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Biomedical subjects

O Nilsson

Publications and source records attributed to O Nilsson.

At least 199 records · Page 11Linked to original sources

Intraocular transplants of a human gastrinoma in immuno-suppressed rats: morphological, chromatographic and functional studies.

Tissue pieces of a metastatic human gastrinoma (ultrastructural Type II) were successfully transplanted to the anterior eye-chamber of rats immunosuppressed with Cyclosporin A. Immunocytochemical investigation of the transplants showed evidence for preserved endocrine activity of tumour cells with immunoreactivity towards the C-terminal of the gastrin/cholecystokinin molecule. Studies of gastric acid secretion in tumour-bearing rats and sham-operated controls with chronic gastric fistulas showed that the basal acid output did not differ between the groups during 3 weeks of study. However, the stimulated gastric acid secretion decreased after 5 days in both groups to remain significantly depressed throughout the study, an effect probably due to Cyclosporin A treatment of the groups. The concentration of immunoreactive gastrin in plasma from rats with tumours in oculo was 5 times higher than in sham-operated rats. Gastrin-34 was the major immunoreactive component in both patient serum and rat plasma. An immunoreactive fraction corresponding to component I was found in the patient serum, but not in the rat plasma, although present in the chamber fluid. Components corresponding to gastrin-17 were found both in the patient serum and in the rat plasma. The chromatographic pattern of the tumour was similar to that in rat chamber fluid. The dominating component corresponded to gastrin-17, while gastrin-34 represented the quantitatively smaller component. Gastrin-34 was, however, relatively more abundant in the tumour extract than in the chamber fluid. The study also indicates that a gastrin-producing tumour transplanted in oculo in immunosuppressed rats may increase the rat plasma concentration of the same molecular forms of gastrin as seen in the clinical situation.

Adolescent↗

Intrahippocampal grafts of fetal basal forebrain tissue alter place fields in the hippocampus of rats with fimbria-fornix lesions.

Intrahippocampal grafts of fetal basal forebrain tissue have been shown to restore several aspects of neural function, including some degree of behavioral recovery in spatial memory tasks, in rats with fimbria-fornix lesions. Place fields, the behavioral correlates of complex-spike unit activity recorded in the hippocampus of rats, are altered by fimbria-fornix lesions, and provide an important measure of the functioning circuitry of the hippocampus after grafts. To investigate the effects of grafts on hippocampal circuitry, complex-spike units were recorded while the rats traversed a radial maze. Quantitative analyses of spatial activity showed that units in normal rats had spatially clustered, reliable place fields that were stable despite alterations of the maze. In contrast, units in rats with fimbria-fornix lesions had more dispersed, less reliable place fields that were disrupted when the maze was covered or rotated. Compared to rats with fimbria-fornix lesions, rats with grafts and units with more tightly clustered, more reliable, and more stable place fields when the maze was altered. The results suggest that: (1) fimbria-fornix lesions disrupt some aspects of complex-spike place field activity; (2) the functioning of hippocampal circuitry is influenced by fetal basal forebrain grafts; and (3) the grafts may ameliorate the effects of lesions on spatial behaviors by influencing critical aspects of place field activity in the hippocampus.

Action Potentials↗

Familial hypocalciuric hypercalcaemia: a study of four kindreds.

Four kindreds with hereditary hypercalcaemia have been investigated. Thirty-seven of 72 subjects examined had hypercalcaemia with an autosomal dominant pattern of inheritance. Hypercalcaemic patients had total serum calcium of 2.91 +/- 0.12 mmol l-1. Serum parathyroid hormone (PTH) was normal while daily urinary calcium excretion was subnormal (below 2.5 mmol) in 45%. Comparison with an age-matched group of patients with primary hyperparathyroidism gave a small overlap regarding serum human PTH, urinary calcium and the ratio between calcium clearance and creatinine clearance. Family screening therefore is of diagnostic importance. Twelve subjects had been subjected to parathyroid surgery before the correct diagnosis was settled, none of the cases had an adenoma. Three patients became normocalcaemic and the others had persistent hypercalcaemia. One male non-abuser had seven episodes of acute pancreatitis before surgery and none after. The findings in all four kindreds are compatible with familial hypocalciuric hypercalcaemia (FHH). This hereditary disorder of unknown aetiology, therefore, also exists in Scandinavia. It is of importance to consider FHH in the differential diagnosis of hypercalcaemia, since this disorder usually has a benign prognosis if untreated.

Calcium↗

Age as a factor determining susceptibility for experimental autoimmune encephalomyelitis in the rat.

The effect of age on the susceptibility to experimental autoimmune encephalitis was studied in different strains of rats and their hybrids. In the Brown-Norway (BN) strain no susceptibility was seen at any age. In the nearly resistant Fischer (F) strain, no change in clinical disease but an increase in histological scoring could be seen with increasing age. When hybrids between F and BN were studied, a clear-cut increase in clinical susceptibility was seen with age but no change in histological scores, while the F1 hybrid between BN and the susceptible Lewis strain showed no change in clinical susceptibility but an increase in histological scores with age. The findings are discussed together with previous data on these strains in terms of different mechanisms of resistance in the F and BN strains.

Aging↗

Blastocyst implantation precedes induction of insulin-like growth factor II gene expression in human trophoblasts.

The cytotrophoblast cell population of the human embryonic conceptus proliferates rapidly during the first month following blastocyst implantation. Since the trophectoderm lineage is established in preimplantation morula/blastocysts, the scenario underlying initiation and maintenance of the rapid proliferative phenotype of cytotrophoblasts is a central issue. The insulin-like growth factor II (IGF-II) gene is highly expressed in proliferative cytotrophoblasts of first trimester placenta and performs as a placenta growth factor. To establish a temporal correlation between IGF-II expression and initiation of highly proliferative trophoblasts in human development, we employed in situ hybridization analysis of the expression of the IGF-II and human chorionic gonadotropin beta-subunit (beta-HCG) genes in human pre- and postimplantation development. The data show that the appearance of high steady-state levels of IGF-II transcripts in trophoblasts is a postimplantation event, whereas beta-HCG transcripts can already be detected in preimplantation development. This observation makes a role for endogenously produced IGF-II in the normal development of preimplantation embryos unlikely, but suggests that endogenously produced IGF-II participates in the formation and subsequent expansion of the rapid proliferative phenotype of the trophoblastic shell, following implantation.

Blastocyst↗

Serotonin-producing carcinoid tumour cells in long-term culture. Studies on serotonin release and morphological features.

Tumour cells from a hepatic metastasis of a midgut carcinoid tumour were studied during 240 days of culture. A cell line could not be established, but the cells regularly formed large clusters and islets. The spontaneous release of serotonin (5-HT) and neuropeptide K-like immunoreactivity from cultures were followed. The amine and the peptide levels were unstable without evident covariation. The response to stimulation with noradrenaline and isoprenaline was studied during the culture period. The tumour cells released 5-HT selectively at stimulation with isoprenaline. This responsiveness also showed considerable variation with long periods of quiescence. Ultrastructurally the tumour cells showed a certain degree of polarization with apical microvilli and a supranuclear Golgi apparatus. When studied by confocal laser scanning the tumour cells were demonstrated to be cylindrical in shape with a cytoplasmic attachment to the matrix.

Carcinoid Tumor↗

H2-receptor blockade induces peptide YY and enteroglucagon-secreting gastric carcinoids in mastomys.

Gastric carcinoid tumor formation has been reported with prolonged achlorhydria in both animals and human beings. The hypothesis in this study was that the ablation of parietal cell function in an animal (mastomys) genetically predisposed to gastric neuroendocrine neoplasia would promote and accelerate tumor formation. Loxtidine, an irreversible H2-receptor blocker, was administered at 1 mg/kg/day in drinking water for 4 months to young mastomys (n = 16). After 4 months of treatment, 14 of 16 animals had gastric carcinoids compared with 0 of 16 young control animals and 4 of 16 older control animals. Ultrastructurally, these tumors were characterized by the presence of neurosecretory granules. Serum gastrin levels were elevated (230 +/- 40 pmol/L) in loxtidine-treated animals compared with control animals (26 +/- 8 pmol/L) (p less than 0.05). In addition, both peptide YY (620 +/- 160 pmol/L) and enteroglucagon (500 +/- 147 pmol/L) were significantly elevated compared with control groups (p less than 0.05). Similarly, in tumor tissue, peptide YY (676 +/- 152 pmol/gm) and enteroglucagon (551 +/- 164 pmol/gm) were found in large quantities, whereas gastrin was undetectable. These observations provide substantial support for the possible pathophysiologic role of gut peptides, particularly gastrin, in the generation of endocrine neoplasia. The advent of endocrine tumors after inhibition of a gut secretory cell (parietal) may be of considerable significance in understanding the genesis of endocrine neoplasia. Whether the drug acts as a neoplastic promoter of enterochromaffin-like cells or the tumor development is related to elevation of peptides such as gastrin cannot be established in this study. Long-term H2-receptor blockade with new potent, irreversible agents as an alternative to surgery may have potential grave implications that require careful consideration.

Animals↗

Long-term results of preperitoneal hernioplasty.

A long-term follow-up study (21-27 years) was performed on 134 patients with 142 inguinal or femoral hernias repaired with preperitoneal hernioplasty. Since their previous follow-up, 1/2-4 years postoperatively, there were nine more recurrences of hernia, viz. 1/12 in the group with direct-type, 8/116 in the indirect-type group, but 0/14 femoral hernias. Three of the eight recurrences in the indirect hernia group appeared many years after the primary operation and were found at reoperation to be of direct type.

Follow-Up Studies↗

Carcinoid tumour cells in long-term culture: release of serotonin but not of tachykinins on stimulation with adrenoceptor agonists.

Tumour cells from a lymph-node metastasis of a midgut carcinoid tumour, immunoreactive for serotonin and substance P, were isolated and kept in culture for 2 months. The formation of large clusters or islets of tumour cells was paralleled by an increase in immunoreactive tachykinins (neuropeptide K and substance P) in the culture medium. The concentration of tachykinins declined subsequently despite good viability of the cells. Spontaneous release of serotonin into the culture medium was much greater than that of tachykinins, and remained stable throughout the study. These findings indicate different turnover rates and/or different storage sites for the peptides and the amine. In stimulation experiments, a dose-dependent release of serotonin, but not of tachykinins, was induced by a beta-adrenoceptor agonist (isoprenaline), while stimulation of alpha-adrenoceptors (noradrenaline) was not effective in releasing any of the substances. Pretreatment of the cultures with a beta-adrenoceptor antagonist (propranolol) or stimulations after calcium deprivation did not influence the isoprenaline-induced release of serotonin. These findings may indicate a modification of genuine beta-adrenoceptors during culture.

Adrenergic alpha-Agonists↗

The pentagastrin test as an indicator of a cure in surgically treated patients with advanced carcinoid disease.

A unique case of midgut carcinoid with advanced disease, engaging lymph nodes and liver but still accessible to curative surgery, is reported. Besides elevated urinary levels of 5-hydroxyindoleacetic acid, the diagnosis was based on a positive provocation test with pentagastrin, i.e., basally elevated levels of serotonin in peripheral whole blood increased twofold 3 min postinjection related to the appearance of carcinoid symptoms. After removal of primary and secondary lesions in a two-step procedure carcinoid symptoms disappeared completely. Biochemically, urinary excretion of 5-hydroxyindoleacetic acid and serotonin levels in peripheral blood before and during provocation with pentagastrin were both normalized after surgery and have remained so during 27 months of follow-up. Computed tomographies of the abdomen at regular intervals do not indicate recurrent disease. Histologically, the carcinoid lesions displayed a mixed growth pattern and signs of local aggressiveness. Immunocytochemically, the majority of the tumour cells (positive against neuron specific enolase) showed a positive reaction with serotonin antisera. Substance P-like immunoreactivity was also found in a large proportion of these cells.

Carcinoid Tumor↗

Electron-microscopic immunocytochemistry of 5-hydroxytryptamine in the ascidian endostyle.

The cellular and subcellular distribution of serotonin (5-hydroxytryptamine, 5-HT) in the endostyle of three species of ascidians, Ciona intestinalis, Corella parallelogramma, Ascidia mentula, was studied by light- (immunoperoxidase) and electron-microscopic (immunogold) immunocytochemistry. At the light-microscopic level 5-HT-like immunoreactivity (5-HT-LI) was exclusively found in cells located in the lateral portion of the endostyle, between zone 7, known to have iodinating capacity, and zone 8, which consists of ciliated cells. At the electron-microscopic level, the 5-HT-immunoreactive cells were found to correspond to cells containing polymorphous, dense granules, 100-300 nm in diameter. The granules were located in the supranuclear cytoplasm facing the endostyle lumen as well as in the infranuclear cytoplasm facing the extracellular space. Quantification showed that the 5-HT-LI was considerably higher (13-67 times) in cytoplasmic areas containing granules as compared to areas devoid of granules. Most, but not all, of the 5-HT-LI was associated with the dense core of the granules. In conclusion, serotonin-containing cells are located in the peripheral portion of the endostyle, between zones 7 and 8. Serotonin is stored in cytoplasmic granules that are present both in the apical and basal cytoplasm. This suggests the possibility that the cells are bipolar and secrete serotonin both in a basal direction to the extracellular space, and in an apical direction to the pharyngeal lumen.

Animals↗

A clinical study of CA-50 as a tumour marker for monitoring of colorectal cancer.

Using a radioimmunoassay we have determined serum levels of the carcinoma-associated antigen CA-50 in 266 patients with colorectal cancer. Elevated CA-50 levels were found in Dukes' A (15%), Dukes' B (43%), Dukes' C (31%) and Dukes' D (65%). Patients who had developed a recurrence had 66% elevated levels. 25% of resected patients with no evidence of disease also had elevated CA-50 levels. From 139 patients operated on for a Dukes' A-C, a rise in CA-50 levels from the pre- to the 6-9 month post-operative sample was demonstrated in 12 cases in the absence of any clinical evidence for a recurrence. On follow-up, a recurrence later developed in all these cases with lead times of CA-50 titre rises ranging from 5 to 40 months. A rise in CA-50 levels after resection of a Dukes' A-C is indicative of a recurrence and may precede any clinical evidence of disease by several months or years. Data is also presented from 552 cases with colorectal cancer analysed with a immunoradiometric assay.

Antigens, Neoplasm↗

Vagal release of serotonin into gut lumen and portal circulation via separate control mechanisms.

The mechanisms controlling vagally induced release of serotonin-like immunoreactivity (5-HTLI) into portal circulation and jejunal lumen were studied in individual cats. In control animals, electrical vagal nerve stimulation significantly enhanced both the endoluminal secretion rate of 5-HTLI and the release of 5-HTLI into the portal vein. The vagally induced release of 5-HTLI into portal circulation was blocked by pretreatment with propranolol or phenoxybenzamine, or by previous removal of the superior cervical ganglia, but was not blocked by atropine or hexamethonium. On the contrary, the luminal secretion of 5-HTLI after vagal stimulation was not blocked by adrenoceptor blocking agents or ganglionectomy, but instead was inhibited by cholinoceptor antagonists. Thus, in the same experimental animals it was shown that vagally induced release of 5-HTLI into portal circulation was mediated by adrenoceptor mechanisms, while endoluminal release of 5-HTLI was regulated via cholinoceptors. Based on indirect estimations, the apical release of 5-HT seems to be quantitatively small in comparison with the release into portal circulation.

Animals↗