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T Jansson

Publications and source records attributed to T Jansson.

At least 19 recordsLinked to original sources
PubMed2006

Gestational and hormonal regulation of human placental lipoprotein lipase.

The fetal demand for FFA increases as gestation proceeds, and LPL represents one potential mechanism for increasing placental lipid transport. We examined LPL activity and protein expression in first trimester and term human placenta. The LPL activity was 3-fold higher in term (n = 7; P < 0.05) compared with first trimester (n = 6) placentas. The LPL expression appeared lower in microvillous membrane from first trimester (n = 2) compared with term (n = 2) placentas. We incubated isolated placental villous fragments with a variety of effectors [GW 1929, estradiol, insulin, cortisol, epinephrine, insulin-like growth factor-1 (IGF-1), and tumor necrosis factor-alpha] for 1, 3, and 24 h to investigate potential regulatory mechanisms. Decreased LPL activity was observed after 24 h of incubation with estradiol (1 micro g/ml), insulin, cortisol, and IGF-1 (n = 12; P < 0.05). We observed an increase in LPL activity after 3 h of incubation with estradiol (20 ng/ml) or hyperglycemic medium plus insulin (n = 7; P < 0.05). To conclude, we suggest that the gestational increase in placental LPL activity represents an important mechanism to enhance placental FFA transport in late pregnancy. Hormonal regulation of placental LPL activity by insulin, cortisol, IGF-1, and estradiol may be involved in gestational changes and in alterations in LPL activity in pregnancies complicated by altered fetal growth.

Adenosine Triphosphate↗
PubMed2006

Placental transport and metabolism in fetal overgrowth -- a workshop report.

Fetal overgrowth in pregnancies complicated by diabetes is the result of an increased substrate availability which stimulates fetal insulin secretion and fetal growth. However, despite strict glycemic control in modern clinical management of the pregnant woman with diabetes, fetal overgrowth remains an important clinical problem. Recent studies in vivo provide evidence for increased delivery of amino acids to the fetus in gestational diabetes (GDM) even when metabolic control is strict. This could be due to that truly normal maternal substrate levels cannot be achieved in diabetic pregnancies and/or caused by altered placental nutrient transport and metabolism. Studies in vitro demonstrate an up-regulation of placental transport systems for certain amino acids in GDM associated with fetal overgrowth. GDM is also characterized by changes in placental gene expression, including up-regulation of inflammatory mediators and Leptin. In type-I diabetes with fetal overgrowth the in vitro activity of placental transporters for both glucose and certain amino acids as well as placental lipoprotein lipase is increased. Furthermore, both clinical observations in type-I diabetic pregnancies and preliminary animal experimental studies suggest that even brief periods of metabolic perturbation early in pregnancy may affect placental growth and transport function for the remainder of pregnancy, thereby contributing to fetal overgrowth. Ultrasound measurements of fetal fat deposits and abdominal circumference as well as 3D ultrasound assessment of placental volume represent non-invasive techniques for in utero diagnosis of fetal and placental overgrowth. It is proposed that these methods represent valuable additions to the clinical management of the diabetic pregnancy. In conclusion, altered placental function may be a mechanism contributing to fetal overgrowth in diabetic pregnancies with apparent optimal metabolic control. It is proposed that detailed information on placental metabolism and transport functions obtained in vitro and in vivo represent a placental phenotype that provides important information and may facilitate diagnosis and improve clinical management of fetal overgrowth.

Amino Acid Transport Systems↗
PubMed2006

IFPA 2005 Award in Placentology Lecture. Human placental transport in altered fetal growth: does the placenta function as a nutrient sensor? -- a review.

Intrauterine growth restriction is associated with a range of alterations in placental transport functions: the activity of a number of transporters is reduced (Systems A, L and Tau, transporters for cationic amino acids, the sodium-proton exchanger and the sodium pump), placental glucose transporter activity and expression are unchanged whereas the activity of the calcium pump is increased. In contrast, accelerated fetal growth in association to diabetes is characterized by increased activity of placental Systems A and L and glucose transporters. Evidence suggests that these placental transport alterations are the result of specific regulation and that they, at least in part, contribute to the development of pathological fetal growth rather than representing a consequence to altered fetal growth. One interpretation of this data is that the placenta functions as a nutrient sensor, altering placental transport functions according to the ability of the maternal supply line to provide nutrients. Placental transporters are subjected to regulation by hormones. Insulin up-regulates several key placental transporters and maternal insulin may represent a "good nutrition" signal to increase placental nutrient transfer and the growth of the fetus. Preliminary evidence suggests that placental mammalian target of rapamycin, a protein kinase regulating protein translation and transcription in response to nutrient stimuli, may be involved in placental nutrient sensing.

Amino Acid Transport Systems↗
PubMed2005

Development of educational image databases and e-books for medical physics training.

Medical physics education and training requires the use of extensive imaging material and specific explanations. These requirements provide an excellent background for application of e-Learning. The EU projects Consortia EMERALD and EMIT developed five volumes of such materials, now used in 65 countries. EMERALD developed e-Learning materials in three areas of medical physics (X-ray diagnostic radiology, nuclear medicine and radiotherapy). EMIT developed e-Learning materials in two further areas: ultrasound and magnetic resonance imaging. This paper describes the development of these e-Learning materials (consisting of e-books and educational image databases). The e-books include tasks helping studying of various equipment and methods. The text of these PDF e-books is hyperlinked with respective images. The e-books are used through the readers' own Internet browser. Each Image Database (IDB) includes a browser, which displays hundreds of images of equipment, block diagrams and graphs, image quality examples, artefacts, etc. Both the e-books and IDB are engraved on five separate CD-ROMs. Demo of these materials can be taken from www.emerald2.net.

Biomedical Engineering↗
PubMed2004

Glucose transporter isoform 4 is expressed in the syncytiotrophoblast of first trimester human placenta.

BACKGROUND: Placental glucose transport mechanisms in early pregnancy are poorly understood. The aims of this study were to investigate the expression of glucose transporter (GLUT) isoforms 1, 3 and 4 in first trimester villous tissue, to assess the effects of insulin on glucose uptake and compare them with term. METHODS: The expression of GLUT isoforms was investigated using immunohistochemistry, Western blot and reverse transcription (RT)-PCR in trophoblast tissue from terminations at 6-13 weeks gestation and term. The effects of insulin (300 ng/ml, 1 h) on glucose uptake were studied in villous fragments. RESULTS: In the first trimester, GLUT1 and GLUT3 were present in the microvillous membrane and the cytotrophoblast, and GLUT4 in perinuclear membranes in the cytosol of the syncytiotrophoblast (ST). GLUT4 protein (48 kDa) and mRNA were identified in trophoblast homogenates. Whereas GLUT1 was expressed abundantly in term placenta, the expression of GLUT3 and 4 was markedly lower at term compared with first trimester. Insulin increased glucose uptake by 182% (n=6, P<0.05) in first trimester fragments, but not in term fragments. CONCLUSIONS: The insulin-regulatable GLUT4 is expressed in the cytosol of first trimester ST compatible with a role for GLUT4 in placental glucose transport in early pregnancy. The placental expression pattern of GLUT isoforms in early pregnancy is distinct from that later in pregnancy.

Blotting, Western↗
PubMed2004

Human placental taurine transporter in uncomplicated and IUGR pregnancies: cellular localization, protein expression, and regulation.

Transplacental transfer is the fetus' primary source of taurine, an essential amino acid during fetal life. In intrauterine growth restriction (IUGR), placental transport capacity of taurine is reduced and fetal taurine levels are decreased. We characterized the protein expression of the taurine transporter (TAUT) in human placenta using immunocytochemistry and Western blotting, tested the hypothesis that placental protein expression of TAUT is reduced in IUGR, and investigated TAUT regulation by measuring the Na(+)-dependent taurine uptake in primary villous fragments after 1 h of incubation with different effectors. TAUT was primarily localized in the syncytiotrophoblast microvillous plasma membrane (MVM). TAUT was detected as a single 70-kDa band, and MVM TAUT expression was unaltered in IUGR. The PKC activator PMA and the nitric oxide (NO) donor 3-morpholinosydnonimine decreased TAUT activity (P < 0.05, n = 7-15). However, none of the tested hormones, e.g., leptin and growth hormone, altered TAUT activity significantly. PKC activity measured in MVM from control and IUGR placentas was not different. In conclusion, syncytiotrophoblast TAUT is strongly polarized to the maternal-facing plasma membrane. MVM TAUT expression is unaltered in IUGR, suggesting that the reduced MVM taurine transport in IUGR is due to changes in transporter activity. NO release downregulates placental TAUT activity, and it has previously been shown that IUGR is associated with increased fetoplacental NO levels. NO may therefore play an important role in downregulating MVM TAUT activity in IUGR.

Adult↗
PubMed2004

Validation of fractional moving blood volume measurement with power Doppler ultrasound in an experimental sheep model.

OBJECTIVE: To compare fractional moving blood volume (FMBV) estimation using power Doppler ultrasound (PDU) with blood flow estimation using radioactive microspheres (RMS) for evaluation of fetal organ blood perfusion. METHODS: Blood flow was measured in the adrenal gland of nine exteriorized fetal lambs. Five fetal lambs underwent total umbilical cord occlusion in order to induce changes in the adrenal blood flow (asphyxia group). Four lambs were used as sham controls (control group). Three RMS injections, with coincident PDU recordings of the adrenal gland, were performed in each lamb. In the asphyxia group, measurements were taken before the cord occlusion, 5 min later and when the mean blood pressure decreased below 25 mmHg. In the control group, the measurements were done with an interval of 5 min. FMBV normalized for attenuation of PDU signals, and mean pixel intensity (MPI) were estimated offline. After completion of the study, adrenal blood perfusion was calculated according to the reference sample microsphere technique, using the isotope activity and expressed in mL/min/100 g. The correlation between RMS and FMBV and MPI, respectively, was analyzed individually for each lamb. RESULTS: In the asphyxia group, all lambs showed a marked reduction in the adrenal blood perfusion towards the third RMS injection. In the control group, the adrenal perfusion showed small variations throughout the experiment. In the total material, there was a higher correlation between FMBV and RMS (median, r = 0.90; range, 0.43-0.99) than between MPI and RMS (median, r = 0.55; range, -0.53 to 0.99). CONCLUSION: The FMBV method of quantifying PDU signals correlates highly with blood flow perfusion estimation using RMS in the fetal lamb adrenal gland.

Adrenal Glands↗
PubMed2004

Fractional moving blood volume estimation in the fetal lung using power Doppler ultrasound: a reproducibility study.

OBJECTIVE: To evaluate the reproducibility of fractional moving blood volume (FMBV) estimation in the fetal lung using power Doppler ultrasound (PDU). METHODS: The lung blood perfusion of 20 normally grown singleton fetuses at 32-35 weeks of gestation was evaluated by two experienced observers using PDU. Each observer recorded two consecutive sequences of images from the posterior part of the fetal lung and calculated FMBV offline. FMBV expresses the percentage of blood movement within a defined region of interest (ROI). Repeatability and agreement were evaluated by means of the intraclass (intraCC) and interclass (interCC) correlation coefficients. RESULTS: FMBV was successfully evaluated in 17/20 fetuses by both observers (kappa index 0.82; 95% CI 0.51-0.93). The intraCC for repeatability for Observer A was 0.92 (95% CI 0.78-0.96), and for Observer B 0.90 (95% CI 0.74-0.96). The mean difference between the first and the second measurement was 0.7% (SD 4.5%). The interCC for repeatability over time and between the operators was 0.70 (95% CI 0.56-0.76) and the mean difference between the observers was 0.6% (SD 4.65%). The interCC for agreement was 0.92 (95% CI 0.84-0.95) and the mean difference in FMBV results when both observers analyzed the same sequences offline was 0.6% (SD 3.85%). CONCLUSION: In the hands of experienced operators, using a well-defined ROI and standard settings, FMBV estimation is a reproducible method of quantifying power Doppler signals recorded from fetal lung blood perfusion.

Blood Flow Velocity↗
PubMed2004

Glucose metabolism in the human preterm and term placenta of IUGR fetuses.

Many fetuses suffering from intrauterine growth restriction (IUGR) are hypoglycaemic. However, the underlying mechanisms are not well established. An increased placental glucose consumption in IUGR could impair glucose transfer across the placenta. In this study we used two different approaches to investigate glucose metabolism in preterm and term placentae of IUGR fetuses. We determined activity and protein expression of the three rate-limiting glycolytic enzymes phosphofructo kinase (PFK), pyruvate kinase (PK) and hexokinase (HXK) in a cytoplasmic fraction of homogenates of placentae obtained from IUGR and appropriate for gestational age (AGA) pregnancies. Protein expression was assessed using Western blot and enzyme activities were determined in a spectrophotometer by measuring the rate of NADH oxidation (PFK and PK) or NADP reduction (HXK) in enzyme reactions coupled to the respective enzyme. To determine the distribution of the glycolytic enzymes immunocytochemistry was performed. We also measured glucose consumption and lactate production in fresh placental villous tissue using a perifusion system. The expression of PFK, PK and HXK as well as the activity of PK and HXK was unaltered in IUGR placentae. The activity of PFK on the other hand was 32 per cent lower in IUGR placentae (n=24, P<0.05). Immunocytochemistry confirmed the distribution of the enzymes to the cytoplasm of the syncytiotrophoblast. Placental glucose consumption in IUGR [0.06+/-0.01 micromol/(min*g), n=5] was not different from AGA [0.06+/-0.005 micromol/(min*g), n=12], whereas lactate production was decreased by 28 per cent in IUGR. These results do not support the hypothesis of increased placental glucose consumption but suggest an altered glycolytic pathway in the IUGR placenta.

Adult↗
PubMed2004

Non-gastric H+/K+ ATPase is present in the microvillous membrane of the human placental syncytiotrophoblast.

In humans, the non-gastric H(+)/K(+)ATPase (ATP1AL1) has previously been shown to be expressed in the epithelia of skin, kidney and colon. In this study we tested the hypothesis that the non-gastric H(+)/K(+)ATPase is localized to the syncytiotrophoblast, the transporting epithelium of the human placenta. Microvillous (MVM) and basal plasma membranes (BM) of the syncytiotrophoblast were isolated from term placenta and membrane proteins were separated using SDS-PAGE. The ATP1AL1 protein was identified as a 114 kD band in both MVM and BM by Western blot, however, the protein was more abundant in the MVM. Using immunocytochemistry H(+)/K(+)ATPase protein was localized in MVM but not BM. We constructed primers specific for ATP1AL1 and performed RT-PCR on RNA isolated from human placenta and human kidney. A product of the expected size could be detected in both tissues after 30 cycles of amplification. The sequence identity of this 517 nucleotide product was confirmed by sequencing and found to be identical to the human non-gastric H(+)/K(+)ATPase. The activity of this proton pump appears to be low in normal healthy placental at term, however, it is speculated that MVM non-gastric H(+)/K(+)ATPase may be important in pathological states. In conclusion, non-gastric H(+)/K(+)ATPase is present in the microvillous plasma membrane of the transporting epithelia of the human placenta.

Blotting, Western↗
PubMed2004

Triglyceride hydrolase activities and expression of fatty acid binding proteins in the human placenta in pregnancies complicated by intrauterine growth restriction and diabetes.

Triglyceride (TG) hydrolases in the placental microvillous plasma membrane (MVM) release fatty acids from circulating lipoproteins and represent the critical initial step in transplacental fatty acid transfer. We investigated the activity of two TG hydrolases in MVM isolated from placentas of appropriately grown for gestational age pregnancies and pregnancies complicated by intrauterine growth restriction (IUGR), insulin-dependent diabetes mellitus (IDDM) or gestational diabetes mellitus (GDM). In addition, we measured protein expression of lipoprotein lipase (LPL) in MVM and two fatty acid binding proteins (L- and C-FABP) in placental homogenates. The TG hydrolase activities were assessed by measuring hydrolysis of (3)H-trioleic acid incorporated into intralipid micelles after incubation with MVM. The placenta-specific TG hydrolase activity (optimum at pH 6) did not differ in the patient groups studied. MVM LPL activity (optimum at pH 8) was reduced by 47% in preterm IUGR (n = 8, P < 0.05), compared with gestational age-matched controls. The LPL activity in placentas of IDDM pregnancies was increased by 39% (n = 8, P < 0.05), compared with controls. No significant differences were observed in cases of GDM. We found no alteration in protein expression of LPL or C-FABP. The expression of L-FABP was increased by 112% (n = 8, P < 0.05) in IDDM and 64% (n = 8, P < 0.05) in GDM. These results indicate that alterations in MVM LPL activity and expression of L-FABP may contribute to the altered lipid deposition and metabolism in IUGR and diabetic pregnancies.

Carrier Proteins↗
PubMed2003

ATP dependent Ca2+ transport across basal membrane of human syncytiotrophoblast in pregnancies complicated by intrauterine growth restriction or diabetes.

Neonates born after pregnancies complicated by diabetes or intrauterine growth restriction (IUGR) have increased incidence of hypocalcaemia. Furthermore, IUGR is associated with reduced bone mineralization in infancy and osteoporosis in adult life. We tested the hypothesis that placental calcium transport is altered in these pregnancy complications. Transport of calcium into syncytiotrophoblast basal plasma membrane (BM) vesicles was studied by rapid filtration and protein expression of Ca(2+) ATPase by Western blot. In IUGR Ca(2+) ATPase activity was increased by 48 per cent (n=13; P< 0.05) whereas protein expression was 15 per cent lower (n=13; P< 0.05) than in controls (n=16). Basal membrane ATP dependent calcium transport was unaltered in gestational diabetes (GDM) but increased by 54 per cent in insulin dependent diabetes (IDDM) compared to controls (P< 0.05; n =14). Diabetes did not affect Ca(2+) ATPase expression in BM. We have previously shown that the mid-molecular fragment of parathyroid hormone related peptide (PTHrP midmolecule) stimulates BM Ca(2+) ATPase in vitro. PTHrP midmolecule concentrations in umbilical cord plasma were measured using radioimmunoassay. The concentrations in umbilical cord plasma were increased in IUGR, but unaltered in diabetes. In conclusion, placental calcium pump is activated in IUGR and IDDM, which may be secondary to increased foetal calcium demand. We speculate that PTHrP midmolecule may be one mechanism for activating BM Ca(2+) ATPase in IUGR.

Adult↗
PubMed2003

Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments.

The activity and expression of placental nutrient transporters are primary determinants for the supply of nutrients to the fetus, and these nutrients in turn regulate fetal growth. We developed an experimental system to assess amino acid uptake in single primary villous fragments to study hormonal regulation of the amino acid transporter system A in term human placenta. Validation of the method, using electron microscopy and studies of hormone production, indicated that fragments maintained ultrastructural and functional integrity for at least 3 h. The activity of system A was measured as the Na(+)-dependent uptake of methylaminoisobutyric acid (MeAIB), and the effect of 1 h incubation in various hormones was investigated. Uptake of MeAIB into villous fragments in the presence of Na(+) was linear up to at least 30 min. Insulin (300 ng/ml, n = 14) increased system A activity by 56% (P < 0.05). This effect was also present at insulin concentrations in the physiological range (+47% at 0.6 ng/ml, n = 10, P < 0.05). Leptin (500 ng/ml, n = 14) increased Na(+)-dependent MeAIB uptake by 37% (P < 0.05). System A activity increased in a concentration-dependent fashion in response to leptin (n = 10). However, neither epidermal GF (600 ng/ml), cortisol (340 ng/ml), nor GH (500 ng/ml) altered system A activity significantly (n = 14). We conclude that primary single isolated villous fragments can be used in studies of hormonal regulation of nutrient uptake into the syncytiotrophoblast. These data suggest that leptin regulates system A, a key amino acid transporter.

Amino Acid Transport System A↗
PubMed2003

Activity and protein expression of Na+/K+ ATPase are reduced in microvillous syncytiotrophoblast plasma membranes isolated from pregnancies complicated by intrauterine growth restriction.

In contrast to classical transporting epithelia, the Na(+)/K(+) ATPase is distributed to both the microvillous membrane (MVM) and the basal membrane (BM) of the placental syncytiotrophoblast. Na(+)/K(+) ATPase is important in maintaining the electrochemical gradient for Na(+), which represents the driving force for Na(+)-coupled transport of nutrients. We hypothesized that syncytiotrophoblast Na(+)/K(+)-ATPase activity is reduced in intrauterine growth restriction (IUGR). We isolated MVM and BM from control (n = 10) and IUGR placentas (n = 11). The protein expression of Na(+)/K(+)-ATPase alpha(1)-subunit was determined by Western blotting and found to be slightly reduced in MVM isolated from IUGR (-10%; P < 0.05) placentas. Na(+)/K(+) ATPase activity was measured as the ouabain-sensitive, K(+)-dependent cleavage of the fluorescent pseudosubstrate 3-O-methylfluorescein phosphate and was reduced by 35% in MVM obtained from IUGR placentas (P < 0.02). To assess the transcriptional levels of Na(+)/K(+)-ATPase mRNA, real time PCR was used. No significant changes in steady state mRNA levels for Na(+)/K(+)-ATPase were detected. The expression of the Na(+)/K(+)-ATPase alpha(1)-subunit and Na(+)/K(+)-ATPase activity in the BM were unaffected in cases of IUGR. These data suggest that Na(+)/K(+)-ATPase activity is reduced in the MVM of placentas from IUGR pregnancies. These changes might impair the function of Na(+)-coupled transporters and contribute to the reduced growth of these fetuses.

Case-Control Studies↗
PubMed2002

Regulation of placental transfer: the Na(+)/H(+) exchanger--a review.

This review article considers the purposes and mechanisms of regulation of placental transfer in general terms and then illustrates some key points with reference to the Na(+)/H(+) exchanger (NHE), a transport protein found in the syncytiotrophoblast. NHE probably has a role in the homeostasis of syncytiotrophoblast intracellular pH and may also be involved in syncytiotrophoblast cell volume regulation as well as H(+) loss from and Na(+) transfer to the fetus. The activity and expression of NHE in the microvillous plasma membrane of the syncytiotrophoblast is reduced in placentas from preterm, growth restricted babies as compared to their gestationally matched normally grown counterparts. There are differential effects of gestation in normal pregnancy on NHE mRNA, NHE protein and NHE activity. There is also evidence of acute modulation of NHE activity. Regulation of NHE in syncytiotrophoblast is therefore complex with control at transcription, post transcription and post translational loci.

Adult↗
PubMed2002

Na(+)/K(+)-ATPase activity and expression in syncytiotrophoblast plasma membranes in pregnancies complicated by diabetes.

Many of the transport processes across the syncytiotrophoblast (ST), such as amino acid transport, are Na(+)-coupled. The maintenance of a low intracellular Na(+) concentration by Na(+)/K(+)-ATPase is therefore crucial for placental transport of nutrients and consequently, foetal growth. In pregnancies complicated by diabetes foetal growth is often accelerated despite rigorous glycemic control of the mother, however the underlying mechanisms are not fully understood. We tested the hypothesis that Na(+)/K(+)-ATPase in ST plasma membranes is up-regulated in diabetic pregnancies associated with accelerated growth. ST microvillous (MVM) and basal (BM) plasma membranes were purified from term placentas of normal pregnancies (control, n=13) and pregnancies complicated by insulin-dependent diabetes mellitus (n=7) or gestational diabetes (n=6). All mothers with diabetes gave birth to large for gestational age babies. The Na(+)/K(+)-ATPase alpha(1)-subunit protein expression (Western blot) in MVM and BM was unaltered by diabetes. Na(+)/K(+)-ATPase activity (K(+)-stimulated, ouabain-sensitive phosphatase activity) in ST plasma membranes was not affected by diabetes. This is the first study of Na(+)/K(+)-ATPase in ST membranes of the human placenta in diabetes. Our data show that accelerated foetal growth in diabetic pregnancies is not associated with elevated ST Na(+)/K(+)-ATPase protein expression or activity.

Adult↗