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Biomedical subjects

S Pettersen

Publications and source records attributed to S Pettersen.

7 recordsLinked to original sources

Modulation of glioma cell invasion and motility by adenoviral gene transfer of PAI-1.

A number of studies have emphasized the role of PAI-1 as an important regulator of tumor cell invasion and metastasis. The hallmark of primary tumors of the central nervous system and glioblastomas in particular is the diffuse invasion into the normal brain tissue. Since PAI-1 is expressed in such tumors, we studied the effect of adenoviral-mediated transfer of the PAI-1 gene in regulating the in vitro invasiveness of D54Mg glioma cells into Matrigel, and into fetal rat brain aggregates. Treatment of D54Mg cells with 50 MOI (multiplicity of infection) of the replication defective vector AdCMVPAI-1 increased PAI-1 expression 23-fold compared to control vectors, and the invasion through Matrigel was reduced by 67%. The motility of the cells was reduced by 58% compared to controls (indicating that inhibition of motility was the principal effect of PAI-1 in these cells). The ability of D54Mg tumor spheroids to invade fetal rat brain aggregates was not reduced by the PAI-1 gene transfer. The results show that overexpression of PAI-1 can inhibit glioma cell motility and invasion through extracellular matrix (ECM) components, like laminin and collagen, but does not inhibit tumor cell invasion in a three-dimensional invasion assay, simulating normal brain tissue having a different ECM and interstitial composition. The different results obtained in the two invasion assays reflect the complex biological effects of the uPA/PAI-1 system, and questions a simplistic view of PAI- I as an inhibitor of brain tumor invasion.

Adenoviridae↗

Expression of matrix metalloproteinases and the metastasis-associated gene S100A4 in human neuroblastoma and primitive neuroectodermal tumor cells.

BACKGROUND: Matrix metalloproteinases (MMPs) and their endogenous inhibitors (tissue inhibitors of MMPs; TIMPs) have been shown to correlate with in vitro invasiveness and clinical outcome in several adult malignancies. The importance of MMP and TIMP expression in neuroblastoma (NB) and primitive neuroectodermal tumors (PNET) is incompletely understood. The aim of the current study was to relate in vitro invasion of NB and PNET cell lines with MMP and TIMP expression and evaluate the effect of a synthetic MMP inhibitor. Furthermore, S100A4 levels were determined because recent reports have suggested a possible association between MMPs, TIMPs, and the metastasis-associated gene S100A4. METHODS: Expression of MMPs, TIMPs, and S100A4 was evaluated at both mRNA and protein levels in 2 human NB and 2 PNET cell lines. In vitro invasion and effects of the synthetic MMP inhibitor Marimastat were assessed in the Transwell chamber assay. RESULTS: The most invasive cells expressed the highest levels of MMPs and S100A4. Marimastat reduced invasion by 30%. CONCLUSIONS: In vitro invasion correlated with MMP and S100A4 expression. The fact that Marimastat reduced in vitro invasion is encouraging for further studies on a possible therapeutic application for proteinase inhibitors.

Blotting, Northern↗

The North Norwegian Health Net.

The North Norwegian Health Net is a comprehensive scheme to connect all health-care institutions in the area to a national computer network. Services available include telemedicine, e-mail and Web access. A general practitioner has responsibility for ensuring that the clinical information is correct. Medical departments are responsible for the content of their own Web pages. All institutions require authorization before connection to ensure data protection and security. Changes in communication between primary- and secondary-care sectors are being monitored. To date the implementation of the network programme has gone smoothly.

Computer Communication Networks↗

Effects of hypothermia and rewarming on phospholipase C-evoked glycerol output in rat myocardial cells.

The combined action of phosphatidylcholine preferring phospholipase C (PC-PLC) and intracellular lipases has recently been shown to cause glycerol output in energy deprived rat cardiomyocytes. In the present study we examined the effect of hypothermia and rewarming on PC-PLC evoked glycerol output in freshly isolated, calcium-tolerant myocytes. The cells were preincubated for 60 min at hypothermic (5 degrees C) or normothermic (37 degrees C) conditions in Krebs-Henseleit bicarbonate buffer (pH 7.4) supplemented with 1 mM DL-carnitine, 1% B.S.A. and 5 mM glucose. Addition of PC-PLC resulted in a significantly higher (P less than 0.05) output of glycerol in myocytes undergoing rewarming than in myocytes kept constantly at 5 degrees C or 37 degrees C. The values obtained for PC-PLC induced glycerol output (difference in glycerol output between incubations with and without PC-PLC) were 6.77 +/- 2.6 (37 degrees C), 4.54 +/- 1.7 (5 degrees C) and 22.85 +/- 5.9 (5-37 degrees C) nmol/10(6) cells.h. Rewarming in addition caused a significantly higher (P less than 0.05) leakage of lactate dehydrogenase (LDH) from the rewarmed cells as compared to cells at constant temperatures (5 degrees C or 37 degrees C). However, there was no additional effect of PC-PLC on LDH leakage. The elevated PC-PLC induced glycerol output in rewarmed myocytes was not related to a fall in the percentage of rod-shaped cells or a reduced cellular content of ATP, since no differences could be detected between the various myocyte preparations with respect to these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Cerebral capillary bed structure of normotensive and chronically hypertensive rats.

In this study cerebral capillary bed structure and the effects of chronic hypertension on these systems have been assessed in 6- to 7-month-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Capillary diameter (D), profile frequency (Na), volume fraction (Vv), and surface area (Sv) were quantitated by light microscopic morphometry of eight brain areas including the sensorimotor cortex and subfornical organ. Previously presented data from normotensive Sprague-Dawley rats (SpD) of similar age were also compared. Within each of the three rat strains, D, Na, Vv, and Sv varied among brain areas. For the sensorimotor cortex and subfornical organ, capillary profile frequency differed significantly among the three rat strains. In SHR and WKY, there was an inverse correlation between profile frequency and diameter, i.e., as Na increased among brain areas, D decreased. In six brain areas capillary volume fraction and surface area were identical in SHR and WKY, but were lower in SpD. Consistent differences between SHR and WKY were found only for the subfornical organ, which suggests some involvement of this structure in hypertension. Since there were few statistically significant differences between SHR and WKY and many statistically significant differences between the two normotensive strains, cerebral capillary bed structure seems to be independent of arterial blood pressure in most brain areas of these rats.

Animals↗

Electrophoretic study of proteins associated with pseudo-exfoliation syndrome.

Lens capsule and aqueous humour from cataractous eyes with and without pseudo-exfoliation syndrome have been studied by SDS-PAGE electrophoresis. Four cataractous lenses with and four without pseudo-exfoliation were used. The pseudo-exfoliation positive capsule revealed two polypeptides not present in the control material, and accordingly, these components were regarded to be pseudo-exfoliation specific. The molecular weight of the respective polypeptides was estimated to be 14,400 and 16,300. No marked differences were found between the pseudo-exfoliation positive and negative aqueous humours.

Aqueous Humor↗

Structural and functional variations in capillary systems within the brain.

The major hypothesis of this study is that there are differences among brain areas in capillary bed structure and function. Three general differences between circumventricular organ and non-CVO capillary beds were found. First, the PS products for AIB were about 300 times greater in CVO capillaries than in non-CVO (blood-brain barrier) capillaries. Second, the frequency of endothelial cell fenestrations was much greater in CVO capillaries than in non-CVO capillaries and the fenestrae may be structural modifications of endothelial cells that permit ready passage of solutes such as AIB. Third, the frequency of mitochondria was greater in BBB capillaries than in CVO capillaries; this high metabolic potential of BBB capillaries may be associated, in part, with "carrier-mediated" transport of various solutes between plasma and cerebral interstitial fluid. Capillary bed differences among all (i.e., both CVO and non-CVO) brain structures were also observed. Among these differences are: rate of blood flow, mean transit time of albumin, capillary volume and surface area, perfused microvessel blood volume, apparent percentage of perfused capillaries, PS products for AIB, and frequency within the endothelium of vesicular profiles.

Aminoisobutyric Acids↗