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Biomedical subjects

B Persson

Publications and source records attributed to B Persson.

At least 163 records · Page 9Linked to original sources

Metabolic adaptation in IUGR neonates determined with microdialysis--a pilot study.

Subcutaneous microdialysis was used to monitor the immediate metabolic changes with respect to glucose, glycerol and lactate in the extracellular space of adipose tissue among five small-for-gestational-age (SGA) and two appropriate-for-gestational-age (AGA) newborns. There was a good correlation between glucose levels in blood and dialysate (r = 0.97, n = 14). The infants showed rapid rises and falls in dialysate glucose levels that are not seen among older children and adults. The levels of lactate were higher than those reported in blood. Lactate may serve as an alternative source of energy for the neonate. Microdialysis is of potential value in increasing our understanding of metabolic events. It provides a safe on-line means of making continuous measurements in these fragile patients in order to detect periods of hypoglycaemia, at least in infants with a birth weight > 1000 g.

Adipose Tissue↗

Short-chain dehydrogenases/reductases (SDR).

Short-chain dehydrogenases/reductases (SDR) constitute a large protein family. Presently, at least 57 characterized, highly different enzymes belong to this family and typically exhibit residue identities only at the 15-30% level, indicating early duplicatory origins and extensive divergence. In addition, another family of 22 enzymes with extended protein chains exhibits part-chain SDR relationships and represents enzymes of no less than three EC classes. Furthermore, subforms and species variants are known of both families. In the combined SDR superfamily, only one residue is strictly conserved and ascribed a crucial enzymatic function (Tyr 151 in the numbering system of human NAD(+)-linked prostaglandin dehydrogenase). Such a function for this Tyr residue in SDR enzymes in general is supported also by chemical modifications, site-directed mutagenesis, and an active site position in those tertiary structures that have been characterized. A lysine residue four residues downstream is also largely conserved. A model for catalysis is available on the basis of these two residues. Binding of the coenzyme, NAD(H) or NADP(H), is in the N-terminal part of the molecules, where a common GlyXXXGlyXGly pattern occurs. Two SDR enzymes established by X-ray crystallography show a one-domain subunit with seven to eight beta-strands. Conformational patterns are highly similar, except for variations in the C-terminal parts. Additional structures occur in the family with extended chains. Some of the SDR molecules are known under more than one name, and one of the enzymes has been shown to be susceptible to native, chemical modification, producing reduced Schiff base adducts with pyruvate and other metabolic keto derivatives. Most SDR enzymes are dimers and tetramers. In those analyzed, the area of major subunit contacts involves two long alpha-helices (alpha E, alpha F) in similar and apparently strong subunit interactions. Future possibilities include verification of the proposed reaction mechanism and tracing of additional relationships, perhaps also with other protein families. Short-chain dehydrogenases illustrate the value of comparisons and diversified research in generating unexpected discoveries.

Amino Acid Sequence↗

Gestational diabetes mellitus and paradoxical fetal macrosomia--a case report.

Gestational diabetes mellitus (GDM) is associated with an increased rate of fetal macrosomia. We describe the outcome of two pregnancies complicated by GDM occurring 2 years apart in a normal-weight woman. Despite adequate maternal blood glucose control during gestation, both infants were markedly oversized at birth (birth weight and length exceeded normal means by 3 and 2 S.D., respectively). The placental weights were far above normal. At birth, the siblings shared the typical appearance of a diabetes fetopathy. The first one developed transient, the second persistent neonatal hypoglycemia associated with hyperinsulinemia, that needed treatment with diazoxide for 2.5 months. Both infants normalized their growth rates during the following months; their psychomotor development assessed at 2 years and at 9 months of age, respectively, was normal. During the last trimester of the second pregnancy, the plasma concentration of placental lactogen (PL) increased to a very high level (19 micrograms/l). The maternal early insulin response to glucose increased significantly with gestation and was much above that in the non-pregnant state. This rise in insulin response could not compensate for the concomitant decrease in insulin sensitivity as assessed by the minimal model according to Bergman [2]. The pronounced fetal macrosomia described cannot be attributed to GDM only. We speculate that excess activity of lactogenic hormones like PL beside glucose contribute to exaggerated fetal beta-cell function with growth acceleration and neonatal hypoglycemia. This hypothesis is in accordance with in vitro evidence indicating that PL may have an important role in the regulation of the maternal and fetal beta-cell mass and function.

Adult↗

Probing the molecular mechanism of action of co-repressor in the E. coli methionine repressor-operator complex using surface plasmon resonance (SPR).

We have studied quantitatively the effect of the corepressor, S-adenosylmethionine (SAM), on the interaction between the E. coli methionine repressor, MetJ, and an idealised operator fragment, by recording measurements of surface plasmon resonance using a BIAcore instrument. We have recorded kinetic binding data in the presence of SAM, which carries a net positive charge, and two corepressor analogues, adenosylornithine (AO) and aza-SAM, which differ in the location of the atom carrying the positive charge. Our data support the hypothesis that the effect of the corepressor is electrostatic in origin. The difference in electrostatic interaction energy between the SAM- and AO-repressor-operator complexes of approximately 3.5 kJ/mol calculated from the known three-dimensional structure is within the range of our experimentally determined values of 2.8-4.3 kJ/mol. These results illustrate the potential of SPR measurements for studying protein-nucleic acid interactions.

Adenosine↗

Real-time monitoring of DNA manipulations using biosensor technology.

The potential of real-time biospecific interaction analysis technology for applications in molecular biology is described. DNA fragments are immobilized onto a biosensor surface using the high-affinity streptavidin-biotin system and subsequently used to monitor different unit operations in molecular biology, e.g., DNA strand separation, DNA hybridization kinetics, and enzymatic modifications. A model system comprising six oligonucleotides was used, which can be assembled into a 69-bp double-stranded DNA fragment. Using this system, the biosensor approach was employed to analyze multistep solid-phase gene assembly and the performance of different enzymes routinely used for the synthesis and manipulation of DNA. In addition, a concept for the determination of single-point mutations in DNA samples is described.

Base Sequence↗

Tumour S-phase activity, nucleotide profile and RNA levels after hepatic artery occlusion and reperfusion in an experimental model of secondary liver carcinoma.

Rats with carcinoma of the colon implanted into the liver were subjected to hepatic arterial occlusion for 30-120 min. Regrowth of the tumour after reperfusion was evaluated by immunohistological determination of S-phase activity after injection of bromodeoxyuridine. Levels of RNA and nucleotides, and energy charge, were also examined. DNA synthesis was observed in the entire tumour except in necrotic areas of controls and after 30-min ischaemia with 2-h reflow. Almost all tumoral DNA synthesis was abolished by 2 h of ischaemia, except in a few cells in the tumour periphery, which after reperfusion for 22 and 40 h grew into a band-like concentric layer. Levels of energy charge, adenosine, uridine and guanosine 5'-triphosphates, and RNA were unchanged in liver tissue after hepatic arterial occlusion but decreased in the tumour. In conclusion 30 min of ischaemia did not damage the tumour cells substantially. Ischaemia for 2 h seemed able to kill the tumour cells except those in the periphery in areas nourished by the portal vein where tumour regrowth was seen. The liver tissue was not damaged.

Animals↗

Ethanol utilization regulatory protein: profile alignments give no evidence of origin through aldehyde and alcohol dehydrogenase gene fusion.

The suggestion that the ethanol regulatory protein from Aspergillus has its evolutionary origin in a gene fusion between aldehyde and alcohol dehydrogenase genes (Hawkins AR, Lamb HK, Radford A, Moore JD, 1994, Gene 146:145-158) has been tested by profile analysis with aldehyde and alcohol dehydrogenase family profiles. We show that the degree and kind of similarity observed between these profiles and the ethanol regulatory protein sequence is that expected from random sequences of the same composition. This level of similarity fails to support the suggested gene fusion.

Alcohol Dehydrogenase↗

Amperometric thin film biosensors based on glucose dehydrogenase and Toluidine Blue O as catalyst for NADH electrooxidation.

Amperometric glucose sensors were constructed based on solid graphite electrodes, surface-modified with NAD+ dependent glucose dehydrogenase (GDH), Toluidine Blue O (TBO), and protective ionic polymers. The electrocatalytic oxidation of NADH was evaluated from cyclic voltammetry with TBO dissolved, adsorbed, and electrostatically or covalently bound to polymers. The NADH and glucose sensors constructed were investigated and operated at 0 mV vs. Ag/AgCl using single potential step chronoamperometry. The operational stability of the glucose sensors was limited by leakage of NAD+. A glucose sensitivity much higher than carbon paste electrode was found. A sensitivity as high as 25 microA cm-2 mM-1 was achieved.

Biosensing Techniques↗

Continuous maternal glucose infusion during labor: effects on maternal and fetal glucose and lactate levels.

Fetal and neonatal glucose and lactate levels and acid-base balance after continuous maternal infusion of 5% dextrose at 180 mL/h (9 g/h) was compared with 0.9% saline solution in a prospective, randomized study from selected monitored labors. An infusion of 5% dextrose produced significantly increased glucose levels in maternal (p < 0.01), cord artery (p < 0.01), and cord vein (p < 0.001) blood. An increased maternal insulin level was also present (p < 0.05), but no differences in cord insulin levels were observed. beta-Hydroxybutyrate was lower in maternal (p < 0.05) and cord vein (p < 0.01), but not in cord artery blood, after maternal dextrose infusion. No significant changes occurred in blood lactate levels between the two groups in either mother, fetus, cord, or neonate. Acid-base balance in cord blood did not differ between the two groups. Maternal infusion of 5% dextrose at 180 mL/h (9 g/h), compared with saline solution, produces higher glucose levels in both mother and fetus, but increased insulin concentrations only in the mother. Dextrose infusion also lowers beta-hydroxybutyrate in maternal and cord vein blood. No differences were seen in lactate levels or cord acid-base balance. Both regimens seem safe according to risks for lactacidosis and neonatal hypoglycemia in the normoxemic, normal size fetus.

3-Hydroxybutyric Acid↗

Myelofibrosis and benzene exposure.

Petrol station attendants are exposed to benzene, a well-known carcinogen for blood malignancies. A case of myelofibrosis in a petrol station attendant is presented, along with other reports of myelofibrosis after benzene exposure obtained from the Swedish Cancer Environment Register. Findings of an increased risk for myelofibrosis in the transport sector also suggest a causal relationship with benzene.

Benzene↗

Antihypertensive effects of moexipril, a new ACE inhibitor, as add-on therapy to nifedipine in patients with essential hypertension.

Moexipril is a new nonpeptide angiotensin-converting enzyme (ACE) inhibitor with an intermediate duration of action. The antihypertensive efficacy and safety of moexipril as add-on therapy to nifedipine retard (20 mg b.i.d) was compared to placebo during 8 weeks in a double-blind trial with a parallel group design. A total of 203 patients with essential hypertension and a sitting diastolic blood pressure (DBP) > or = 95 mm Hg on nifedipine alone were randomly assigned to placebo or moexipril 3.75 mg o.d., 7.5 mg o.d., or 15 mg o.d.. At endpoint, the adjusted mean reductions in DBP from baseline were 6 mm Hg, 9 mm Hg (p < 0.01), and 9 mm Hg (p < 0.05) in the moexipril 3.75 mg, 7.5 mg, and 15 mg groups, respectively, compared to 5 mm Hg in the placebo group. All dosages of moexipril were well tolerated, and the overall percentages of patients who reported adverse experiences were smaller than in the placebo group. We concluded that moexipril as add-on therapy to nifedipine is well tolerated and gives additional antihypertensive effects.

Adolescent↗

Indications of low sex hormone binding globulin (SHBG) in young females with type 1 diabetes, and an independent association to microalbuminuria.

Sex hormone binding globulin (SHBG) is normally decreased during puberty and inversely related to insulin resistance. Microalbuminuria is rare before puberty in Type 1 diabetes implicating that sex hormones may contribute to its development. We investigated SHBG levels in young females with > 5 years of Type 1 diabetes, and the association to microalbuminuria. Ten diabetic females with, and 15 without microalbuminuria, and 17 healthy controls in pubertal stage 4-5 were compared regarding anthropometric data, fasting serum levels of SHBG, testosterone, insulin, insulin-like growth factor-1 (IGF-1), lipids and lipoproteins. Multiple regression analyses were performed to study variables with independent influences on SHBG and albumin excretion rate (AER), respectively, in Type 1 diabetes. SHBG was lower and testosterone/SHBG ratio higher in normoalbuminuric females with diabetes than in controls. This was further emphasized in diabetic patients with microalbuminuria. IGF-1 was lower in Type 1 diabetes than in controls, and significantly decreased in microalbuminuric as compared to normoalbuminuric diabetic patients. IGF-1 was only correlated to SHBG in healthy controls. In Type 1 diabetes, applying stepwise multiple regression analysis, insulin dose, BMI, and HbA1c had a significant and independent inverse influence on SHBG (r2 = 0.77, p < 0.001). With log AER as the dependent variable, low SHBG, low IGF-1, HbA1c, and age added to the regression (r2 = 0.65, p = 0.004), whereas BMI, insulin dose and blood pressure did not. In conclusion, SHBG is decreased in young females with Type 1 diabetes, influenced by increased insulin requirements, BMI and HbA1c. In turn, low SHBG seems to be independently associated to elevated AER in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Scalp blood lactate: a new test strip method for monitoring fetal wellbeing in labour.

OBJECTIVE: To determine fetal scalp blood lactate with a new test strip method in parturients with normal and abnormal cardiotocograms during labour and to describe the relation to maternal lactate, fetal scalp blood pH, cord artery lactate and acid-base balance. SETTING: Labour wards at the University Hospitals of Huddinge and Lund and at the County Hospital of Ostersund, Sweden. MATERIALS AND METHOD: Fetal scalp blood was sampled for lactate (n = 269) and pH (n = 285) determination in 177 parturients with abnormal intrapartum CTG. Lactate and pH were also analysed in a group of 64 women with normal pregnancies and with a reactive fetal heart rate tracing prior to sampling of fetal scalp blood. At fetal blood sampling lactate was also determined in maternal capillary blood, while at birth lactate and acid-base balance in cord artery blood was performed in almost all cases. MAIN OUTCOME MEASUREMENTS: Medians and percentiles (lactate and acid-base balance). Correlation between fetal scalp blood lactate (dependent) and scalp blood pH, cord artery blood lactate and acid-base parameters and labour time prior to fetal blood sampling. RESULTS: In the group with abnormal cardiotocograms, fetal scalp and umbilical artery blood lactate and acid-base parameters differed significantly from the same parameters in the normal group. The fetal-maternal lactate gradient changed from negative in the normal group to positive in the fetal distress group. Multiple regression analysis, with scalp lactate as the dependent parameter, revealed a significant correlation with fetal scalp blood pH (P < 0.001) and umbilical artery lactate (P < 0.01). CONCLUSIONS: Intrapartum scalp blood lactate was significantly correlated with pH and cord artery lactate. The results indicate that increased lactate levels in fetal blood sampling describes fetal lactacidosis. The new disposable test strip requiring only 5 microliters of blood for lactate determination may be better than traditional methods for monitoring fetal wellbeing in labour.

Acid-Base Equilibrium↗

Influence of body temperature on thyrotropic hormone release and lipolysis in the newborn infant.

The present study investigated possible interactions between body temperature, lipolysis and thyrotropin (TSH), the only hormone with a documented lipolytic effect in vitro in newborn infants. Healthy infants were either nursed in the usual way (n = 18) or protected from a decrease in body temperature (n = 17) during the first postnatal hour. The infants' axillary temperatures were measured immediately after birth and after 10 and 60 min. Blood samples were collected from the umbilical vein and from the infants 10 and 60 min after birth for analysis of TSH, glycerol, free fatty acids, 3-OH-butyric acid and glucose. We found that the mean (+/- SD) infant axillary temperature was 37.6 +/- 0.4 degrees C immediately after birth. In the routinely nursed infants, body temperature decreased to 37.0 +/- 0.5 degrees C at 10 min (p = 0.01) and to 36.6 +/- 0.4 degrees C at 60 min (p = 0.01); the cold-protected infants maintained their fetal temperature at 60 min of age. There was a four-fold increase in plasma TSH levels at 10 min, independent of the infant's body temperature, and the hormone level remained invariably high at 60 min. Plasma glycerol levels increased progressively at 10 min (p = 0.01) and 60 min (p = 0.01) in both infant groups, but were higher (p = 0.02) in the routinely nursed infants at 60 min. No significant relationship was found between TSH and glycerol levels. Infant body temperature did not affect the levels of free fatty acids, 3-OH-butyric acid or glucose. We conclude that the change in environmental temperature as a result of extrauterine adaptation causes thermal stimulation of the infant's body surface which leads to activation of the hypothalamic-pituitary TSH axis, resulting in maximal TSH release, and thus to induction of the lipolytic process. A decrease in body temperature may be an additive stimulus for further enhancement of lipolysis.

Body Temperature↗

Enzymuria in a population living near a cadmium battery plant.

OBJECTIVES: To study the body burden of cadmium and signs of tubular dysfunction in a rural population living near a closed nickel cadmium battery plant. METHODS: Cadmium and N-acetyl-beta-glucosaminidase (NAG) in urine were measured in 72 subjects who lived close to the plant. RESULTS: Residents living close to the plant had higher median urinary cadmium concentrations than those living farther away (1.01 v 0.46 nmol/mmol creatinine) and than a control group (0.2 nmol/mmol creatinine). There was a significant correlation between urinary cadmium and the excretion of NAG in urine as well as signs of tubular dysfunction in residents who excreted urinary cadmium above 0.5 nmol/mmol creatinine. CONCLUSION: Tubular dysfunction may appear in environmentally exposed subjects at lower cadmium body burdens than previously anticipated.

Acetylglucosaminidase↗