Biomedical subjects

T Vik

Publications and source records attributed to T Vik.

At least 37 records · Page 2Linked to original sources

PubMed1997

Overexpression of human stem cell factor impairs melanocyte, mast cell, and thymocyte development: a role for receptor tyrosine kinase-mediated mitogen activated protein kinase activation in cell differentiation.

Stem cell factor (SCF) is synthesized as both soluble (S) and membrane-associated (MA) proteins. Indirect insight into the function of MA and S isoforms of SCF has come from studies performed in Steel (Sl) mutant mice. However, the physiologic role(s) of these two isoforms remain unknown. In an attempt to better understand the in vivo role of c-kit/SCF interactions on various cell lineages, transgenic mice were generated that overexpress MA isoform of human SCF (hSCF). In murine cells, hSCF behaves as an antagonist to normal SCF function, due to interference with the interaction between endogenous murine SCF and its receptor, c-kit, encoded by the dominant white spotting (W) gene. Mice expressing the hSCF transgene display a variety of phenotypic abnormalities, which are accentuated when combined with W alleles. Here we show that mice homozygous for the hSCF transgene demonstrate a coat color deficiency seen in some mice homozygous for mild W alleles. Specifically, homozygous hSCF transgenic mice (hSCF220) display a pronounced forehead blaze, with additional white spots over the cervical region, as well as a very large belly spot. Doubly heterozygous animals that carry both a mutated W allele and the hSCF transgene also display an unusual pigment defect and a dramatic reduction in the number of dermal mast cells. Furthermore, overexpression of MA hSCF in the thymus results in abnormal thymocyte differentiation and proliferation, which is associated with reduced mitogen activated protein (MAP) kinase activation. Thus, MAP kinase activation by a receptor tyrosine kinase, such as c-kit, may be critical for the differentiation of thymocytes in vivo.

Animals↗

PubMed1997

Prenatal growth in symmetric and asymmetric small-for-gestational-age infants.

We tested the hypothesis that growth retardation in symmetric small-for-gestational-age (SGA) infants may start in the first trimester of pregnancy, whereas in asymmetric SGA infants, it may start in the third trimester. We also examined if there may be a brain sparing effect in asymmetric SGA infants. Infants were classified as symmetric or asymmetric SGA infants, and 474 non-SGA infants. Intrauterine growth was assessed by prenatal ultrasonic measurements of fetal abdominal diameter, femur length and biparietal diameter at week 17, 25, 33 and 37 of gestation. Cross-sectional data as well as longitudinal growth curves suggested that growth retardation in both SGA groups started in the second trimester, and followed similar patterns until birth. Thus, our results did not support the hypothesis that symmetric and asymmetric growth retardation is associated with clear temporal differences in growth, and we found no sign of brain sparing in asymmetric compared to symmetric SGA infants.

Abdomen↗

PubMed1997

Counterregulatory hormone and symptom responses to hypoglycaemia in diabetic children.

The hormonal responses to, and symptoms of, hypoglycaemia were investigated in 19 diabetic children (mean age 14.2 (SD 1.4) years, mean HbA1c 9.8 (SD 1.2)%) and 16 non-diabetic children (14.4(1.0) years) during a gradual reduction in plasma glucose with the glucose clamp technique. Plasma glucose was reduced from approximately 5.7 to approximately 2.6 mmol l(-1) in the diabetic children and from approximately 5.7 to approximately 2.9 mmol l(-1) in the non-diabetic children over 200 min. The mean glycaemic thresholds for adrenaline, and for autonomic and total symptom score, were similar in the diabetic and non-diabetic groups, and were found at plasma glucose levels between 3.4 and 3.7 mmol l(-1). The mean glucose levels which elicited increase of cortisol, growth hormone, and glucagon were lower (p < 0.01), and the mean incremental responses of adrenaline, cortisol, and glucagon were smaller in the diabetic than in the non-diabetic children. In the diabetic children, a correlation was found between Body Mass Index (BMI) and the hypoglycaemic thresholds for autonomic and total symptom scores (r = 0.64, p < 0.01 and r = 0.72, p = 0.001, respectively). We conclude that counterregulatory hormone responses are attenuated in diabetic as compared to non-diabetic children, whereas recognition of autonomic symptoms is similar in the two groups. Diabetic children with a higher BMI seem to have increased awareness of a declining plasma glucose level.

Adolescent↗

PubMed1997

Cerebral magnetic resonance imaging and mental and motor function of very low birth weight children at six years of age.

In this follow-up study, 20 of a geographically based year cohort of 31 surviving non-disabled VLBW (birthweight < 1500 g) children were examined at six years of age. The aim of the study was to relate cerebral MRI findings to neuro-development in these non-disabled children at six years of age. All MRI scans were evaluated for myelination pattern, periventricular gliosis, ventricular dilation and cortical atrophy. The Peabody motor test and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) were used in the evaluation of motor, mental and perceptual function. A diagnosis of attention deficit disorder with hyperactivity was made based on the examiner's impression of the child during the examination and based on the parent's history. We found that ten (50%) of the children had periventricular gliosis, mainly in centrum semiovale (CS) (nine children) and in central occipital white matter (COW) (six children). Gliosis in CS was related to lower scores on the Peabody gross motor test for locomotion, indicating involvement of corticospinal tracts. Additional gliosis in COW was related to both fine motor and gross motor impairments. We speculate that this indicates damage to both motor and visual pathways, affecting eye-hand coordination and balance function. No relationship between MRI deviations at six years and mental function based on performance, verbal and total IQ scores was found. However, there was a significant relationship between periventricular gliosis in COW and C5 and low scores on the WPPSI performance subtests: Picture completion test and Block design test. This may indicate visual and spatial perception problems, caused by damage to posterior visual pathways and occipito-thalamic tracts dealing with visuo-motor integration.

Analysis of Variance↗

PubMed1997

Dubowitz assessment of gestational age and agreement with prenatal methods.

We compared assessment of gestational age by Dubowitz score with ultrasonic measurement of the biparietal diameter (BPD), and then evaluated how infants were classified by these methods as small-for-gestational age (SGA), and as pre- or post-term births. BPD gestational age was assessed at week 17 to 20 of pregnancy while the Dubowitz scoring was done at birth. "Limits of agreement" between methods and kappa values were calculated and used to evaluate agreement. Among 839 included infants, there was moderate agreement between Dubowitz score and BPD (limits of agreement; -2.3; +2.1 weeks; weighted kappa: 0.46) in the assessment of gestational age. Agreement between Dubowitz score and BPD in the classification of SGA (kappa: 0.75, 95% confidence interval [CI]: 0.69-0.81) and preterm infants (kappa: 0.68, 95% CI: 0.56-0.80) was good, whereas agreement on infants born post-term was no better than chance (kappa: 0.14, 95% CI: -0.02(-)+0.30). We conclude that despite moderate agreement between Dubowitz score and BPD in the assessment of gestational age, agreement in the classification of low-birth-weight infants as SGA and as premature births was good.

Cephalometry↗

PubMed1997

A recombinant human fibronectin fragment facilitates retroviral mediated gene transfer into human hematopoietic progenitor cells.

Gene transfer into hematopoietic progenitor cells is increased when these cells are adherent to the carboxy-terminal chymotryptic fragment of human plasma fibronectin (FN30/35) containing the heparin binding domain (HBD) and the alternatively spliced type three connecting segment (IIICS) region. We report herein the production of a recombinant human fibronectin fragment comprised of the HBD and IIICS regions expressed by Sf9 insect cells following recombinant baculovirus infection. The resulting isolated peptide, HuBacFN, facilitated gene transfer into human hematopoietic cell lines and primary human hematopoietic progenitors to a level achieved with the purified human plasma FN30/35 peptide.

Base Sequence↗

PubMed1997

Cognitive function in type 1 diabetic children with and without episodes of severe hypoglycaemia.

We assessed the effect of diabetes and of episodes of severe hypoglycaemia on cognitive function in 28 diabetic children. Fifteen diabetic children (age 12.9 (SD 2.0) years) had experienced 1-4 episodes of severe hypoglycaemia. Five of these children diseased before the age of 5 years (SH-eod subgroup), and ten diseased after this age (SH-lod subgroup). Thirteen diabetic children (age 13.1 (SD 2.0) years) had not experienced episodes of severe hypoglycaemia (non-SH group). Each diabetic child was compared with a healthy control child of the same age and gender and with a similar social background. Neuropsychological assessment was blinded. The neuropsychological tests were grouped into one of seven cognitive domains. We found no effect on cognitive performance from diabetes per se or from severe hypoglycaemia in children with late-onset diabetes. However, early-onset diabetes was associated with low scores in two cognitive domains: psychomotor efficiency and attention. The SH-eod subgroup had lower scores than the SH-lod subgroup in psychomotor efficiency (p < 0.05) and also had lower scores than the SH-lod subgroup and the non-SH group in measures of attention (p < 0.05). Our results may indicate a slight cognitive dysfunction in children with early-onset diabetes who have experienced episodes of severe hypoglycaemia early in childhood.

Adolescent↗

PubMed1997

Relationship between intrauterine growth retardation and early postnatal superior mesenteric artery blood flow velocity.

During the first week of life, we examined the changes in the systemic, intestinal and cerebral circulation, and the circulatory responses to feeding in 10 small for gestational age (SGA) infants using the ultrasound Doppler technique. From day 1 to day 3, preprandial cardiac output decreased (p < 0.01), whereas mean blood pressure (p < 0.01), superior mesenteric artery mean flow velocity (Vmean; p < 0.01) and middle cerebral artery Vmean (p < 0.01) increased. On day 1, cardiac output was higher in the SGA than in those of term and preterm appropriate for gestational age infants reported from our laboratory. Preprandial superior mesenteric artery Vmean was inversely related to the degree of growth retardation (r = 0.63, p < 0.05). However, growth retardation did not influence the postprandial increase in superior mesenteric artery Vmean and end-diastolic flow velocity, or the cerebral circulation.

Blood Flow Velocity↗

PubMed1997

Postnatal changes in mechanisms mediating acetylcholine-induced relaxation in piglet femoral arteries.

We studied the nitric oxide-cGMP pathway in endothelium-dependent relaxation in femoral arterial rings from piglets at different postnatal ages. Responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined in phenylephrine-precontracted rings from newborn (10-22-h) and 7 d (7-10-d)-old piglets. Relaxant responses were investigated in endothelium-denuded rings and endothelium-intact controls, and in endothelium-intact rings incubated with the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine acetate (L-NMMA), indomethacin, or the superoxide anion generator 6-anilinoquinoline-5,8-quinone (LY83583). Arterial rings from both age groups relaxed to a similar degree in response to ACh. Relaxation in rings from newborn piglets was insensitive to NOS inhibition by L-NMMA, whereas in artery rings from 7-d-old piglets, the relaxant response was significantly inhibited by L-NMMA. Incubation with LY83583 gave an inhibition of ACh-induced relaxation very similar to that of L-NMMA. Incubation with indomethacin had no significant effect on ACh-induced relaxation in either age group. Artery rings from both age groups relaxed 100% to SNP; the 7-d-old group was more sensitive than the newborn. NOS inhibition potentiated SNP-induced relaxation in both groups, but the potentiating effect was of greater magnitude in the newborn. Our results indicate a difference in the mechanism(s) underlying ACh-induced relaxation in the femoral artery from newborn and 7-d-old piglets, with an intact relaxant response in rings from the newborn despite NOS inhibition. The SNP results indicate a down-regulated soluble guanylate cyclase in the newborn, possibly related to a difference in basal NO release between the two age groups.

Aging↗

PubMed1997

Urinary excretion of adrenaline and noradrenaline during hypoglycaemic clamp in diabetic and non-diabetic adolescents.

The urinary excretion of non-conjugated adrenaline and noradrenaline during hypoglycaemic clamp was investigated in 16 diabetic and 15 non-diabetic adolescents. In the diabetic adolescents, the mean excretion of adrenaline was approximately nine times higher in clamp urine than in morning urine (p < 0.0001). In the non-diabetic adolescents, the mean excretion of adrenaline was 20-30 times higher in clamp urine than in morning urine (p < 0.0001). Plasma catecholamines were measured, and the area under the plasma concentration-time curve (AUC) and renal clearance of catecholamines were calculated. There was a linear correlation between the AUC and the urinary excretion of adrenaline (r = 0.57, p = 0.001) and noradrenaline (r = 0.49, p = 0.006) during the hypoglycaemic clamp. The renal clearance of adrenaline and noradrenaline did not differ between the diabetic and non-diabetic subjects. In the diabetic group, there was a positive correlation between HbA1c and the adrenaline excretion in clamp urine (r = 0.60, p = 0.015). The eight diabetic subjects with HbA1c < 10% had lower adrenaline excretion in clamp urine than the subjects with HbA1c > 10% and the non-diabetic subjects (all p values < 0.05). We conclude that there is a marked increase in urinary adrenaline excretion during hypoglycaemia in diabetic and non-diabetic adolescents. The increase in adrenaline excretion during hypoglycaemia was attenuated in the better-controlled diabetic adolescents in our study.

Adolescent↗

PubMed1997

Body proportions and early neonatal morbidity in small-for-gestational-age infants of successive births.

BACKGROUND: We wanted to examine if infants who were small for gestational age (SGA) at term had increased perinatal mortality or morbidity compared to non-SGA infants, and if this could be related to the infant's body proportions, or to whether the mother previously had delivered a low-birthweight infant ("repeater") or not ("non-repeater"). METHODS: From a cohort of 5722 para 1 and para 2 women, we compared perinatal mortality in 541 SGA (birthweight < 10th percentile) and 4737 non-SGA infants. From the same cohort, early neonatal morbidity was studied in 368 SGA and 462 control infants without congenital malformations. RESULTS: SGA infants had a 6.4 (95% CI: 2.6-15.7) higher risk of perinatal death than controls, but when infants who died with congenital malformations were excluded, this risk was not significantly increased. SGA infants were more often transferred to an intensive care unit than controls (1.7, 95% CI: 1.0-2.9). Among SGA births, infants with asymmetric body proportions (i.e. low ponderal index) more often had symptoms in the neonatal period (RR: 2.5; 95% CI: 1.4-4.3) and were more often transferred to an intensive care unit (3.4; 95% CI: 1.6-7.4) than symmetric SGA infants, whereas there were no differences between SGA infants of repeaters and non-repeaters. CONCLUSIONS: We found that SGA infants had higher perinatal mortality than controls, but this was due to a higher prevalence of congenital malformations. Among SGA infants without malformations, our results indicated increased neonatal morbidity in infants with asymmetric body proportions.

Abnormalities, Multiple↗

PubMed1997

Small-for-gestational-age (SGA) infants born at term: growth and development during the first year of life.

BACKGROUND: The purpose was to compare growth patterns and psychomotor development of healthy small-for-gestational-age (SGA) and non-SGA infants, and identify factors predictive of outcome at 13 months of age. METHOD: A total of 265 SGA infants and 329 non-SGA controls were identified from a multicenter cohort of 5722 para 1 and 2 women who had been followed during pregnancy. The infants were examined at 2 days and at 13 months of age. Psychomotor development at 13 months was assessed with The Bayley Scale of Infant Development. RESULTS: The SGA infants showed partial catch-up growth, but had still lower (mean +/- SEM, p < 0.0001) weight (9750 +/- 65 vs 10505 +/- 67 g), crown-heel length (75.9 +/- 0.2 vs 77.5 +/- 0.2 cm) and head circumference (46.9 +/- 0.1 vs 47.7 +/- 0.1 cm) than the non-SGA infants at 13 months. The SGA children scored equally well on the motor (PDI 106.8 +/- 1.0 vs 107.2 +/- 0.8) but lower on the mental scale (MDI 112.1 +/- 0.8 vs 116.5 +/- 0.7, p < 0.0001) of the Bayley Scale, and the asymmetric SGA scored lower than the symmetric SGA infants (MDI 110.2 +/- 1.3 vs 113.3 +/- 0.9, p = 0.05). In a multivariate regression analysis the parents' growth parameters had the greatest effect on growth measures at 13 months while education and maternal smoking had no significant effect. SGA vs non-SGA status had the greatest effect on growth velocities during infancy. For mental development only SGA vs non-SGA status and the mothers' education made significant contributions, but only accounted for 6% of the variance. CONCLUSION: The negative impact of intrauterine factors on growth are partly abolished by catch-up growth during infancy, and growth parameters at one year of age are mostly determined by genetic factors even in SGA infants. Decreased intrauterine growth may possibly have a negative effect on brain growth and mental developmental potential.

Case-Control Studies↗

PubMed1996

Fibronectin improves transduction of reconstituting hematopoietic stem cells by retroviral vectors: evidence of direct viral binding to chymotryptic carboxy-terminal fragments.

Efficient transduction of reconstituting hematopoletic stem cells (HSC) is currently only possible by cocultivation of target cells directly on producer cell lines, a method not applicable to human gene therapy protocols. Our laboratory has previously shown adhesion of primitive hematopoletic stem and progenitor cells to the carboxy-terminal 30/35-kD fragment of the extracellular matrix molecule fibronectin (FN 30/35) (Nature 352:438, 1991) and increased transduction of human hematopoietic progenitor cells via retroviral vectors while adherent to this fragment (J Clin Invest 93:1451, 1994). Here we report that (1) transduction of reconstituting murine HSC assayed 12 months after infection with retrovirus supernatant on FN 30/35 is as effective as cocultivation directly on producer cells; (2) recombinant retrovirus particles directly adhere to FN 30/35 in a quantitative and dose-dependent fashion; and (3) increased transduction efficiency on FN 30/ 35 does not appear to be associated with increased cell proliferation or activation of protein phosphorylation typically induced by integrin-fibronectin interactions. Therefore, we speculate that supernatant infection of HSC on FN 30/35 leads to colocalization of retrovirus particles and target cells on FN 30/35 molecule with a large increase in local virus titer presented to the cell. These findings have direct and important implications for the modification of current human gene therapy protocols.

3T3 Cells↗

PubMed1996

Pre- and post-natal growth in children of women who smoked in pregnancy.

Pre- and post-natal growth was studied from week 17 of pregnancy until 5 years of age in children of women who reported daily smoking at the time of conception, and compared to the growth in children of non-smokers. Fetal abdominal diameter, femur length and biparietal diameter were measured in weeks 17 and 37 of pregnancy, and weight, height and head circumference were measured at birth, and at 6, 13 and 60 months of age in 185 children of smokers and 345 children of non-smokers. Cross sectional data at birth showed that infants of smokers had lower weight and length, but similar ponderal index as infants of non-smokers and this may suggest a symmetrical growth retardation. Longitudinal growth curves indicated that the growth retardation took place in the second half of pregnancy. During the first 5 years of life, children of smokers had complete catch-up growth in weight, a partial catch-up in height, and no catch-up growth in head circumference. At 5 years, children of smokers had a higher ponderal index and skinfold thickness, suggesting that these children, on average, were more obese than children of non-smokers.

Body Height↗

PubMed1996

Xenogeneic expression of human stem cell factor in transgenic mice mimics codominant c-kit mutations.

Mutations of c-kit, which encodes a transmembrane receptor tyrosine kinase, have been identified in mice by abnormal coat color, anemia, and germ cell defects. Mice heterozygous for mutations of c-kit have a white forehead blaze and a white ventral spot, leading these mutants to be termed dominant White spotting (W). We have previously demonstrated that the membrane-associated isoform of human stem cell factor (hSCF220, the ligand for c-kit) is inefficiently processed in murine stromal cell transfectants. Thus, in murine cell lines analyzed in vitro, hSCF220 transfectants present SCF as a membrane restricted protein in contrast to the murine SCF220 cDNA protein product, which is slowly cleaved and secreted. We show here that transgenic mice expressing the human SCF220 isoform in vivo display a phenotype indistinguishable from some alleles of W. Specifically, hSCF220-expressing transgenic mice display a prominent forehead blaze and a white ventral spot. Generations of doubly heterozygous animals that carry both a mutated c-kit allele and the hSCF220 transgene display a more severe coat color abnormality. This phenotype appears to be due to occupancy of murine c-kit by human SCF and diminished cell surface expression of endogenous murine SCF. Normal signaling events that lead to cell survival or proliferation appear to be disrupted in vivo in these transgenic mice.

Alleles↗

PubMed1996

Morbidity during the first year of life in small for gestational age infants.

Postneonatal morbidity during infancy was studied in 284 small for gestational age (SGA) and 359 non-SGA term infants. None of these babies had congenital malformations and they were born to para 1 and para 2 mothers. SGA infants had an increased risk (OR: 1.7, 95% confidence interval: 1.1-2.6) of being admitted to hospital compared with non-SGA infants. The principal cause was respiratory tract infections. Increased hospitalisation among SGA infants was a factor only if the mother was a smoker-that is, smoked cigarettes at the time of conception. Among subgroups of SGA babies, there was an increased risk for infants of non-repeaters (women without a previous SGA child) (OR: 2.4, 95% CI: 1.4-3.8) and for infants with symmetric (OR: 2.0, 95% CI: 1.2-3.3) body proportions compared with non-SGA infants. The results suggest that, beginning in early pregnancy, growth retardation may have long term consequences for subsequent infant morbidity, particularly if the mother is smoker.

Adult↗

PubMed1996

Mesenteric blood flow velocity and its relation to transitional circulatory adaptation in appropriate for gestational age preterm infants.

We investigated the early postnatal changes of the mesenteric circulation and its relation to the systemic circulation in 15 preterm infants. The infants were studied before the first feeding on d 1 and pre- and postprandially on d 3, 4, 5, and 7. Blood flow velocity was measured by ultrasound Doppler in the superior mesenteric artery, middle cerebral artery, and the aortic orifice for cardiac output calculations. Blood pressure and heart rate were monitored. From d 1 to d 3, the preprandial stroke volume decreased [1.5 +/- 0.3 to 1.3 +/- 0.2 mL/kg (mean +/- SD), p < 0.05], whereas blood pressure (36 +/- 3 to 50 +/- 7 mm Hg, p < 0.001), superior mesenteric artery mean velocity (Vmean) (0.17 +/- 0.08 to 0.30 +/- 0.11 m/s, p < 0.05), and middle cerebral artery Vmean increased (0.15 +/- 0.05 to 0.22 +/- 0.03 m/s, p < 0.001). From d 3 through d 7, the preterm infants demonstrated higher preprandial end diastolic flow velocity in the superior mesenteric artery than we previously reported in term infants (0.15 +/- 0.05 versus 0.12 +/- 0.04, p < 0.05). Like the term infants, preterm infants increased their superior mesenteric artery Vmean by 83% postprandially and maintained a stable cerebral circulation with feeding. Unlike the term infants, feeding in the preterm infants induced a blood pressure decrease (51 +/- 6 to 48 +/- 6 mm Hg, p < 0.01) and a cardiac output increase (176 +/- 30 to 188 +/- 32 mL/kg/min, p < 0.001). These findings suggest that, in contrast to term infants, healthy preterm infants require compensatory systemic hemodynamic changes in response to feeding.

Adaptation, Physiological↗

PubMed1994

[Diabetes mellitus in children. Therapeutic control, social conditions and self care].

We present a descriptive study of children with diabetes mellitus in Sør-Trøndelag county. The study included 66 children. Eight of these children had at least one other chronic disease in addition to diabetes. 31 children used more than two insulin injections daily. The median value of HbA1c was 8.6%. HbA1c was positively correlated with duration of diabetes. However, for the children who were out of remission, HbA1c was positively correlated with age and negatively with number of meals per day. Children whose parents were divorced or single had higher HbA1c than children whose parents were married or lived together. HbA1c was also higher among children who received special lessons at school than among children who did not receive such lessons. Thus, age, duration of diabetes and psychosocial factors were the most important determinants for metabolic control in our study.

Adolescent↗