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Biomedical subjects

J Nilsson

Publications and source records attributed to J Nilsson.

At least 217 records · Page 12Linked to original sources

Mononuclear leukocytes exposed to oxidized low density lipoprotein secrete a factor that stimulates endothelial cells to express adhesion molecules.

In animals fed a hypercholesterolemic diet, development of atherosclerosis is preceded by attachment of mononuclear leukocytes to the arterial endothelium. Early lesions begin to develop as monocytes migrate into the intima and ingest lipids. A major part of these lipids is believed to be derived from oxidatively modified low density lipoprotein (LDL). In the present study we demonstrate that human mononuclear leukocytes exposed to low concentrations of copper-oxidized LDL secrete one or several factors that stimulate the expression of intercellular adhesion molecule-1 (ICAM-1, CD54), vascular cell adhesion molecule (VCAM-1) and endothelial selectin (E-selectin-1, ELAM-1), whereas native LDL was found to be without effect. Exposure of endothelial cells to non-conditioned medium containing oxidized LDL did not influence the expression of adhesion molecules. Incubation of endothelial cells with conditioned medium from mononuclear cells grown in the presence of oxidized LDL also resulted in a three-fold increase in the binding of monocytoid U937 cells. The present findings suggest that mononuclear leukocytes exposed to oxidatively modified LDL in early atherosclerotic lesions may stimulate the recruitment of other leukocytes by secreting cytokines which induce the expression of adhesion molecules on the endothelium.

Cell Adhesion↗

Rat heart smooth muscle cells express high and low affinity receptors for somatostatin-14, which are involved in regulation of cell proliferation.

We demonstrate that rat heart coronary artery smooth muscle cells express specific binding sites (receptors) for somatostatin-14. The sigmoidal shape kinetics of the somatostatin-14 binding by the cells suggests the presence of either an allosteric binding site or binding sites with different affinities towards the ligand. Scatchard analysis reveals presence of high affinity (Kd = 0.039 x 10(-9)M) and low affinity (Kd = 0.602 x 10(-9)M) binding sites. Somatostatin-14 and Angiopeptin can displace each other from the binding sites. The concentrations of Angiopeptin required to displace 28%-48% of bound somatostatin-14 (10(-9)M) are in the range of 10(-4)-10(-3)M. The concentrations of somatostatin-14 required to displace 8-27% of bound Angiopeptin (10(-6)M) are in the range of 10(-6)-10(-5)M. Thus, somatostatin-14 seems to possess much higher binding affinity than Angiopeptin. Binding of somatostatin-14 and Angiopeptin to rat smooth muscle cells triggers intracellular event(s) leading to inhibition of smooth muscle cell proliferation. Exposure of smooth muscle cells to somatostatin-14 and Angiopeptin decreases amount of phosphorylated tyrosine residues. The effect of somatostatin-14 and Angiopeptin on the expression of phosphotyrosine precedes and is most likely responsible, at least in part, for the inhibition of smooth muscle cell proliferation. This demonstrates that rat heart smooth muscle cells express physiologically active receptor(s) for somatostatin-14.

Animals↗

A flow-through microsampling device applied to an ion-exchange chromatography system.

A flow-through microsampling device that can be inserted in the column elution flow line of a chromatographic system has been developed. A sample drop (volume 2.2 nl) is ejected when a voltage pulse is applied to a piezo-electric transducer. The drops can be ejected with up to 70 Hz frequency, giving a sample flow range of 0-9 microliters/min. Samples were collected on a moving agarose surface during elution of freshly prepared human serum. The precipitate pattern obtained after immunoelectrophoresis is similar to what would be obtained in a fused rocket electrophoresis of multiple samples from a fraction collector.

Blood Proteins↗

Principles of digital sampling of a physiologic signal.

The practice of clinical neurophysiology requires fast, reliable and accurate assessment of a variety of biologic signals. Appropriate filters and rates of analog-to-digital sampling must be used to avoid distorting the signal. Using principles of sampling theory and examples, we describe the frequency content of signals encountered in clinical neurophysiology laboratories, offer guidelines for band-limiting frequencies, and give rules for determining minimal sampling frequencies. Errors introduced by undersampling (aliasing) are illustrated. When sophisticated computational techniques, such as discrete Fourier transform, are used to reconstruct the original wave form, a sampling frequency just above the double of the highest frequency content of the signal is adequate. Sampling neurophysiologic wave forms for direct display, however, requires a sampling frequency at least 4 times as high as that of the upper frequency filter.

Electromyography↗

Sensory nerve findings by tactile stimulation of median and ulnar nerves in healthy subjects of different ages.

We studied orthodromic sensory conduction velocity along the distal and proximal segments of the median and ulnar nerves by tactile stimulation of the distal phalanx of the 3rd and 5th digits in 44 healthy subjects divided into 2 age groups: from 16 to 35 years and from 63 to 81 years. In the same nerves, we used selective electrical stimulation of the corresponding digital nerves to obtain sensory potentials. In both groups, responses to tactile stimuli had a longer latency and smaller amplitude than those to electrical stimulation, and they were distributed in a series of 6-7 main deflections, apparently regardless of whether the recording site was distal or proximal. Moreover, irrespective of the nerve and of subject age, conduction velocity along both the digit-wrist and the wrist-elbow nerve segments was significantly slower with tactile stimuli than with electrical stimuli. However, independently of the stimulus used, conduction velocity along the proximal nerve segment was significantly faster than that measured along the digit-wrist nerve segment. In both the median and ulnar nerves, maximum potential amplitude, cumulative area and conduction velocity were significantly reduced in the older age group. This finding could reflect the smaller number of Meissner's corpuscles in older subjects, and the loss of large nerve fibres in individuals over 60.

Adolescent↗

Cytokines and smooth muscle cells in atherosclerosis.

For several years it has been recognised that the common denominator for many of the well known risk factors for cardiovascular disease is that they all may give rise to chronic inflammatory reactions in vascular tissues. New tools made available through rapid progress in the fields of immunology and molecular biology have made it possible to reach a better understanding of the molecular events leading to the development of atherosclerosis. These developments have resulted in a renewed interest in the role of inflammatory and immune reactions in atherogenesis. During recent years it has also become increasingly clear that the release and ability to respond to cytokines is not restricted to the cells classically included in the immune system. At least in vitro, smooth muscle cells and endothelial cells produce and respond to cytokines in a manner suggesting that they play active roles in inflammatory reactions. Several cytokines have been found to influence the growth of smooth muscle cells, suggesting a possible link between two of the major characteristics of atherosclerotic lesions: the inflammatory reaction, and the intimal proliferation of smooth muscle cells. Of particular interest is the ability of interleukin-1 and TGF beta to induce autocrine PDGF loops in smooth muscle cells. By this mechanism a transient secretion of cytokines from activated leucocytes may give rise to prolonged activation of smooth muscle cell proliferation. However, the effects of cytokines on vascular cells are very complex and it cannot be taken for granted that the inflammatory reaction generally encountered in atherosclerotic lesions only serves to promote the progress of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

Coronary angiographic changes during 2 years after myocardial infarction largely undetected by repeated tomographic thallium-201 scintigraphy and not reflected by clinical symptoms.

Repeated coronary angiographies and single photon emission computed tomographies (SPECT) were performed at 9 and 33 months after myocardial infarction (MI) in 47 young men. Coronary lesions were classified in eight grades with respect to the reduction of the luminal diameter. The progression and regression of two steps or more in lesions of grade 2 or more, the recanalization of coronary thrombosis and an increase in collaterals were recorded. Patients were divided into three groups with regard to (A) deterioration, (B) improvement and (C) no changes in the three major coronary regions, respectively. Overall, 23 patients (49%) showed changes between the first and the second investigation. A simplified method using summarized short-axis slices for evaluation of the thallium-201 SPECT showed a significant difference in change of regional myocardial uptake of thallium-201 between groups A and B (P = 0.047) but not between the groups A and C, in lateral myocardial regions. No significant differences were found between any of the groups in respect of the anterior or inferior myocardial regions. These findings were not explained by changes in clinical status, maximum heart rate or workload, or by changes in medication. Our results suggest that substantial changes in coronary morphology can take place during the 2 years following MI without consistent changes in clinical symptoms or regional myocardial perfusion.

Adult↗

Mitogenic activity in connection with coronary angioplasty.

The aim of this study was to assess the plasma mitogenic activity in connection with percutaneous transluminal coronary angioplasty (PTCA) and the relation to restenosis. Plasma samples were taken on the morning before, 1 and 24 h after, 2 weeks after and 6 months after elective PTCA in 50 patients. Follow-up coronary angiography was carried out after 6 months or earlier if clinically warranted. Samples were also taken from 17 patients undergoing coronary angiography without PTCA. The mitogenic activity, expressed as the fraction of labelled nuclei after incubation of arterial smooth muscle cells with plasma in the presence of 3H-thymidine, was higher 1 h after PTCA than before (53.1 +/- 7.4 vs 26.8 +/- 7.3, P < 0.001). Later values were not elevated and no increase was seen after coronary angiography. The groups with (n = 19) and without (n = 31) restenosis did not differ in mitogenic activity. These results indicate that the plasma level of mitogenic activity increases immediately after PTCA. The pathophysiological significance of this increase for the development of restenosis is unclear, since the magnitude of the increase does not seem to be related to restenosis.

Aged↗

Plasma growth factor activity and cardiac wall thickness.

OBJECTIVES: The aim of this study was to investigate the growth factor activity in plasma (GFAP) in hypertension, and the correlation of GFAP to blood pressure levels, cardiac structural changes and platelet activation at rest and during exercise. SUBJECTS: Fifteen untreated hypertensive subjects and 15 normotensive controls were recruited from a blood pressure screening programme. INTERVENTIONS: GFAP before and after 30 min of strenuous exercise was analysed as the ability of patient or control plasma to stimulate incorporation of 3H-thymidine in cultured human smooth muscle cells. M-mode echocardiography was performed and platelet activity was measured by the excretion of the urinary metabolite of thromboxane A2. RESULTS: There were no significant differences in GFAP or platelet activation at rest or after exercise between the groups. The fractions of labelled cells were 52.6% vs. 56.6% (HT vs. NT) at rest. Septum and posterior wall end-diastolic thicknesses (PWT[D]) were significantly increased in the HT group (10.4 +/- 0.3 vs. 9.2 +/- 0.3 mm and 11.4 +/- 0.5 vs. 10.0 +/- 0.4 mm, respectively, P < 0.05). PWT(D) was significantly correlated to GFAP (r = 0.40, P = 0.04) and to blood pressure (r = 0.53, P < 0.005) but there was no correlation between blood pressure and GFAP. CONCLUSION: The data suggest that GFAP could play a role in the early development of cardiac hypertrophy in hypertension, but that this effect does not seem to be directly linked to blood pressure levels alone.

Adult↗

Pathophysiological mechanisms for restenosis following coronary angioplasty: possible preventive alternatives.

Restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) remains an unsolved medical problem. The search for the underlying pathophysiological mechanisms have identified intimal proliferation of smooth muscle cells (SMC) to be the prevailing cause of late restenosis, with endothelial cells (EC) and platelets being important participators in the process. According to the most accepted present theory, SMC would be stimulated to migrate and proliferate shortly after the angioplasty by the release of growth factors from injured EC and accumulated platelets. However, clinical trials of agents interfering with these mechanisms have not significantly diminished the rate of restenosis, which suggest both that our knowledge of the process is incomplete, and that new ways of administering the agents may be required.

Angioplasty, Balloon, Coronary↗

Endogenous activation of c-myc expression and DNA synthesis in serum-starved neonatal rat smooth muscle cells.

Earlier studies have shown that smooth muscle cells (SMC) from arteries of neonatal and adult rats differ markedly in their in vitro growth characteristics. Since some of these differences may be relevant to the proliferation of SMC in atherosclerotic plaques we examined the expression of three proto-oncogenes (c-fos, c-jun, and c-myc) and an SMC-specific differentiation marker (alpha-actin) in cultured SMC. In presence of serum cultured adult SMC contained lower levels of alpha-actin mRNA than neonatal cells. In neonatal cells serum-starvation resulted in a distinct increase in both c-myc and alpha-actin mRNA levels, whereas the expression of these genes appeared to be unaffected in adult cells. Transfer of adult SMC proliferating in the presence of fetal calf serum to serum-free medium for 48 h almost completely inhibited DNA synthesis, whereas transfer of neonatal SMC to serum-free medium reduced DNA synthesis only to about 50%. Serum-starved adult and neonatal SMC did not contain c-fos or c-jun transcripts, but in both cell types serum-stimulation resulted in a comparable increase in the expression of both genes. The present results demonstrate clear differences in the mechanisms regulating gene expression in adult and neonatal SMC.

Actins↗

Antioxidant treatment inhibits the development of intimal thickening after balloon injury of the aorta in hypercholesterolemic rabbits.

The effect of the antioxidant butylated hydroxytoluene (BHT) on the accumulation of intimal smooth muscle cells (SMC) and development of intimal thickening after balloon catheter injury of the aorta were studied in rabbits with dietary-induced hyperlipidemia. Two sets of New Zealand White rabbits (eight rabbits in each group) were fed either 0.25% cholesterol or 0.25% cholesterol/1% BHT for a total of 6 wk. Serum lipid levels did not differ between the two groups. 3 wk after the start of the study, a balloon injury of the aorta was performed, after which the rabbits were kept on their respective diets for another 3 wk. After this period of time, the rabbits were killed and their aortas were investigated. The BHT-treated rabbits had only one fourth of the intimal thickness (P < 0.0001) and half the number of SMC/mm intima (P < 0.001), as compared to the rabbits fed only cholesterol. There was also a lower number of macrophages in the BHT-treated group. T lymphocytes were present in the intima of cholesterol-fed rabbits, whereas no such cells could be identified in the BHT-fed animals. There were significantly lower levels of autooxidation products of cholesterol (7-oxocholesterol, cholesterol-5,6-epoxide, and 7 beta-hydroxycholesterol) in the aortas of BHT-treated rabbits, P < 0.001. In conclusion, the antioxidant BHT effectively inhibited the accumulation of intimal SMC and the development of intimal thickening of the aorta in hypercholesterolemic rabbits after a balloon catheter-induced injury. These results indicate that antioxidants may modify intimal response to injury.

Actins↗

Growth-regulatory effects of sensory neuropeptides, epidermal growth factor, insulin, and somatostatin on the non-transformed intestinal epithelial cell line IEC-6 and the colon cancer cell line HT 29.

A non-transformed small-intestinal cell line from the rat (IEC-6) and a human colon cancer cell line (HT 29) were examined for their trophic response to sensory neuropeptides. Substance P, neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and peptide YY (PYY) were tested. Epidermal growth factor (EGF), insulin, and somatostatin-14 were also used. Interaction studies were performed on IEC-6 cells by combining EGF or insulin with somatostatin-14. The sensory neuropeptides had no effect either on IEC-6 cell growth and DNA synthesis or on HT29 cell growth. EGF and insulin stimulated cell growth and DNA synthesis in IEC-6 cells and cell growth in HT 29 cells in a dose-dependent fashion. Somatostatin-14 had no effect either alone or in combination with EGF or insulin on IEC-6 cell growth and DNA synthesis. HT 29 cell growth was inhibited by somatostatin-14 only in the presence of serum with a maximal and significant response at 10(-7) M. Our observations suggest that the sensory neuropeptides do not exert a direct growth-regulatory effect either on IEC-6 cells or on HT 29 cells. Somatostatin, however, inhibits serum-induced HT 29 cell growth but does not interfere directly with the proliferative effect of serum, EGF, or insulin on IEC-6 cells in this model.

Animals↗

Analysis of lipoprotein diene formation in human serum exposed to copper.

The susceptibility of low density lipoprotein (LDL) to oxidative modification can be determined by analyzing the lag phase for initiation of diene formation in isolated LDL exposed to Cu2+. However, the applicability of this assay for clinical studies is limited by the requirement of a preparative ultracentrifugation of LDL and that the influence of water soluble antioxidants and other lipoproteins is not accounted for. The present paper describes a modification of this assay allowing determination of lag phase for lipoprotein diene formation in serum. The formation of dienes in serum exposed to Cu2+ begins following the consumption of serum alpha-tocopherol, correlates to the formation of thiobarbituric acid reactive substances (r = 0.987, n = 8), is inhibited by the addition of ascorbic acid and is absent in lipoprotein-deficient serum. It is also accompanied by an increased mobility of serum lipoproteins on agarose gel electrophoresis and with an ability of serum to displace isolated copper-oxidized LDL from binding sites mediating degradation in mouse peritoneal macrophages. The coefficient of variance of the analysis is below 3%. It is concluded that this technique allows analysis of lipoprotein oxidation susceptibility in serum samples and may prove to be useful in clinical analysis of the lipoprotein oxidation susceptibility.

Animals↗

Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man.

Animal studies indicate a possible role for lipid oxidation in the development of atherosclerosis. We set out to investigate whether there was a relation between the ability of low-density lipoprotein (LDL) to resist oxidation in vitro and the severity of coronary atherosclerosis in man. 35 unselected young (mean [SD] age 39.9 [4.2] years) male survivors of myocardial infarction underwent angiography, and LDL was isolated from their plasma by density gradient ultracentrifugation. In-vitro LDL susceptibility to oxidation was assessed by determination of the lag phase for the formation of conjugated dienes in the presence of copper ions. An inverse relation was found between lag phase and quantitative estimates of global coronary atherosclerosis (r = -0.45; p less than 0.02). Multivariate analysis indicated that the lag phase for oxidative modification of LDL and LDL cholesterol concentration correlated independently with severity of coronary atherosclerosis. The lag phase for oxidation of LDL was also related to the triglyceride content of the LDL fraction (r = -0.55; p less than 0.002). The finding that susceptibility to LDL oxidation is associated with severity of coronary atherosclerosis may indicate that lipid oxidation promotes premature coronary atherosclerosis and that individuals with an LDL enriched in triglycerides are at particular risk.

Adult↗

Adenosine receptors, cyclic AMP accumulation, and DNA-synthesis in aortic smooth muscle cell cultures of adult and neonatal rats.

The effects of two adenosine analogs on cyclic AMP (cAMP) accumulation and DNA synthesis were studied in cultured smooth muscle cells (SMCs) isolated from adult and neonatal rat arteries. N-ethylcarboxamido adenosine (NECA) dose-dependently increased intracellular cAMP levels and appeared to be more potent in adult than in neonatal SMCs. R-phenylisopropyl adenosine (R-PIA), in nanomolar concentrations, counteracted the increase in cAMP evoked by 10 microM forskolin in adult but not in neonatal SMCs, indicating that the enhanced "A2" response seen in adult SMCs was not due to a lack of "A1" receptors in these cultures. Binding experiments performed using the adenosine antagonist XAC did not reveal any differences in the number or affinity of the adenosine receptors between neonatal and adult SMCs. This indicates effects presumably on the G-protein level. A high capacity to spontaneously synthesize DNA and a weak response to platelet-derived growth factor (PDGF) were seen in the neonatal SMCs. Furthermore, NECA had no effect on PDGF-induced DNA synthesis in these cells. In contrast, adult SMCs presented a low rate of spontaneous DNA synthesis and a marked proliferative response to PDGF, which was inhibited by NECA. This inhibition paralleled the increase in cAMP elicited by NECA. Our findings suggest that neonatal and adult SMCs differ both in their response to growth factors and growth inhibitors.

Adenosine↗

Demonstration of digital radiographs by means of ink jet-printed paper copies: pilot study.

Different digital medical images have been printed on paper with a continuous ink jet printer, and the quality has been evaluated. The emphasis has been on digital chest radiographs from a computed radiography system. The ink jet printing technique is described as well as the handling of the image data from image source to printer. Different versions of paper prints and viewing conditions were compared to find the optimum alternative. The evaluation has been performed to maximize the quality of the paper images to make them conform with the corresponding film prints and monitor images as much as possible. The continuous ink jet technique offers high-quality prints on paper at a considerably lower cost per copy compared with the cost of a film print. With a future switch-over from diagnosing of digital images on film to diagnosing them on monitors, hard copies for demonstration purposes will occasionally be needed. This need can be filled by ink jet-printed paper copies.

Copying Processes↗