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Biomedical subjects

S Nilsson

Publications and source records attributed to S Nilsson.

At least 91 records · Page 5Linked to original sources
PubMed1999

Lymphohematopoietic stem cell engraftment.

Traditional dogma has stated that space needs to be opened by cytoxic myeloablative therapy in order for marrow stem cells to engraft. Recent work in murine transplant models, however, indicates that engraftment is determined by the ratio of donor to host stem cells, i.e., stem cell competition. One hundred centigray whole body irradiation is stem cell toxic and nonmyelotoxic, thus allowing for higher donor chimerism in a murine syngeneic transplant setting. This nontoxic stem cell transplantation can be applied to allogeneic transplant with the addition of a tolerizing step; in this case presensitization with donor spleen cells and administration of CD40 ligand antibody to block costimulation. The stem cells that engraft in the nonmyeloablated are in G0, but are rapidly induced (by 12 hours) to enter the S phase after in vivo engraftment. Exposure of murine marrow to cytokines (IL-3, IL-6, IL-11 and steel factor) expands progenitor clones, induces stem cells into cell cycle, and causes a fluctuating engraftment phenotype tied to phase of cell cycle. These data indicate that the concepts of stem cell competition and fluctuation of stem cell phenotype with cell cycle transit should underlie any new stem cell engraftment strategy.

Animals↗
PubMed1999

Dental abnormalities associated with failure of tooth eruption in src knockout and op/op mice.

c-src knockout and op/op mice develop osteopetrosis as a result of defective osteoclast function and osteoclast formation, respectively. The mutant mice can be distinguished readily from their wild-type littermates around 10-12 days after birth because their incisors do not erupt, but the morphology of their teeth and surrounding bone has not been reported previously in detail. Histologic examination of jaws of src-mutant mice reveals unerupted, abnormal incisors within their bony crypts. The tooth roots are distorted by foci of haphazard proliferation of odontogenic epithelium associated with primitive tooth structures that strongly resemble the tumor-like lesions in humans, known as odontomas. The crowns of the incisors are fused to the adjacent bone, and the developing periodontal ligament is disordered and hypocellular. Osteoclasts are present in the bone surrounding the distorted teeth, but as in other bones in these mice they lack ruffled borders and thus do not resorb effectively. Similar odontogenic proliferation is present around unerupted incisors in op/op mice which form very few osteoclasts, but the amount is significantly less than in src mutant mice. Molars fail to erupt in both types of mutant mice, but they are not accompanied by aberrant odontogenic proliferation. These findings and previous reports of similar abnormalities in jaws from op/op rats suggest that failure of incisor eruption and associated proliferation of odontogenic epithelium in osteopetrotic rodents are a direct result of defective osteoclastic bone resorption.

Animals↗
PubMed1999

Gel--sol transition in kappa-carrageenan systems: microviscosity of hydrophobic microdomains, dynamic rheology and molecular conformation.

The effect of gel-sol transition in kappa-carrageenan systems on the microviscosity of hydrophobic microdomains, as well as its relation to macroscopic rheology and molecular conformation, was studied in kappa-carrageenan systems. The microdomains were probed by 1,3-di(-1-pyrenyl)propane (P3P) for which the excimer intensity (Ie) provides relative measures of the microviscosity in the immediate probe surroundings. In particular the applicability of P3P to monitor the gel--sol transition was proved, the results showing a dramatic decrease in microviscosity in the vicinity of the transition point. The corresponding changes in rheological properties and carrageenan conformation were investigated by dynamic viscometry (DV) and optical rotation (OR), respectively. The temperature of onset of the transition as indicated by the microviscosity data (T0) was found to correlate well with the OR and DV-results. The application of microviscosity and OR-measurements allowed an estimation of the helical content at T0 to be determined. P3P-data indicate a microenvironment viscosity for the probe sites in the kappa-carrageenan system comparable to that found in SDS micelles.

Carbohydrate Conformation↗
PubMed1999

Quantitation of atherosclerosis by magnetic resonance imaging and 3-D morphology operators.

The objective was to ascertain whether MRI and image processing can be used to quantify atherosclerosis by measuring wall thickness in rabbit aorta. The abdominal aortas of 2 healthy and 5 atherosclerotic rabbits were examined with a gradient-echo inflow angiography sequence (2DI) and a proton density weighted turbo-spin-echo sequence (PDW). Using thresholding by four observers and 3D morphology operators, segmentation of the artery and vein lumina was performed from the 2DI sequence, and of surrounding fat and muscle from the PDW sequence. Remaining voxels adjacent to the aortic lumen were classified as vessel wall. By measuring the vessel wall volume and the lumen volume, the wall percentage was calculated. The values were significantly higher for the diseased animals than for unaffected individuals (p < 0.01). It is concluded that aortic wall thickening in atherosclerotic rabbits can be measured quantitatively by using MRI combined with 3D morphology image processing operators.

Animals↗
PubMed1999

Amphiphilic association of ibuprofen and two nonionic cellulose derivatives in aqueous solution.

The aqueous interaction of the sodium salt of ibuprofen with the cellulose ethers ethyl hydroxyethyl cellulose, EHEC, and hydroxypropyl methyl cellulose, HPMC, has been investigated in the concentration range 0-500 mM ibuprofen and 0.1-1% (w/w) polymer, by cloud point, capillary viscometry, equilibrium dialysis, and fluorescence probe techniques. Ibuprofen forms micelles in pure water, with the critical micelle concentration, cmc, at 180 mM. A combination of time-resolved and static fluorescence quenching shows that micelle-like ibuprofen aggregates are formed in the solution. The average aggregation number of pure ibuprofen micelles in water is about 40. In the presence of EHEC or HPMC the aggregation numbers decrease. The interaction of ibuprofen with cellulose ethers is similar to the normally accepted model for polymer-surfactant interaction, although more complex. Ibuprofen adsorbs to the polymer in the form of mixed polymer-drug micelles, noncooperatively up to cmc and cooperatively when cmc is passed. The interaction starts below 50 mM ibuprofen as monitored by the fluorescent probes pyrene and 1,3-di(1-pyrenyl)propane, P3P, with a maximum in microviscosity below cmc, corresponding to polymer-dense mixed micelles. The study illustrates the importance of a precise apprehension of the aggregation behavior as a background for transport studies in drug-polymer systems.

Adsorption↗
PubMed1999

Treatment with high dose [(111)In-DTPA-D-PHE1]-octreotide in patients with neuroendocrine tumors--evaluation of therapeutic and toxic effects.

Carcinoid tumors and endocrine pancreatic tumors often express somatostatin receptors (sst). Tumor spread may be visualized by sst scintigraphy using [(111)In-DTPA-D-Phe1]-octreotide. In this study, tumor targeting therapy with [(111)In-DTPA-D-Phe1]-octreotide at high doses (6 GBq every third week) was used to treat patients with sst-expressing tumors. Five patients entered the protocol and three were evaluable for response, while all could be evaluated for toxicity. Two patient responded with a significant reduction in tumor markers (> 50%). The third patient showed increasing levels of tumor markers. Side effects were expressed as depression of bone-marrow function. In one patient a grade 4 reduction in platelet count was observed requiring several thrombocyte transfusions. In another two patients platelet counts decreased significantly. We conclude that treatment with [(111)In-DTPA-D-Phe1]-octreotide can be used in patients with neuroendocrine tumors but blood parameters have to be carefully monitored to avoid severe side effects.

Aged↗
PubMed1999

Calculated effects of displacement errors in external beam radiotherapy of prostatic adenocarcinoma.

In order to evaluate the impact on the biological effective dose (BED) of irradiation delivered to a tumour with large displacement errors (LDE) and to estimate the effect on local control, simulated treatment of prostatic adenocarcinoma was performed. The calculation of BED in combination with the critical-voxel model and the LQ model was used to evaluate the effect of different combinations of LDEs. The model is called the Dose Volume Inhomogeneity Corrected BED (DVIC-BED) model. The dose-response curve was assumed to follow Poisson statistics. Different combinations of radiobiological parameters were used to test the model. A simulated clinical treatment with a dose of 66-80 Gy in 2 Gy fractions was carried out to evaluate displacement errors and non-optimal dose distributions. Five random LDEs excluding 33% of the target volume corresponded to an overall dose reduction of 3-5 Gy compared with a 10 Gy reduction if 100% of the target is missed five times. A 5 Gy decrease in dose corresponds to a reduction in clinical or chemical control up to 10-25% in the interval 65-85 Gy. LDEs in different directions are less deleterious than errors occurring in the same direction. Different alpha/beta-ratios (3-15) had little effect on the DIC-BED, but the effect of different alpha values (0.05, 0.2 and 0.5) was large. However, the results depend on radiobiological parameters for prostatic adenocarcinoma, which not are well known, and further studies in the field should be encouraged.

Adenocarcinoma↗
PubMed1999

Radioimmunotherapy of DU-145 tumours in nude mice--a pilot study with E4, a novel monoclonal antibody against prostate cancer.

The anti-tumour effect of the 131I-labelled antiprostate monoclonal antibody (MAb) E4 was studied in an experimental model with 41 nude mice, subcutaneously xenografted with a human prostate cancer cell line (DU-145). The mice were divided into four study groups, i.e. one receiving single and another repeated injections of the radiolabelled MAb. A third group was injected with non-labelled MAb, and the fourth served as an untreated control group. The tumour volumes increased similarly in all groups during the 27-day observation period. The tumour tissue was morphologically disintegrated in the group that received repeated radioimmunotherapy (RIT). The tumours from this group contained large fluid-filled cystic parts and demonstrated pronounced cellular and subcellular polymorphism in the remaining viable tumour tissue. The untreated control tumours and single therapy tumours remained solid. The proportion of the total tumour volume that consisted of viable tumour cells, as determined by morphometric techniques, was significantly lower in the 131I-E4-treated groups. The use of 131I-labelled E4 MAb has thus demonstrated a promising therapeutic potential.

Animals↗
PubMed1999

Patient positioning using artificial intelligence neural networks, trained magnetic field sensors and magnetic implants.

The purpose of this study was to evaluate the precision of a sensor and to ascertain the maximum distance between the sensor and the magnet, in a magnetic positioning system for external beam radiotherapy using a trained artificial intelligence neural network for position determination. Magnetic positioning for radiotherapy, previously described by Lennernäs and Nilsson, is a functional technique, but it is time consuming. The sensors are large and the distance between the sensor and the magnetic implant is limited to short distances. This paper presents a new technique for positioning, using an artificial intelligence neural network, which was trained to position the magnetic implant with at least 0.5 mm resolution in X and Y dimensions. The possibility of using the system for determination in the Z dimension, that is the distance between the magnet and the sensor, was also investigated. After training, this system positioned the magnet with a mean error of maximum 0.15 mm in all dimensions and up to 13 mm from the sensor. Of 400 test positions, 8 determinations had an error larger than 0.5 mm, maximum 0.55 mm. A position was determined in approximately 0.01 s.

Humans↗
PubMed1999

[111In-DPTA-D-Phe1]-octreotide scintigraphy in the management of patients with advanced renal cell carcinoma.

Somatostatin receptor scintigraphy using the 111In-labelled somatostatin analogue octreotide (Octreoscan) was performed in 9 patients with metastatic renal cell carcinoma. In total 11 scintigraphies were performed. Positive tumor uptakes were observed in 9 patients. The results of the octreotide scans were correlated to diagnostic CT and/or X-ray images. Forty (59%) out of 68 known tumor localizations were visualized with the octreotide scan. A second scan following therapy was performed in two patients. These patients showed progressive disease despite treatment and also exhibited intensified uptakes at octreotide scintigraphy. One false positive lesion was observed in the 40 lesions visualized in scintigraphy. It was concluded that renal cell carcinoma expresses somatostatin receptors, as could be visualized with Octreoscan scintigraphy. The scintigraphic technique can be used as an instrument for in vivo characterization of the disease. The data could also form a basis for future investigations regarding the possible therapeutic effect of octreotide in the management of renal cell cancer.

Aged↗
PubMed1999

High pregnancy rates and successful prevention of severe ovarian hyperstimulation syndrome by 'prolonged coasting' of very hyperstimulated patients: a multicentre study.

In a multicentre trial, 65 in-vitro fertilization (IVF)-embryo transfer cycles were severely hyperstimulated. Instead of cancelling the cycle, gonadotrophins were withheld for a 'coasting period' until serum oestradiol concentrations had dropped below 10,000 pmol/l (mean 4.3 days), and then human chorionic gonadotrophin was administered. Four cycles were cancelled and there were 61 oocyte aspirations. A total of 103 fresh embryos was transferred to 53 patients, resulting in a pregnancy rate of 42% per started cycle (51% per embryo transfer), with an implantation rate of 31%. Only one patient developed severe ovarian hyperstimulation syndrome (OHSS). Four patients developed moderate OHSS. In all, two patients were hospitalized for OHSS. In order to optimize the coasting procedure, it seems important that each IVF centre identifies its appropriate cut-off limits for serum oestradiol concentrations and follicle size for initiating and ending of the coasting period. Correctly handled, it seems to be a major advance in the search for improved stimulation policies for high-responders.

Adult↗
PubMed1999

The estrogen receptor family.

A significant flow of new data is currently being generated within the field of estrogen receptors and their mechanisms of action. This is primarily a result of the development of estrogen receptor knockout mice and the discovery of the second estrogen receptor, estrogen receptor beta. Both estrogen receptors appear to be involved in a multitude of regulatory events, the details of which will be worked out within the next few years. Estrogen receptor alpha appears to play a major role in the regulation of reproductive events and estrogen receptor alpha knockout female mice are completely infertile. Estrogen receptor beta knockout females have severe but incomplete infertility. Estrogen receptor beta gene mutations may, therefore, be of great clinical interest because they could perhaps explain some cases in which ovarian dysfunction leads to human infertility. Both receptors appear to be of essence for the cardiovascular system. Future studies will determine the relative importance of estrogen receptors alpha and beta in bone, the urogenital tract, the immune system, and the central nervous system, as well as in other estrogen target tissues.

Animals↗
PubMed1999

Defecographic study of rectal evacuation in constipated patients and control subjects.

PURPOSE: To validate a computer-based area calculation method of quantification of rectal evacuation by using defecography videotapes and to use that method to compare evacuation in constipated patients with that in control subjects. MATERIALS AND METHODS: For validation of the method, simultaneous defecography and weight measurements were compared in 36 patients with constipation or incontinence. Evacuation was calculated as the rate of change of the contrast medium-covered rectal area (percentage per second) or of the evacuated amount of contrast medium (percentage per second [relative] and grams per second [absolute]). After method validation, from a series of 215 consecutive constipated patients, individuals with an isolated radiologic diagnosis of intussusception greater than 0.6 cm (n = 27), rectocele greater than 2 cm (n = 19), enterocele (n = 12), or paradoxic puborectal muscle contraction (n = 12) were selected. Rectal evacuation in these groups was compared with that in 30 control subjects. RESULTS: Rectal evacuation rates measured at defecography correlated well with weighed amounts of evacuated contrast medium during the initial and total evacuation periods in 21 patients without contrast medium leak (r = 0.92, P < .001). Constipation overall, a rectocele greater than 2 cm, or paradoxic puborectal muscle contraction were associated with impaired evacuation (P < .001). CONCLUSION: Area calculations of rectal evacuation reflect rectal emptying. A rectocele greater than 2 cm or a paradoxic puborectal muscle contraction may be associated with obstructed defecation.

Adult↗
PubMed1999

Signal transduction pathways involved in the synergistic stimulation of prostaglandin production by interleukin-1beta and tumor necrosis factor alpha in human gingival fibroblasts.

Accumulating evidence indicates that prostaglandins play an important role in the pathogenesis of periodontal disease. In this study, the effects and interactions between IL-1beta and TNFalpha on prostaglandin production and its regulation were investigated. The cytokines IL-1beta and TNFalpha stimulated prostaglandin E2 (PGE2) and prostacyclin (PGI2) production in gingival fibroblasts. Simultaneous treatment of the cells with IL-1beta and TNFalpha resulted in a synergistic stimulation of PGE2 and PGI2 formation. IL-1beta and, to a lesser extent, TNFalpha stimulated the release of 3H-arachidonic acid (3H-AA), and simultaneous addition of IL-1beta and TNFalpha further increased the release of 3H-AA from pre-labeled gingival fibroblasts. Furthermore, IL-1beta and, to a lesser extent, TNFalpha induced the expression of cyclooxygenase-2 (COX-2) mRNA. Simultaneous addition of IL-1beta and TNFalpha synergistically enhanced COX-2 mRNA levels, accompanied by a corresponding stimulation of PGE2 synthesis. Neither IL-1beta, TNFalpha, nor the combination of these two cytokines affected COX-1 mRNA levels. PMA, known to activate protein kinase C (PKC), enhanced the stimulatory effect of IL-1beta, TNFalpha, and the combination on COX-2 mRNA levels accompanied by a corresponding increase in PGE2 production. The phospholipase A2 (PLA2) inhibitor, BPB, and the PKC inhibitor, BIS, reduced PGE2 production, whereas dexamethasone, indomethacin, and NS-398 completely abolished PGE2 production induced by IL-1beta, TNFalpha, and the combination. The study indicates that the synergistic stimulation of prostaglandin production by IL-1beta, and TNFalpha is mediated partly at the level of COX-2 and partly at the level of PLA2 and that PKC is involved in the signal transduction of the synergy between the two cytokines. The synergy between IL-1beta and TNFalpha may play an important role in the inflammatory processes in gingival tissue in vivo.

Arachidonic Acid↗
PubMed1999

The estrogen receptor enhances AP-1 activity by two distinct mechanisms with different requirements for receptor transactivation functions.

Estrogen receptors (ERs alpha and beta) enhance transcription in response to estrogens by binding to estrogen response elements (EREs) within target genes and utilizing transactivation functions (AF-1 and AF-2) to recruit p160 coactivator proteins. The ERs also enhance transcription in response to estrogens and antiestrogens by modulating the activity of the AP-1 protein complex. Here, we examine the role of AF-1 and AF-2 in ER action at AP-1 sites. Estrogen responses at AP-1 sites require the integrity of the ERalpha AF-1 and AF-2 activation surfaces and the complementary surfaces on the p160 coactivator GRIP1 (glucocorticoid receptor interacting protein 1), the NID/AF-1 region, and NR boxes. Thus, estrogen-liganded ERalpha utilizes the same protein-protein contacts to transactivate at EREs and AP-1 sites. In contrast, antiestrogen responses are strongly inhibited by ERalpha AF-1 and weakly inhibited by AF-2. Indeed, ERalpha truncations that lack AF-1 enhance AP-1 activity in the presence of antiestrogens, but not estrogens. This phenotype resembles ERbeta, which naturally lacks constitutive AF-1 activity. We conclude that the ERs enhance AP-1 responsive transcription by distinct mechanisms with different requirements for ER transactivation functions. We suggest that estrogen-liganded ER enhances AP-1 activity via interactions with p160s and speculate that antiestrogen-liganded ER enhances AP-1 activity via interactions with corepressors.

Binding Sites↗
PubMed1999

Expression of prostasome-like granules by the prostate cancer cell lines PC3, Du145 and LnCaP grown in monolayer.

Prostasomes are a granular type of secretory product in the human prostate gland cells. It is not known, whether in vitro grown cells derived from human prostate cancers also express prostate secretory components containing granules with properties similar to the prostasomes. Therefore, we carried out the present investigation and found that cytospins of in vitro grown PC3, DU145 and LNCaP cells generally expressed a granular secretion. DU145 demonstrated the highest ratio of cells with granules (about 90%), while cytospins of PC3 and LNCaP contained less stained cells (50-70%). Purified granules from PC3 cells were immunoreactive with a monoclonal antibody (mAb78) originally raised against human seminal prostasomes. The PC3 granules also shared the property with human seminal prostasomes having an elevated UV260/UV280 absorbance ratio. On the other hand we found a low aminopeptidase activity in PC3 granules contrary to that of human prostasomes. Prostasomes may form a heterogeneous group with different properties due to the source from which they are isolated and perhaps it is justified to recognize them as different members of a prostasome family.

Aminopeptidases↗