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T Jansson

Publications and source records attributed to T Jansson.

At least 37 records · Page 2Linked to original sources
PubMed2002

Glucose transport and system A activity in syncytiotrophoblast microvillous and basal plasma membranes in intrauterine growth restriction.

The mechanisms underlying the reduced fetal plasma concentrations of amino acids and glucose associated with intrauterine growth restriction (IUGR) remain to be fully established. The activity of the amino acid transporter system A has been shown to be reduced in the syncytiotrophoblast microvillous membrane (MVM) in IUGR, however the impact of these changes on transplacental transport is difficult to assess without information on system A activity in the basal plasma membrane (BM). In this study we measured system A activity and mediated D-glucose uptake using radiolabelled substrates and rapid filtration techniques, and glucose transporter isoform 1 (GLUT 1) protein expression using Western blots in MVM and BM isolated from human placentas. In term IUGR (n=11) MVM system A activity was unaltered compared to controls (n=9). In contrast, system A activity in MVM was reduced by 50 per cent (P< 0.05) in preterm IUGR (n=8, gestational age 28-36 weeks) as compared to controls (n=8, gestational age 28-35 weeks). BM system A activity was unaltered in both IUGR groups. Similarly, MVM and BM GLUT 1 expression and mediated D-glucose uptake was not affected by IUGR. In all preterm IUGR pregnancies signs of severe fetal compromise were present whereas term IUGR fetuses were less affected. These data support the view that MVM system A activity is related to the severity of compromise in IUGR. The markedly reduced system A activity in MVM in preterm IUGR together with the unaltered activity in BM is consistent with a decreased transplacental transport of neutral amino acids in this pregnancy complication. The hypoglycemia present in utero in some IUGR fetuses is not caused by a decreased glucose transport capacity across the syncytiotrophoblast plasma membranes.

Adult↗
PubMed2002

Activity and protein expression of the Na+/H+ exchanger is reduced in syncytiotrophoblast microvillous plasma membranes isolated from preterm intrauterine growth restriction pregnancies.

Regulation of syncytiotrophoblast intracellular pH is critical to optimum enzymatic and transport functions of the placenta. Previous studies of Na(+)/H(+) exchanger (NHE) activity in the placenta from pregnancies complicated by intrauterine growth restriction (IUGR) have produced conflicting results. The possible role of altered placental pH regulation in the development of acidosis in some fetuses subjected to IUGR remains to be fully established. We investigated the activity and protein expression of the NHE in syncytiotrophoblast microvillous (MVM) plasma membranes isolated from preterm and term placentas obtained from uncomplicated and IUGR pregnancies. Western blotting showed that the expression of NHE isoforms 1, 2, and 3 was approximately 10-fold greater in MVM than in basal plasma membrane (BM). Immunohistochemistry localized NHE-1 and NHE-2 to MVM and BM and NHE-3 to the MVM, BM, and cytoplasm of the syncytiotrophoblast. NHE-1 expression in MVM from preterm IUGR placentas was reduced by 55%, compared with gestational age-matched controls (P < 0.05, n = 6 and n = 16, respectively), whereas NHE-1 expression was unaltered in term IUGR placentas (n = 8). The activity (amiloride-sensitive Na(+) uptake) of NHE in MVM from IUGR preterm placentas was reduced by 48% (P < 0.05, n = 6). In contrast, MVM NHE activity was unchanged in term IUGR (n = 7). Using Northern blotting, no difference could be demonstrated in NHE-1 mRNA expression between IUGR and control groups. The reduced activity and expression of NHE in MVM of preterm IUGR placentas may compromise placental function and may contribute to the development of fetal acidosis in preterm IUGR fetuses.

Blotting, Northern↗
PubMed2002

Parathyroid hormone-related peptide (38-94) amide stimulates ATP-dependent calcium transport in the Basal plasma membrane of the human syncytiotrophoblast.

The final step in the maternal-fetal transfer of calcium in the placenta involves transport against a concentration gradient across the syncytiotrophoblast basal plasma membrane (BM). Based on animal studies, it has been proposed that parathyroid hormone-related peptide (PTHrP) plays a major role in maintaining the maternal-fetal concentration gradient of calcium. In this study, we tested the hypothesis that a highly conserved mid-region fragment (38-94) of PTHrP directly affects the ATP-dependent calcium transport across BM isolated from full-term human placentas. PTHrP (38-94) stimulated ATP-dependent calcium transport at a concentration within the physiological range (5 pg/ml) and the effect (10-38% increase) was concentration dependent over the range 5 pg/ml to 5 ng/ml (n=8; P<0.05). In contrast, PTH, PTHrP (1-34), PTHrP (67-86) and calcitonin increased BM calcium transport only at concentrations much higher than physiological. The increased calcium uptake was inhibited by the protein kinase C (PKC) inhibitor chelerythrine (n=6; P<0.05). In addition, PTHrP (38-94) increased inositol trisphosphate (IP(3)) production and PKC phosphorylation in human placental BM (n=12; P<0.05). Our data indicate that PTHrP (38-94) stimulates Ca(2+)ATPase in the human syncytiotrophoblast BM vesicles by activating the IP(3)-DAG-PKC pathway. We suggest that PTHrP (38-94) is important in maintaining the calcium concentration gradient across the placental barrier in the human.

Adenosine Triphosphate↗
PubMed2001

Placental glucose transport in gestational diabetes mellitus.

OBJECTIVE: We have previously reported that type 1 diabetes mellitus with hyperglycemia during the first trimester is associated with an up-regulation of placental glucose transport at term. We speculated that glucose concentrations regulate placental glucose transporters only during early pregnancy. To test this hypothesis we studied placental glucose transport in gestational diabetes mellitus, which is associated with hyperglycemia mainly during the second half of pregnancy. STUDY DESIGN: Syncytiotrophoblast microvillous membrane vesicles and basal membrane vesicles were isolated from uneventful pregnancies (control group, n = 32) and pregnancies complicated by gestational diabetes mellitus (n = 18). Glucose uptake and glucose transporter 1 expression were studied by means of radiolabeled tracers and Western blotting, respectively. RESULTS: Gestational diabetes mellitus was not associated with alterations in placental glucose transport. Separate analysis of 6 patients in the gestational diabetes mellitus group with large-for-gestational-age babies did not affect these results. CONCLUSION: These findings are consistent with the hypothesis that the sensitivity of placental glucose transporters to regulation by nutrient availability is limited to early pregnancy.

Adenylyl Cyclases↗
PubMed2001

Amino acid transporters in the human placenta.

Amino acid transport across the human placenta is active, mediated by specific transporters in syncytiotrophoblast plasma membranes. Using functional criteria such as substrate specificity and sodium dependence, approximately 15 transport systems have been identified in the human placenta. Recently, the area of molecular biology of amino acid transporters has evolved rapidly and at least 25 cDNA clones coding for mammalian amino acid transporters or transporter subunits have been identified. The primary objective of this review is to integrate the available functional data on placental amino acid transport systems with recent molecular information on mammalian amino acid transporters. Furthermore, models for the mechanisms for net materno-fetal transfer of amino acids are discussed. Finally, the evidence to suggest that alterations in placental amino acid transport systems may play a crucial role in the regulation of fetal growth are presented briefly.

Amino Acid Transport Systems↗
PubMed2001

Strategy to decrease the risk of adverse effects of fragrance ingredients in cosmetic products.

In spite of extensive self-regulation of the fragrance industry, fragrance ingredients are still major causes of allergic contact dermatitis. There are indications that the problem is increasing in some countries, and that many nonregulated compounds are involved in the development of allergies. The use of essential oils in fragrance compounds might add both allergenic and carcinogenic compounds to a product and the exact composition of such ingredients is difficult to control. Herein, we propose a simple strategy to decrease the risk of adverse effects of fragrance ingredients in cosmetic products. This strategy consists of four major steps: (1) limit the concentration of fragrance compound in the products, (2) follow legislation and guidelines, (3) limit the concentration of a number of well-known sensitizing fragrance chemicals, and (4) limit the concentration of essential oils and materials with unknown composition. The strategy is discussed as an alternative to animal testing and in relation to other more resource-demanding approaches to the same problem.

Animal Testing Alternatives↗
PubMed2000

Local breast cancer recurrence caused by mammographically guided punctures.

PURPOSE: To evaluate the risk of needle track seeding or tumor cell implantation as the cause of locally recurrent breast cancer after breast conserving surgery. MATERIAL AND METHODS: We reviewed recurrences from a consecutive series of 303 clinically nonpalpable breast cancers treated with breast conserving surgery after pre-operative localization. The median mammographic follow-up was 5.4 years. The suspicion of seeding or implantation was based on the location of the recurrent lesion in comparison with the needle path in two orthogonal mammographic projections. Pre-operative percutaneous biopsies had been done in 71% (214/303) of the cases. Postoperative radiotherapy was administered to 82% (194/238) of the invasive cancers and to 28% (18/65) of the ductal cancers in situ (DCIS). RESULTS: Locally recurrent cancer occurred in 11% (33/303) of the cases. Radiotherapy demonstrated a protective effect from relapse among invasive cancers but not for DCIS. Seeding or implantation was suspected in 3 recurrent invasive cancers which had not been subject to radiotherapy. The histopathological diagnosis of the primary cancer and the recurrent cancer were the same in these cases: adenoid cystic, mucinous and tubuloductal cancer. CONCLUSION: Seeding or implantation was suspected as the cause of local recurrence in 7% (3/44) of the invasive cancers which did not receive radiotherapy.

Adenocarcinoma↗
PubMed2000

Na(+)-K(+)-ATPase is distributed to microvillous and basal membrane of the syncytiotrophoblast in human placenta.

Despite its importance for placental function, syncytiotrophoblast Na(+)-K(+)-ATPase has not been studied in detail. We purified syncytiotrophoblast microvillous (MVM) and basal (BM) membranes from full-term human placenta. Western blotting with isoform-specific antibodies demonstrated the presence of the alpha(1)-subunit, but not the alpha(2)- or alpha(3)-subunits, in MVM and BM. Relative density per unit membrane protein in BM was 48 +/- 1% (mean +/- SE, n = 4, P < 0.02) of that in the MVM. The activity of Na(+)-K(+)-ATPase was lower in BM (1.4 +/- 0.14 micromol. mg(-1). min(-1), n = 8, P < 0.02) than in MVM (3.9 +/- 0.25 micromol. mg(-1). min(-1)). Immunocytochemistry confirmed the distribution of Na(+)-K(+)-ATPase to MVM and BM. These findings suggest that the syncytiotrophoblast represents a type of transporting epithelium different from the classical epithelia found in the small intestine and kidney, where Na(+)-K(+)-ATPase is confined to the basolateral membrane only. This unique polarization of the Na(+) pump does not, however, preclude a net transcellular transport of Na(+) to the fetus.

Animals↗
PubMed2000

Activity and expression of the Na(+)/H(+) exchanger in the microvillous plasma membrane of the syncytiotrophoblast in relation to gestation and small for gestational age birth.

The effect of gestational age, low birth weight, and umbilical plasma pH on the activity and expression of the Na(+)/H(+) exchanger in the microvillous plasma membrane (MVM) of the placental syncytiotrophoblast was investigated. MVM were isolated from placentas of fetuses delivered in the first and second trimesters and from appropriately grown for gestational age (AGA) and small for gestational age (SGA) babies born at term. Na(+)/H(+) exchange activity (amiloride-sensitive Na(+) uptake) was higher (p<0.05) in second trimester and term AGA MVM versus first trimester MVM (median [range]: 1.80 [1.01-3.03], 1.72 [1.16-3.15] versus 1.48 [0.92-1.66] nmol/mg protein/30s, respectively, n = 6, 12, and 9). As regards exchanger isoforms, Western blotting showed that NHE1 expression did not change across gestation, but NHE2 and NHE3 expression were lower (p<0.01) in the first and second trimesters than in term AGA MVM. There were no differences in Na(+)/H(+) exchanger activity or in NHE1-3 expression in term AGA MVM versus SGA (n = 11) MVM. There was no correlation between exchanger activity and umbilical artery or vein plasma pH, although with a relatively small number of samples (n = 12 and 15, respectively). We conclude that there is differential regulation of the activity and expression of Na(+)/H(+) exchanger isoforms in the MVM over the course of gestation in normal pregnancy; this is not affected in pregnancies resulting in SGA babies at term.

Female↗
PubMed1999

Composition and permeability of syncytiotrophoblast plasma membranes in pregnancies complicated by intrauterine growth restriction.

The objective of this study was to determine placental membrane permeabilities to water, urea and mannitol in intrauterine growth restriction (IUGR) and compare them to normal gestational age matched controls. Further, we wished to investigate whether potential changes in permeability were related to changes in membrane fluidity, cholesterol or phospholipid fatty acid content of the membranes. Syncytiotrophoblast microvillous (MVM) and basal membranes (BM) were isolated from normal and IUGR placentas at term. Passive permeability to water, urea, and mannitol showed no significant alterations in IUGR compared to controls. Cholesterol content in BM, but not in MVM, was lower in placentas from pregnancies complicated by IUGR. However, membrane fluidity did not change in these pregnancies. The phospholipid fatty acid composition of the plasma membranes isolated from all placentas showed a predominance of unsaturated fatty acid species in the BM and saturated species in the MVM. In the MVM from IUGR, mead acid (20:3), behenic acid (22:0) and nervonic acid (24:1) constituted higher percentages of the total when compared to normally grown controls. In the BM from IUGR, mead acid (20:3) was increased relative to the total phospholipid fatty acid content. In conclusion, the syncytiotrophoblast membranes exhibit only minor changes in passive permeability and composition when the pregnancy is complicated by IUGR.

Case-Control Studies↗
PubMed1999

Placental glucose transport and GLUT 1 expression in insulin-dependent diabetes.

OBJECTIVE: Altered transport functions in the placenta might contribute to adverse outcome of pregnancies in women with diabetes. Therefore we studied placental glucose transport in this pregnancy complication. STUDY DESIGN: Syncytiotrophoblast microvillous membrane vesicles and basal membrane vesicles were isolated from women with uneventful pregnancies (control subjects, n = 21) and from women with pregnancies complicated by insulin-dependent diabetes mellitus, White class D (n = 7). Glucose uptake and GLUT 1 (glucose transporter 1) expression were studied by means of radiolabeled tracers and Western blot, respectively. RESULTS: In the group with insulin-dependent diabetes mellitus, values for hemoglobin A1c were moderately elevated in the first trimester (6.61 +/- 0.35) but not later in pregnancy and 4 of the 7 neonates were large for gestational age. In the basal membrane vesicles, insulin-dependent diabetes mellitus was associated with a 40% increase in GLUT 1 expression and a 59% higher mediated uptake of d -glucose. No alterations could be demonstrated in microvillus membrane vesicles. CONCLUSION: Placental glucose transport capacity appears to be increased in insulin-dependent diabetes mellitus. These alterations might explain the occurrence of macrosomia despite well-controlled diabetes.

Adult↗
PubMed1999

High resolution light diffraction tomography: nearfield measurements of 10 MHz continuous wave ultrasound

Light diffraction tomography is an ultrasound measurement method that offers possibilities to make high spatial resolution measurements. The aim of this study was to investigate the spatial resolution of light diffraction tomography by characterizing the complex pressure and phase patterns 0.5-1 mm from the surface of a 5 mm diameter 10 MHz ultrasound transducer. Three different transducers were measured with a detection width of 5 microm, sample distances of 20-40 microm and 50-100 projections/180 degrees. They were excited with a 10 Vpp CW-signal. To verify the results the optical measurements were compared with 75 microm diameter hydrophone measurements and with theoretical calculations. The light diffraction tomography results show very good agreement with the hydrophone measurements and pressure peaks separated 160 microm were resolved. Comparison with the theoretical calculation shows that small distortions, caused by defects in the matching layer or in the piezo-electric disc, disturb the symmetric ring-pattern characteristic of an ideal piston source.

Journal Article↗
PubMed1999

Cross-comparison of two quality of life instruments used in a randomized study of combination chemotherapy in advanced breast cancer.

Twenty-six patients from a randomized study of combination chemotherapy in advanced breast cancer were included in a cross-comparison between two quality of life instruments: a categorical linear analogue scale (C-LASA) based on the instrument of Priestman and Baum and a Swedish instrument developed by Glimelius et al. Quality of life was assessed on day 1 and day 10 of each chemotherapy cycle and the instruments were compared using correlation and kappa analysis. For the physical dimension, the mean correlation coefficient on day 1 was 0.89 and the kappa coefficient was 0.62; and on day 10 the correlation coefficient was 0.83 and the kappa coefficient 0.62. For the emotional dimension the correlation and kappa coefficients were 0.89 and 0.71 and 0.89 and 0.61 on days 1 and 10, respectively. The corresponding values for the global dimension were 0.76 and 0.56 and 0.80 and 0.57 on days 1 and 10, respectively. A correlation was also demonstrated over time. The instruments gave similar measurements of quality of life for chemotherapy-treated patients with advanced breast cancer, but the feasibility of the C-LASA instrument was better.

Adult↗
PubMed1999

Effect of intrauterine growth restriction on blood pressure, glucose tolerance and sympathetic nervous system activity in the rat at 3-4 months of age.

OBJECTIVE: Epidemiological studies suggest that intrauterine growth restriction (IUGR) due to maternal undernutrition during pregnancy represents a major risk factor for hypertension and diabetes in adult age. However, placental insufficiency, rather than maternal malnutrition, is the main cause of IUGR in the Western world. We therefore studied the relationship between birth weight and adult blood pressure and glucose tolerance in an established animal model of placental insufficiency. DESIGN: IUGR was induced by uterine artery ligation in pregnant rats and the offspring were studied at 3-4 months of age. METHODS: In one subgroup of animals (n = 41, birth weight range 3.2-6.6 g) blood pressure was recorded over 72 h using telemetry and hypothalamic tissue levels of noradrenaline was measured. In another subgroup (n = 30, birth weight range 3.0-6.8 g) the activity of the sympathetic nervous system (SNS) was assessed by noradrenaline isotope dilution techniques and glucose tolerance determined by an intravenous glucose load. RESULTS: Adult blood pressure was independent of birth weight Haemodynamic responses of IUGR rats to moderate sound stress was unaltered. In male rats neither SNS activity, hypothalamic noradrenaline concentrations nor glucose tolerance was associated with birth weight In contrast, IUGR in female rats was associated with increased SNS activity, elevated fasting blood glucose as well as lower insulin and higher glucose levels in response to a glucose load. CONCLUSION: IUGR is not linked to an elevated blood pressure at 3-4 months of age in this model. However, in female rats, IUGR is associated with increased SNS activity and impaired glucose tolerance in adult life.

Animals↗
PubMed1999

Estimation of blood perfusion using ultrasound.

Ways to measure blood perfusion using ultrasound techniques such as continuous-wave Doppler, pulsed Doppler, colour Doppler and power Doppler will be reviewed. From a certain standpoint, blood perfusion may be defined as the difference between arterial inflow and arterial outflow from a considered volume, i.e. capillary flow. The low velocities and small blood volumes involved make the signal-to-noise ratio, dynamic range and frequency resolution critical factors in the detection system. Another limiting factor is tissue motion which obscures the blood signal. Perfusion may still under certain conditions be estimated with the first moment of the Doppler power spectrum, as obtained with any Doppler ultrasound method. Modern flow mapping techniques also make it possible to estimate perfusion by counting the number of pixels that indicate flow, but low flow velocities cannot be included in the estimate. Future high-frequency systems may, however, provide very detailed images of minute flow distributions in superficial layers. Contrast agents are widely used today to enhance the blood signal, and a technique named harmonic imaging can suppress movement artefacts from surrounding tissue. Transient signals from disrupting contrast agent particles in an ultrasound field can potentially be used for perfusion quantification. Future developments to extract the blood flow signal from its noisy environment, aside from contrast agents, may be multiple sample volumes, frequency compounding and/or improved signal processing. The lack of an adequate perfusion phantom for verification of measurements of microcirculatory flow becomes, however, more apparent with improved detectability of slow flows.

Artifacts↗
PubMed1998

Mechanisms of chloride transport across the syncytiotrophoblast basal membrane in the human placenta.

Chloride transport mechanisms in isolated plasma membrane vesicles were studied to characterize pathways for transcellular transport of chloride. Microvillous membrane (MVM) and basal membranes (BM) vesicles were isolated from term placentae. Western blot analysis of the anion exchanger isoform 1 (AE1) demonstrated that the density of AE1 was 12-fold higher on the MVM compared to the BM. At 30 sec, the Cl- uptake in the absence of a potential difference (p.d.) was 457.3 +/- 69.7 and 111.0 +/- 29.1 pmol/mg protein in MVM and BM, respectively (mean +/- SEM, n=6). Chloride transport pathways were characterized using diisothiocyano-2'2-disulphonic stilbene. (DIDS, 0.1 mM) and diphenylamine-2-carboxylate (DPC, 0.5 mM) in the absence or presence of inside positive membrane potentials. Anion exchange (DIDS-sensitive uptake at zero mV) was found in the MVM only. Both MVM and BM showed increased chloride uptake in the presence of inside positive potentials, suggesting the presence of chloride conductance pathways. The chloride uptake with a 25-mV inside positive p.d. could be inhibited by both DIDS and DPC in MVM and BM. However greater potentials (50 mV) showed no significant inhibition by DIDS or DPC in BM. In conclusion, the anion exchanger is unlikely to contribute significantly to chloride fluxes across BM. The data also suggest the presence of Cl- conductance pathways in both the MVM and BM which are sensitive to both DIDS and DPC.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Radiotherapy of breast cancer after breast-conserving surgery: an improved technique using mixed electron-photon beams with a multileaf collimator.

BACKGROUND AND PURPOSE: Loco-regional radiotherapy after breast cancer surgery significantly reduces the risk of recurrences. An increase of cardiac deaths for irradiated breast cancer patients has been reported in some studies, especially for women with tumours in the left breast. The aim of this study was to compare retrospectively the conventionally used technique using two opposed tangential photon beams with a modified technique using a combination of photon and electron beams to find an optimal technique with respect to dose homogeneity in the breast and surrounding regional lymph nodes and a minimal dose in the organs at risk. MATERIALS AND METHODS: Thirty patients with stage II breast cancer who received different types of adjuvant systemic therapy were included in the investigation. Comparative dose planning of two techniques was performed, i.e. an isocentric technique with two photon beams with coplanar medial beam edges and a technique with one electron and three photon beams with a common isocentre for all beams aided by a multileaf collimator. RESULTS: The mixed technique was selected for eight of 12 patients with left-sided breast cancers because of significantly lower doses to the heart. However, the decision-making was influenced by many factors such as dose coverage of the target volume combined with minimizing of the doses to the organs at risk and the contralateral breast. CONCLUSION: The use of the mixed technique will optimize the loco-regional radiotherapy after breast-conserving surgery for many left-sided breast cancers.

Adult↗