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Biomedical subjects

B Persson

Publications and source records attributed to B Persson.

At least 73 records · Page 4Linked to original sources

Effect of angiotensin converting enzyme inhibitor or beta blocker on glomerular structural changes in young microalbuminuric patients with Type I (insulin-dependent) diabetes mellitus.

AIMS/HYPOTHESIS: To investigate the influence of angiotensin converting enzyme inhibitors and beta blockers on the progression of early diabetic glomerulopathy. METHODS: Thirteen patients with Type I (insulin-dependent) diabetes mellitus (mean age 18.8 years) with microalbuminuria 31 (19-160) microg/min were randomised to treatment with enalapril (group 1, n = 7) or metoprolol (group 2, n = 6). Renal biopsies were taken before and after 38 (36-48) months of treatment. Albumin excretion rate, blood pressure and HbA1c were measured every third month. A reference group without antihypertensive treatment (group 3, n = 9), with similar age, diabetes duration and degree of microalbuminuria as group 1 and 2, had baseline and follow-up renal biopsies taken previously with an interval of 26-34 months, analysed at the same laboratory. Glomerular structures were measured by stereological methods. RESULTS: Measurements of basement membrane thickness, mesangial and matrix volume fractions were similar among groups at baseline. Structural variables were only increased in group 3 at follow-up. Delta values in basement membrane thickness and diabetic glomerulopathy index per 24 months were lower in group 1 and 2 than in group 3 (p < 0.05). Microalbuminuria returned to normal in group 1 and 2 only. Decreased albumin excretion rate tended to inversely correlate with increased basement membrane thickness (p = 0.08) and diabetic glomerulopathy index (p = 0.05). Mean HbA1c was similar between groups. Mean diastolic blood pressure was lower in group 1 and 2 than in group 3 (p < 0.01). Mean HbA1c and mean diastolic blood pressure correlated to changes in basement membrane thickness, mesangial volume fraction and diabetic glomerulopathy index (p < 0.05). CONCLUSION/INTERPRETATION: Contrary to findings in the group without antihypertensive treatment, no progression of glomerulopathy was seen in those treated with enalapril or metoprolol.

Adolescent↗

Initiation of Escherichia coli ribosomes on matrix coupled mRNAs studied by optical biosensor technique.

The optical biosensor technique, based on the surface plasmon resonance (SPR) phenomenon, has been used to study the initiation of protein synthesis by E. coli ribosomes on surface coupled mRNA. mRNA was first periodate oxidized and then hydrazide coupled to the surface of a CM5 sensor chip. The formation of initiation complexes on the surface coupled mRNA was monitored in real-time with a BIACORE 2000 instrument. Mature 70S*mRNA*fMet-tRNA(Met) initiation complexes were assembled on mRNA by sequential introduction of the 30S and 50S subunits supplemented with appropriate initiation factors and fMet-tRNA(Met). We show that the formation of 70S*mRNA complexes on the surface coupled mRNA proceeds efficiently only in the presence of tRNA. Moreover, 70S*mRNA*fMet-tRNA(Met) complexes formed with fMet-tRNA(Met) are more stable than similar complexes formed with deacylated tRNAs. The efficient formation and slow dissociation of mature 70S*mRNA*fMet-tRNA(Met) initiation complexes are most easily explained by the stabilization of the interaction of the ribosomal subunits by fMet-tRNA(Met). This work demonstrates the feasibility of the BIACORE technique for studying the initiation of protein synthesis.

Base Sequence↗

Temperament traits in male suicide attempters and violent offenders.

With the purpose of comparing temperament traits in subjects who have been violent towards others and with subjects who have shown self-directed violence, 34 male suicide attempters and 34 male violent offenders were matched for age and psychiatric diagnosis. Violent offenders with a history of suicide attempts were excluded. Temperament traits were assessed by means of the Karolinska Scales of Personality. The temperament profiles of suicide attempters and violent offenders were very similar, with high trait anxiety and very low socialization. Violent offenders displayed significantly higher social desirability (P < 0.001). Suicide attempters tended to have higher indirect aggression and monotony avoidance. Impulsiveness, verbal aggression, and inhibition of aggression were within the normal range in both groups. There were substantial temperamental similarities between suicide attempters and violent offenders. In order to disentangle the differential mechanisms behind aggression towards self and others, we probably need to consider historical as well as current situation factors in a systematic way.

Adult↗

Multivariate parameter evaluation of pharmaceutically important cellulose ethers.

A set of nonionic cellulose ethers with varying hydrophobicity and molecular weight has been investigated by principal component analysis (PCA). Several experimental variables such as dynamic surface tension, diffusion coefficient, microviscosity as monitored by a fluorescence probe technique, and intrinsic viscosity are included in the analysis. The experimental variables and observations (polymer fractions) are analyzed in models with good predictive capacities. The apparent equilibrium surface tension correlates to the cloud point and to the critical aggregation concentration in the presence of surfactant. The microviscosity is shown to be a predictive parameter for the degree of hydrophobic substitution. The irreversible process of dynamic surface tension is dependent on the diffusion coefficient but to an even larger degree on the polymer concentration, which is well illustrated by the PCA models.

Algorithms↗

Surface activity and concentration dependent intestinal permeability in the rat.

PURPOSE: To investigate the relation between intestinal effective permeability (P(eff)) and surface activity of fluvastatin and verapamil. METHODS: P(eff)-values were determined for fluvastatin, antipyrine and D-glucose following colon perfusions in the rat in situ. The perfusion solitions differed regarding concentrations of fluvastatin (0-2500 microM) and surface tension (58.9-43.7 mN/m). A cellulose derivative, ethyl-(hydroxyethyl) cellulose (EHEC), was added to lower the surface tension of one of the perfusion solutions. The surface tension of perfusion solutions containing R/S-verapamil (8-814 microM) and R/S-verapamil + chlorpromazine (814 microM + 10 mM) were related to the corresponding P(eff)-values from the literature. RESULTS: The P(eff)of fluvastatin correlated inversely (r2 = 0.985, p < 0.05) with the surface tension of the perfusion solutions below the critical micelle concentration (CMC, 1 mM). Decreasing the surface tension with EHEC increased the P(eff) of fluvastatin by 36% (p < 0.001), but not to the extent anticipated from the correlation between the P(eff) and the surface tension. EHEC also increased the P(eff) of antipyrine by 49% (p < 0.01 ) but not for D-glucose. The P(eff) of R/S-verapamil correlated inversely with the surface tension (r2 = 0.980, p < 0.001). CONCLUSIONS: The ability of fluvastatin to decrease the surface tension at the membrane surface can partly explain the concentration dependent colonic P(eff) of fluvastatin. This study shows that the surface activity of the drug molecule itself is an important physicochemical factor that should be taken into consideration when evaluating drug absorption studies performed in vitro or in situ.

Animals↗

Elapid venom toxins: multiple recruitments of ancient scaffolds.

Nigroxins A and B, two myotoxic phospholipases A2 (PLA2s) from the venom of the American elapid Micrurus nigrocinctus, belong to a new PLA2 subclass. Their primary structures were established and compared with those of PLA2s that have already been studied with respect to myotoxic activity. The combination of amino acid residues Arg15, Ala100, Asn108 and a hydrophobic residue at position 109 is present exclusively in class I PLA2s that display myotoxic activity. These residues cluster within a surface region rich in positive charges and are suggested to play a role in the interaction with the target membrane of the muscle fibers. It is concluded that the myotoxic PLA2s resulted from recruitment of an ancient scaffold. Dendrotoxins and alpha-neurotoxins are similarly derived from other old structures, which are, however, now also present in nontoxic proteins that are widely distributed throughout the animal kingdom. The evolutionary pathways by which elapid PLA2s acquired myotoxicity and dendrotoxins acquired K+-channel blocker activity are traced. They demonstrate how existing scaffolds were adapted stepwise to serve toxic functions by exchange of a few surface-exposed residues.

Amino Acid Sequence↗

Symptoms of depression are important to psychological adaptation and metabolic control in children with diabetes mellitus.

AIMS: Sixty-two children (37 girls, 25 boys) between 9 and 18 years of age were enrolled to investigate: (1) the relationship between adaptation to diabetes mellitus (DM) and psychological functioning; (2) if adaptation or psychological functioning was related to metabolic control; and (3) if the patients' ability to cope with diabetes as assessed by physicians, was correlated to adaptation or psychological functioning. METHODS: Psychological functioning was measured by three general psychological instruments for depressive symptoms, self-esteem and fear. Diabetes adaptation was evaluated by questionnaires and coping with diabetes by an assessment of the physicians. Metabolic control was expressed by the individual HbA1c measured during the last year. RESULTS: Adaptation to diabetes correlated to psychological functioning (depression, P<0.001; self-esteem, P<0.01; and fear, P<0.01). Multiple regression analyses showed that metabolic control was predicted by adaptation (P=0.0013) with monitoring of diabetes as the only significant aspect of the adaptation (P < or = 0.0001). In turn, adaptation was predicted by symptoms of depression and metabolic control (P<0.0001). In support of this observation, a depressed (n = 9) and a non depressed (n= 53) group showed significant differences in metabolic control (P < or = 0.01), adaptation (P < or = 0.001) and self-esteem (P < or = 0.001). The only significant variable for the physicians assessment was metabolic control, which explained 35 % of the variance (P < 0.001). CONCLUSIONS: The major conclusion is that symptoms of depression affect both adaptation and metabolic control. It should be of concern to identify patients with depressive symptoms, offer treatment for their emotional difficulties and increase the support for taking care of their diabetes.

Adaptation, Psychological↗

Leptin concentrations in cord blood in normal newborn infants and offspring of diabetic mothers.

Leptin has been implicated in the regulation of body weight and energy balance; Leptin is produced by adipocytes and placental tissue. Chronic fetal hyperinsulinemia and accelerated fetal growth with increased amounts of body fat are frequent findings in the offspring of diabetic mothers. In this study, we examined whether leptin levels in cord blood of infants of type 1 diabetic mothers (n = 29), gestational diabetic mothers (n = 6 and controls (n = 96) correlated with level of maternal glucose control, maternal leptin level at delivery, gender, fetal and placental size, and C-peptide in cord blood at birth. Leptin was significantly elevated in infants of type 1 diabetic (24.7 ng/ml) and gestational diabetic mothers (29.3 ng/ml) as compared to controls (7.9 ng/ml). C-peptide was also significantly higher in infants of type 1 diabetic (0.91 nmol/l) and gestational diabetic mothers (0.99 nmol/l) vs controls (0.34 nmol/l). Infants of type 1 diabetic mothers with a leptin level in cord blood above the upper normal range, i.e. > 30 ng/ml (n = 13), had an average maternal HbA1c level of 5.4% (normal < 5.5%) that was not different from 5.2% in infants with a leptin level < 30 ng/ml (n = 15). In both neonatal groups of diabetic mothers, leptin in cord blood did not correlate with maternal leptin concentrations, placental weight, birthweight, gender and cord blood C-peptide. In controls, leptin in cord blood was higher in girls than in boys (p = 0.044) and correlated significantly with birthweight (p = 0.41, p < 0.001) and cord blood C-peptide (p = 0.44, p < 0.001) but not with maternal leptin level or placental weight. The 3-4 times higher leptin levels in the offspring of diabetic mothers than normal could reflect increased adipose tissue mass and/or increased contribution from other sources such as placental tissue.

Birth Weight↗

Glutamate decarboxylase (GAD) autoantibody epitope shift during the first year of type 1 diabetes.

Autoantibodies in Type 1 diabetes patients may differentiate between glutamate decarboxylase (GAD65) cloned from human, mouse and rat with a significant better binding to the human antigen. A subgroup of 15% (27/183) patients showed significantly better binding to rodent than to human GAD65. The aim of this study was to determine whether the autoantibody specificity would remain anti-rodent during longitudinal follow-up for one year. We observed 1) that the average slope of the difference between human and mouse GAD65 autoantibodies binding increased between onset and after one year, which demonstrates reduced binding to rodent GAD65 and 2) that, in a group followed every third month, 9/11 (80%) children with rodent specific GAD65 autoantibodies at onset converted within one year to preference against human GAD65. This shift in preference was confirmed by significantly lower EC50 values in the initially anti-rodent GAD65 autoantibodies compared to samples taken one year after clinical diagnosis as determined in displacement studies with unlabeled human GAD65. We speculate that the evolution of GAD65 autoantibodies in Type 1 diabetes includes reactivity to a non-human GAD65 N-terminal end conformation. Progression towards Type 1 diabetes is, however, associated with a maturation of the immune response towards human GAD65 autoreactivity.

Adolescent↗

KIND-a non-redundant protein database.

SUMMARY: KIND (Karolinska Institutet Nonredundant Database) is a protein database where identical sequences, both full length and partial, have been removed. The database contains nearly 274 900 sequences, half of which originate from the protein sequence databases Swissprot and PIR, while the other half come from translated open reading frames in GenPept and TrEMBL. AVAILABILITY: KIND is downloadable from ftp://ftp.mbb.ki.se/pub/KIND.

Algorithms↗

Common structural features of MAPEG -- a widespread superfamily of membrane associated proteins with highly divergent functions in eicosanoid and glutathione metabolism.

A novel superfamily designated MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism), including members of widespread origin with diversified biological functions is defined according to enzymatic activities, sequence motifs, and structural properties. Two of the members are crucial for leukotriene biosynthesis, and three are cytoprotective exhibiting glutathione S-transferase and peroxidase activities. Expression of the most recently recognized member is strongly induced by p53, and may therefore play a role in apoptosis or cancer development. In spite of the different biological functions, all six proteins demonstrate common structural characteristics typical of membrane proteins. In addition, homologues are identified in plants, fungi, and bacteria, demonstrating this superfamily to be generally occurring.

Amino Acid Sequence↗

Insulin induced hypoglycaemia: comparison of glucose and glycerol concentrations in plasma and microdialysate from subcutaneous adipose tissue.

AIMS: To investigate the dynamics between plasma and dialysate glucose during hypoglycaemia in children. STUDY DESIGN: Six children in prepuberty or early puberty were investigated by multiple blood sampling and microdialysis of subcutaneous adipose tissue during a standard arginine-insulin tolerance test. Glucose and glycerol, as an index of lipolysis, were measured in samples from both compartments. Plasma concentrations of insulin and the main counterregulatory hormones were also measured. RESULTS: Plasma and dialysate glucose concentrations were very similar at baseline and increased in concert after infusion of arginine, probably in response to glucagon release. After insulin injection, glucose in both plasma and dialysate fell in parallel. The subsequent hypoglycaemic stress response induced a rapid rebound in the plasma concentration with a mean (SD) delay in the dialysate of 16 (3) minutes. Plasma glycerol was approximately fivefold lower than in the dialysate and did not fluctuate significantly. Dialysate glycerol decreased with arginine infusion and reached a nadir immediately following insulin administration. Subsequently, the antilipolytic effect of insulin was overcome by the hypoglycaemic stress response, and lipolysis prevailed in spite of hyperinsulinaemia. CONCLUSION: After rapidly induced hypoglycaemia, rebound of interstitial glucose concentrations is significantly delayed compared with plasma concentrations, and the antilipolytic effect of hyperinsulinaemia is opposed possibly by the hypoglycaemic stress response.

Adipose Tissue↗

Is carbohydrate metabolism altered among women who have undergone a preeclamptic pregnancy?

OBJECTIVE: To compare women after a preeclamptic pregnancy with women after a normal pregnancy with respect to androgenic-anabolic status and carbohydrate and lipid profiles. METHOD: Twenty-one patients and 22 controls were followed up to 26-119 weeks after delivery. Blood was sampled for analyses of insulin, glucose, insulin growth factor-1, lipids, androgens, sex hormone-binding globulin (SHBG) and uric acid. Anthropometric data and blood pressure were recorded. Data are presented as median and ranges (within parentheses) or mean +/- SEM where appropriate. Comparisons were made by unpaired t test or Mann-Whitney U test, respectively. RESULTS: Significantly higher values were found in the preeclampsia than in the control group for fasting insulin, fasting glucose, fasting insulin resistance index (FIRI, fasting glucose x fasting insulin/25), serum triglycerides, uric acid and blood pressure. There were no differences in androgen status and IGF-1 levels. CONCLUSION: Patients with a recent history of preeclampsia demonstrate signs of relative insulin resistance, hypertriglyceridemia and hyperuricemia as well as increased blood pressure as compared with women who had a normal pregnancy. However, in contrast to other women with insulin resistance, they have a normal androgen status.

Adult↗

Dearterialization of colorectal liver cancer: institutional experience.

BACKGROUND/AIMS: Preliminary clinical trials have suggested that dearterialization (interruption of arterial blood supply) is beneficial to patients with liver tumours. The aim of this report was to review the outcome of all patients undergoing dearterialization for colorectal liver metastases and to analyze whether refinement of the technique was followed by improvement in outcome. METHODS: Retrospective review of 57 patients undergoing temporary (16 h) dearterialization during 1972-1984 (n = 24) or repeated transient dearterialization (1-2 h once or twice daily) during 1985-1995 (n = 33). RESULTS: The median survival after start of treatment was 1.1 years, and the 5-year survival rate was 0%. There was no significant difference in survival between temporary and repeated transient dearterialization. Liver tumour volume and extrahepatic metastases varied negatively with survival. The temporary dearterialization procedure was followed by hepatic or intra-abdominal abscess formation in 6 patients (24%), leading to postoperative death in 2 patients (operative mortality 8%). Complications after repeated transient dearterialization were related mainly to technical problems with the occluder device. CONCLUSION: Although this was not a randomized study, it appears that dearterialization is of no benefit in colorectal liver cancer.

Catheterization↗

Species-specific autoantibodies in type 1 diabetes.

GAD65 autoantibodies (GAD65Ab) are important markers for type 1 (insulin-dependent) diabetes mellitus. Although most patients have GAD65Ab at the time of clinical diagnosis, there are also GAD65Ab-positive individuals in the population at low risk of developing type 1 diabetes. The aim of this study was to test the hypothesis that the GAD65Ab reactivity to GAD65 cloned from human, mouse, and rat in newly diagnosed type 1 diabetic patients differ from antibody-positive healthy individuals. Sera from 254 new-onset 0- to 34-yr-old type 1 diabetic patients and 270 controls were assayed for their reactivity to human, mouse, and rat GAD65. Among the type 1 diabetic patients there was a significant better binding of human GAD65 compared to either mouse (P = 0.03) or rat GAD65 (P = 0.0005). The preference for human GAD65 increased with increasing age at onset (P = 0.0002). This differentiation was not observed in 88 GAD65Ab-positive control subjects. Our data indicate that recognition of epitopes by GAD65Ab in type 1 diabetes is different from that in nontype 1 diabetes, GAD65Ab-positive individuals.

Aging↗

Some risk factors for non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) has been subject to several epidemiological studies and various occupational and non-occupational exposures have been identified as determinants. The present study is a pooled analysis of two earlier methodologically similar case-referent studies encompassing 199 cases of NHL and 479 referents, all alive. Exposure information, mainly on occupational agents, was obtained by mailed questionnaires to the subjects. Exposure to white spirits, thinner, and aviation gasoline as well as work as a painter was connected with increased odds ratios, whereas no increased risk was noted for benzene. Farming was associated with a decreased odds ratio and exposure to phenoxy herbicides, wood preservatives, and work as a lumberjack showed increased odds ratios. Moreover, exposure to plastic and rubber chemicals and also contact with some kinds of pets appeared with increased odds ratios. Office employment and housework showed decreased odds ratios. This study indicates the importance of investigating exposures not occurring very frequently in the general population. Solvents were studied as a group of compounds but were also separated into various specific compounds. The present findings suggest that the carcinogenic property of solvents is not only related to the aromatic ones or to the occurrence of benzene contamination, but also to other types of compounds.

Humans↗

The Swedish family: transition to parenthood.

Family interaction during pregnancy and the transition to parenthood creates the social environment in which the fetus becomes part of the family, family relationships and roles are reorganized, and the infant's temperament appears. The purpose of this study was to examine the relationships among family dynamics, parental-fetal attachment, and infant temperament across the transition to parenthood. A sample of 91 families in Helsingborg, Sweden completed the Family Dynamics Measure and the Maternal/Paternal Fetal Attachment Scale during the third trimester of pregnancy. When the infant was 8-9 months old, mothers (n = 62) and fathers (n = 54) again completed the Family Dynamics Measure. The mother completed the Revised Infant Temperament Questionnaire as well. Overall, we found small changes in family dynamics, with an increase in perceived role conflict and mutuality reported by mothers. Fathers reported greater fetal attachment than their partners. Greater paternal- and maternal fetal attachment was related to more positive family dynamics, and maternal-fetal attachment was positively related to infant mood at 8 months. The stability of family dynamics across the transition to parenthood is a sign that most families negotiate this transition without difficulty.

Demography↗