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Biomedical subjects

A Berg

Publications and source records attributed to A Berg.

At least 19 recordsLinked to original sources

Distribution of lipoprotein species (LpA-I, LpA-I:A-II) in serum and HDL subfractions of untrained and trained normolipemic men.

The distribution of lipoprotein species (LpA-I, LpA-I:A-II) in serum and within HDL subfractions (HDL2b, HDL2a, HDL3) was examined in 26 sedentary and 19 endurance trained normolipemic male individuals. The concentrations of lipids and apolipoproteins in serum and HDL subfractions and the concentrations of LpA-I and LpA-I:A-II were determined. Significant differences (Mann-Whitney-U-test) were found in serum concentrations of apoB (P < 0.05), apoA-II (P < 0.01) and LpA-I:A-II (P < 0.001). In HDL3 apoA-II concentration was significantly lower in the trained group (P < 0.05) but in HDL2 subclasses the concentrations of apoA-I and apoA-II did not differ between the groups. Despite similar concentrations of the two apolipoproteins, there were difference in the distribution of lipoprotein species within HDL2 subfractions. The concentrations of LpA-I did not differ, but the concentrations of LpA-I:A-II particles were higher in the trained group. Untrained and trained had similar concentrations of apoA-II (in HDL2b) but obviously more apoA-II containing particles and this leads to the assumption that within HDL2 of endurance trained individuals LpA-I:A-II particles have a lower apoA-II content compared with particles of untrained individuals. The data emphasize, that normolipemic individuals of different maximum oxygen uptake have a different distribution and composition of lipoprotein species (LpA-I, LpA-I:A-II).

Adult

A semiautomated, 96-well plate assay for collagen synthesis.

We have established a rapid method for the measurement of collagen synthesis in large numbers of cell cultures. 3H-labeled collagen in microwell cultures was salt precipitated, harvested, and washed using a commercially available cell harvester and the filtered collagen was directly counted. The cell number could then be assessed either by methylene blue staining or by dissolving the cells in NaOH and estimating the protein content with bicinchoninic acid. In all of these procedures, the samples remain in microtiter plates, thus ensuring that minimal amounts of reagents are used and minimizing the amount of manipulation necessary. The intergroup variability is 3 to 9% and the recovery of 3H-labeled collagen is greater than 90%. Using this method, large numbers of samples can be assessed for collagen synthesis quickly, conveniently, and for minimal cost.

Animals

Probucol, incorporated into LDL particles in vivo, inhibits generation of lipid peroxides more effectively than endogenous antioxidants alone.

One of the first steps in lipid autoxidation leads to the generation of lipid peroxides (LPO). The time course of LPO generation during Cu++ catalyzed oxidation of LDL before and after treatment with probucol was determined in this study. Before analysis the samples had been stored for about 3 years at -20 degrees C. The results show that in LDL samples without probucol the total antioxidative potential had been depleted during the long-term storage. In contrast, LDL containing probucol showed almost no signs of lipid autoxidation. In addition, the ratio of vitamin E to cholesterol was significantly higher in serum samples containing probucol. We conclude that, in vivo, probucol is incorporated into LDL particles in concentrations high enough to inhibit even early steps of lipid autoxidation.

Antioxidants

Low density lipoproteins inhibit endotoxin activation of monocytes.

Human serum and low density lipoproteins (LDLs) were shown to inactivate endotoxin (lipopolysaccharide [LPS]) by testing the effect of LPS interactions with serum or LDL on the activation of human monocytes. Sera and LDL preparations from four patients with familial hypercholesterolemia were used to demonstrate the inhibition of LPS from inducing interleukin-1 release. Before LDL removal by immunoapheresis, the patients' sera were able to inactive approximately fivefold more LPS than after LDL removal. The LPS-inactivating capacity lost during apheresis could essentially be retrieved in the LDL-rich eluate from the immunoadsorption columns. Because patients were treated frequently with immunoapheresis, their LDL levels before LDL removal were not markedly elevated. These patients' sera before LDL removal were shown to inactivate amounts of LPS comparable to those inactivated by the sera from three healthy volunteers. LDL prepared by ultracentrifugation showed similar LPS inactivation as LDL prepared by immunoapheresis. We conclude that the inhibition of LPS-induced monocyte activation by human serum is dependent to a large extent on the LDL fraction. LDLs were demonstrated to inhibit LPS from inducing interleukin-1 release by human monocytes.

Adult

[Metabolic and cardiovascular adaptation and the performance of professional tennis players].

14 professional tennis players of world rank were examined (7 men, mean age 23 +/- 3 years; 7 women, mean age 18 +/- 2 years). Heart volume (HV) was 11.9 +/- 0.9 ml/kg in women, 12.7 +/- 1.3 ml/kg in men, 20-30% higher than in untrained persons. Correspondingly, end-diastolic (EDV) and end-systolic volume, left-ventricular muscle mass (LVM) and stroke volume (SV) were elevated, while contractility parameters as well as the ratios of SV and of LVM to EDV and HV were within normal limits. The changes are to be taken as adaptations in the sense of athlete's heart. Maximal treadmill speed was 18 km/h in women and 19.3 km/h in men, with maximal lactate levels of 9.3 mmol/l (women) and 11.4 mmol/l (men). Anaerobic threshold was reached at a treadmill speed of 13.3 km/h (women) and 14.8 km/h (men). These data indicate a good performance range and were clearly better than in earlier groups of tennis players. This adaptation requires additional interval and endurance training. In 11 tennis players the serum concentration of magnesium and in 5 that of iron was below the recommended lower limit (magnesium: 0.8 mmol/l; iron: 14 mumols/l). Serum concentrations of creatine kinase and of lactate dehydrogenase were always two to three times higher than normal, if tennis training had taken place the day before, but all other biochemical values were within normal limits.

Adaptation, Physiological

Influence of acute maximal exercise on lecithin:cholesterol acyltransferase activity in healthy adults of differing aerobic performance.

To document the possible influence of a single episode of maximal aerobic stress on the serum lecithin:cholesterol acyltransferase (LCAT) activity in subjects with differing histories of training, two groups of healthy male adults [controls (C), n = 18, 28.6 years, SD 5.2, 50.1 ml.kg-1.min-1 maximal O2 uptake (VO2max), SD 5.3; endurance trained athletes (T), n = 18, 31.4 years, SD 8.8, 65.0 ml.kg-1.min-1 VO2max, SD 2.8] were examined in a maximal aerobic stress test. In addition to the routine assessment of lipid status, LCAT activity was measured immediately before and after exercise. At rest nearly identical LCAT activity values were found in both groups: C 64.4 nmol.ml-1.h-1, SD 16.7 vs T 65.0 nmol.ml-1.h-1, SD 20.9. The post-exercise LCAT values induced by the maximal stress test increased significantly to (C) 95.7 nmol.ml-1.h-1, SD 23.5, +48.6%, P less than 0.001; (T) 83.5 nmol.ml-1.h-1, SD 24.3, +29.1%, P less than 0.01. Neither the pre nor the postexercise individual LCAT activity values showed any significant correlation to the corresponding data on physical performance.

Adolescent

Central venous catheter-related complications in newborns and infants: a 587-case survey.

In an attempt to identify factors determining central venous catheter-related complications in newborns and infants, 587 cases have been retrospectively analyzed. Attention has been paid to the influence of the incidence of babies' body weight, site of insertion, and technique of placement of the catheter and the material used, ie, silicone (SI) or polyurethane (PU). Overall complications occurred in 28% of the catheters with 2 deaths due to cardiac tamponade. Mechanical complications happened in 22% of the catheters, including dislodgement (11.6%), extracorporeal perforation (5.3%), and obstruction (5%). Septic complications occurred in 4% catheters, including proven bacteriemia (2.5%), abscess at the entry site (1%), and isolated fever (0.8%). Clinically evident caval thrombosis occurred in 1% of the catheters. Overall complications were significantly higher when the body weight was lower than 2,500 g (P less than .01) due to a significantly higher incidence of septic complications (P less than .05). When a proximal site of placement of the catheter was used, both septic and mechanical complications were more frequent than in the distal approach (P less than .01). The incidence of complications was similar in surgically and in percutaneously placed catheters as in SI and PU catheters. Nevertheless, fatal complications occurred only in PU catheters, leading us to avoid the choice of such material in newborns and small infants.

Body Weight

Immunologic mediators as parameters of the reaction to strenuous exercise.

Both the unspecific and the specific branch of the immune system are triggered and governed by contact and by a set of cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). These mediators, which are produced by activated macrophages and other cells, have also multiple (pleiotropic) effects on different cells and organs. While TNF and IL-1 have strongly proinflammatory effects and seem to play a critical role in clinical situations such as septic shock, IL-6 has more restorative effects by being the main inducer of the acute phase response of the liver. The monokines also induce fever and release of ACTH in the brain. Strenuous exercise leads to a significant elevation of cytokines in the serum thereby eliciting an acute phase response. Analysis of systemic cytokines in the serum of marathon runners by the 7TD1 cell line assay revealed that the observed activity is very likely IL-6.

Acute-Phase Reaction

Nocturnal melatonin secretion in thyroid disease and in obesity.

OBJECTIVE: The purpose was to investigate whether the function of the pinealocytes is changed in patients with disturbed metabolic rate or in subjects with marked obesity. DESIGN: Venous blood was sampled every second hour between 1800 and 0800 h, and urine collected between 2200 and 0700 h. PATIENTS: Eight patients with thyrotoxicosis, six with primary hypothyroidism, eight with maturity-onset obesity, and 12 healthy controls were included in the study. MEASUREMENTS: Peak serum melatonin values during the night, total nocturnal melatonin secretion (estimated by melatonin incremental areas), and urinary excretion of melatonin were determined in each participant. RESULTS: Patients with hypothyroidism were found to have higher peak serum melatonin values, total nocturnal melatonin secretion, and urinary excretion of melatonin than normal individuals (Peak melatonin values: 0.55 +/- 0.13 vs 0.27 +/- 0.04 nmol/l, respectively; P less than 0.05. Melatonin incremental areas: 3.38 +/- 0.80 vs 1.45 +/- 0.26 nmol/l h; P less than 0.05. Melatonin excretion: 0.140 +/- 0.023 vs 0.081 +/- 0.013 nmol/9 h; P less than 0.05). Neither of these values differed significantly from the normal in patients with thyrotoxicosis or obesity. Although thyrotoxic patients thus released a normal amount of melatonin during the night, their melatonin secretion peak was phase advanced (melatonin secretion peak appearing at 1.1 +/- 0.5 h in thyrotoxic, and at 3.4 +/- 0.5 h in normal participants; P less than 0.01). No such phase shifts were seen in patients with obesity or hypothyroidism. CONCLUSIONS: These findings imply that both hypothyroid and thyrotoxic patients have disturbed pineal function, which is not the case in patients with obesity. The mechanism underlying these observations remains to be elucidated.

Adult

Further studies of the defective stimulus-response coupling for the oxidative burst in neutrophils in polycythemia vera.

We have previously reported that the chemiluminescence (CL) response of neutrophils (PMN) from patients with polycythemia vera (PV) was abnormally low when induced by surface receptor-dependent stimuli, fMLP and leukotriene B4, but normal when elicited by phorbol myristate acetate (PMA). This study documents that this discrepancy of the CL response to fMLP and PMA remained over a wide range of stimuli concentrations, was not due to iron-deficient PV cells and was also observed with the nitroblue tetrazolium assay. Moreover, another surface receptor-dependent agonist, platelet-activating factor, conferred a significantly lower CL response in PV PMN relative to controls. Treatment with alpha interferon or GM-CSF, to increase fMLP receptors, resulted in a similar enhancement of fMLP-induced CL in PV and controls. CL was normal when induced by a number of non-surface receptor-dependent stimuli. Release of lactoferrin in response to fMLP (and PMA) was normal (as was previously reported fMLP-induced chemotaxis and adherence). Thus, this defect is highly specific for oxidative metabolism, and localized to discrete step(s) of the stimulus-response coupling for fMLP, leukotriene B4 and PAF, but conceivably not due to impairment of the dynamic interaction of fMLP with its receptor.

Aged

Considerations for the treatment of ethylene glycol poisoning based on analysis of two cases.

The clinical picture as well as the principles of treatment in ethylene glycol poisoning differ with the time after ingestion. These time-related differences are illustrated by two case reports. During the first hours of ethylene glycol poisoning, the patient suffers from drunkenness, vomiting and somnolence due to the intoxicant effect of ethylene glycol on the central nervous system. In the following hours a poisoning with glycolate and oxalate develops, with increasing acidosis, renal and brain damage. A patient admitted within a few hours of an overdose, with no or only slight metabolic acidosis, may be successfully treated with ethanol. If the serum concentration of ethylene glycol is very high, hemodialysis may be deferred until the necessary staff and equipment are available. If the patient is admitted with severe metabolic acidosis, hemodialysis must be started immediately. The need for ethanol administration during hemodialysis merits reevaluation.

Acidosis

Gaucher disease: heterologous expression of two alleles associated with neuronopathic phenotypes.

To investigate the molecular basis for the distinct neuronopathic phenotypes of Gaucher disease, acid beta-glucosidases expressed from mutant DNAs in Gaucher disease type 2 (acute) and type 3 (subacute) patients were characterized in fibroblasts and with the baculovirus expression system in insect cells. Expression of the mutant DNA encoding a proline-for-leucine substitution at amino acid 444 (L444P) resulted in a catalytically defective, unstable acid beta-glucosidase in either fibroblasts from L444P/L444P homozygotes or in insect cells. This mutation was found to be homoallelic in subacute neuronopathic (type 3) Gaucher disease. In comparison, expression of the mutant cDNA encoding an arginine-for-proline substitution at amino acid 415 (P415R) resulted in an inactive and unstable protein in insect cells. This allele was found only in a type 2 patient with the L444P/P415R genotype. The substantial variation in the type 3 phenotype (L444P homozygotes) suggests the complex nature of the molecular basis of phenotypic variation in Gaucher disease. Yet, the association of neuronopathic phenotypes with alleles producing severely compromised (L444P) or functionally null (P415R) enzymes indicates that the effective level of residual activity at the lysosome is likely to be a major determinant of the severity of Gaucher disease.

Acute Disease

Clinical and therapeutic use of probucol.

Previous studies showed that probucol significantly lowered both LDL cholesterol and HDL cholesterol. In addition, there is evidence that as an essential antioxidant probucol causes variations in cellular interactions and cardiovascular functions in patients. Therefore, 14 hypercholesterolemic men were investigated before and during probucol treatment in order to document both serological and cardiovascular changes with special regard to (1) serum apolipoproteins (A-I, A-II, B, C-II, C-III, E) (2) composition and distribution of HDL and LDL subfractions, (3) cardiovascular performance using a maximum exercise stress test, and (4) induced platelet aggregation. In contrast to reduced total, LDL-, and HDL-cholesterol values, highly significant changes in serum apolipoproteins were found in apoA-I only; apoA-II was unchanged both in serum and in HDL subfractions. Despite unchanged serum apoB levels, the results showed that probucol has a significant influence on the composition (TG/FC ratio) of LDL particles of d less than 1.019 g/ml. In addition to lipoprotein-related changes, significant decreases in heart rate data and cardiac work and in lactic acid accumulation during exercise were induced by probucol administration; furthermore, adrenaline-induced platelet aggregation was also decreased. The results found significantly demonstrate that probucol acts by way of more mechanisms than cholesterol lowering alone. This aspect may be of special interest in the clinical use of probucol, because a coronary-risk-reducing therapy should not affect the lipoprotein profile only.

Adult