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Biomedical subjects

B Lind

Publications and source records attributed to B Lind.

At least 73 records · Page 4Linked to original sources

Speciation of mercury in the primate blood and brain following long-term exposure to methyl mercury.

Total (T-Hg) and inorganic (I-Hg) mercury in blood and brain of female Macaca fascicularis monkeys, exposed to daily peroral doses of methyl mercury (MeHg; 50 micrograms Hg/kg body wt) for 6, 12, or 18 months, or to continuous iv infusion of HgCl2 (200 micrograms Hg/kg body wt) for 3 months, were determined. In normal weight monkeys (2.4-4.1 kg body wt) exposed to MeHg, steady state of T-Hg in blood (1.1 micrograms Hg/g) was reached in about 4 months. The elimination T1/2 in blood was 26 days. I-Hg constituted 7% of T-Hg in blood. The average concentration of MeHg in occipital pole and thalamus was about 3 micrograms Hg/g at 6 months and 4.5 micrograms Hg/g at 12-18 months. Accumulation in brain seemed to be biphasic. Following termination of 12 months exposure, elimination T1/2 for MeHg in brain was 35 days. I-Hg constituted about 9% of T-Hg in brain at 6-12 months, 18% at 18 months, and 74% at 6 months after termination of exposure. The I-Hg concentrations were somewhat higher in thalamus than in occipital pole. The elimination T1/2 for I-Hg was extremely long, on the order of years. Most likely, the I-Hg was formed by demethylation of MeHg in the brain. In monkeys exposed to HgCl2, blood levels of 0.6 micrograms I-Hg/g gave rise to brain I-Hg levels of about 0.1 micrograms/g only. In three heavy weight monkeys (5.0-6.1 kg body wt) exposed to MeHg, blood Hg increased to about 2 micrograms Hg/g, indicating a limited distribution of MeHg to fat. The Hg concentrations in brain (7-22 micrograms Hg/g) were considerably higher than those in normal weight monkeys, due to the high blood Hg levels in combination with a high brain-to-blood distribution ratio.

Administration, Oral↗

Cadmium in blood in Alzheimer's disease and non-demented subjects: results from a population-based study.

Blood cadmium concentrations were studied in Alzheimer's disease (AD) and non-demented subjects. The 29 individuals were randomized from the ongoing population survey on ageing and dementia in Stockholm, the Kungsholmen Project. Smokers had, as expected, higher cadmium levels than non-smokers. Cadmium concentrations in blood were related to diastolic blood pressure in non-smoking, non-demented individuals. In contrast to previous reports no differences in blood cadmium levels were found between AD sufferers and non-demented subjects. Furthermore, there were no correlations between cadmium levels in blood and age or cognitive functions. The importance of quality assurance in sample collection and analysis of cadmium as well as scrutinizing smoking habits is emphasized.

Aged↗

A pilot study of lead and cadmium exposure in young children in Stockholm, Sweden: methodological considerations using capillary blood microsampling.

A capillary blood microsampling technique was tested among urban young children in Stockholm. Blood lead (BPb) and hemoglobin (Hb) concentrations were determined in capillary blood obtained by fingerstick from 41 children, 13-20 months old, and the accompanying parent. The quality control included control for lead (Pb) and cadmium (Cd) contamination of material and equipment used for blood sampling, washing procedures for the hands and fingers to be punctured, comparisons of Pb and Cd concentrations in blood obtained by fingerstick and by brachial vein puncture from the same individuals, analysis of external quality control samples for Pb and Cd in blood together with the collected samples, and evaluation of the analytical performance using linear regression analysis. The results showed that blood sampling material may contaminate the blood samples with amounts of Pb and Cd that would seriously influence the monitoring results in the low concentration range (< 100 micrograms Pb/L and < 1 microgram Cd/L). However, it is possible to obtain reliable BPb concentrations (> 10 micrograms Pb/L), but not BCd concentrations (< 1 microgram Cd/L), with the capillary blood microsampling technique tested provided that a strict quality control is applied. The sampling procedure tested was well accepted by the children and their parents. The children's median BPb concentration (27 micrograms/L; range 9-73 micrograms/L) was similar to the median BPb concentration of their parents (27 micrograms/L; range 7-74 micrograms/L). However, the correlation between child and parent BPb concentrations was poor (R2 = 0.20), which may indicate different sources to Pb exposure in children and parents.

Adult↗

Physical disability in older adults: a physiological approach. Cardiovascular Health Study Research Group.

Measures of physical function have been developed primarily to assess health status, prognosis, and service needs. They are now, increasingly, being used as outcome measures in studies seeking to determine the causes of disability. However, the extent to which these standardized measures, as they currently are constituted, are meaningful for the evaluation of underlying pathophysiology is not defined. To assess evidence for an etiologic rationale for these measures, we evaluated self-report of difficulty in physical function in the Cardiovascular Health Study, a study of 5201 men and women 65 years and older in four U.S. communities. We determined (by factor analysis) that self-reported difficulty with each of 17 tasks of daily life aggregates in four groups; i.e. difficulty in one task is associated with having difficulty in the other tasks in the group. These groups include (1) activities primarily dependent on mobility and exercise tolerance; (2) complex activities heavily dependent on cognition and sensory input; (3) selected basic self-care activities; and (4) upper extremity activities. Groups 2 and 3 are similar, but not identical, to Instrumental Activities of Daily Living (IADL) and Activities of Daily Living (ADL), respectively. We then tested whether these groupings were associated with different underlying impairments. Multiple logistic regression analyses indicate that there are constellations of physiologic and disease characteristics significantly (p < 0.01) associated with difficulty in each of these four groups of activities, among 15 chronic diseases and conditions ascertained. Some diseases are uniquely associated with difficulty in one group of tasks; some overlap, and are associated with 2, 3 or 4 groups of tasks. The associations found with difficulty in performing tasks in groups 2 and 3 were frequently stronger than those with the larger groups of ADL or IADL tasks, suggesting increased specificity of associations found with these new groupings. These results suggest that re-grouping of tasks of daily life may provide a more refined physiologically-based outcome measure for use in evaluating causes of disability. The ability to define risk factors for disability may be enhanced by choosing outcome measures with a demonstrated physiologic rationale.

Activities of Daily Living↗

The role of neuroimaging in the initial management of patients with minor head injury.

STUDY OBJECTIVE: To determine whether omitting neuroimaging in the primary assessment of patients with minor head injuries in the emergency department is safe. DESIGN: Prospective cohort study. SETTING: University hospital, Copenhagen County Hospital, Glostrup, Denmark. PARTICIPANTS: The study group consisted of 2,204 patients presenting to the ED after sustaining minor head injuries. Only patients able to talk and walk were included. MEASUREMENTS AND MAIN RESULTS: The decision to admit was based exclusively on clinical guidelines in which the findings in the ED were of highest priority. Seven patients (0.3%) had a skull radiograph; computed tomography was not used in the primary evaluation. Four hundred thirty patients (19.5%) were admitted. After hospitalization, four patients developed intracranial complications. One required surgery, two required hyperventilation, and one was observed. Follow-up demonstrated that no patient with an intracranial complication had been missed. CONCLUSION: We found it safe to exclude neuroimaging in the primary assessment of patients with minor head injuries in the ED, and to rely instead on clinical criteria.

Adolescent↗

Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis.

Heterozygosity for a G-->C mutation converting the highly conserved Gln184 (CAG) to His (CAC) was identified at the last nucleotide of exon 7 of the protein C gene in two family members with deep vein thrombosis. As the nucleotide is a part of the 5 splice site of intron G, it was examined how the mutation affected splicing of protein C pre-mRNA. Relevant protein C cDNA fragments were amplified with polymerase chain reaction after reverse transcription of ectopic mRNA from peripheral blood lymphocytes. Southern blot analysis and nucleotide sequencing of these fragments showed a fragment (A) corresponding to correctly spliced mRNA originating from the normal allele and a fragment (B) corresponding to a truncated mRNA lacking exon 7, originating from the mutant allele. A third fragment (C) lacking exons 7 and 8 was identified in both affected and unaffected family members, as well as in normal controls. Analysis of human liver protein C mRNA indicated that the ectopic lymphocyte mRNA was qualitatively representative for the tissue-specific mRNA. In conclusion, evidence is provided showing that the mutation abolishes formation of correctly spliced mRNA. This agrees with the observation that the mutation results in a type 1 protein C deficiency.

Adult↗

The effects of induced hypertension and acute graded compression on impulse propagation in the spinal nerve roots of the pig.

Injuries caused by compression of spinal nerve roots are frequently encountered clinically. Experimental studies show that several different factors affect the pathophysiologic changes that occur after these injuries. However, the effect of hypertension in conjunction with graded compression of spinal nerve roots is yet unclear. A previously established porcine model was employed, in which the spinal nerve roots were exposed and compressed by an inflatable balloon. Impulse propagation across the compressed nerve segment was studied by the recording of efferent and afferent nerve action potentials, and nerve conduction velocity. The systemic blood pressure was increased by administration of Neo-Synephrine hydrochloride (phenylephrine HCl) (Winthrop Pharmaceuticals, New York, NY) and elevated 40 +/- 5 mm Hg above the normal (100 +/- 5 mm Hg), and electrophysiologic baseline values were recorded. The spinal nerve roots were then compressed for 2 hours with either 0 (control), 50, 100, or 200 mm Hg. The balloon was deflated and the nerve roots were allowed to recover for 1.5 hours. Impulse propagation was studied every 15 minutes and hypertension was maintained throughout the experiment. The results showed no significant changes of the efferent and afferent nerve action potentials at 0.50 or 100 mm Hg. At 200 mm Hg, efferent and afferent nerve action potentials decreased rapidly and were almost abolished within 20 minutes of compression. Some but not significant recovery was seen of the nerve impulse. Compared to data from normotensive pigs in an earlier experiment, the current study showed that hypertension significantly decreases the susceptibility of the spinal nerve roots to compression at and below 100 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Iron content of human 5-lipoxygenase, effects of mutations regarding conserved histidine residues.

Recombinant human 5-lipoxygenase was expressed in Escherichia coli and purified to more than 95% homogeneity by ammonium sulfate precipitation and agarose-ATP column chromatography. The specific activity of the purified enzyme was 21-28 mumol/mg, as assessed by the generation of 5-hydro(pero)xyeicosatetraenoic acid. The iron content was analyzed by graphite furnace atomic absorption spectrophotometry for six preparations of the enzyme. The average value of the iron content was 0.86 mol/mol (iron/protein) with a range of 0.74-1.15 mol/mol. All lipoxygenases that have been sequenced contain 6 conserved histidine residues. Mutants of 5-lipoxygenase, with substitutions of these 6 conserved histidines, were purified and analyzed. Mutants H372Q and H550Q had no detectable enzyme activity and were also practically devoid of iron. Three mutants regarding His367 (H367Q, H367N, and H367S) were all inactive but had partial iron contents (0.5, 0.2, and 0.5 mol/mol, respectively). Finally, the mutated proteins H362Q, H390Q, and H399Q displayed reduced enzyme activity but contained similar amounts of iron as non-mutated 5-lipoxygenase. We conclude that histidines 372 and 550 constitute two of the iron ligands in 5-lipoxygenase. Also His367 is necessary for the enzyme activity, but this residue is not crucial for binding of iron.

Arachidonate 5-Lipoxygenase↗

Activity of antioxidative enzymes in erythrocytes and concentration of selenium in plasma related to mercury exposure.

The activity of catalase and glutathione peroxidase (GSH-Px) in erythrocytes and concentration of selenium in plasma and mercury in whole blood, plasma, and urine were analyzed in 36 individuals occupationally exposed to mercury vapor, in 14 individuals with skin hypersensitivity to inorganic mercury, and in 17 individuals with subjective symptoms alleged to result from dental amalgam fillings. The control group consisted of 39 individuals with amalgam fillings, but no occupational exposure to mercury. Selenium in plasma was determined by GFAAS with Zeeman background correction. After exclusion of individuals with reported intake of selenium supplement the median plasma selenium concentration in the group with occupational exposure to mercury was 1.24 mumol/L, in the allergy group 1.22 mumol/L, in the amalgam group 1.25 mumol/L, and in the control group 1.22 mumol/L. The activities of catalase and GSH-Px were similar in all groups. However, in females lower GSH-Px activity was found in the amalgam group compared with females in the control group. GSH-Px activity in smokers was slightly lower than in non-smokers. No correlations were found between concentration of selenium or mercury in plasma and activity of glutathione peroxidase or catalase in erythrocytes.

Adult↗

A specific immunologic assay for functional plasminogen activator inhibitor 1 in plasma--standardized measurements of the inhibitor and related parameters in patients with venous thromboembolic disease.

A new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-1 complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.

Blood Specimen Collection↗

Factors influencing mercury evaporation rate from dental amalgam fillings.

Factors influencing mercury evaporation from dental amalgam fillings were studied in 11 volunteers. Air was drawn from the oral cavity for 1 min and continuously analyzed with a mercury detector. In six volunteers the median unstimulated evaporation rate was 0.1 ng Hg/s, range 0.09-1.3 ng Hg/s. After chewing gum for 5 min the highest evaporation rate was 2.7 ng Hg/s. Chewing paraffin wax gave only a small increase in evaporation rate. Changes in airflow rates between 1.5 and 2.5 1/min during the 1 min sampling did not change the amount of mercury drawn from the oral cavity. Sampling with different mouthpieces and closed mouth was compared to open mouth sampling with a thin plastic tube. It was found that the latter method could result in lower values for some volunteers due to simultaneous mouth breathing. After placing individual plastic teeth covers in the mouth, the intraoral evaporation of mercury decreased immediately by 89-100% of previous levels. This technique could be used to detect mercury evaporation from separate amalgam fillings or to reduce the intraoral mercury vapor concentration. Rinsing the mouth with heated water for 1 min increased the mean evaporation rate by a factor of 1.7 when the water temperature increased from 35 degrees C to 45 degrees C.

Adult↗

Very low cadmium concentrations stimulate DNA synthesis and cell growth.

Uptake of cadmium into cultured cells and its effects on cell growth and DNA synthesis are measured over a range of Cd concentrations of seven orders of magnitude. Cd uptake is found to be proportional to the external Cd concentration and to incubation time over a very broad range of concentrations. At least 200 mmol cadmium per kg dry weight of cells can be accumulated in this way, leading to exhaustion of the major intracellular Cd binding sites before cell death. On the other hand, very low cadmium concentrations down to 100 pM stimulate cell growth and DNA synthesis significantly. Stimulation is found in all three mammalian cell types examined: namely L6J1, a rat permanent myoblast cell line, LLC-PK1 porcine renal epithelial cells, and a primary rat chondrocyte culture. Cd acts as a cofactor with serum in L6J1 cultures, but is stimulatory only in serum-free cultures of chondrocytes. Stimulation occurs at Cd concentrations too low to result in a measurable induction of metallothionein. This might implicate the action of response amplifiers in the chain of events leading to Cd-stimulated DNA replication and cell growth.

Animals↗

Integrated personal monitoring of cadmium exposure in Sweden.

Methods for the personal monitoring of human exposure to cadmium from air, food and beverages were studied in a group of 15 non-smoking women in Stockholm. Particles in the breathing zone air and duplicates of all food and beverages ingested were collected during seven consecutive days, as were faeces corresponding to the food ingested. Spot samples of blood and urine were also taken. The main sampling problems were caused by the noise of the personal air monitors and the short operation time of the batteries. On average, dietary cadmium (8.5 micrograms per day) contributed 99% of the total cadmium absorbed. There were large day-to-day variations in intake, most peaks corresponding to the consumption of seafood. Faecal cadmium was shown to reflect the total amount of cadmium ingested. There was a significant (p < 0.05) correlation between cadmium concentrations in blood (median 0.3 microgram/l) and average daily dietary intake of cadmium, but the blood cadmium levels could vary by a factor of four at one and the same average daily intake. The median urinary cadmium level was 0.2 microgram/l.

Adult↗

Biological characterization of infectious molecular clones derived from a human immunodeficiency virus type-1 isolate with rapid/high replicative capacity.

In order to molecularly characterize rapidly and slowly replicating HIV-1 variants, molecular clones were obtained from a rapid/high virus isolate. This isolate, 4803, had only been passaged in peripheral blood mononuclear cells (PBMC) prior to cloning. Molecular cloning was done in bacteriophage lambda-dash using high molecular weight DNA of isolate 4803 infected PBMC. Seven recombinant phages were identified. The clones were found to be related to each other and differed only at 1 or 2 restriction sites (out of 28). The molecular clones were transfected into various cell types by electroporation. The phenotype of progeny viruses was found to be dependent on the cell type used for transfection. Progeny viruses produced by PBMC cultures differed from the parental isolate in that they did not form syncytia and lacked the capacity to replicate in cell lines. Since transfection of PBMC yielded progeny viruses within 1 week, this phenotype is considered to be the true phenotype of the clones. Transfection of the T-lymphoid HUT-78 cell line and of the monocytoid U937-2 cell line yielded progeny viruses after considerable delay (more than 1 month). Progeny viruses from HUT-78 cells were similar to the parental isolate in that they formed syncytia in PBMC and replicated in all cell lines tested. Progeny viruses from U937-2 cells showed an intermediate phenotype in that they replicated in U937-2 but not in T-lymphoid cell lines. These results indicate that molecular clones of a rapid/high virus may have a restricted replicative capacity compared to the parental, genetically heterogenous virus isolate.

Cell Line↗

Personal monitoring of lead and cadmium exposure--a Swedish study with special reference to methodological aspects.

Methods for determining personal exposure to lead and cadmium were tested in Stockholm in 1988. Lead and cadmium in breathing-zone air, 24-h duplicate diets, and feces of 15 nonsmoking women (27-46 years of age) were studied. Blood was collected at the beginning of and immediately after the test period (seven consecutive days). An extensive quality assurance program was included. Most technical problems were encountered in the 24-h collection of airborne particles. The pumps were noisy, and the batteries had to be recharged every 6-8 h. The lead and cadmium levels in feces were found to be useful indicators of the total ingested amounts of these metals. Because of the large day-to-day variation in the dietary intake of lead and cadmium, the sampling period for duplicate diets and feces should be at least 5-6 d.

Adult↗

Spinal cord injuries. Clinical, functional, and emotional status.

Ninety-eight patients with traumatic spinal cord injury, at a median age of 33.5 years (range, 16-72 years), with nonremarkable distributions of neurologic characteristics were investigated at a median of 2.3 years (range, 0.1-23 years) after injury. Functioning, mood disturbances, and overall quality of life were recorded with established self-assessment instruments. Physical dysfunction levels were moderate, being proportionate to neurologic impairment. Psychosocial functions, mood states, and quality-of-life perceptions did not differ from those of a control population sample. Psychosocial function and mood disturbances varied greatly during the first 4 years after injury, but patients' later recordings expressed predominantly a balanced emotional state and a rewarding social life. Progress in this direction consisted of clearly lessened physical dysfunction 1 year after injury and better psychosocial function and well-being after 2 years, whereas patterns of social activities and contacts became gradually less inhibited during a 4-year period after injury. Analysis of complications in patients' histories that affected function and mood showed severe pain to be the only complication that related to lower quality-of-life scores. Urinary incontinence and infection and autonomous dysreflexia related to inhibited self-care performance; spasticity related to impaired ambulation and feeding skills. Gainful employment was the only demographic factor linked to high quality-of-life scores.

Activities of Daily Living↗

The role of fragment X polymers in the fibrin enhancement of tissue plasminogen activator-catalyzed plasmin formation.

When thrombin-mediated fibrin formation and tissue plasminogen activator (t-PA)-mediated fibrinolysis proceed in dynamic interaction, desA-(desB beta 1-42)-fragment X polymers are shown to be the predominant fibrin derivatives present during the rapid second phase of Glu1- and Lys78-plasminogen activation. To further investigate the effect of this intermediate, a method was developed for the production and purification of fibrinogen-derived desA-(desB beta 1-42)-fragment X, deprived of both COOH-terminal A alpha-chains, but still capable of thrombin-mediated polymerization. DesA-(desB beta 1-42)-fragment X polymer was compared to intact fibrin with regard to its stimulatory effect on Glu1-, Lys78-, and Val443-plasminogen activation, and its binding of Glu1- and Lys78-plasminogen. Pure fragment X polymer gave rise to a biphasic activation pattern like that of fibrin, demonstrating similar kinetics of rapid phase activation. The dissociation constant for the binding of plasminogen to the effector decreases by a factor of 14, and the stoichiometry increases by a factor of 2 upon plasmin-catalyzed cleavage of both native Glu1- to Lys78-plasminogen, and fibrin to fragment X polymer. We conclude that desA-fibrin protofibril formation is sufficient to initiate fibrin enhancement of t-PA-catalyzed plasminogen activation, and that optimal stimulation depends on further plasmin-mediated modification of the fibrin effector to desA-fragment X-related moieties. Optimal stimulation is dependent on the presence of the kringle 1-4 domains of plasminogen and probably results from altered and increased binding of both plasminogen and t-PA to the modified effector.

Amino Acid Sequence↗