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Biomedical subjects

B Lind

Publications and source records attributed to B Lind.

At least 55 records · Page 3Linked to original sources

Concentrations of copper, zinc and selenium in brain and kidney of second trimester fetuses and infants.

The concentrations of copper (Cu), zinc (Zn) and selenium (Se) in the brain and kidneys of second trimester fetuses (abortion cases) and infants (deceased before three months of age) were determined. Concentrations of Cu in brain, 0.31-1.6 mg/kg wet weight, increased with age, and were, on the average, three times higher in the brains of infants than of fetuses. In kidneys, Cu concentrations ranged between 0.34 and 2.9 mg/kg, and increased with age after birth. Concentrations of Zn in the brain decreased significantly with age in the fetuses, from about 7 mg/kg at post-conceptional week 12 to less than 5 mg/kg at week 20, but increased again postnatally. In kidneys, Zn concentrations (12-37 mg/kg) increased in parallel with the increase in tissue density. Concentrations of Se in brain, 0.072-0.14 mg/kg, decreased with age in the fetuses, but increased with age postnatally. Kidney Se concentrations (0.16-0.55 mg/kg) did not change significantly with age during the fetal period, but increased about 2.5 times during the postnatal period. There was a significant association between the concentrations (on molar basis) of Zn and Cu in kidneys, but not in brain. There was no correlation between the concentrations of Cu, Zn or Se and those of mercury, cadmium and lead, previously determined in the same samples, with the exception of mercury and Se in kidneys.

Brain↗

Spinal cord injuries: a shortened measure of function and mood.

A brief quality-of-life (QL) questionnaire was derived empirically from a cross-sectional study of 98 SCI-patients (83% men, median age 33.5 years, and median time after injury 2.3 years). A comprehensive general battery of well-established questionnaires (Sickness Impact Profile (SIP), Mood Adjective Check List (MACL), and Hospital Anxiety and Depression (HAD) scale) was combined with a study-specific set of questions to constitute patients' QL. A stepwise analysis model was used to define key areas and questions to be included in a brief SCI-adapted questionnaire. The central areas that independently mattered for SCI-patients' perception of good QL included mental health (no depressive feelings), physical and psychosocial dysfunction (no, or few and minor, limitations in mobility, body care and movement and social interaction), and SCI-related problems (no or little perceived difficulty with loss of independence due to injury). A 22-item questionnaire is suggested for routine clinical follow-up to assess more accurately when optimal treatment and services have been delivered.

Activities of Daily Living↗

Hemodynamic response to adenosine infusion before and after coronary artery bypass surgery.

This study describes the hemodynamic dose-response characteristics of a titrated, continuous adenosine infusion before and 1 h (anesthetized), 1 week, and 1 year after coronary artery bypass graft (CABG) surgery. Average tolerated adenosine infusion rates were less 1 h and 1 week after surgery (128 +/- 23 and 118 +/- 27 microg/kg/min, respectively) than before (156 +/- 29 microg/kg/min) and 1 year after surgery (156 +/- 24 microg/kg/min). Heart rate (HR) increased with a 120-microg/kg/min adenosine infusion rate both preoperatively (21 +/- 11%) and 1 year postoperatively (16 +/- 8%). Systolic blood pressure (BP) decreased 26 +/- 11%, 14 +/- 7%, and 9 +/- 6% with 120 microg/kg/min adenosine for the three postoperative examinations. The integral of the outflow tract velocity with 120 microg/kg/min adenosine increased 49 +/- 22% and 29 +/- 12% after 1 h and 1 week, respectively, whereas its product with HR increased equally for all examinations (40 +/- 22%, 62 +/- 27%, 46 +/- 13%, and 39 +/- 11%). The average preoperative left ventricular area shortening was 45 +/- 10% and neither it nor end-diastolic left ventricular area (preload) changed with surgery, time after surgery, or with adenosine. A titrated adenosine infusion is well suited to patients requiring a pharmacologic provocation to expose reversible myocardial ischemia during the first hours or days after CABG surgery. The anesthetized and anemic patient are particularly unsuited for the commonly used fixed-infusion-rate protocol.

Adenosine↗

The impact of law enforcement activity on a heroin market.

It may be argued that seizing large quantities of heroin being imported into the country should decrease its supply and hence increase its price, resulting in a reduction in the quantity of the drug being purchased or consumed. To date, however, there has been no empirical evidence that heroin seizures in Australia have any effect on the price of heroin at street level. This article describes a 2-year research study during which the price and purity of street-level heroin were regularly monitored. It was found that heroin seizures had no effect on the price, purity or perceived availability of heroin at street level. It was further found that admissions to methadone treatment were not affected by the price or perceived availability of heroin or by local arrests for heroin use/possession, nor was any relationship found between these arrests and the price of street-level heroin. Nevertheless, two-thirds of those who sought entry to local methadone programmes indicated the price as a reason for stopping using heroin. This paper argues that supply-side law enforcement should only be used as a strategy for maintaining high heroin prices if the demand for heroin can be shown to be price-elastic and, further, that the costs of such a strategy need to be weighted against the benefits.

Australia↗

Concentrations of mercury, cadmium and lead in brain and kidney of second trimester fetuses and infants.

The concentrations of mercury (Hg), cadmium (Cd) and lead (Pb) in brain (cerebrum) and kidney during fetal (second trimester terminations or abortions, n = 20) and postnatal (infants deceased before three months of age, n = 15) development have been studied. Information on possible sources of exposure was obtained from the mothers of the fetuses, but not from those of the infants. The median concentration of Hg in the brain was 4 micrograms/ kg wet weight in both fetuses and infants (total range < or = 2-23 micrograms/kg). The concentrations of Hg in the kidneys were significantly higher than in brain, median of Hg 6 micrograms/kg (range < or = 5-34 micrograms/kg) in fetuses and 10 micrograms/kg (< or = 7-37) in infants. There was a tendency of increasing concentration of Hg in the fetal kidney, but not in the brain, with increasing number of amalgam fillings in the mothers. The concentration of Cd in the brain was less than 1 microgram/kg in most cases, both in fetuses and infants. The concentration of Cd in the kidneys was significantly higher, with a median of about 2 micrograms/kg (1-8 micrograms/kg) in both groups. There was no detectable association between tissue Cd concentrations and the smoking habits of the mothers. The concentration of Pb in brain was below 10 micrograms/kg in most cases. In the kidneys, the concentrations of Pb were significantly higher, with a median of 12 micrograms/kg in the fetuses (range < or = 6-20 micrograms/kg) and 15 micrograms/kg (< or = 9-36 micrograms/kg) in the infants. In general, the concentrations of Cd and Pb were lower than in previously reported studies.

Brain Chemistry↗

An estimation of the relative biological effectiveness of 50 MV bremsstrahlung beams by microdosimetric techniques.

An efficient algorithm has been developed to estimate the relative biological effectiveness (RBE) from experimental RBE data and measured single-event energy deposition spectra. As benchmarks for the calculations well established RBE data for crypt cell survival and associated microdosimetric distributions from a number of therapeutic high- and low-LET beams was used. As a by-product of the calculations the RBE for this system was determined for the lineal energy range 0.1-5000 keV microns-1 in very good agreement with experimental data. These data have been applied to estimate the biological effectiveness of therapeutic high-energy bremsstrahlung beams characterized by microdosimetric measurements with a wall-less proportional counter. The absorbed dose component due to photoneutrons and charged particles from photonuclear reactions in scanned 50 MV bremsstrahlung beams was measured to be about 2% of the total absorbed dose. The RBE of 50 MV scanned bremsstrahlung beams was estimated to be 1.09 for jejunum crypt cell survival as the biological endpoint at absorbed doses of the order of 10 Gy, in fair agreement with reported results based on radiobiological experiments. The RBE is fairly independent of the bremsstrahlung target used. Using the estimated increase in the RBE of neutrons compared to photons for absorbed dose levels applied in clinical fractionation schedules increases the RBE further to 1.13 at absorbed doses per fraction of the order of 2 Gy.

Algorithms↗

Clinical expression of a rare beta-globin gene mutation co-inherited with haemoglobin E-disease.

A single nucleotide substitution and the effect on the phenotype in an Indonesian family with beta-thalassaemia, HbE-trait and HbE-beta-thalassaemia is described. In the proposita (female, age 20 (Hb 7.4 mmol/l; MCV 72 fl; MCH 1.45 fmol; HbA2 3.5%; HbF 2.4%)). An A/G mutation in the RNA cleavage and polyadenylation sequence was detected (AATAAA/AATAGA). Her sister (Hb 8.2 mmol/l; MCV 77 fl; MCH 1.60 fmol; HbA2/HbE 32.4%), carried a different mutation in the beta-globin gene (codon 25; G129/A), and consequently had HbE-trait. Their mother had a haemoglobin concentration of 6.4 mmol/l (MCV 56 fl; MCH 1.20 fmol; HbA2/HbE 55.8%). She was compound heterozygous for the mutation in the poly A-signal and HbE-trait. Using restriction enzyme analysis and linkage studies, we subsequently identified six family members with HbE-beta-thalassaemia, five with beta-thalassaemia and six with HbE-trait. Two individuals were unaffected. The mutation in the polyadenylation sequence causes a mild form of beta (+)-thalassaemia. The MCV and MCH in individuals with both beta-thalassaemia and HbE-trait were significantly lower, yet on average they were only slightly more anaemic than those carrying only the thalassaemic gene.

Adolescent↗

Two mutations in exon XII of the protein S alpha gene in four thrombophilic families resulting in premature stop codons and depressed levels of mutated mRNA.

Sixteen Danish unrelated thrombophilic families with plasma protein S deficiency of type 1 (or III) are currently under investigation in our laboratory for defects in the protein S alpha gene. The present paper describes a part of this work, which deals with the identification and phenotypical presentation of two unique mutations in exon XII of the protein S alpha gene in four of these families. The mutations were identified by SSCP screening followed by nucleotide sequence analysis or by direct nucleotide sequence analysis. The mutation found in one family (D) is a novel deletion of an A in either the codon for Gly448 (GGA) or Ile449 (ATI) resulting in a frameshift and a premature stop codon at position 454. The other mutation shared by three families (F, G and J) is a previously reported C-->T transition within a hypermutable CG dinucleotide sequence converting Arg410 (CGA) to Stop (TGA). All affected individuals are heterozygotes for their mutation and in each family the protein S genotype, the plasma protein S phenotype (not shown for Family J) and the clinical phenotype cosegregate. The two mutations can fully explain the abnormal protein S phenotype since premature stop codons are known to disrupt gene function of the mutated allele. Analysis of protein S mRNA from platelets showed that both mutations result in a marked reduction in the amount of protein S mRNA from the mutated alleles indicating that the mutations exert their deleterious effects on gene expression at the transcriptional level. The Arg410-->Stop mutation in Families F, G and J is in all instances linked to a G at the site of a common neutral dimorphism in the codon for Pro626 (CCA/G) in exon XV. This indicates that the mutation in these families could have arisen in a common ancestor. The Arg410 (CGA)-->Stop (TGA) mutation is also seen in exon XII of the normal protein S alpha gene. This gives rise to the speculation as to whether the mutation in the protein S alpha gene is the result of an interaction with the protein S beta gene leading to double homologous unequal crossing-over or gene conversion of a short DNA sequence. However, this is unlikely since none of the 7 other protein S beta-specific nucleotides are present in the mutated exon XII sequence of the protein S alpha gene. The common Arg506-->Gln Leiden mutation in coagulation factor V is not an additional risk factor for thrombosis in any of the four families studied.

Adult↗

Dithiocarbamates induce apoptosis in thymocytes by raising the intracellular level of redox-active copper.

Dithiocarbamates are metal-chelating compounds that can exert either pro-oxidant or antioxidant effects in different situations. They have recently been found to potently inhibit apoptotic cell death, an activity attributed to their antioxidant action. However, when thymocytes were exposed to pyrrolidine dithiocarbamate, an oxidation of the glutathione pool occurred within 90 min. Longer incubation resulted in cell shrinkage, chromatin fragmentation, glutathione depletion, and eventual cell lysis, which is typical of apoptosis in these cells. These changes were inhibited by inclusion of non-permeable metal chelators in the incubation medium, suggesting that pyrrolidine dithiocarbamate exerts its toxic effect by transporting a redox-active metal into the cell. This was directly confirmed when sustained 8-fold elevations of intracellular copper were detected after addition of pyrrolidine dithiocarbamate. In agreement with this, supplementation of the incubation medium with submicromolar concentrations of copper significantly potentiated pyrrolidine dithiocarbamate toxicity. We conclude that pyrrolidine dithiocarbamate exerts a powerful pro-oxidant effect on thymocytes due to its ability to transport external redox-active copper into cells. The resulting increase in glutathione disulfide may also explain the temporary anti-apoptotic activity of this compound described in other systems.

Animals↗

Spinal nerve root compression.

The pathophysiology of sciatica is not completely understood, although our understanding of its causes is increasing. Mechanical alterations combined with inflammatory changes lead to pain. Compression alters nerve root conduction and compromises the nutritional support of spinal nerve roots (through intrinsic and extrinsic vascularity and cerebral spinal fluid percolation). Mechanical forces can lead to intraneural damage and functional changes in nerve roots. Chemical and metabolic effects can create an inflammatory response. Varying causes of inflammation coupled with varying degrees of compression can occur anywhere along the cauda equina or spinal nerve root, including the dorsal root ganglia, and contribute to the pain response and neurologic deficits associated with sciatica.

Animals↗

Mutations at the C-terminal isoleucine and other potential iron ligands of 5-lipoxygenase.

The non-heme iron centre in human 5-lipoxygenase was studied. Recombinant enzyme was expressed in Escherichia coli, purified and assayed for iron content and enzyme activity. For non-mutated enzyme, the iron content was 1.01 +/- 0.19 mol/mol. Deletion of the C-terminal Ile673 resulted in an iron content of 0.03 +/- 0.07 mol/mol and undetectable lipoxygenase activity. Mutations at His367, Glu376 and Asn554 led to drastically decreased enzyme activity (< 2% of non-mutated control) but iron was still present. In addition to Glu376, eight other conserved acidic residues (Asp/Glu) in 5-lipoxygenase were replaced, none of which was crucial for enzyme activity. We conclude that Ile673 is an iron ligand in 5-lipoxygenase, while our results do not support that Glu376 or Asn554 have this function. The possible role of His367 as a replaceable iron ligand is discussed.

Arachidonate 5-Lipoxygenase↗

Selenium concentrations in brain after exposure to methylmercury: relations between the inorganic mercury fraction and selenium.

Three groups of female monkeys (Macaca fascicularis) were exposed to methylmercury (MeHg, p.o. 50 micrograms Hg/kg body wt per day) for 6, 12, or 18 months. One group was exposed to MeHg for 12 months and kept unexposed for 6 months before sacrifice. Another group of three monkeys was exposed to HgCl2 i.v. for 3 months. Total and inorganic mercury concentrations in occipital pole and thalamus were determined by cold vapor atomic absorption spectroscopy. Selenium concentrations were analyzed by hydride generation atomic absorption spectroscopy. The results indicated an association between concentrations of inorganic mercury and selenium in both occipital pole and thalamus in the MeHg-exposed animals. A linear regression model using concentrations of inorganic mercury (nmol/g wet wt) as independent variable, and selenium concentrations (nmol/g wet wt) as the dependent variable showed significant correlations between the variables in both occipital pole and thalamus (r = 0.85 and r = 0.91, P < 0.0001). The intercept of the regression line was slightly lower (about 2 nmol Se/g wet wt) than the selenium concentrations found in control monkeys (about 3 nmol Se/g wet wt). There was a tendency to a "hockey stick"-shaped relationship between concentrations of selenium and inorganic mercury in the thalamus of monkeys with ongoing exposure to MeHg. An important role for selenium in the retention of mercury in brain is indicated.

Animals↗

Effect of moderate ethanol intake on the heart: biochemical and morphological studies with isolated cardiomyocytes from rats fed a low-protein diet.

OBJECTIVE: It has been shown that chronic consumption of ethanol can impair myocardial function and result in morphological changes of the heart. The purpose of this work was to evaluate relations between changes in energy metabolism and changes of cell morphology. METHOD: Long-term effects of moderate ethanol consumption on the heart were examined in isolated cardiomyocytes from rats fed a pellet with low-protein content for 6 months. Digitonin treatment of the cardiomyocytes was used to separate mitochondrial and cytosolic fractions. RESULTS: A greater fraction of contracted myocytes was isolated from ethanol- and glucose-treated rats, than from rats fed only glucose and/or water as liquid supplement. There were changes of the ultrastructure of myocytes from ethanol and glucose-treated rats, which included mitochondrial degeneration, accumulation of fat droplets and depletion of the glycogen content. An elevated cytosolic level of nucleotides (ATP, ADP and NAD) and disappearance of magnesium from the mitochondrial fraction were observed in myocytes from rats fed ethanol and glucose. The release of adenosine was also found to be inhibited in these cells. CONCLUSIONS: Our results show that moderate ethanol consumption by rats during protein-restricted conditions produces subclinical changes of cardiomyocyte ultrastructure and alteration of cell morphology. Furthermore, the results indicate that changes of the energy homeostasis in myocytes and inhibition of sarcolemmal adenosine transport are early events that appear to precede the histological alterations.

Alcohol Drinking↗

Six different point mutations in seven Danish families with symptomatic protein C deficiency.

Six different point mutations of the protein C gene are described in seven Danish families with protein C deficiency associated with an increased risk of venous thromboembolism. All affected family members are heterozygotes for the mutated protein C genotype. One mutation is a G2992-->A transition at position +5 in the 5' splice site of intron D. The other five mutations affect the protein coding region. One is a C1432-->T transition in exon III converting the highly conserved Arg15 to Trp in the Gla-domain. Another mutation is a G3157-->C transversion in exon V converting the non-conserved Gly72 to Arg in the epidermal growth factor domain. The remaining three mutations are located in non-conserved amino acid positions in exon IX and affect the serine proteinase domain. The first is a G8559-->C transversion converting Gly282 to Arg. The second is a C8571-->T transition (present in two families) converting Arg286 to Cys. The third is a C8695-->T transition converting Pro327 to Leu. In each family the protein C deficiency cosegregates or probably cosegregates (one family, G8559-->C) with the mutation. All affected family members exhibit a reduction of both the antigen and the functional plasma concentration of protein C to approximately 50% of normal indicating that the mutated protein C is not present (type 1 deficiency) or only present in low amounts in plasma. Agarose gel electrophoresis followed by Western blotting shows that the Arg15-->Trp substitution is associated with a normal as well as an abnormal migrating plasma protein C band.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Binswanger disease. A blood pressure-related dementia].

Interest in Binswanger's disease has increased during the past decade, owing to the possibility of detecting white matter changes with computerised and magnetic resonance tomography. This paper consists in a summary of clinical symptoms and signs and possible diagnostic criteria, discussion of differential diagnosis, and the presentation of two own cases. Both patients manifested mild dementia and gait disturbance, and one had frequent drop attacks. Severe supra- and infra-tentorial white matter changes were present in both cases. It is important to consider a possible diagnosis of Binswanger's disease, as treatment of the appropriate risk factors may prevent or delay the development of dementia.

Aged↗