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Biomedical subjects

B Persson

Publications and source records attributed to B Persson.

At least 109 records · Page 6Linked to original sources
PubMed1998

Lactate compared with pH analysis at fetal scalp blood sampling: a prospective randomised study.

OBJECTIVE: Fetal scalp blood sampling is a widely used method for assessing fetal condition in the event of ominous fetal heart rate patterns. The purpose of this randomised trial was to compare the value of fetal scalp blood lactate and pH management in cases of abnormal intrapartum fetal heart rate tracings. METHODS: Of 341 cases of ominous fetal heart rate patterns, 169 were randomly assigned to pH analysis, and 172 to lactate measurements. Lactate was measured using a lactate card requiring 5 microL of blood and yielding the result within 60 seconds. pH analysis was performed with an ABL 510 acid-base analyser requiring 35 microL of blood and yielding the results within 47 seconds. RESULTS: Unsuccessful fetal blood sampling procedures (no result or an unreliable result) occurred significantly more often in the pH subgroup than in the lactate subgroup (OR 16.1 with 95% CI 5.8-44.7). In the pH subgroup the failure rate was inversely related to the degree of cervical dilatation. Compared with the pH subgroup, the lactate subgroup was characterised by fewer fetal scalp incisions per blood sampling attempt (median 1.0 [interquartile range (IQR) 1-1] vs 2.0 [IQR 1-2]), and significantly less time required for the sampling procedure (median 120 s [IQR 90-147] vs 230 s [IQR 180-300]). The groups did not differ in mode of delivery, neonatal outcome and umbilical artery acid-base balance and lactate levels. CONCLUSION: This trial showed the levels of lactate and pH in fetal scalp blood to be comparable in predicting perinatal outcome, but the procedure to measuring lactate was more successful than that for pH. Owing to its simplicity of performance, lactate analysis is an attractive alternative for intrapartum fetal monitoring.

Female↗
PubMed1998

Cadmium may be a risk factor for osteoporosis.

OBJECTIVES: The primary study aim was to examine the possible role of cadmium as a risk factor for osteoporosis by determining the bone mineral density (BMD) in workers previously exposed to cadmium. A second objective was to validate the BMD data obtained with a movable instrument. METHODS: 43 workers who were exposed to cadmium for < or = 5 years before 1978 were studied. Cadmium in blood (B-Cd) and urine (U-Cd) were used as dose estimates. The BMD was assessed in the forearm, the spine, and the hip (neck and trochanter) with a dual energy x ray absorptiometry (DXA) instrument. Age and sex matched reference populations were used to compute Z scores, commonly used to assess osteoporosis. RESULTS: The mean forearm Z score was -0.60 (95% confidence interval (95% CI) -1.08 to -0.12) in the group exposed to cadmium. The mean Z score for the spine was -0.47 (95% CI -0.92 to -0.03), for the hip neck -0.40 (95% CI -0.75 to -0.05), and for the hip trochanter -0.22 (95% CI -0.52 to -0.07). The decrease in forearm BMD was correlated with age (p = 0.002) and B-Cd (p = 0.040). No such correlations were found for the other sites. Workers with tubular proteinuria had a lower forearm BMD (p = 0.029) and a lower Z score (p = 0.072) than workers without tubular proteinuria. CONCLUSIONS: There was a suggested dose-effect relation between cadmium dose and bone mineral density. Furthermore, there was a dose-response relation between cadmium dose and osteoporosis. Cadmium may be a risk factor for the development of osteoporosis at lower doses than previously anticipated.

Absorptiometry, Photon↗
PubMed1998

Serum leptin levels in young females with insulin-dependent diabetes and the relationship to hyperandrogenicity and microalbuminuria.

To investigate the relationship between leptin levels and IDDM with and without microalbuminuria, fasting serum levels of leptin, insulin, insulin-like growth factor-1 (IGF-1), sex hormone-binding globulin (SHBG), testosterone (SHBG) ratio, blood pressure and body mass index (BMI) were measured in 18 normo- and 11 microalbuminuric females with >5 years of IDDM, and 24 healthy controls in late puberty. Leptin levels were higher in micro- than normoalbuminuric IDDM patients, and lower in healthy controls than in both IDDM groups (p < 0.05, respectively). In multiple regression analysis, presence of IDDM and BMI independently contributed to increased leptin values (R2 = 0.34, p < 0.001). Including IDDM females only, solely low IGF-1 and high testosterone/SHBG were associated with leptin (R2 = 0.39, p = 0.009). Albumin excretion rate (AER) was correlated to leptin (r = 0.48, p = 0.01). With AER as the dependent variable only serum leptin and diastolic blood pressure added to the regression (R2 = 0.59, p < 0.001). In conclusion, serum leptin, independently of BMI, is: (1) increased in IDDM females of late puberty; (2) associated with low IGF-1 and hyperandrogenemia, and (3) related to increased albumin excretion rate in IDDM females.

3-Hydroxybutyric Acid↗
PubMed1998

Vasoconstriction during acute hypervolemic hemodilution in hypertensive patients is not prevented by calcium blockade.

The reduction of blood viscosity by moderate acute hypervolemic hemodilution in untreated hypertensives can be associated with a secondary vasoconstriction. The aim of this study was to examine whether a vasodilating therapy prevents this hemodynamic reaction. Twelve hypertensive patients (WHO stage II) were treated with the vasoselective calcium channel blocker isradipine in a placebo-controlled, double-blind, crossover study. Acute hypervolemic hemodilution was performed twice: at the end of the placebo period and after two months of treatment. Hemodilution was achieved by the intravenous infusion of 1000 mL saline over a 10- to 15-minute period. Arterial blood pressure, heart rate, cardiac output (dye dilution), renal blood flow, glomerular filtration, natriuresis, hematocrit, whole blood, and plasma viscosity were assessed before and after infusion. Flow resistance and vascular hindrance in the central and renal circulation were calculated. Acute hemodilution associated with a significant reduction of blood (P<0.01) and plasma (P<0.01) viscosity did not influence the mean arterial pressure and cardiac output. Consequently, the total flow resistance remained unchanged. However, as a result of hemodilution, the calculated vascular hindrance index in the systemic circulation increased, indicating a vasoconstrictive reaction, both with placebo (from 5.22 to 6.07 U x mPa(-1) x s(-1), P < 0.05) and during chronic treatment with calcium blockade (from 3.75 to 4.22 U x mPa(-1) x s(-1), P<0.02). Vasoconstriction was not observed in the renal circulation, either during the placebo or active treatments. The results of this study indicate that the systemic vasoconstriction evoked by the acute moderate hypervolemic hemodilution in hypertensive patients was not prevented by a calcium channel blockade.

Antihypertensive Agents↗
PubMed1998

Mortality from asthma and cancer among sulfite mill workers.

OBJECTIVES: The aims of the present case-referent study were to investigate whether sulfite workers show increased mortality from asthma, chronic obstructive pulmonary disease or certain malignancies of interest in relation to sulfite mill work. The main exposure from the pulping processes is from sulfur dioxide, wood dust and terpenes. METHODS: The subjects of the study were all the men who died between 1960 and 1989 and who were aged 40 to 75 years at death (N = 780) in the parishes surrounding 3 sulfite mills. The men who died from asthma (N = 13), COPD (N = 20), lung cancer (N = 33), stomach cancer (N = 35), or brain tumor (N = 10) formed the case group. All the subjects, except the cases in question, were used as referents. As a proxy variable of exposure, job titles from the registers of deaths and burials were used, and 24% of the subjects were classified as exposed. RESULTS: There was an increased mortality from asthma [odds ratio(OR) 2.8, 90% confidence interval (90% CI) 1.1-6.8] and brain tumors (OR 3.3, 90% CI 1.2-8.9) among the sulfite workers. The mortality due to lung cancer was not significantly increased (OR 1.4, 90% CI 0.7-2.6), and there was a reduced mortality from stomach cancer (OR 0.4, 90% CI 0.2-0.9). CONCLUSIONS: The increased asthma mortality may be due to accidental exposure to irritating gases, such as sulfur dioxide. The increased risk for brain tumors has no obvious explanation.

Adult↗
PubMed1998

Neonatal morbidities in gestational diabetes mellitus.

The currently accepted definition of gestational diabetes mellitus (GDM) is rather broad. One might expect that fetal and neonatal complications that may occur in GDM pregnancy would be similar to those in pregestational diabetic pregnancy. Comparative evaluation of reported data on morbidity in GDM are often hampered by confounding variables (maternal age, parity, obesity) as well as the influence of factors such as ethnic origin, diagnostic criteria, and intervention during pregnancy. Recent observations indicate that GDM may be associated with increased incidence of fetal malformation and perinatal mortality. Such poor outcome is likely confined to a subset of GDM patients in whom diabetes was present but unrecognized before pregnancy. The most frequent and significant morbidity is fetal macrosomia, which in turn is associated with increased risk of birth injuries and asphyxia. In a nationwide study in Sweden (1991-1993) of a large series (n = 3.322) of treated GDM pregnancies, perinatal mortality rate was not increased; but the rate of preeclampsia was doubled, and the rate of emergency cesarean section was 1.6 times higher than in the background population. The rates of fetal macrosomia (> or = 4,500 g), asphyxia, and transient tachypnea were two to three times higher than normal Erb's palsy was 0.7 and 5% in vaginally delivered infants weighing < 4,500 and > or = 4,500 g, respectively. There is a clear need to define the various levels of glucose intolerance in the mother that may have an adverse effect on the offspring. Of equal importance is to standardize and systematize the criteria used to assess the significance of any such impact.

Diabetes, Gestational↗
PubMed1998

Superantigen-targeted therapy: phase I escalating repeat dose trial of the fusion protein PNU-214565 in patients with advanced gastrointestinal malignancies.

Antibody-directed, superantigen-induced cytotoxicity has been shown to have potent in vitro and in vivo antitumor effects in preclinical models. In the present study, PNU-214565, a recombinant fusion protein consisting of the Fab of the monoclonal antibody C242 and staphylococcal enterotoxin A (SEA), was used in an escalating repeat dose Phase I clinical trial in patients with advanced gastrointestinal malignancies. A prior single-dose Phase I clinical trial had demonstrated safety at doses of 1.5 ng/kg with toxicities of fever and hypotension that were not dose related. Twenty-seven patients (age range, 36-75 years; median, 62; 14 males and 13 females; 23 colorectal and 4 pancreatic) were treated in the present study with one cycle of four consecutive daily 3-h infusions of PNU-214565 at doses of 0.15 ng/kg (n = 3); 0.5 ng/kg (n = 3), 1.5 ng/kg (n = 4), 2.75 ng/kg (n = 12), and 3.5 ng/kg (n = 5). All patients had a good performance status [Eastern Cooperative Oncology Group: PS = 0 (n = 15), PS = 1 (n = 12)]. As in the single-dose trial, fever and hypotension were the most common toxicities. Dose-limiting toxicity (DLT), consisting of transient hypotension responsive to dopamine, was experienced by one patient treated at the 2.75 ng/kg dose level. One patient with pancreatic cancer metastatic to the liver experienced a partial response of hepatic metastases with stable pancreatic head abnormalities by computed tomography scan. Further dose escalation was suspended when two patients treated in a companion repeat dose Phase I study experienced DLT at the 4 ng/kg dose level. Multiparameter analyses on all patients treated in the two companion single-dose and two-repeated-dose Phase I trials revealed that the levels of patients' pretreatment anti-SEA antibodies protected against toxicity at a given drug dose. By jointly considering weight and the baseline anti-SEA concentration in a patient, it is possible to assign a PNU-214565 dose that will induce systemic cytokine release (a surrogate test to assess for the presence of uncomplexed drug and its ability to induce systemic cellular activation) without DLT. This pharmacodynamically based dosing scheme will be tested in future repeated-dose clinical trials and will define maximally tolerated doses of this powerful new immunotherapy approach.

Adult↗
PubMed1998

Male reproductive pattern in a glass producing area.

The objective of the study was to evaluate the reproductive pattern among male crystal glassworkers in comparison to other males in a restricted area in the south-east part of Sweden. The parish register information was gathered for all men with job titles registered, decreased at the age above 20 years during 1950-1982. The comparison of reproductive patterns was made between groups of glassworkers, farmers and workers of other occupations. As an indicator of fertility, birth rates and time to first child-birth were calculated. Male sex ratios (number of boys/all child-births) were calculated as a measure of reproductive disturbances. The total birth rates as well as the birth rates for sons were slightly decreased among glassworkers when compared to the group of non-farmers/non-glassworkers and significantly decreased when compared to farmers. The total birth rate of the non-farmer/non-glassworker group was also significantly decreased compared to farmers. No differences in sex ratios among children born or in time to first child-birth were seen between the three groups. Among the glassworkers, the reduction in birth rates was most pronounced among engravers/grinders both in comparison to farmers and others. The results indicate that paternal exposure in crystal glassworks might somewhat negatively affect the male reproduction at least in a historical perspective. The mechanisms behind this cannot be concluded from this study.

Adult↗
PubMed1997

Alanine insertion scanning mutagenesis of lactose permease transmembrane helices.

A priori, single residue insertions into transmembrane helices are expected to be highly disruptive to protein structure and function. We have carried out a systematic analysis of the phenotypes associated with Ala insertions into transmembrane helices in lactose permease, a multispanning Escherichia coli inner membrane protein. Insertion of alanine into the center of 7 transmembrane helices was found to abolish stable integration of lactose permease into the membrane or uphill lactose transport. A more detailed Ala insertion scan was made of transmembrane helix III. The results pin-point a central region of approximately 2 helical turns that is crucial for lactose permease stability and/or activity. A Trp scan in this region identified 2 residues essential for lactose permease stability. From these results, it appears that transmembrane helices have differential sensitivities to single residue insertions and that such mutations may be useful for identifying structurally and/or functionally important helix segments.

Alanine↗
PubMed1997

Function, gene organization and protein structures of 11beta-hydroxysteroid dehydrogenase isoforms.

Enzymatic interconversion of active and inactive glucocorticoid hormone is important, and is carried out physiologically by 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isoforms, explaining their role in cellular and toxicological processes. Two forms of the enzyme, 11beta-HSD-1 and 11beta-HSD-2, belonging to the protein superfamily of short-chain dehydrogenases/reductases, have been structurally and functionally characterised. Although displaying dehydrogenase and reductase activities in vitro, the dominant in vivo function of the type-1 enzyme might be to work as a reductase, thus generating active cortisol from inactive cortisone precursors. On the other hand, for adrenal glucocorticoids the type-2 enzyme seems to be exclusively a dehydrogenase and, by inactivating glucocorticoids, confers specificity to peripheral mineralocorticoid receptors.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Cellular UDP-glucose deficiency caused by a single point mutation in the UDP-glucose pyrophosphorylase gene.

We previously isolated a mutant cell that is the only mammalian cell reported to have a persistently low level of UDP-glucose. In this work we obtained a spontaneous revertant whose UDP-glucose level lies between those found in the wild type and the mutant cell. The activity of UDP-glucose pyrophosphorylase (UDPG:PP), the enzyme that catalyzes the formation of UDP-glucose, was in the mutant 4% and in the revertant 56% of the activity found in the wild type cell. Sequence analysis of UDPG: PP cDNAs from the mutant cell showed one missense mutation, which changes amino acid residue 115 from glycine to aspartic acid. The substituted glycine is located within the largest stretch of strictly conserved residues among eukaryotic UDPG:PPs. The analysis of the cDNAs from the revertant cell indicated the presence of an equimolar mixture of the wild type and the mutated mRNAs, suggesting that the mutation has reverted in only one of the alleles. In summary, we demonstrate that the G115D substitution in the Chinese hamster UDPG:PP dramatically impairs its enzymatic activity, thereby causing cellular UDP-glucose deficiency.

Amino Acid Sequence↗
PubMed1997

Mycothiol-dependent formaldehyde dehydrogenase, a prokaryotic medium-chain dehydrogenase/reductase, phylogenetically links different eukaroytic alcohol dehydrogenases--primary structure, conformational modelling and functional correlations.

Prokaryotic mycothiol-dependent formaldehyde dehydrogenase has been structurally characterized by peptide analysis of the 360-residue protein chain and by molecular modelling and functional correlation with the conformational properties of zinc-containing alcohol dehydrogenases. The structure is found to be a divergent medium-chain dehydrogenase/reductase (MDR), at a phylogenetic position intermediate between the cluster of dimeric alcohol dehydrogenases of all classes (including the human forms), and several tetrameric reductases/dehydrogenases. Molecular modelling and functionally important residues suggest a fold of the mycothiol-dependent formaldehyde dehydrogenase related overall to that of MDR alcohol dehydrogenases, with the presence of the catalytic and structural zinc atoms, but otherwise much altered active-site relationships compatible with the different substrate specificity, and an altered loop structure compatible with differences in the quaternary structure. Residues typical of glutathione binding in class-III alcohol dehydrogenase are not present, consistent with that the mycothiol factor is not closely similar to glutathione. The molecular architecture is different from that of the 'constant' alcohol dehydrogenases (of class-III type) and the 'variable' alcohol dehydrogenases (of class-I and class-II types), further supporting the unique structure of mycothiol-dependent formaldehyde dehydrogenase. Borders of internal chain-length differences between this and other MDR enzymes coincide in different combinations, supporting the concept of limited changes in loop regions within this whole family of proteins.

Actinomycetales↗
PubMed1997

Guinea pig and bovine zeta-crystallins have distinct functional characteristics highlighting replacements in otherwise similar structures.

zeta-Crystallin, a major cytosolic protein of guinea pig lens, has been characterized as an NADPH:quinone oxidoreductase (EC 1.6.5.5) [Rao et al. (1992) J. Biol. Chem. 267, 97-103]. A bovine lens homolog with 83% sequence identity was found to have very different functional characteristics. While the bovine lens zeta-crystallin exhibits similar physicochemical properties, such as molecular weight, hydropathy profile, and predicted secondary structure, and exhibits strong immunological cross-reactivity with the guinea pig and human lens zeta-crystallins, it shows minimal quinone oxidoreductase activity. On the other hand, bovine lens zeta-crystallin, but not guinea pig zeta-crystallin, showed a strong binding affinity to single-stranded DNA (ssDNA) that could be competed with NADPH, the specific cofactor of zeta-crystallin. NADH and dextran sulfate did not affect this characteristic of bovine zeta-crystallin and the enzyme showed no binding affinity for the heparin-Ultragel A4R. Two-dimensional electrophoresis of bovine lens zeta-crystallin showed a distinct pattern of posttranslational charge modification as compared to the guinea pig protein. Alignment of eight zeta-crystallin sequences, and computer modelling of the bovine and human forms based on the crystallographically analyzed Escherichia coli form, suggest that if loss of a functional residue accounts for the lowered catalytic activity of the bovine protein, Tyr 52 of the E. coli enzyme, and the equivalent Tyr present in all known mammalian forms except the bovine, is the likely candidate. In the bovine form this tyrosine is replaced by histidine.

Amino Acid Sequence↗
PubMed1997

Analysis of oligonucleotide probe affinities using surface plasmon resonance: a means for mutational scanning.

A novel strategy for real-time analysis of oligonucleotide probe hybridization based on detection by surface plasmon resonance is described. The design of the analysis, exploiting the rapid dissociation kinetics of short oligonucleotides from their hybridization templates, allows monitoring in genuine sensor mode of equilibrium hybridization responses, circumventing the need for regeneration between sample cycles. Applied to a model system comprising oligonucleotide probes and different immobilized hybridization targets the effects of temperature, probe length, and nucleotide substitutions in template were investigated. The procedure described was observed to have an efficient discriminatory power with respect to end-mismatch situations. Affinity determinations of octamer probes showed good correlation between calculated Tm-values and probe affinities. From affinity data collected at different temperatures thermodynamic parameters were determined, which correlated well with data obtained from theoretical calculations. The technique, modified to a simplified form, allowed detection of single nucleotide substitutions in a target template, suggesting that procedures for confirmatory DNA sequencing can be envisioned.

Biotin↗
PubMed1997

The reciprocal translocation t(9;16)(q22;p13) is a primary chromosome abnormality in basal cell carcinomas.

The reciprocal translocation t(9;16)(q22;p13) was identified in three short-term cultured basal cell carcinomas (BCCs). The t(9;16) was the sole anomaly in one clone in two tumors and was accompanied by a second change that also affected the long arm of chromosome 9 in the third. In addition, other cytogenetically unrelated abnormal clones were also found in all three BCCs. The identification of t(9;16)(q22;p13) as a primary chromosomal abnormality in a subset of BCCs (we found it in 3 of 22 tumors) is especially intriguing against the background that the PTCH gene, which when mutated in the germ line presumably gives rise to the autosomal dominant basal cell nevus or Gorlin's syndrome, maps to chromosome band 9q22. None of the genes rearranged in the BCC-specific t(9;16)(q22;p13) translocation have been identified, but we hypothesize that the translocation represents the cytogenetic corollary of a tumorigenic recombination of PTCH with an as yet unknown gene in 16p13. If so, this would be the first time that a tumor suppressor gene causally involved in a hereditary cancer is shown to be frequently rearranged through a specific translocation in sporadic carcinomas of the same type.

Aged↗
PubMed1997

Active site directed mutagenesis of 3 beta/17 beta-hydroxysteroid dehydrogenase establishes differential effects on short-chain dehydrogenase/reductase reactions.

Mutagenetic replacements of conserved residues within the active site of the short-chain dehydrogenase/reductase (SDR) superfamily were studied using prokaryotic 3 beta/17 beta-hydroxysteroid dehydrogenase (3 beta/17 beta-HSD) from Comamonas testosteroni as a model system. The results provide novel data to establish Ser 138 as a member of a catalytically important "triad" of residues also involving Tyr151 and Lys155. A Ser-->Ala exchange at position 138 results in an almost complete (> 99.9%) loss of enzymatic activity, which is not observed with a Ser-->Thr replacement. This indicates that an essential factor for catalysis is the ability of side chain 138 to form hydrogen bond interactions. Mutations in the NAD(H) binding region, in strands beta A, beta D, and adjacent turns, reveal two additional residues, Thr12 and Asn87, which are important for correct binding of the coenzyme and with a differential effect on the reactions catalyzed. Thus, mutation of Thr12 to Ala results in a complete loss of the 3 beta-dehydrogenase activity, whereas the 3-oxoreductase activity remains unchanged. On the other hand, a T12S substitution yields a protein with unaltered catalytic constants for both reactions, revealing that a specific hydrogen bond is critical for the dehydrogenase activity. Our interpretation of the available crystal structure of 3 alpha/20 beta-HSD from Streptomyces hydrogenans suggests a hydrogen bond in that enzyme between the Thr12 side chain and the backbone NH of Asn87 rather than the coenzyme, indicating that this hydrogen bond to the beta D strand might determine a crucial difference between the reductive and the oxidative reaction types. Similarly, mutation of Asn87 to Ala results in an 80% reduction of kcat/Km in the dehydrogenase direction but also unchanged 3-oxoreductase properties. It appears that the binding of NAD+ to the protein is influenced by local structural changes involving strand beta D and turn beta A to alpha B.

17-Hydroxysteroid Dehydrogenases↗
PubMed1997

Assessment of therapy in gestational diabetes by substrate and hormone responses to a standardized test meal.

Postprandial substrate and hormone responses to a standard mixed meal (400 kcal) was determined at two occasions, A and B, in 11 women with gestational diabetes (GDMs) and 11 normoglycaemic controls, matched for age, body mass index, and gestational age. Levels of circulating glucose, non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate (3-HBA), individual amino acids, insulin, and C-peptide were analysed. A was performed when GDMs were considered inadequately controlled with diet alone, B later during gestation following initiation of insulin therapy because of hyperglycaemia. Fasting glucose, glycerol, total and individual amino acids (alanine, valine, isoleucine, leucine), insulin, and C-peptide were not different from normal during A and B, neither were postprandial amino acid levels. During test A, GDMs had elevated fasting and postprandial 3-HBA (p < 0.001), greater postprandial rise of glucose (p < 0.001), elevated NEFA (p < 0.05), but normal and parallel decreases of NEFA and glycerol. Insulin and C-peptide responses were delayed and prolonged. During B, GDMs had higher glucose response (p < 0.005), higher fasting 3-HBA (p < 0.02) but similar and parallel decreases of NEFA, glycerol, and 3-HBA as controls. The C-peptide response was not significantly different from normal; insulin response was higher (p < 0.05). In conclusion, the relative insulin deficiency characterizing GDMs, also when treated with insulin, is associated with selected defects in insulin action; mainly affecting glucoregulation, whereas suppression of lipolysis and proteolysis remain normal.

3-Hydroxybutyric Acid↗