| 11. |
- Lammi, Mikko, 1961-
(författare)
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Influences of in vivo and in vitro loading on the proteoglycan synthesis of articular cartilage chondrocytes
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this study, the biosynthesis of proteoglycans (PGs) was examined in articular cartilage of canine hip joint after long-distance running experiment and in bovine chondrocyte cultures during in vitro loading with hydrostatic pressure. In addition, new assays were developed for more sensitive quantitation of glycosaminoglycans (GAGs) and PGs.Anterior (weight-bearing) and posterior (less weight-bearing) areas of the femoral head from young beagles were labeled after long-term, longdistance running exercise. Total sulpahte incorporation rates were determined and distribution of of the incorporated sulphate in the tissue was localized by quantitative autoradiography. Concentration and extractability of the PGs were determined, and PG structures were studied by gel filtration, agarose gel electrophoresis, and chemical determinations. In the less weight-bearing area, the amount of extractable PGs was decreased, simultaneously with an increased concentration of residual GAGs in the tissue after 4M GuCl extraction. In the weight-bearing area, no marked alterations were noticed. The congruency of the femoral head seems to protect the cartilage from untoward alterations that occur in the femoral head condyles subjected to the same running program.The effect of hydrostatic pressure on PG metabolism of chondrocyte cultures was examined during 20 hours' exposure of chondrocytes to 5 and 30 MPa pressures. The continuous 30 MPa pressure reduced total PG synthesis by 37 % as measured by [35S]sulphate incorporation, in contrast to the 5 MPa which had no effect. Continuous 30 MPa hydrostatic pressure also reduced the steady-state mRNA level of aggrecan. The cyclic pressures showed a frequency dependent stimulation (0.5 Hz, + 11 %) or inhibition (0.017 Hz, -17 %). Aggrecans secreted under continuous 30 MPa pressure showed a retarded migration in 0.75 % SDS-agarose gel electrophoresis and also eluted earlier on Sephacryl S-1000 gel filtration, indicative of larger molecular size. The results demonstrate that high hydostatic pressure can influence the synthesis of PGs in chondrocytes both at the transcriptionl and translational/posttranslational levels.
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| 12. |
- Bixo, Marie, 1957-
(författare)
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Ovarian steroids in rat and human brain : effects of different endocrine states
- 1987
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ovarian steroid hormones are known to produce several different effects in the brain. In addition to their role in gonadotropin release, ovulation and sexual behaviour they also seem to affect mood and emotions, as shown in women with the premenstrual tension syndrome. Some steroids have the ability to affect brain excitability. Estradiol decreases the electroshock threshold while progesterone acts as an anti-convulsant and anaesthetic in both animals and humans. Several earlier studies have shown a specific uptake of several steroids in the animal brain but only a few recent studies have established the presence of steroids in the human brain.In the present studies, the dissections of rat and human brains were carried out macroscopically and areas that are considered to be related to steroid effects were chosen. Steroid concentrations were measured by radioimmunoassay after extraction and separation with celite chromatography. The accuracy and specificity of these methods were estimated.In the animal studies, immature female rats were treated with Pregnant Mare's Serum Gonadotropin (PMSG) to induce simultaneous ovulations. Concentrations of estradiol and progesterone were measured in seven brain areas pre- and postovulatory. The highest concentration of estradiol, pre- and postovulatory, was found in the hypothalamus and differences between the two cycle phases were detected in most brain areas. The preovulatory concentrations of progesterone were low and the highest postovulatory concentration was found in the cerebral cortex.In one study, the rats were injected with pharmacological doses of progesterone to induce "anaesthesia". High uptake of progesterone was found and a regional variation in the formation of 5<*-pregnane-3,20-dione in the brain with the highest ratio in the medulla oblongata.Concentrations of progesterone, 5a-pregnane-3*20-dione, estradiol and testosterone were determined in 17 brain areas of fertile compared to postmenopausal women. All steroids displayed regional differences in brain concentrations. Higher concentrations of estradiol and progesterone were found in the fertile compared to the postmenopausal women.In summary, these studies show that the concentrations of ovarian steroids in the brain are different at different endocrine states in both rats and humans and that there are regional differences in brain steroid distribution.
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| 13. |
- Peetre, Christina, et al.
(författare)
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A tumor necrosis factor binding protein is present in human biological fluids
- 1988
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 41:5, s. 414-419
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Tidskriftsartikel (refereegranskat)abstract
- Tumor necrosis factor (TNF) possesses both beneficial and toxic bioactivities. Mechanisms may operate to counteract harmful effects. We have identified a TNF binding protein (TNF-BP), which shows increased levels in serum and urine of patients on regular hemodialysis treatment (RDT). TNF-BP inhibited the specific binding of human recombinant TNF (rTNF) to its cell surface receptor. Results from gel chromatography demonstrated the presence in serum and urine of a macromolecule with an apparent molecular weight of 50,000, which formed a complex with rTNF. A 62-fold purification of TNF-BP from urine of patients on RDT was achieved by ion exchange chromatography and gel chromatography. Partially purified TNF-BP reduced the growth inhibitory effect of rTNF on a susceptible leukemia cell line. TNF-BP may act as a regulator of the biological activity of TNF and could have beneficial effects in certain inflammatory conditions.
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| 14. |
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| 15. |
- Arner, Anders, et al.
(författare)
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Effects of Ca2+ on force-velocity characteristics of normal and hypertrophic smooth muscle of the rat portal vein
- 1985
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 124:4, s. 525-533
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Tidskriftsartikel (refereegranskat)abstract
- Portal hypertension was induced in rats by partial ligation of the hepatic branches of the portal vein. After 5 days of hypertension the portal veins were taken out and mounted for isometric and quick-release experiments. Portal veins from sham-operated normal rats served as controls. The ligated veins had an increased cross-sectional area, indicating smooth-muscle hypertrophy. Although the absolute magnitude of active force of these veins was increased, the active force per cross-sectional area was decreased, indicating an alteration in the properties of the contractile system. No difference in the Ca2+ concentration-response relations to K+-activated intact control and hypertrophic veins was found. In chemically skinned preparations, devoid of functional plasma membranes, the hypertrophic veins had similar Ca2+ sensitivity (in the presence of I microM calmodulin) but a lower force per cross-sectional area. Force-velocity relations were determined in K+-activated intact preparations. In control veins a reduction in extracellular Ca2+ was associated with a significant reduction in both isometric force and maximal shortening velocity (Vmax). In hypertrophic veins the decreased isometric force at maximal activation was associated with a low Vmax. A comparison between hypertrophic and submaximally stimulated control vessels showed corresponding Vmax and isometric force values. We conclude that the low isometric force of hypertrophic veins is associated with a lower rate of cross-bridge turnover. This could be an effect of alterations in the activation mechanisms or in the intrinsic properties of the contractile system itself.
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| 16. |
- Arner, Anders, et al.
(författare)
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Energy turnover and lactate dehydrogenase activity in detrusor smooth muscle from rats with streptozotocin-induced diabetes
- 1993
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 147:4, s. 375-383
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Tidskriftsartikel (refereegranskat)abstract
- Force generation and tissue glucose metabolism were measured in the urinary bladder smooth muscle from rats with streptozotocin-induced diabetes (7-8 wk duration). Bladder wet wt was almost 4-fold higher in the diabetic animals compared with the untreated controls. Morphological analysis showed that the growth was associated with hypertrophy of the smooth muscle component in the bladder wall. Force generation of isolated bladder strip preparations was measured in vitro at different ambient oxygen tensions. Activation of intramural nerves, with electrical field stimulation, induced contractions that were unaffected by reduction of oxygen tension down to PO2 100 mmHg for both control and diabetic muscle strips. At zero PO2 force was reduced by approximately 10-20%, in both groups. High-K+ solution induced 'tonic' contractions that were slightly more inhibited by lowering PO2. At intermediate PO2 (between 100 and 20 mmHg) the diabetic muscle gave slightly higher force. At zero PO2 no significant difference could be detected between strips from control and diabetic animals. Oxygen consumption and lactate production in the preparations were determined at a PO2 of 290 mmHg and related to the volume of smooth muscle. At zero PO2, lactate formation increased 3- to 4-fold. The metabolic tension cost was lower at zero PO2. No differences in basal and contraction related metabolic rates could be detected between the two groups under normoxic and anoxic conditions. The maximal activity of lactate dehydrogenase (LDH) determined in tissue samples was about 2-fold higher in the diabetic bladder muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 17. |
- Arner, Anders, et al.
(författare)
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Metabolism and force in hypertrophic smooth muscle from rat urinary bladder
- 1990
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Ingår i: American Journal of Physiology: Cell Physiology. - 1522-1563. ; 258:5 Pt 1, s. 923-932
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Tidskriftsartikel (refereegranskat)abstract
- Ten days of urinary outlet obstruction in the rat induced a threefold increase in bladder weight. Active force of control and hypertrophic bladder muscle strips was measured at varying PO2 levels after high-K+, carbachol, or electrical field stimulation. Highest force output was obtained with carbachol. Force per muscle area was lower in the hypertrophic muscles. The basal rates of oxygen consumption and lactate formation were similar in the two groups. The metabolic tension cost (ATP turnover/active force) was similar in the two groups for activation with high K+ and carbachol. In anoxia the active force decreased, but this was less pronounced in the hypertrophied muscle. Hypertrophied muscle could, in contrast to the controls, maintain a sustained K+ contracture in anoxia. Basal metabolic rates and tension cost were markedly reduced in anoxia for both groups. The lower force per area with unaltered tension cost, in hypertrophic muscles under all experimental conditions, may reflect unaltered intrinsic properties of the contractile system, although the amount of contractile material has decreased relative to cell volume. The increased resistance to anoxia may reflect a metabolic adaptation to impaired oxygen supply to the hypertrophied tissue.
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| 18. |
- Arner, Anders, et al.
(författare)
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Structural and mechanical adaptations in rat aorta in response to sustained changes in arterial pressure
- 1984
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 122:2, s. 119-126
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Tidskriftsartikel (refereegranskat)abstract
- Structural and mechanical adaptations in response to sustained changes in arterial pressure were studied on abdominal aorta of the male rat. Two models were used: 1. Aortic ligature (L), immediately below the renal arteries producing hypotension distal to the knot (duration before sacrifice 6 weeks or 3 months). 2. One-clip renal hypertensive rats (H) (duration 6 weeks). Normotensive sham-operated rats (C) served as controls. At sacrifice mean tail artery pressure was L: 58 +/- 1, C: 110 +/- 3, and H: 163 +/- 5 mmHg (SE, N=6). Segments of abdominal aorta were mounted in vitro for determination of their length-tension relations (activation: High-K+ solution with 2.5 mM Ca2+). At end of experiments the vessels were supramaximally stimulated at optimal circumference (1o) for active force (activation: High-K+ solution with 10 mM Ca2+, and 10(-5) M noradrenaline), and then fixated for light and electron microscopy. Passive and active length-tension relations were shifted towards lower and higher circumference values for hypo- and hypertensive vessels, respectively. The 1o values were L: 3.60 +/- 0.13, C: 4.44 +/- 0.19, and H: 4.91 +/- 0.29 mm. The media thickness at 1o was reduced in L: 56.0 +/- 3.3, and increased in H: 81.3 +/- 2.4 compared to C: 73.4 +/- 1.8 micron. Maximal active wall stress was L: 46.6 +/- 9.8, C: 74.2 +/- 7.0, and H: 83.8 +/- 7.7 mN/mm2. Intracellular volume (ICV) in the media was L: 30 +/- 2, C: 45 +/- 3, and H: 44 +/- 1% (n=4 for each).
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| 19. |
- Chen, Y, et al.
(författare)
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Increase in insulin-like growth factor I in hypertrophying smooth muscle
- 1994
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Ingår i: American Journal of Physiology - Endocrinology and Metabolism. - 1522-1555. ; 266:2 Pt 1, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- The present study focuses on the role of the insulin-like growth factor (IGF) system in the development of smooth muscle hypertrophy. Hypertrophy was initiated by partial ligation of portal vein or urethra in female Sprague-Dawley rats weighing approximately 220 g. Levels of mRNA were analyzed by solution hybridization. Seven days after ligation, the wet weight of the portal vein was increased about threefold and the concentration of IGF-I mRNA was increased fourfold. The bladder wet weight was increased twofold 3 days after ligation and fourfold 10 days after ligation. IGF-I mRNA in the bladder was elevated 3-fold after 3 days and 2.5-fold after 10 days, whereas IGF binding protein 2 mRNA was increased approximately 2-fold after 3 days and 5-fold after 10 days. IGF-I receptor mRNA in the hypertrophying bladder remained unchanged. Increased levels of IGF-I were demonstrated with immunohistochemistry in both hypertrophying portal vein and urinary bladder. The results show a specific increase in IGF-I mRNA as well as an increased IGF-I immunoreactivity during hypertrophy of smooth muscle, which suggests that the local IGF-system may play a role in smooth muscle hypertrophy.
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| 20. |
- Malmqvist, Ulf, et al.
(författare)
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Contractile and cytoskeletal proteins in smooth muscle during hypertrophy and its reversal
- 1991
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Ingår i: American Journal of Physiology: Cell Physiology. - 1522-1563. ; 260:5, s. 1085-1093
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Tidskriftsartikel (refereegranskat)abstract
- Hypertrophy of rat urinary bladder smooth muscle was induced by partial urethral obstruction. Bladder weight increased from 70 to 240 mg after 10 days and to 700 mg after 7 wk. Removal of the obstruction after 10 days caused a regression of bladder weight to 130 mg. The relative volume of smooth muscle in the bladder wall increased during hypertrophy. The concentration of myosin in the smooth muscle cells decreased in 10-day hypertrophied bladders, whereas the concentration of actin was unchanged. The actin-myosin ratio was 2.3 in controls, 3.3 in 10-day obstructed bladders, and 2.9 in 7-wk obstructed bladders. After removal of obstruction, the ratio was normalized. Two isoforms of myosin heavy chains were identified (SM1 and SM2). The relative amount of SM2 decreased during hypertrophy. The relative proportion of actin isoforms (alpha, beta, and gamma) was altered toward more gamma and less alpha. These changes were reversible upon removal of the obstruction. Desmin was the dominating intermediate filament protein. The concentration of desmin and filamin increased in the hypertrophic bladders. The increased desmin-actin and filamin-actin ratios in obstructed bladders were normalized after removal of the obstruction. The results suggest that the turnover of contractile and cytoskeletal proteins is fast and can be regulated in response to changes in the functional demands in smooth muscle.
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