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Biomedical subjects

J Nilsson

Publications and source records attributed to J Nilsson.

At least 145 records · Page 8Linked to original sources
PubMed1997

Effect of bezafibrate treatment over five years on coronary plaques causing 20% to 50% diameter narrowing (The Bezafibrate Coronary Atherosclerosis Intervention Trial [BECAIT]).

Recent reports indicate that most coronary events originate from plaques causing <50% diameter stenosis. A subgroup analysis of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) data was undertaken to determine the effects of bezafibrate in relation to baseline narrowing. BECAIT included 92 male postacute myocardial infarction patients <45 years of age. Each received double-blind treatment with bezafibrate (200 mg 3 times daily) or placebo for 5 years, together with a low-fat diet. Coronary angiography was performed at baseline and after 2 and 5 years. The mean minimum lumen diameter of lesions causing 20% to <50% diameter stenosis at baseline did not narrow over 5 years in the bezafibrate group and decreased by 0.15 mm in the placebo group (p <0.05). In segments with > or =50% diameter stenosis at baseline, no change was seen in either of the 2 groups. In the analysis including only segments with 20% to <50% stenosis at baseline, coronary events were seen in 7 of 40 patients with a progression in minimum lumen diameter of more than the median value and in 3 of 41 patients with a change less than the median value. Thus, bezafibrate had a preferential effect in slowing the progression of narrowings causing <50% stenosis at baseline in young men followed up for a 5-year period after acute myocardial infarction.

Adult↗
PubMed1997

GRID/GOLPE 3D quantitative structure-activity relationship study on a set of benzamides and naphthamides, with affinity for the dopamine D3 receptor subtype.

In the search for drugs against schizophrenia and depression without extrapyramidal side effects, compounds that selectively antagonize the dopamine D3 receptor subtype are thought to be a solution. In order to create a model with which the D3 activity can be predicted and that can generate new ideas for future synthesis, we performed a comparative molecular field analysis (CoMFA). In our model 30 ligands were described quantitatively in the GRID program, and the model was optimized by selecting only the most informative variables in the GOLPE program. We found the predictive ability of the model to increase significantly when the number of variables was reduced from 25110 to 784. A Q2 of 0.65 was obtained with the final model, confirming the predictive ability of the model. By studying the PLS coefficients in informative 3D contour plots, ideas for the synthesis of new compounds can be generated.

Algorithms↗
PubMed1997

Localization of sterol 27-hydroxylase immuno-reactivity in human atherosclerotic plaques.

It has recently been shown that extrahepatic cells can eliminate intracellular cholesterol by enzymatic conversion into 27-hydroxy-cholesterol and 3 beta-hydroxy-5-cholestenoic acid. Using immunohistochemical methods, we studied the presence of the enzyme responsible for these conversions, sterol 27-hydroxylase, in human carotid atherosclerotic plaques. All plaques examined were found to contain sterol 27-hydroxylase immuno-reactive cells. While some endothelial cells stained for sterol 27-hydroxylase, the majority of the immunoreactive cells co-localized with macrophages. Accumulation of sterol 27-hydroxylase-positive cells were often observed in macrophage-rich core regions of complicated lesions. High concentrations of 27-hydroxycholesterol were found in plaques, while the concentration in non-atherosclerotic human vessels was lower by two orders of magnitude. The rabbit, which is particularly sensitive to dietary cholesterol and easily develops fatty streaks, had low plasma levels of 27-hydroxycholesterol, 3 ng/ml compared to 150 ng/ml in humans. The concentration of 27-hydroxycholesterol in the atherosclerotic rabbit vessels was also lower compared to human atherosclerotic plaques. The results are consistent with our hypothesis that sterol 27-hydroxylase may be utilized by human macrophages as a defence towards a high cholesterol load. This mechanism may be less important in some other species.

Animals↗
PubMed1997

Production of a thermostable DNA polymerase by site-specific cleavage of a heat-eluted affinity fusion protein.

A novel strategy is described for bacterial expression and affinity purification of a recombinant truncated version of the heat-stable DNA polymerase I from Thermus aquaticus. The DNA polymerase (deltaTaq) was produced as a fusion to a serum albumin binding affinity handle (ABP) derived from streptococcal protein G. Based on the thermostability of the deltaTaq DNA polymerase, affinity-purified ABP-deltaTaq could be heat-eluted from HSA columns by incubation at 85 degrees C. To produce free deltaTaq DNA polymerase, efficient site-specific cleavage of the affinity tag was performed using a recombinant coxsackievirus 3C protease (3Cpro), also produced as an ABP affinity fusion. Thus, an integrated strategy could be devised where both the cleaved ABP affinity tag and the protease fusion could be recovered after site-specific cleavage using HSA-affinity chromatography. The flow-through fraction contained essentially pure deltaTaq DNA polymerase with full enzymatic activity.

Affinity Labels↗
PubMed1997

Abdominal and hip flexor muscle activation during various training exercises.

The purpose of this study was to provide objective information on the involvement of different abdominal and hip flexor muscles during various types of common training exercises used in rehabilitation and sport. Six healthy male subjects performed altogether 38 different static and dynamic training exercises trunk and hip flexion sit-ups, with various combinations of leg position and support, and bi- and unilateral leg lifts. Myoelectric activity was recorded with surface electrodes from the rectus abdominis, obliquus externus, obliquus internus, rectus femoris, and sartorius muscles and with indwelling fine-wire electrodes from the iliacus muscle. The mean electromyogram amplitude, normalised to the highest observed value, was compared between static and dynamic exercises separately. The hip flexors were highly activated only in exercises involving hip flexion, either lifting the whole upper body or the legs. In contrast, the abdominal muscles showed marked activation both during trunk and hip flexion sit-ups. In hip flexion sit-ups, flexed and supported legs increased hip flexor activation, whereas such modifications did not generally alter the activation level of the abdominals. Bilateral, but not unilateral, leg lifts required activation of abdominal muscles. In trunk flexion sit-ups an increased activation of the abdominal muscles was observed with increased flexion angle, whereas the opposite was true for hip flexion sit-ups. Bilateral leg lifts resulted in higher activity levels than hip flexion sit-ups for the iliacus and sartorius muscles, while the opposite was true for rectus femoris muscles. These data could serve as a basis for improving the design and specificity of test and training exercises.

Abdominal Muscles↗
PubMed1997

Cell death in human atherosclerotic plaques involves both oncosis and apoptosis.

The aim of the present study was to analyze the frequency and mechanism of cell-death in atherosclerotic plaques with a recent history (< 6 months) of rupture. Atherosclerotic plaques were obtained from patients with symptomatic ipsilateral carotid stenosis > 70% diameter reduction undergoing carotid endarterectomy. In situ tailing and nick translation of fragmented DNA, agarose gel electrophoresis of plaque DNA and electron microscopy were used to identify cell death by apoptosis (programmed cell death) and oncosis. The mean number of cells containing fragmented DNA in the plaques was 12.7 +/- 3.5% (n = 15). Focal accumulations of cells with DNA fragmentation occurred in the fibrous cap, at sites of rupture, close to lipid deposits and necrosis and was always accompanied by the presence of inflammatory cells. Electrophoretic separation of DNA isolated from part of plaques, where the presence of DNA fragmentation had previously been demonstrated by in situ DNA nick translation, resulted in multiple ladders of 180-200 base pairs characteristic of apoptosis. Electron microscopic analysis revealed presence of cells with morphological signs of degeneration in a frequency even higher than that found by in situ nick translation. Some of these cells had a characteristic apoptotic appearance with condensed chromatin and cytoplasm, but the large majority of the cells had an ultrastructure typical for cells undergoing cell death by oncosis with membrane disruption and swollen, disintegrating organelles. Thus, although apoptosis clearly takes place in atherosclerotic plaques, oncosis appears to be a much more common mechanism for cell death.

Aged↗
PubMed1997

Nuclear factor-kappaB activity and arterial response to balloon injury.

We studied the effect of arterial balloon injury on nuclear factor-kappaB (NF-kappaB) mobilization and ICAM-1 expression in untreated rats and rats treated with aspirin. Baseline NF-kappaB nuclear binding in smooth muscle cells (SMC) increased two-fold within 6 h after balloon injury. The binding returned to baseline 3 days after injury. Consistently nuclear staining of p65 active subunit increased in the medial SMC following balloon injury. There was no baseline ICAM-1 expression. Within 3 days after balloon injury there was marked medial ICAM-1 expression, that localized to neointima 7 days after injury and to regrowing endothelial cells 14 days after injury. Treatment with aspirin inhibited NF-kappaB nuclear translocation and binding and was associated with reduction of ICAM-1 expression, SMC proliferation and neointimal thickening following balloon injury. These data suggest that transient mobilization of NF-kappaB in vascular SMC after balloon injury mediates ICAM-1 expression and is involved in arterial response to balloon injury.

Animals↗
PubMed1997

Immunization with homologous oxidized low density lipoprotein reduces neointimal formation after balloon injury in hypercholesterolemic rabbits.

OBJECTIVES: In this study we tested the hypothesis that immunization with homologous oxidized low density lipoprotein (oxLDL) would inhibit the neointimal response to balloon injury in hypercholesterolemic rabbits. BACKGROUND: Immunization with homologous oxLDL has been shown to markedly reduce aortic atherosclerosis in LDL receptor-deficient as well as cholesterol-fed rabbits; however, the effect of this strategy on the balloon injury-induced neointimal lesion is unknown. METHODS: New Zealand White rabbits were immunized with 280 microg of homologous native LDL (n = 5), copper-oxidized LDL (n = 5) or phosphate buffer as control (n = 5) and fed a 1% cholesterol diet. Rabbits were reimmunized after 3 weeks, and balloon injury of the right ileofemoral artery was performed 1 week later. Four weeks after balloon injury, rabbits were killed, and the neointimal lesion area was measured by computerized morphometry after perfusion fixation of the arteries. Circulating antibodies against oxLDL were measured by enzyme-linked immunosorbent assay. RESULTS: In comparison with the control animals, those immunized with oxLDL had a 58% reduction in the neointimal area (0.53 +/- 0.13 vs. 1.27 +/- 0.26 mm2; p = 0.01). The group immunized with native LDL had a 19% reduction in the neointimal area compared with the control group (p = NS). Circulating cholesterol levels and antibody titers against oxLDL were comparable in the three groups. There was a trend toward reduced immunoreactivity for T cells and oxLDL in the neointima of oxLDL-immunized animals. CONCLUSIONS: Hypercholesterolemic rabbits immunized with homologous oxLDL have a markedly reduced neointimal area after balloon injury despite severe hypercholesterolemia. Together with previous work, these data suggest that an immunization strategy (vaccination) against atherosclerosis and restenosis warrants further investigation.

Animals↗
PubMed1997

Retardation of coronary atherosclerosis: the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) and other angiographic trials.

A large number of both primary and secondary preventive trials suggest that treatment of elevated plasma lipids may reduce the frequency of coronary heart disease (CHD) events. Meta-analyses indicate that for every 10% reduction of cholesterol, CHD mortality is lowered by 13% and all-cause mortality by 10%. Experience from several angiographic trials also suggests that coronary atherosclerosis can be retarded, and in some instances limited regression induced, by low-density lipoprotein (LDL)-cholesterol reduction and/or high-density lipoprotein (HDL)-cholesterol elevation. Coronary angiographic studies have shown that although the effects on retardation/regression of altherogenic lesions have been small, with luminal diameter changes of around 0.10 mm, the effects on clinical events were more substantial, with reductions of the order of 50%. There is also evidence that it is the mild and moderate lesions that are of particular concern with respect to the occurrence of clinical coronary events. The progression of atherosclerosis and the occurrence of coronary events are probably not exclusively dependent on a lowering of LDL-cholesterol concentrations. Analyses from the Monitored Atherosclerosis Regression Study (MARS), the Cholesterol Lowering Atherosclerotic Study (CLAS), and the Programs on the Surgical Control of the Hyperlipidaemias (POSCH) indicate that triglyceride-rich lipoproteins may also be of importance for the progression of mild/moderate lesions in subjects treated with cholesterol-lowering regimens. Recently, the results of the 5-year Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) demonstrated that bezafibrate significantly retarded the progression of coronary atheroma and coronary events in young male survivors of myocardial infarction, as assessed by changes in minimum lumen diameter. This positive outcome is most likely due to the beneficial treatment effects on the levels of serum triglycerides (-31%), plasma fibrinogen (-12%), and HDL cholesterol (+9%). The results of the BECAIT on progression of coronary atherosclerosis are comparable with those of two recent angiographic trials with HMG-CoA reductase inhibitors, the Multicenter Anti-Atheroma Study (MAAS), and the Regression Growth Evaluation Statin Study (REGRESS), despite different lipid and metabolic effects. BECAIT is the first controlled angiographic study to show that a fibrate can significantly retard the progression of coronary atherosclerosis. The exact mechanisms by which this occurs remain to be elucidated. However, the results of BECAIT illustrate the importance of factors other than LDL cholesterol in the progression of coronary atherosclerosis.

Bezafibrate↗
PubMed1997

Intramuscular EMG from the hip flexor muscles during human locomotion.

The purpose was to investigate the activation pattern of five major hip flexor muscles and its adaptation to changing speed and mode of progression. A total of 11 healthy subjects performed walking and running on a motor-driven treadmill at speeds ranging from 1.0 to 6.0 m s-1. Intramuscular fine-wire electrodes were used to record myoelectric signals from the iliacus, psoas, sartorius, rectus femoris and tensor fascia latae muscles. The basic pattern, with respect to number of activation periods, remained the same irrespective of speed and mode of progression. However, differences in the relative duration and timing of onset of activation occurred between individual muscles. Over the speed range in walking, a progressively earlier onset was generally seen for the activation period related to hip flexion. Changes in EMG amplitude were measured in the iliacus and psoas muscles and showed a marked increase and difference between walking and running at speeds above 2.0 m s-1. Thus, the alternating flexion-extension movements at the hip during locomotion appear to be governed by a rather fixed 'neural program' which normally only needs minor modulations to accomplish the adjustments accompanying an increase in speed of progression as well as a change from walking to running.

Adult↗
PubMed1997

Flow-cytometric quantitation of anti-D antibodies.

OBJECTIVES: Quantitation of Rh antibodies is important clinically in predicting the risk of hemolytic disease of the newborn. We describe a flow cytometry method for the quantitation of anti-D antibodies that we developed in parallel to a recently described method. METHODS: As a secondary antibody we used whole IgG instead of Fab molecules. The advantages, besides lower cost, include a strong fluorescence signal with no need for amplification, and the possibility of diluting samples to minimize the risk of agglutination by IgM antibodies. We did extensive studies on reproducibility. RESULTS: Reproducibility was superior to the autoanalyzer method. The two methods were roughly in agreement in estimating low, medium, or high levels of anti-D with a correlation coefficient of 0.89. The autoanalyzer measures the in vitro agglutination of all anti-D antibodies whereas flow cytometry measures the amount of IgG anti-D bound to red cells, which is more like the in vivo situation. CONCLUSION: Further studies in a clinical setting will show whether flow-cytometric quantitation may improve the diagnostic value of anti-D concentration measurement.

Erythrocyte Aging↗
PubMed1997

Computer-aided determination of the silent period.

Silence of electromyographic (EMG) activity after an evoked muscle twitch has been studied extensively. However, different criteria have been used to determine the level at which the silence of muscle activity ends, and the purpose of this work was to develop an objective method able to determine the silent period even when data were acquired using different EMG instruments. The silent period evoked by transcranial magnetic stimulation was determined bilaterally from abductor pollicis brevis (APB) muscles in 11 subjects, from trapezius muscles in 9 subjects, and from sternocleidomastoid muscles in 11 subjects. All subjects were healthy controls and gave their informed consent to participate in the study. Muscle activity was recorded via surface electrodes. Recordings from 10 stimuli were rectified, averaged, and plotted logarithmically by dividing the mean of the prestimulus EMG activity into the whole trace. Plotted in this way, the one-level represents the mean rectified EMG amplitude of the prestimulus activity. The end of the silent period was measured automatically as the moment at which Student's t test was no longer significantly different, when testing the window of mean prestimulus EMG activity with respect to a 4-ms window centered around the assumed end of the silent period (resolution 0.1 ms). The mean silent periods were 183.7 +/- 49.8 ms for APB, 194.2 +/- 28.8 ms for trapezius, and 194.8 +/- 73.6 ms for sternocleidomastoid muscles, measured from the M-response latency (mean latency: APB 19.7 +/- 1.9 ms, trapezius 7.8 +/- 0.6 ms, and sternocleidomastoid 6.7 +/- 0.8 ms). Computer-aided measurement proved to be a fast and objective tool able to standardize determination of the silent period.

Adult↗
PubMed1997

DNA fragmentation and ultrastructural changes of degenerating cells in atherosclerotic lesions and smooth muscle cells exposed to oxidized LDL in vitro.

Degeneration of smooth muscle cells in the fibrous cap of atherosclerotic lesions is an important factor in plaque rupture. Recent studies have suggested that many plaque cells are in a process of apoptosis as determined by positive deoxyribonucleotide-transferase-mediated dUTP end labeling. In this study, we demonstrate the existence of a colocalization between deoxyribonucleotide-transferase-mediated dUTP end labeling-positive smooth muscle cells and oxidized LDL immunoreactivity in human carotid plaques. Oxidized LDL was found to induce deoxyribonucleotide-transferase-mediated dUTP end labeling positivity in cultured human smooth muscle cells, but only in the presence of tumor necrosis factor-alpha and interferon-gamma. Electron microscopic analysis of cultured smooth muscle cells exposed to oxidized LDL in the absence of cytokines demonstrated cytoplasmic swelling and disruption of the plasma membrane, suggesting cell death by oncosis. Cells exposed to both oxidized LDL and cytokines were characterized by chromatin and cytoplasmic condensation compatible with cell death by apoptosis. These findings further support the notion that oxidized lipids play a role in plaque cell death.

Arteriosclerosis↗
PubMed1997

Tumor necrosis factor-alpha activates smooth muscle cell migration in culture and is expressed in the balloon-injured rat aorta.

In experimental models of atherosclerosis, activation of smooth muscle cell (SMC) migration from the media to the intima is preceded by intimal accumulation of inflammatory cells, suggesting that cytokines may be involved in this process. The present study demonstrates that tumor necrosis factor-alpha (TNF-alpha) regulates cytoskeletal organization of SMCs by inducing depolymerization of actin stress fibers and dispersion of vinculin from sites of focal adhesion and stimulates the migration of cultured human SMCs in a dose-dependent manner. Moreover, TNF-alpha induces rapid activation of the c-ets-1 gene, which codes a transcription factor known to regulate enzymes important for matrix degradation during cell migration. Balloon catheter injury of the rat femoral artery resulted in medial expression of TNF-alpha within 6 hours. This expression appeared to be localized to SMCs and remained elevated until SMCs began to migrate into the intima 7 days after injury. These findings demonstrate that TNF-alpha has a stimulatory effect on SMC migration and suggest that TNF-alpha may be involved in the intimal recruitment of SMCs during plaque formation.

Animals↗
PubMed1997

Heat-mediated activation of affinity-immobilized Taq DNA polymerase.

A novel strategy for heat-mediated activation of recombinant Taq DNA polymerase is described. A serum albumin binding protein tag is used to affinity-immobilize an E. coli-expressed Taq DNA polymerase fusion protein onto a solid support coated with human serum albumin (HSA). Analysis of heat-mediated elution showed that elevated temperatures (> 70 degrees C) were required to significantly release the fusion protein from the solid support. A primer-extension assay showed that immobilization of the fusion protein resulted in little or no extension product. In contrast, fusion protein released from the HSA ligand by heat showed high polymerase activity. Thus, a heat-mediated release and reactivation of the Taq DNA polymerase fusion protein from the solid support can be obtained to allow for hot-start PCR with improved amplification performance.

Chromatography, Affinity↗
PubMed1997

The female pelvic floor: a dome--not a basin.

BACKGROUND: Classically and based on necropsy observations, the muscles of the pelvic floor (the levator ani and coccygeus muscles) have been described as having the shape of a basin. In a previous study by Hugosson et al. (1991), magnetic resonance imaging revealed the dome shape of the pelvic floor in live subjects when muscular tonus is present. METHODS: The normal anatomy and the dynamic movements of the female pelvis were examined with magnetic resonance imaging including conventional and fast sequences. Six nulliparous and six parous healthy women without signs or symptoms of pelvic relaxation were studied in the supine position at rest, during voluntary pelvic contractions and during bearing down. RESULTS: The levator ani muscle was dome-shaped at rest. During voluntary pelvic contractions the muscle straightened, becoming more horizontal and during bearing down it descended, becoming basin-shaped. The width of the genital hiatus was the same in both groups at rest and it widened during bearing down in all but two 3-para women. The bladder base was lifted upward and forward during voluntary pelvic contractions but during bearing down it descended. The rectum at rest had a posterior angle which decreased during voluntary pelvic contractions and increased during bearing down. CONCLUSIONS: MRI of the female pelvis is valuable in anatomic and dynamic analysis in healthy women and offers new information about the female pelvic floor. The female pelvic floor is shaped like a dome-not like a basin.

Adult↗