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Biomedical subjects

B Persson

Publications and source records attributed to B Persson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Sorbitol dehydrogenase of Drosophila. Gene, protein, and expression data show a two-gene system.

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.

Alcohol Dehydrogenase↗
PubMed1998

Lactate, lactate/pyruvate ratio and catecholamine interrelations in cord blood at delivery in complicated pregnancies.

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.

Asphyxia Neonatorum↗
PubMed1998

Survival in treated hypertension: follow up study after two decades.

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.

Adrenergic beta-Antagonists↗
PubMed1998

A highly active microsomal glutathione transferase from frog (Xenopus laevis) liver that is not activated by N-ethylmaleimide.

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.

Animals↗
PubMed1998

Characterization of a malignant eccrine poroma by cytogenetic and fluorescence in situ hybridization techniques.

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).

Acrospiroma↗
PubMed1998

Overview of clinical trials employing antibody-targeted superantigens.

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.

Journal Article↗
PubMed1998

[Is antihypertensive treatment a risk factor of coronary disease? Therapy-related triglyceride increase nor diabetes increase the risk].

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.

Adrenergic beta-Antagonists↗
PubMed1998

Studies of interactions with weak affinities and low-molecular-weight compounds using surface plasmon resonance technology.

Interactions between the immobilized weak-affinity monoclonal IgG antibody 39.5, which is specific for the glucose-alpha 1,4-glucose motif, and various oligosaccharides were studied with surface plasmon resonance technology. The antibody was immobilized at high levels on the surface of the sensor chip and different concentrations of the analytes were injected at 25 and 40 degrees C. The 39.5 antibody exhibited specific binding to maltose, tetraglucose and maltotriose, with dissociation constants Kd in the range from 0.07 mM (25 degrees C) to 1.0 mM (40 degrees C). Association and dissociation rate constants (ka and kd) were rapid and baseline was obtained almost immediately after the end of each antigen injection. This excluded the need for a regeneration step but also made calculation of the kinetic values impossible. Owing to the weak affinity and the small size of the analytes (< 1000 Da), a careful design of control surfaces is demanded to exclude artefactual results.

Animals↗
PubMed1998

Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study.

The reason why 10% to 20% of all patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma (CC) remains unknown. The aim of this study was to compare the clinical and biochemical presentation in PSC patients with and without hepatobiliary malignancy and to look for risk factors for developing hepatobiliary carcinoma in PSC. All PSC patients (n = 20) with hepatobiliary carcinoma treated at Huddinge Hospital between 1984 and 1995 were age- and sex-matched to 20 PSC patients with end-stage disease without carcinoma. Clinical and biochemical data from four different occasions (time of onset of PSC, 12 and 6 months before and at the time of cancer diagnosis or liver transplantation [Ltx]) were registered. Seventeen patients had CC, 2 had hepatocellular carcinoma (HCC), and 1 had gallbladder carcinoma (GBC). Eighteen of the cancer patients and 19 controls had inflammatory bowel disease (IBD). The number of patients who smoked or were former smokers was significantly higher in the cancer group (P < .0004). The duration of IBD and PSC, extra- and intrahepatic distribution of PSC, surgical and medical treatments did not differ between the two groups. Abdominal pain was the only symptom that was more frequent among cancer patients at the time of cancer diagnosis/Ltx compared with controls. Evaluation of biochemical data did not indicate a more rapid deterioration among cancer patients. The mean value of the tumor marker, CA 19-9, in the cancer group was 700 kU/L; in the control group, it was 46 kU/L (P < .05), although data were only available in 10 cancer patients and 7 controls. Bile duct dysplasia was found in over 60% of patients with PSC and CC in nontumorous liver tissue apart from the tumor. Clinical and biochemical presentation of PSC patients with and without hepatobiliary carcinoma did not differ during the year before cancer diagnosis/Ltx. Smoking seems to be a risk factor for developing hepatobiliary carcinoma in patients with PSC.

Adult↗
PubMed1998

The three-dimensional structures of two toxins from snake venom throw light on the anticoagulant and neurotoxic sites of phospholipase A2.

The three-dimensional structures of the class II anticoagulant phospholipase A2 (PLA2) toxin RVV-VD from the venom of Russell's viper, Vipera russelli russelli, and the class I neurotoxic PLA2 Notechis II-5 from the, Australian tiger snake, Notechis scutatus scutatus, were determined to 2.2 A and 3.0 A resolution, respectively. Both enzymes are monomeric and consist of 121 and 119 residues, respectively. A comparison of ten class I/II PLA2 structures showed, among other differences, that the beta-sheet of these enzymes (residues 76-83) is about 90 degrees less twisted in class I than in class II PLA2s. This, along with the insertion of some residues in the region 57-59 in class I enzymes (the elapid loop), could be the main reason for the significant difference in the anticoagulant and (presynaptic) neurotoxic properties between the two classes of PLA2. It seems apparent from sequence and structural comparisons that the toxic site of PLA2 responsible for the strong anticoagulancy of these toxins consists of a negatively charged part, Glu53, together with a positively charged ridge of lysine residues free for intermolecular interactions. These lysines differ between the two classes of PLA2.

Amino Acid Sequence↗
PubMed1998

Nonrandom numerical chromosome abnormalities in basal cell carcinomas.

Clonal chromosome abnormalities were found in 22 of 23 short-term cultured basal cell carcinomas (BCC) of the skin. The karyotypic abnormalities were nonrandom and in several cases included evidence of clonal evolution. Especially in cultures showing an epithelial growth pattern, simple numerical changes, most commonly +18, +9, +20, +7, and +5, predominated and presumably constitute pathogenetically important aberrations present in the neoplastic parenchyma. Also, several structural rearrangements of chromosome arm 9q were seen, which may be of particular interest against the background that a gene for familial BCC (Gorlin syndrome), the PTCH gene, maps to this region. Finally, most of the clonal aberrations detected in predominantly fibroblast-like cultures are likely to reflect changes acquired by cells of the tumor stroma, which raises the question whether mutations also of this tumor component may play a pathogenetic role in BCC development.

Adult↗
PubMed1998

Epidemiology of pregnancy-induced hypertension and preeclampsia in type 1 (insulin-dependent) diabetic pregnancies in Sweden.

BACKGROUND: The object of this study was to examine if there is an association between pregnancy-induced hypertension (PIH) and/or preeclampsia (PE) and glycemic control assessed by HbA1c in early type 1 diabetic pregnancy, as well as factors such as maternal age, parity, duration of diabetes, presence of diabetes microangiopathy. METHODS: The nationwide collaborative study included 491 type 1 diabetic pregnancies corresponding to about 80%, of the diabetic pregnancies during the study period 1983-1985. A blood sample for determination of HbA1c was obtained in early gestation (median 9 (5-16) weeks). RESULTS: The rate of PIH/PE was 20.6% in the type 1 diabetic pregnancies compared to 5.0% in the background population. The type 1 diabetic pregnancies complicated by PIH/PE were associated with significantly longer duration of diabetes, higher initial HbA1c (8.1% vs 7.4%, p < 0.01), higher rate of nephropathy and retinopathy, while there were no significant differences in maternal age or parity compared to those without PIH/PE. Discriminant analysis revealed that occurrence of nephropathy (p<0.001), retinopathy (p<0.01) and high HbA1c (p<0.01) in early pregnancy were independently and significantly associated with occurrence of PIH/PE. Among the 463 patients without prepregnancy proteinuria 38 (8.2%) had PIH and 53 (11.5%) PE. The group with PE had, compared to the no PIH/PE group, significantly higher HbA1c (8.2% vs 7.4%, p<0.01). HbA1c was not significantly different between the PIH and the no PIH/PE group (7.5% vs 7.4%). Both the PIH and the PE group had significantly higher rate of retinopathy compared to the no PIH/PE group. If early HbA1c was equal to or above control mean by +8 s.d., i.e. > or =10.1% the PI rate was 31.0% compared to 10.2% in those with HbA1c below that value. CONCLUSIONS: We conclude that poor glycemic control in early pregnancy is associated with increased risk of PE in non-proteinuric type 1 diabetic pregnancies.

Adult↗
PubMed1998

Feasibility of a nurse-monitored, outpatient-care programme for elderly patients with moderate-to-severe, chronic heart failure.

AIMS: To evaluate the feasibility of a nurse-monitored, outpatient-care program for elderly patients previously hospitalized with chronic heart failure. METHODS AND RESULTS: Patients with chronic heart failure hospitalized in the medical wards were screened to find those eligible for a randomized study to compare the effect of a nurse-monitored, outpatient-care programme aiming at symptom management, with conventional care. The inclusion criteria were patients classified in New York Heart Association classes III-IV, age 65 years, and eligibility for an outpatient follow-up programme. The total in-hospital population of patients discharged with a heart-failure diagnosis was surveyed. Eighty-nine per cent of all the hospitalized patients (n=1541) were 65 years old. Of these, 69% (n=1058) were treated in the medical wards which were screened. The study criteria were met by 158 patients (15%). No visits to the nurse occurred in 23 cases among the 79 patients randomized to the structured-care group (29%), mainly on account of death or fatigue. The numbers of hospitalizations and hospital days did not differ between the structured-care and the usual-care groups. CONCLUSIONS: Given the selection criteria and the outline of the interventions, the outpatient, nurse-monitored, symptom-management programme was not feasible for the majority of these elderly patients with moderate-to-severe, chronic heart failure, mainly because of the small proportion of eligible patients and the high drop-out rate. Management of these patients would have to be more adjusted to their home situation.

Aged↗
PubMed1998

Metabolic control in children with insulin-dependent diabetes mellitus 5 y after diagnosis. Early detection of patients at risk for poor metabolic control.

Children (n = 38) aged 3-15 y were randomly chosen, at the time of diabetes diagnosis, for conventional management at a hospital ward, or for treatment partly in a training apartment where the family was offered problem-based education and special therapeutic support. HbA1c, blood glucose stability, urinary C-peptide excretions and incidence of hypoglycaemic attacks and diabetes ketoacidosis (DKA) were monitored and some standardized, self-estimated psychological tests were performed during the first 2 y after diagnosis. During the 3 y thereafter, HbA1c, presence of DKA, microalbuminuria, retinopathy and hypertension were monitored. None of the patients demonstrated signs of diabetes microangiopathy or DKA. The overall mean HbA1c level was 7.2% 5 y after diagnosis and 30% of the children had HbA1c values <6.3%. There were no differences in the HbA1c values for the patients treated by the different management regimens. Blood glucose variability (SD) was also similar, with 75% of the values in the range of 3-10 mmol/l. Patients with poor glycaemic control (mean HbA1c >8.3%) year 5 after diagnosis had already the second year after diagnosis significantly higher HbA1c values and blood glucose variability. The fathers of these patients demonstrated a higher degree of maladjustment. On the basis of increasing HbA1c values, high blood glucose variability and psychosocial risk factors such as their fathers' emotional responses, patients at risk for poor metabolic control in the future can be identified within 2 y after diagnosis. Efforts and resources can thus be focused at an early stage on this group.

Adaptation, Psychological↗
PubMed1998

Hunger behaviour contributes to early nutritional homeostasis.

OBJECTIVES AND METHODS: Our goal was to describe nutritional homeostasis in healthy exclusively breastfed infants (n = 175) during their first 5 d, by cross-sectional measurements of body weight, blood glucose, plasma insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding-protein-1 (IGFBP-1), free fatty acids (FFA), glycerol, ketone (3-OH-butyric acid) and lactate. We also investigated whether nutrition affected feeding behaviour by timing the interval between feedings. RESULTS: A progressive loss of body weight, as percentage of birthweight, occurred up to 2 d of age, with a maximal decrease of 5.8 +/- 2.1% (mean +/- SD); this was accompanied by inhibition of anabolic hormone and metabolic pathways and an increased mobilization of stored fat and ketogenesis. The interval between feedings decreased between d 1 and 2. Weight gain occurred at 3 d and the following re-feeding phase returned fuel stores to their previous levels and established an anabolic hormonal and metabolic situation. Infants with weight loss exceeding 10% had a further accentuation in their peripheral picture of starvation and a further 7% shortening of the interval between feedings. CONCLUSIONS: breastfeeding on demand is accompanied by a balanced nutritional situation and an increased drive to eat when weight reduction is <6%. However, a weight loss of > or = 10%, probably elicits hunger sensations in response to decreased fuel availability.

Analysis of Variance↗