrine or paracrine regulator of carcinoid tumour-cell growth.

Adult↗
PubMed1992

Response to repeated inoculations with Ascaris suum eggs in pigs during the fattening period. I. Studies on worm population kinetics.

This experimental study on pigs was designed to simulate natural, long-term exposure to Ascaris suum under modern management conditions. Parasite kinetics were followed in pigs receiving A. suum eggs as repeated trickle inoculations at two dose levels beginning at a body weight of 25 kg until their slaughter at 90 kg (baconers). In pigs inoculated twice weekly with 500 eggs, there was an initial marked rise in the numbers of hepatic milk spots, but as early as around week 6 after the start of inoculations and until week 16, at which time the last pigs were slaughtered, the numbers of spots diminished drastically. In pigs receiving only 25 eggs twice weekly, low and moderately fluctuating numbers of spots were seen throughout the experiment. Larvae recoverable from the livers and lungs were observed mainly during the beginning of the experiment. Before patency, immature intestinal worms were found in moderate numbers that showed a rough positive correlation with the dose levels, but at the time at which adult worms started to appear, immature parasites could practically no longer be found. In all, only 10 of 40 pigs harbored adults, and 4 of these 10 pigs harbored 80% of the total worm population. The results show that acquired dose-dependent host responses to A. suum play an important role in regulating the worm population along the migratory route of the parasite and that the final burden of worms in the small intestine is dose-dependent and highly variable.

Animals↗
PubMed1992

Sensitivity and specificity of CA242 in gastro-intestinal cancer. A comparison with CEA, CA50 and CA 19-9.

A serological assay for the quantitative determination of the novel tumour-associated epitope CA242 was developed and used for determination of sensitivity and specificity of CA242 in gastrointestinal cancer. The CA242 assay showed a better tumour specificity than CA50 (and CA 19-9). This was most noticeable in benign hepatobiliary disease. The sensitivity at 90% specificity cut-off level was approximately three times higher for CA242 compared to CA50 in colo-rectal cancer Dukes A, B and C, while in pancreatic cancer the sensitivity of CA242 and CA50 was similar. CA242 was expressed independently of CEA, and the combination of CEA and CA242 gave in colo-rectal cancer considerably higher sensitivity than the use of only one of the markers. This was most pronounced in Dukes A and Dukes B patients. CA242 is a novel tumour marker of potential clinical use, particularly in colo-rectal cancer.

Animals↗
PubMed1992

Long-term prognosis of ischemic stroke in young adults.

Prognostic information is provided for 74 young adults (age 16-40 yrs, mean age at stroke 29.5 yrs), who suffered from ischemic stroke and survived the first month after the stroke. The patients were followed for 13-26 yrs; in total for 1190 yrs after their stroke. At follow-up 12 of the patients were dead, mostly from severe underlying disease that was complicated by ischemic stroke. In 3 cases death was unrelated to cerebrovascular disease. Among the surviving 62 patients, 7 had experienced recurrent ischemic events (3 reinfarctions, 4 TIA:s). These 7 patients all had risk factors for cerebrovascular complications already at the time of their primary stroke. It is concluded that the long-term prognosis for ischemic stroke in the young adult is favourable. The recovery from neurological deficits is usually good (exceptions are occlusions within the internal carotid and middle cerebral arteries), the risk for recurrence is low (1.1-1.2% annually), and the social prognosis with respect to working capacity and family relation is fair.

Adolescent↗
PubMed1992

Aspects on diagnosis and treatment of the foregut carcinoid syndrome.

Eight patients with the foregut carcinoid syndrome (two gastric and six bronchial primary tumors) are reported. The patients presented with complex clinical symptoms including ectopic production of adrenocorticotrophic hormone and growth hormone-releasing factors. The most alarming symptoms were facial flush and edema, accompanied by severe bronchoconstriction, which easily was misinterpreted as asthmatic attacks. Conventional bronchodilatory drugs may be potentially dangerous in these patients, in whom combined blockade of histamine receptors and treatment with cortisone and octreotide are recommended. Owing to the patients' age and general condition individualized long-term therapy was instituted. Surgical therapy under optimal protection by drugs can be of substantial value also in patients with advanced disease. One patient with life-threatening hormonal symptoms underwent hyperthermic perfusion of the liver with cytotoxic drugs, resulting in good palliation.

Aged↗
PubMed1992

Carbohydrate antigens in human lung carcinomas.

Lung carcinomas represent a heterogeneous group of tumours with large variations in the biochemical, clinical, morphological and pathological manifestations. Despite the neuroendocrine features of small cell lung cancer (SCLC), it is today generally accepted that all types of lung cancer emanate from a common endodermally derived multipotent stem cell of the bronchial epithelium. NCAM (neutral cell adhesion molecule) has been shown to be a sensitive marker of SCLC. The presence of NCAM, with the alpha (2,8) polysialic acid units characteristic of embryonal NCAM, in SCLC and in a portion of NSCLC, seems to correlate with the malignant behaviour and prognosis of the tumours, suggesting that NCAM may have a functional role in the clinicopathological manifestations of lung cancer. Fuc-GM1 with 2-hydroxy fatty acids as a characteristic component of the ceramide has been found to be a unique ganglioside of SCLC, detected in the tissues as well as in serum from SCLC patients using specific monoclonal antibodies. Accumulation of sialylated and fucosylated polylactosamine type 2 carbohydrate glycolipid and glycoprotein antigens was found in serum and tissues of lung tumours in accordance with what is described in gastrointestinal carcinomas, and these antigens may be regarded as general carcinoma antigens irrespective of organ. Sialylated and fucosylated type 1 antigens, and gangliosides with NeuAc alpha (2,6)Gal linkage were also accumulated in lung cancer. The human immune system has been found to recognize lung cancer carbohydrate antigens, which might be human lung cancer autoantigens.

Antibodies, Neoplasm↗
PubMed1992

[Immunological contraception--future possibilities in family planning].

In principle, immunological contraception is primarily a question of producing antibodies to block or inactivate a vital functional process. The antibodies can be used to elicit the corresponding antigen which, more or less modified, may then be used as a vaccination immunogen. The antibodies may also serve as the starting point in the production of new (antiidiotypic) antibodies, which have a certain potential function as a vaccine, owing to their antigenic capacity to stimulate the formation of functionally active antibodies. In addition to their use in developing a method of contraceptive vaccination (active immunisation), functional antibodies can also be used in passive immunisation. Such treatment during early gestation would result in abortion, and might be an alternative means of terminating pregnancy. In such cases, the antibodies might be combined with a toxin, yielding an immunotoxin exerting highly specific effects on the conceptus.

Antibodies↗
PubMed1991

Purification and characterization of a membrane-bound and a secreted mucin-type glycoprotein carrying the carcinoma-associated sialyl-Lea epitope on distinct core proteins.

Two mucin-type glycoproteins detected by the monoclonal antibody C50, which reacts with the carcinoma-associated sialyl-Lewis a and sialyl-lactotetraose epitopes, were found in secreted and solubilized materials from the colon carcinoma cell line COLO 205. The larger glycoprotein (H-CanAg; heavy cancer antigen) was predominantly found in extracts of cells grown in vitro or as nude mice xenografts whereas the smaller species (L-CanAg; light cancer antigen) was the major component in spent culture medium and serum from grafted mice. Using detergent in the extraction buffer doubled the yield of H-CanAg, suggesting that this glycoprotein is membrane bound whereas the yield of L-CanAg was relatively unaffected. The two glycoproteins were purified from xenograft extracts and spent culture medium using perchloric acid precipitation, monoclonal antibody affinity purification, ion exchange chromatography, and gel filtration. Both glycoproteins were unaffected by reduction and alkylation in guanidine HCl. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, relative molecular masses were estimated to be 600-800 kDa for H-CanAg and 150-300 kDa for L-CanAg. Carbohydrate analysis revealed that the CanAg glycoproteins were highly glycosylated (81-89% carbohydrate by weight), carrying carbohydrate chains with average lengths of 13-18 sugars which were rich in fucose and sialic acid (2-3 residues/chain for each sugar). L-CanAg isolated from spent medium was glycosylated to a higher degree than its counterpart from xenograft extract. Immunochemical studies of the intact glycoproteins showed that both H-CanAg and L-CanAg expressed the monoclonal antibody-defined, sialic acid-containing carbohydrate epitopes CA203 and CA242 as well as the Lewis a blood group antigen whereas only H-CanAg appeared to carry the sialyl-Lewis x epitope. The amino acid compositions were typical of mucins, containing high amounts of serine, threonine (more than 25% together), and proline (11-18%). Significant differences in amino acid composition between H-CanAg and L-CanAg were found. A rabbit antiserum against the cytoplasmic C-terminal part of the MUC1 gene product, core protein of the carcinoma-associated polymorphic epithelial mucin (PEM) and DU-PAN-2, reacted with H-CanAg. After deglycosylation with trifluoromethanesulfonic acid, H-CanAg but not L-CanAg was recognized by the monoclonal antibodies SM-3 and HMFG-2, directed to the tandem repeat of the PEM apoprotein. However, these antibodies which react with PEM from mammary carcinomas without prior deglycosylation were unable to recognize intact H-CanAg, probably as a consequence of a more extensive glycosylation of this glycoprotein.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1991

Comparison of serological expression of different epitopes on the CA50-carrying antigen CanAg.

C203 and C242 are mouse monoclonal antibodies (MAbs) generated using a human colon carcinoma cell line. They recognize novel tumour-associated epitopes present in elevated levels in sera from patients with colon and pancreatic cancer. These epitopes were found to be co-expressed with sialylated Lewisa on the CanAg molecule. To study the association and distribution of the epitopes of CanAg in sera, these new antibodies, together with C50, were used in different combinations in time-resolved fluoroimmunoassays. Relative serum concentrations were examined in patients with various types of carcinoma and in patients with ulcerative colitis and benign pancreatic, and hepatobiliary diseases. A double-determinant assay using C50 and C242 was shown to distinguish carcinoma from benign biliary and hepatocellular diseases better than a single-determinant assay based on C50 as both catching and tracing antibody. The number of sera with elevated CanAg levels from patients with benign obstructive biliary disease was 17 out of 29 using the single-determinant CA50 assay. This was reduced to 4 out of 29 in the double-determinant assay. When sera from patients with liver cirrhosis were analyzed, 16 of 23 patients showed elevated CanAg levels with the C50-C50 combination, but only 4 of 23 patients had elevated antigen values using the C50-C242 assay. The increased specificity was obtained without loss of sensitivity. MAb C203 was evaluated both in a double-determinant combination with C50 and in an homologous assay, but did not contribute either increased sensitivity or specificity as compared with C50-C50.

Animals↗
PubMed1991

Stability and fluctuations of the potato carboxypeptidase A protein inhibitor fold: a molecular dynamics study.

A 120ps non-inertial solvent (NIS) molecular dynamics (MD) trajectory of the potato carboxypeptidase A protein inhibitor (PCI) was calculated and analyzed. It is shown that, in spite of a very low content of regular secondary structure, the PCI fold has a large degree of stability, judged from the fairly good agreement between the average MD and X-ray structures. The N-terminal and C-terminal regions behave differently, both in their isoatomic positional shifts with respect to the X-ray structure, and in atomic fluctuation pattern. Positional shifts up to 9A are detected in the exposed N-terminal region as it folds back on the inhibitor's core. This large deviation is most likely caused by the absence of the receptor protein or by the lack of supporting solvent molecules. In contrast, the C-terminal region, which is the primary contact site with the enzyme, has an average structure similar to the X-ray conformation; this feature is probably due to a hydrogen bond network to the central core of PCI. The C-terminal tail shows larger fluctuations than the core. The secondary contact site retains its structure in this simulation. The results evidence an intrinsically stable PCI fold which favors a spatially well defined, fairly flexible, structuration of the primary and secondary contact sites that optimizes PCI's interaction with its target enzyme.

Binding Sites↗
PubMed1991

A molecular dynamics study of a model built Pro-36-Gly mutant derived from the potato carboxypeptidase A inhibitor protein.

A 120ps molecular dynamics (MD) trajectory was calculated and analyzed for a putative Pro-36-Gly mutant of the potato carboxypeptidase A (CPA) protein inhibitor (PCIm). The mutant protein's fold shows a large degree of stability, judged from its low alpha-carbon r.m.s. deviation from the X-ray structure of the wild type PCI (PCIw). The N-terminal tail of PCIm differs slightly less from the X-ray structure than it does in PCIw, while the mutant's C-terminal tail (the primary contact site with CPA) and residues 13-17 present deviations as they approach each other. Differences in fluctuation pattern exist between PCIm and PCIw in residues 2-4 (the N-terminal tail), 13-17, 22-23, 28-31 (the secondary contact site with CPA) and 37-38 (the C-terminal tail); the latter region is rigidified in PCIm. Results show that the MD method is able to sense local perturbative effects produced by amino acid substitutions in flexible regions of protein molecules. The simulation suggests that the conformation of the C-terminal tail is less favorable for interaction with the target protein in the mutant than it is in the wild type protein. The Pro-36-Gly mutant is predicted to be a less potent inhibitor.

Carboxypeptidases↗
PubMed1991

The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells.

The use of a somatostatin analogue (SMS 201-995) has greatly facilitated the treatment of patients with the midgut carcinoid syndrome. Clinical studies have shown that SMS reduces the peripheral levels of tumour-produced serotonin (5-HT) and tachykinins, e.g. neuropeptide K (NPK), basally and after pentagastrin provocation. Some studies have indicated an inhibitory effect of SMS on tumour cell growth as well. In the present study we have investigated the effects of SMS on four different human midgut carcinoid tumours maintained in long term culture. Media levels of 5-HT and NPK-LI in tumour cell cultures decreased rapidly during incubation with SMS (10(-8)-10(-10) M) in all four tumours studied without evidence for tachyphylaxis (up to 6 weeks observation period). SMS treatment (10(-8) M) during 4 days reduced the media concentrations of 5-HT by 56%, while the intracellular contents of 5-HT were decreased by 27% indicating dual inhibitory effects on synthesis and secretion of 5-HT from tumour cells. The DNA contents of cultures were not affected by SMS (10(-8) M or 10(-10) M) treatment for 4 or 14 days. When tumour cell cultures were challenged with isoprenaline (IP) (10(-6) M) no reduction of the IP induced release of 5-HT could be detected after pretreatment of tumour cell cultures with SMS (10(-8) M) for 1 h, 4 h or 4 days. These studies provide evidence for a direct action of the somatostatin analogue on midgut carcinoid tumour cells, reducing both synthesis and secretion of hormones from tumour cells. This effect appears not to be related to inhibition of tumour cell growth. The inhibition of 5-HT secretion from tumour cells by SMS seems to operate via a second messenger system different from the one mediating the beta-adrenoceptor stimulated release of 5-HT.

Aged↗
PubMed1991

Production of transferable neuronotrophic factor(s) by human midgut carcinoid tumour cells; studies using cultures of rat fetal cholinergic neurons.

A co-culture system was established between human midgut carcinoid tumour cells and rat fetal cholinergic neurons. In monocultures in serum-free media, only tumour cells survived, while neurons deteriorated. In serum-free co-cultures, neurons displayed outgrowth of neuritic processes. Neurons of neuronal serum-free monocultures thrived if supplemented with conditioned media from tumour cell cultures grown serum-free. This indicates that tumour cells produce transferable growth factor(s) with potent neuronotrophic actions. Immunocytochemical studies indicate that this growth factor resembles nerve growth factor immunologically, since tumour cells were strongly immunoreactive after incubation with a rabbit anti-nerve growth factor antiserum, and furthermore expressed immunoreactive nerve growth factor receptors.

Animals↗
PubMed1991

Clinical evaluation of tumour marker combinations in the differential diagnosis of benign and malignant liver disease.

CEA, CA19-9 and CA50 are tumour associated antigens defined by monoclonal antibodies which have been raised against adenocarcinoma cell lines. The aim of this study was to determine whether their combined use could improve diagnostic accuracy in patients with primary and secondary liver tumours. An immunoradiometric assay was used for the detection of CEA and CA19-9 and the Delfia system for CA50. Serum was collected from 65 normal subjects, 40 with hepatobiliary carcinoma (26 primary, 14 secondary) and 17 with benign hepatobiliary disease. The cut-off levels were calculated as the mean of the control group plus 2 standard deviations. All three antibodies contributed to improving the correct classification of secondary liver tumours (multivariant discriminant analysis p less than 0.05), but only CA19-9 and CA50 contributed to the diagnosis of primary liver tumours (multivariant analysis p less than 0.05). The diagnostic accuracy versus benign disease was 81% for primary carcinoma and 91% for secondary carcinoma. Combined use of CEA, CA19-9 and CA50 helps to differentiate benign from malignant hepatobiliary disease.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

Novel epitopes on the CA50-carrying antigen: chemical and immunochemical studies.

Novel tumour-associated epitopes showing elevated levels in sera from patients with colon carcinoma were studied by means of monoclonal antibodies with respect to co-expression with the tumour-associated epitope CA50 on the cancer antigen (CanAg) glyco-conjugate complex. Co-expression of the different epitopes and CA50 was found on CanAg both from COLO 205 spent medium and sera from patients with colorectal cancer. In a few sera from patients with non-mucinous ovarian tumours, the CanAg complex was also found to express the CA125 epitope. The chemical characterisation showed that all of the novel epitopes on CanAg were of carbohydrate nature, and the results may suggest a structural relationship between several of them.

Adenocarcinoma↗