Biomedical subjects
Publications and source records attributed to B Persson.
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.
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.
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.
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.
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.
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.
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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.
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.
The Drosophila melanogaster sorbitol dehydrogenase (SDH) is characterized as a two-enzyme system of the medium chain dehydrogenase/reductase family (MDR). The SDH-1 enzyme has an enzymology with Km and kcat values an order of magnitude higher than those for the human enzyme but with a similar kcat/Km ratio. It is a tetramer with identical subunits of approximately 38 kDa. At the genomic level, two genes, Sdh-1 and Sdh-2, have a single transcriptional start site and no functional TATA box. Expression is greater in larvae and adults than in pupae, where it is very low. At all three stages, Sdh-1 constitutes the major transcript. Sdh-1 and Sdh-2 genes were located at positions 84E-F and 86D in polytene chromosomes. The deduced amino acid sequences of the two genes show 90% residue identity. Evaluation of the sequence and modeling of the structure toward that of class I alcohol dehydrogenase (ADH) show altered loop and gap arrangements as in mammalian SDH and establishes that SDH, despite gene multiplicity and larger variability than the "constant" ADH of class III, is an enzyme conserved over wide ranges.
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The interrelationships between lactate, lactate/pyruvate (L/P) ratio and catecholamines (CA) in cord artery and vein blood were studied in 56 pregnancies who had complications in the antenatal period or during labour. This group of babies had higher CA levels and were more acidaemic than fetuses after normal pregnancies and labour. There were stronger correlations between lactate and noradrenaline (NA) (R = 0.56, P < 0.001), adrenaline (A) (R = 0.41, P = 0.002) and dopamine (DA) (R = 0.42, P = 0.001) in cord artery blood, than previously reported for normal deliveries. Correlations between L/P ratio and CAs were also significant, although weaker. Multiple regression analysis, using cord artery lactate as the dependent variable, revealed significant correlations for pH (P = 0.01) and pyruvate (P < 0.001) but not for the CAs. The subgroups with high lactate (> 75th centile) had significantly higher NA (P = 0.007) and DA (P < 0.001) in cord artery and NA (P < 0.001) and A (P < 0.001) in cord vein blood, as compared with the subgroup who had lower lactate concentrations. We conclude that fetal hypoxia induces fetal CA production as well as anaerobic metabolism with lactate production. However, the adrenergic stimulation seems not to contribute significantly to the fetal lactate production.
OBJECTIVE: To compare survival and cause specific mortality in hypertensive men with non-hypertensive men derived from the same random population, and to study mortality and morbidity from cardiovascular diseases in the hypertensive men in relation to effects on cardiovascular risk factors during 22-23 years of follow up. DESIGN: Prospective, population based observational study. SUBJECTS AND METHODS: 686 hypertensive men aged 47-55 at screening compared with 6810 non-hypertensive men. The hypertensive men were having stepped care treatment with either beta adrenergic blocking drugs, thiazide diuretics, or combination treatment. Mortality, morbidity, and adverse effects were registered at yearly examinations and from death certificates. MAIN OUTCOME MEASURES: All cause mortality and cause specific mortality. RESULTS: Treated hypertensive men had significantly impaired probability of total survival as well as survival from coronary heart disease and stroke. All cause mortality as well as coronary heart disease and stroke mortality were very similar in hypertensive men and normotensive men during the first decade, but increased steadily thereafter despite continuous good blood pressure control. Smoking, signs of target organ damage, and high serum cholesterol levels, but not blood pressure at screening, were significantly related to the incidence of coronary heart disease during follow up. In time dependent Cox's regression analysis, the incidence of coronary heart disease was significantly related only to serum cholesterol concentrations in the study. Cancer mortality was almost similar in treated hypertensive men (61/686, 8.9%) and non-hypertensive men (732/6810, 10.8%). CONCLUSION: Treated hypertensive men had impaired survival and increased mortality from cardiovascular disease compared with non-hypertensive men of similar age. These differences were observed during the second decade of follow up. During an observation period of 22-23 years-about 15 000 patient years-hypertensive men receiving diuretics and beta blockers had no increased risk of cancer or non-cardiovascular disease.
Microsomal glutathione transferase has hitherto only been purified from mammalian species. N-ethylmaleimide and trypsin activation (discriminating features of this enzyme) has only been observed in microsomes from mammals. In this paper we describe the first isolation and characterization of a non-mammalian microsomal glutathione transferase from frog (Xenopus laevis) liver. This protein has a molecular weight similar to that of the mammalian enzyme (approximately 17 kDa), but cannot be activated by N-ethylmaleimide or trypsin. In fact the enzyme is rapidly inactivated by this sulfhydryl reagent and protease. It thus appears that N-ethylmaleimide activation is not an obligatory property of microsomal glutathione transferase. The frog liver microsomal glutathione transferase has one of the highest specific activities towards the second substrate 1-chloro-2,4-dinitrobenzene (CDNB) (200 mumol/min mg) obtained with any glutathione transferase and accounts for the high activity found in frog liver microsomes. The kcat/K(m) for glutathione and CDNB are 0.017 and 1.1 x 10(6) M-1 s-1, respectively. The enzyme also functions as a glutathione peroxidase (dilinoleoyl phosphatidylcholine hydroperoxide is reduced (5.2 mumol/min mg)). It is now evident that a highly active microsomal glutathione transferase, with a molecular weight similar to that of the mammalian enzymes also exists in a non-mammal species.
We have cytogenetically and by fluorescence in situ hybridization (FISH) analyzed short-term cultures from a malignant eccrine poroma, a type of tumor in which chromosomal abnormalities have previously not been reported. Combining the results from G-banding and FISH, the karyotype was interpreted as 50,XX,t(3;11;12)(q21;p15;q15),+5,+7,+9, +9,t(12;22)(q13;q13),+del(12)(q15),der(15)t(3;15) (q23;p13),der(17)t(8;17)(q22;p13),-20,add(22)(q13).
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Two Phase I clinical trials have been conducted using PNU-214565, a recombinant fusion protein of C242Fab and staphylococcal enterotoxin A (SEA). The initial escalating single dose trial was performed to determine safety and define toxicities. Cumulative doses determined to be safe as single doses were incorporated in an escalating, repeated dose regimen. Twenty-one patients were treated in the single dose and 27 in the repeated dose trials. Patient demographics were equivalent in both, as were the toxicities encountered - primarily fever and hypotension. Three patients in the single dose regimen treated at 0.5 ng/kg experienced grade 3 fever and/or hypotension, and one patient in the repeated dose trial had a dose-limiting grade 4 hypotension (2.75 ng/kg). TNFalpha and IL-2 induction in circulating blood preceded the development of clinical symptoms. One partial response was observed in the repeated dose trial. Pre-existing anti-SEA plasma antibodies protect patients against toxicity at a given drug dose. Based on these findings, a pharmacodynamically-based dosing scheme is currently being tested in a new repeated dose trial.
In an observational study designed to determine whether metabolic changes during long-term antihypertensive drug treatment are associated with an increased risk of coronary heart disease (CHD), 686 middle-aged hypertensive men recruited from a random population screening sample were followed up for 15 years. Antihypertensive treatment predominantly consisted of beta-adrenoceptor blockers and/or thiazide diuretics. CHD and diabetes mellitus were checked for at annual examinations. Time-dependent Cox regression analysis was used to determine correlation between the incidence of CHD and entry characteristics, the monitored serum levels of cholesterol and triglyceride concentrations and the development of diabetes mellitus. Univariate analysis showed the presence of diabetes mellitus a entry to the study and increased baseline serum concentrations of cholesterol and of triglycerides each to be a significant predictor of CHD, the respective relative risks (RR) being 2.12, 1.21 and 1.21. However, analysis of monitored levels of metabolic variables during follow-up showed only an increased serum cholesterol concentration to be significantly and independently associated with CHD (RR 1.07). Although serum triglyceride concentrations increased slightly during follow-up, they were unrelated to the incidence of CHD; nor was onset of diabetes mellitus during follow-up significantly associated with an increased risk of CHD (RR 1.48. Thus, the study showed the presence of metabolic disturbances such as diabetes mellitus and hyperlipidaemia before the start of antihypertensive treatment to be of positive predictive value in middle-aged hypertensive men, and an increase in the monitored serum cholesterol level to be an independent predictor of CHD, whereas neither drug-related diabetes nor an increase in the monitored serum triglyceride concentration seemed to be associated with the occurrence of CHD.