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Biomedical subjects

O Nilsson

Publications and source records attributed to O Nilsson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Biokinetics of 111In-DTPA-D-Phe(1)-octreotide in nude mice transplanted with a human carcinoid tumor.

The long time biokinetics of the radiolabeled somatostatin analogues 111In-DTPA-D-Phe(1)-octreotide was studied in nude mice transplanted with the human carcinoid tumor, GOT1. The results were compared with those from the patient with the original tumor. This patient has been diagnosed and later treated with 111In-DTPA-D-Phe(1)-octreotide. The animals received about 2 MBq 111In-DTPA-D-Phe(1)-octreotide (0.1 microg) by injection into a tail vein. The animals were killed 0.5 h-14 d after injection of the radiopharmaceutical. Tumor tissue and normal tissues were collected and weighed and measured for 111In activity. The 111In uptake in the tumor was higher than in all normal tissues except the kidneys. The tumor-to-normal-tissue activity concentration, TNC, increased with time for all normal tissues studied. These data were similar to those observed for the original tumor in the patient. The similar biokinetics for 111In-DTPA-D-Phe(1)-octreotide in the tumor-bearing mice and the patient makes this animal model suitable as a model for evaluation of therapy of somatostatin receptor (sstr) expressing tumors with radiolabeled somatostatin analogues. Furthermore, the increase with time of TNC both in mice and the patient indicates that long-lived radionuclides are preferred for therapy with radiolabeled somatostatin analogues.

Animals↗
PubMed2001

Interleukin (IL)-13 and IL-4 inhibit proliferation and stimulate IL-6 formation in human osteoblasts: evidence for involvement of receptor subunits IL-13R, IL-13Ralpha, and IL-4Ralpha.

Interleukin-13 (IL-13) inhibits cell proliferation and stimulates interleukin-6 (IL-6) formation in isolated human osteoblasts (hOBs). Because the related cytokine, interleukin-4 (IL-4), is known to exert effects similar to IL-13 in other tissues, and because IL-4 has been implicated as a regulator of bone metabolism, we compared the effects of IL-13 and IL-4 on cell proliferation, IL-6 synthesis, the expression of osteoblastic phenotypic markers in hOB cultures. Also, the receptor proteins mediating these effects in hOBs have been partly characterized. IL-4 and IL-13 dose-dependently inhibited [(3)H]-thymidine incorporation into the DNA of human osteoblasts and stimulated secretion of IL-6 into culture supernatants. IL-13 and IL-4 also increased the mRNA levels of IL-6, as measured by RNAse protection assay. Furthermore, IL-13 and IL-4 dose-dependently enhanced alkaline phosphatase (ALP) activity, but did not affect osteocalcin or collagen type I synthesis. IL-4 was tenfold more potent than IL-13 in inducing both ALP activity and IL-6 secretion, whereas the cytokines were equipotent as inhibitors of cell proliferation. The expression of mRNA for receptor subunits previously implicated in IL-4 and IL-13 signaling was investigated by reverse transcriptase-polymerase chain reaction. IL-13R, IL-13Ralpha, and IL-4Ralpha mRNA were repeatedly detected in hOBs, whereas mRNA for IL-2Rgamma(C) was not detected. Receptor-blocking antibodies to IL-4Ralpha inhibited the induction of IL-6 formation by both IL-4 and IL-13, indicating that both cytokines utilize this receptor subunit in signaling. However, the antibodies did not affect the IL-4/-13-induced inhibition of [(3)H]-thymidine incorporation or the stimulation of alkaline phosphatase (ALP), suggesting that IL-4Ralpha does not mediate these effects of IL-4/-13 in hOBs. We conclude that the cytokines IL-13 and IL-4, through sharing of receptor components, induce similar effects on hOBs, causing inhibition of cell proliferation, stimulation of IL-6, and enhanced ALP activity.

Antibodies, Monoclonal↗
PubMed2001

Pharmacological properties of cannabinoid receptors in the avian brain: similarity of rat and chicken cannabinoid1 receptor recognition sites and expression of cannabinoid2 receptor-like immunoreactivity in the embryonic chick brain.

The pharmacological properties of brain cannabinoid receptors were investigated in brains of 35 day-old chickens, since little is known about the avian cannabinoid system. The cannabinoid1 receptor-selective antagonist ligand [3H]SR 141716A bound to chicken brain membranes with K(D) and Bmax values of 0.92+/-0.28 nM and 790+/-58 fmol/mg protein, respectively. The binding was inhibited by CP 55,940 with a pI50 value of 7.63+/-0.14 and by a series of compounds with the order of potency CP 55,940>R(+)WIN 55,212-2>R-1 methanandamide approximately DAK. S(-)WIN 55,212-3 and AM404 were without inhibitory effect at 1 microM. Similar results were found for rat brain membranes. For both rat and chicken brain membranes, addition of the non-hydrolysable GTP analogues Gpp[NH]p and GTPgammaS shifted the CP 55,940 inhibition curve to the right, consistent with an intact coupling to G-proteins in the preparations. Fatty acid amidohydrolase in chicken brain membranes was less sensitive to inhibition by phenylmethylsulphonyl fluoride and arachidonoyl serotonin than its rodent equivalent. However, when fatty acid amidohydrolase activity in the preparations was reduced by use of a lower assay membrane concentration, anandamide was found to inhibit the binding of [3H]SR 141716A to chicken membranes with a pI50 value of 6.39+/-0.16. Using a novel antibody raised to amino acids 346-359 from the C-terminal tail of the human cannabinoid2 receptor, it was found that embryonic chick brain tissue (and embryonic chick neurones in primary culture) expressed a approximately 53 kDa immunoreactive band. This immunoreactivity, which was prevented by preincubation of the antibody with the immunising peptide, was also seen in cells expressing the recombinant human cannabinoid, receptor, but was not seen in adult chicken brain homogenates or in rat cerebellar homogenates. However, a "classical" cannabinoid2-receptor component of [3H]WIN 55212-2 binding (i.e. a fraction inhibited by low concentrations of the cannabinoid2-receptor-selective antagonist SR 144528) was not found.

Amidohydrolases↗
PubMed2001

CEA, CA 50 and CA 242 in patients surviving colorectal cancer without recurrent disease.

AIMS: To establish a baseline and intraindividual fluctuations of the tumour markers CEA, CA 50 and CA 242 in patients cured from colorectal cancer, and to test the hypothesis that serum concentrations and intraindividual fluctuations do not differ from the concentrations in cancer-free individuals. PATIENTS AND METHODS: Ninety patients with colorectal cancer, who had undergone surgery with curative intent, were still alive at least 5 years after surgery with no signs of recurrent disease. Serum levels of tumour markers CEA, CA 50 and CA 242 before and up to 2 years after surgery were analysed after the prospective study was terminated. RESULTS: The pre-operative serum levels of CEA, CA 50 and CEA 242 were elevated in 36%, 16% and 20% of the patients. They were lowered after curative surgery. A small increase of CEA levels was found after the initial post-operative decrease. The intraindividual fluctuations for CA 50 and CA 242 did not exceed 15% but in 24% of the patients the serum levels of CA 50 were high and oscillating. The patients cured from Dukes >> C cancer had higher serum concentrations of CEA than patients who had a Dukes >> B cancer, which were higher than in patients who had Dukes >> A cancer. Concentrations of CA 242 were higher in patients cured from Dukes >> A than patients cured from Dukes>> B or C cancers. CONCLUSIONS: During the first 2 years after curative surgery for colorectal cancer the serum levels of CEA did not differ from those levels in normal cancer-free subjects. The serum levels of CEA were related to Dukes >> staging whereas the levels of CA 242 were inversely related to Dukes >> staging.

Adult↗
PubMed2001

Long-term course in collagenous colitis and the impact of bile acid malabsorption and bile acid sequestrants on histopathology and clinical features.

BACKGROUND: Bile acid malabsorption is common in collagenous colitis, although long-term follow-up data on the impact of bile acids are limited. The aim was to study whether bile acid malabsorption is a permanent finding, with an impact on histopathology and clinical features in collagenous colitis. METHODS: The objective was to reinvestigate 27 patients with collagenous colitis > or = 3 years after index investigation. The clinical course was evaluated by means of an interview, a review of the hospital records and registration of symptoms over a period of 7 days. The patients were invited to undergo a repeat colonoscopy and 75SeHCAT measurement. Initial and follow-up data and 75SeHCAT values from 29 controls were compared. RESULTS: The median follow-up time was 4.2 (range 3-5.3) years. Twenty-two patients underwent a repeat 75SeHCAT test, 23 patients a colonoscopy and in 25 patients the clinical course could be evaluated. The 75SeHCAT values were abnormal in 32% at follow-up versus 44% at index, and the median retention value was 19% (range 2-69) versus 12% (range 0.5-41) (P = 0.024) although lower than in the control groups figure of 38% (range 8-91) (P < 0.005). Histopathology had improved independently of bile acid malabsorption, gender, smoking and autoimmune disease at follow-up. Four were normalized. Patients on bile acid binders had no significant change of histopathology. Four patients had recovered, seven displayed an intermittent course and 14 had continuous diarrhoea. CONCLUSIONS: Collagenous colitis and bile acid malabsorption seem to be associated yet independent disorders. The histopathology improves during the long-term course although only a few patients resolve.

Bile Acids and Salts↗
PubMed2001

High serum S100B levels for trauma patients without head injuries.

OBJECTIVE: Studies of patients with head trauma have demonstrated a correlation between a serum marker of brain tissue damage, namely S100B, and neuroradiological findings. It was recently demonstrated that the increases in serum S100B levels after heart surgery have extracerebral origins, probably surgically traumatized fat, muscle, and bone marrow. The current study examined multitrauma patients without head trauma, to determine whether soft-tissue and bone damage might confound the interpretation of elevated serum S100B concentrations for patients after head trauma. METHODS: A commercial assay was used to determine serum S100B concentrations for a normal population (n = 459) and multitrauma patients without head injury (n = 17). Concentrations of the two subtypes of S100B (S100A1B and S100BB) were determined using separate noncommercial assays. RESULTS: The mean serum S100B concentration for a normal healthy population was 0.032 microg/L (median, 0.010 microg/L; standard deviation, 0.040 microg/L). The upper 97.5% and 95% reference limits were 0.13 and 0.10 microg/L, respectively. No major age or sex differences were observed. Among trauma patients, serum S100B levels were highest after bone fractures (range, 2-10 microg/L) and thoracic contusions without fractures (range, 0.5-4 microg/L). Burns (range, 0.8-5 microg/L) and minor bruises also produced increased S100B levels. S100A1B and S100BB were detected in all samples. CONCLUSION: Trauma, even in the absence of head trauma, results in high serum concentrations of S100B. Interpretation of elevated S100B concentrations immediately after multitrauma may be difficult because of extracerebral contributions. S100B may have a negative predictive value to exclude brain tissue damage after trauma. Similarly, nonacute S100B measurements may be of greater prognostic value than acute measurements.

Adolescent↗
PubMed2001

The dynamics, prevalence and impact of nematode infections in organically raised sheep in Sweden.

A three-year survey (1997-99) was carried out on organically reared sheep flocks throughout Sweden. The aim was to determine the prevalence and intensity of nematode infections and to establish relationships between sheep management practices and parasite infections. Faecal samples from ewes and lambs were collected from 152 organic flocks around lambing-time and during the grazing-period for analysis. Results were compared with the different management practices that farmers use to prevent parasitism in their flocks. A high proportion of the flocks was infected with nematodes. The most prevalent species were Haemonchus contortus, Teladorsagia circumeincta, Trichostrongylus axei. T. colubriformis and Chabertia ovina and infections progressively increased during summer in lambs grazing on permanent pastures. Severity of parasitic infection in lambs was highly dependent on egg output from the ewes. H. contortus was found in 37% of the flocks, even at latitudes approximating the Polar Circle. Nematodirus battus was recorded for the first time in Sweden during the course of this study. Lambs turned out onto permanent pasture showed higher nematode faecal egg counts (epg) than lambs that had grazed on pastures, which had not carried sheep the previous year. This beneficial effect of lambs grazing non-infected pastures persisted if the ewes were treated with an anthelmintic before turn-out and if the lambs were kept on pastures of low infectivity after weaning. In lambs, the prevalence and the magnitude of their egg counts were higher during autumn in flocks where lambs were slaughtered after 8 months of age, compared with flocks where all lambs were slaughtered before this age. These results will be used in providing advice to farmers of ways to modify their flock management in order to minimise the use of anthelmintics, but at the same time efficiently produce prime lambs.

Animals↗
PubMed2000

Elevated inflammatory parameters are associated with lower platelet density in acute myocardial infarctions with ST-elevation.

OBJECTIVE: Platelets and granulocytes play important roles in coronary disorders. We therefore, investigated platelet and granulocyte alterations in myocardial infarctions (MIs). PATIENTS AND STUDY DESIGN: A total of 36 individuals having MI with raised ST-segments who were receiving thrombolytic therapy were studied. Sampling was carried out after thrombolysis within 24 h after hospital admission. After 3 to 6 months of recovery, 25 patients were reinvestigated. At the infarction, peak platelet density was determined using a special designed computerised apparatus. In addition, we did counts on platelets, neutrophils and monocytes. Moreover, plasma levels of soluble P-selectin, myeloperoxidase and interleukin 6 were determined to estimate the degree of platelet, neutrophil and monocyte activation, respectively. Peak platelet density was analysed at the MI. All other parameters were determined at the acute event and at recovery. RESULTS: At the MI, compared to the recovery, platelet counts were lower (P<0.001). In addition, increased neutrophil counts (P<0.001), elevated monocyte counts (P<0.001), enhanced myeloperoxidase (P<0.001) and interleukin 6 (P<0.001) levels were demonstrated. We failed to show elevated soluble P-selectin. Compared to individuals with ST-segment elevations and low platelet density (less than or = 1.058 kg/l), patients having peak platelet densities >1.058 kg/l displayed lower neutrophil counts (P<0.01) and decreased interleukin 6 levels (P<0.01). Furthermore, we demonstrate that individuals with higher inflammatory response at the MI had higher neutrophil (r = 0.6; P<0.01) and higher monocyte counts (r = 0.6; P<0.001) at recovery. CONCLUSION: W conclude that MI is associated with an inflammatory response. However, a subgroup of patients having MI with ST-elevations and low peak platelet density was identified. Compared to subjects with higher platelet density, they had more severe inflammatory characteristics. The differences persisted during recovery.

Aged↗
PubMed2000

Analysis of film coating thickness and surface area of pharmaceutical pellets using fluorescence microscopy and image analysis.

A method is presented which enables geometrical characterisation of pharmaceutical pellets and their film coating. It provides a high level of details on the single pellet level. Image analysis was used to determine the coating thickness (h) applied on the pellets and the surface area (A) of the pellet cores. Different definitions of A and h are evaluated. Hierarchical analysis of variance was used to resolve different sources contributing to the total variance. The variance within pellets and the variance between pellets were found as significant sources of variation. Special emphasis was put on evaluation of A/h due to its influence on the release rate of an active drug substance from the pellet core. The pellet images were thus used to predict variations in the release rate using a mathematical model as a link between the image data and the release rate. General aspects of image analysis are discussed. The method would be useful in calibration of near infrared spectra to h in process analytical chemistry.

Microscopy, Fluorescence↗
PubMed2000

The expression of lymphocyte surface antigens in bronchial biopsies, bronchoalveolar lavage cells and blood cells in healthy smoking and never-smoking men, 60 years old.

In this study we investigated if smoking subjects with a normal or slightly decreased lung function differ in the lymphocyte pattern compared to never-smokers. In a group of 'healthy' smokers (n = 58) and never-smokers (n = 34) 60 years old, we investigated the lymphocyte pattern in both BAL (n = 30 and n = 18 respectively), bronchial epithelium and lamina propria (n = 14 and n = 10 respectively) and blood. We found that all subjects, despite smoking history, had a higher number of CD8+ cells per mm2 in the epithelium compared to the lamina propria in the bronchial biopsies. In smokers, these CD8+ cells were significantly negatively correlated to FEV1 (r = -0.56, P = 0.04). In smokers, the number of CD8+ lymphocytes was higher and the T cell activation markers (CD57+ and CD28+) were lower in BAL, than in never-smokers. This last finding was also seen in blood for CD3+ 57+. We conclude, that in 'healthy' smokers the lymphocyte patterns are different compared to never-smokers, to some extent in BAL. There is also a relation between lymphocytes in the bronchial mucosa and lung function. This has previously been shown in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis but not in asymptomatic smokers.

Antigens, Surface↗
PubMed2000

Interventional treatment of gastrointestinal neuroendocrine tumours.

Neuroendocrine (NE) tumours of the gastrointestinal tract (carcinoids and endocrine pancreatic tumours) are rare diseases. In the presence of liver metastases these patients may suffer from disabling symptoms due to hormone overproduction. Patients with localized disease can be resected for cure and also patients with liver metastases can undergo potentially curative tumour resection. However, long-term follow-up of the latter cases indicates frequent recurrence of tumour. Using close biochemical monitoring of tumour markers combined with newer techniques for tumour visualization, these recurrences can often be diagnosed at an early stage so that repeat surgical procedures can be performed. During the last years very active surgery has been recommended for NE tumours, many of which have a relatively slow growth. Even in patients not amenable to curative liver surgery, debulking can be considered if the main tumour burden can be safely excised. The primary aim of this type of treatment is palliation of hormonal symptoms. An important question is whether the aggressive treatment actually prolongs survival. No prospective studies have been performed. Such studies are hampered by the lack of strict surgical programs running over long periods and the relative rarity of NE tumours. Liver transplantation may be another treatment modality in selected cases.

Biomarkers, Tumor↗
PubMed2000

Multicolor spectral karyotype analysis of a transplantable human ileal carcinoid.

In this report we present the results of a combined cytogenetic and multicolor spectral karyotype (SKY) analysis of a transplantable human ileal carcinoid (GOT1). By using SKY it was possible to identify the origin and organization of all clonal marker chromosomes and to identify cryptic translocations not detectable by conventional chromosome banding. The stemline karyotype of low passage GOT1 cells was interpreted as 43,XX, der(1)del(1)(?), inv(2)(p25q13), del(3)(p21), del(5)(q13q31), del(6)(q13), -9, -13, -15, del(16) (q22). Analysis of the GOT1 cells after about 2.5 years of propagation in nude mice allowed us to follow the in vivo progression of this tumor. Relatively few additional rearrangements had occurred during this period, indicating that the GOT1 cells are genetically stable. Most of the abnormalities detected result in loss of whole or parts of chromosomes, suggesting that loss of multiple chromosomal regions, presumably containing tumor suppressor genes, might be important genetic events in ileal carcinoids.

Animals↗
PubMed2000

111In-DTPA-D-Phe1-octreotide binding and somatostatin receptor subtypes in thyroid tumors.

UNLABELLED: The purpose of this study was to evaluate the potential for therapy of thyroid tumors using the radiolabeled somatostatin (SS) analog octreotide. METHODS: Concentrations of 111In activity in human thyroid tumors and normal thyroid tissue and blood samples were determined 1-15 d after intravenous injection of 111In-diethylenetriaminepentaacetic acid-Phe1-octreotide. The results were compared with SS receptor (sstr subtype profile (by Northern blot analysis) and the relative expression of the second subtype, sstr2 (by ribonuclease protection assay, RPA). The true tumor volumes in lymph node metastases from 1 patient were estimated. In total, tissues from 68 patients were included in the study. RESULTS: The highest tumor-to-blood ratio (T/B) for medullary thyroid carcinoma (MTC) was 360; for follicular adenoma (FA), 190; for Hurthle cell adenoma (HCA), 140; and for Hurthle cell carcinoma (HCC) and papillary carcinoma (PC), 70. The corresponding value was 7-18 for normal thyroid tissue, with higher values for colloid goiter (8-48) and thyroiditis (7-120). A high T/B was related to a large fraction of tumor cells in lymph node metastases. T/Bs were higher for the tumor samples with expression of sstr2 at Northern blot analysis than for those without. All thyroid tumor types regularly expressed sstr1, sstr3, sstr4, and sstr5. sstr2 was expressed in most MTC tumors but was not detected in FA or PC and was irregularly expressed in HCA and HCC. However, RPA analysis detected sstr2 in all tumors studied. CONCLUSION: Despite the lack of sstr2 at Northern blot analysis in most of the thyroid tumors studied, high T/Bs were in general found when compared with corresponding values for normal thyroid tissue. The sometimes extremely high ratios are promising and indicate a possibility of using radiolabeled octreotide for radiation therapy of sstr-positive tumors in the future.

Blotting, Northern↗
PubMed1999

Altered influence of CCK-B/gastrin receptors on HDC expression in ECL cells after neoplastic transformation.

Gastrin is one of the main factors controlling enterochromaffin-like (ECL) cell endocrine function and growth. Long-standing hypergastrinemia may give rise to ECL cell carcinoids in the gastric corpus in man and in experimental models. We have analysed the expression and function of CCK-B/gastrin receptors in normal ECL cells and in ECL cell tumours (gastric carcinoids) of the African rodent Mastomys natalensis. Hypergastrinemia induced by short-term (5 days) histamine2-receptor blockade (loxtidine) resulted in increased histidine decarboxylase (HDC) mRNA expression in the gastric oxyntic mucosa. This increase was significantly and dose-dependently reversed by selective CCK-B/gastrin receptor blockade (YM022). Long-term (12 months) hypergastrinemia, induced by histamine2-receptor blockade, gave rise to ECL cell carcinoids in the gastric oxyntic mucosa. CCK-B/gastrin receptor mRNA was only slightly elevated while HDC mRNA expression was eight-fold elevated in ECL cell carcinoids and was not influenced by CCK-B/gastrin receptor blockade. Thus CCK-B/gastrin receptor blockade of hypergastrinemic animals reduces the HDC mRNA expression in normal mucosa but not in ECL cell carcinoids. These results demonstrate that HDC mRNA expression in neoplastic ECL cells is not controlled by CCK-B/gastrin receptors.

Animals↗
PubMed1999

[Nesidiodysplasia. A rare cause of hyperinsulinemia in an adult patient].

Adult hyperinsulinaemia is usually caused by benign insulinomas. These tumours are often small, and are associated with excellent outcome of surgical removal. In cases of negative outcome of surgical exploration, or of persistent hyperinsulinaemic hypoglycaemia, the possibility must be considered of some rare condition such as the presence of metastatic insulinoma, B-cell hyperplasia, multiple micro- or macro-adenomas, hyperinsulinaemia factitia, or nesidiodysplasia. The latter is the most common cause of hyperinsulinaemia in children but is rare in adults. It is defined as a maldistributed islet cell mass within the normal exocrine pancreas, with disturbed control of hormone synthesis/secretion resulting in hormone overproduction, usually hyperinsulinaemia. In persistent hyperinsulinaemic hypoglycaemia of infancy, inactivating mutations of the sulphonylurea receptor gene is one possible cause of nesidiodysplasia. Adult nesidiodysplasia is discussed in the article, and illustrated by the case of a patient undergoing distal pancreatectomy for hyperinsulinaemia, the diagnosis being subsequently established histologically. Following spleen- and duodenum-preserving subtotal (95%) pancreatectomy, the patient was symptom-free.

Adult↗