Search PubMed⌕ Search

Biomedical subjects

J Nilsson

Publications and source records attributed to J Nilsson.

At least 163 records · Page 9Linked to original sources
PubMed1997

Direct effects of somatostatin analog octreotide on insulin-like growth factor-I in the arterial wall.

Local vascular expression and action of insulin-like growth factor-I (IGF-I) appear to be important in the biologic events that follow arterial wall injury. Octreotide, a long-acting somatostatin analog, is a potent inhibitor of the growth hormone/IGF-I axis. We examined the effects of octreotide on the vascular IGF-I and IGF-binding proteins (IGFBP), gene regulation, smooth muscle cell proliferation, and neointimal thickening after arterial wall injury. Treatment with octreotide selectively decreased IGF-I mRNA expression in normal rat arteries by 70% and prevented the induction of the IGF-I gene after balloon injury. Because up-regulation of platelet-derived growth factor-A gene was not affected, and because there was no change in plasma growth hormone, IGF-I, and glucagon levels, it appears that this effect is selective and mediated locally. Of the IGFBP, IGFBP-4 was modestly up-regulated after balloon injury, whereas treatment with octreotide had no effect on IGFBP-4 expression. The inhibitory effects of octreotide on vascular IGF-I were associated with a decrease in the number of proliferating cell nuclear antigen-positive cells and an up to 90% reduction in neointimal thickening after balloon injury in a dose-dependent fashion.

Angioplasty, Balloon↗
PubMed1997

Development of tympanosclerosis: can predicting factors be identified?

HYPOTHESIS: The etiological hypothesis is that there might be factors triggering an immunological chain reaction that eventually leads to tympanosclerosis formation. BACKGROUND: Tympanosclerosis is a condition leading to a calcification process in the middle ear and, occasionally, also to the lining of the inner ear. This sometimes leads to hearing loss due to fixation of the middle ear ossicles. In severe cases. deafness may occur as a result of the inner ear impairment. Surgery is the treatment offered, often with poor long-term results, and, alternatively, prescription of hearing aids. Some patients develop tympanosclerosis after mild inflammatory otitis media processes whereas some heal without tympanosclerosis after more aggressive infections. This difference may be due to individual variations in the inflammatory response. The biological mechanism of calcification in tympanosclerosis is probably similar to that occurring in other calcifying tissues due to diseases. METHODS: The present investigation was performed to develop methods for immunohistochemical analyses of this delicate tissue consisting of both hard bone and the very thin tympanic membrane. Sprague-Dawley rats were inoculated with a suspension of Streptococcus pneumoniae, type 3, into the middle ear and sacrificed after 1 week up to 6 months. A new technique was elaborated where the whole specimen was prefixed briefly and then en bloc incubated with the primary antibodies and after that decalcified in edetic acid (EDTA). Primary antibodies against macrophages were used for the immunohistochemical staining. RESULTS: Acute otitis media was successfully induced in the rats and myringosclerosis was seen in 30% of the animals, often localized close to the bony frame where macrophages could also be detected. CONCLUSIONS: Acute otitis media and myringosclerosis were introduced in the animals. Conventional immunological techniques were tested on this delicate tissue. A new method for immunohistochemical staining was elaborated in which specimens were stained en bloc before decalcification and sectioning were performed. Expression of macrophages was demonstrated in the tympanic membrane.

Animals↗
PubMed1997

Ca2+ channel blockers verapamil and nifedipine inhibit apoptosis induced by 25-hydroxycholesterol in human aortic smooth muscle cells.

We have characterized the death of human aortic smooth muscle cells induced by 25-hydroxycholesterol, an oxidation product of cholesterol. Chromatin condensation characteristic of apoptosis was observed by enzymatic (TUNEL) staining of chromatin, and by electron microscopy. Fourteen percent of cells treated with 5 microg/ml of 25-hydroxycholesterol for 24 h displayed chromatin degradation as determined by positive TUNEL staining. Addition of TNF alpha (10 ng/ml) and IFN gamma (20 ng/ml) increased the proportion of TUNEL positive cells to 30%, whereas the cytokines alone were without effect. After 48 h, 40% of the cells treated with 5 microg/ml of 25-hydroxycholesterol were TUNEL positive, and 21% of the cells displayed chromatin condensation. Oligonucleosomal DNA fragmentation typical of apoptosis was demonstrated by agarose gel electrophoresis. Furthermore, activation of the ICE-like protease caspase 3 (CPP32) was observed in cells treated with 25-hydroxycholesterol. Addition of the Ca2+ entry blockers verapamil or nifedipine to the culture medium inhibited apoptosis by more than 70% and reduced cytotoxicity, while removal of Ca2+ from culture medium reduced apoptosis by 42%. Within a few minutes after addition, 25-hydroxycholesterol induced intracellular Ca2+ oscillations with a frequency of approximately 0.3-0.4 min(-1). Thus it appears that Ca2+ influx through plasma membrane channels is an important signal in oxysterol-induced apoptosis. Addition of TNF alpha and IFN gamma enhanced cytotoxicity and resulted in a higher proportion of apoptotic cells, suggesting that inflammatory cytokines can increase the cytotoxicity of lipid oxidation products.

Aorta↗
PubMed1996

The effect of probucol on low density lipoprotein oxidation and femoral atherosclerosis.

The Probucol Quantitative Regression Swedish Trial (PQRST) investigated the effect of the lipid lowering and antioxidant drug probucol on the development of atherosclerosis in humans. 303 hypercholesterolemic patients were randomized to receive either probucol or placebo, in combination with dietary advice and cholestyramine for a three-year period. Probucol was not found to effect progression regression of femoral atherosclerosis significantly as assessed by quantitative arteriography. To evaluate the effectiveness of probucol as an antioxidant during the study period, detailed analyses were performed on 42 of the randomized patients. During the trial, probucol-treated patients (n = 26) had 15% lower total cholesterol (P < 0.01) and 35% lower high density lipoprotein (HDL) cholesterol (P < 0.0001) compared with controls (n = 16). Low density lipoprotein (LDL) from probucol treated individuals was more resistant to oxidation by Cu2+ as determined by the lag phase for the formation of conjugated dienes (220 +/- 8 vs. 82 +/- 7 min (mean +/- S.E)), showed a 13 times lower formation of lipid peroxides, a 97% reduction in macrophage degradation and close to 90% less decrease in LDL receptor binding following oxidation as compared with controls (P < 0.001 for all differences). The results demonstrate that although probucol provided a significant protection against Cu(2+)-induced oxidative modification of LDL, it lacked effect on the development of femoral atherosclerosis. The relevance of these observations for the proposed role of lipid oxidation in atherosclerosis is discussed.

Adult↗
PubMed1996

Integrated production of human insulin and its C-peptide.

The potential for the development of an integrated process for production of human insulin and its C-peptide in Escherichia coli has been investigated. Human proinsulin was produced intracellularly in E. coli fused to two synthetic IgG-binding domains (ZZ) derived from staphylococcal protein A. High expression levels (3 g/l culture) of the gene product, which accumulated as inclusion bodies, was obtained. Solubilization of inclusion bodies by oxidative sulfitolysis and subsequent renaturation was performed directly after cell lysis and pellet wash. IgG affinity chromatography was used for efficient recovery of pure proinsulin fusion protein in a single step. Monomers of the proinsulin fusion protein constituted approximately 70%. A single step conversion of the fusion protein into insulin and C-peptide by trypsin and carboxypeptidase B treatment was achieved by engineering the junction between proinsulin and its affinity handle, ZZ. Characterization of the cleavage products by reversed phase chromatography (RPC) verified that human insulin and C-peptide were generated and that the ZZ affinity handle was resistant to cleavage. Human insulin and C-peptide were recovered with high yields by preparative reversed-phase high performance liquid chromatography (RP-HPLC). The potential use of the presented scheme for large-scale production of recombinant insulin and/or its C-peptide is discussed.

Biotechnology↗
PubMed1996

Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients.

BACKGROUND: Bezafibrate has effects on lipid metabolism and haemostatic function. We undertook a double-blind, placebo-controlled intervention trial, the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), to establish whether bezafibrate (200 mg three times daily) could retard or prevent the progression of atherosclerotic lesions in dyslipidaemic male survivors of myocardial infarction who were younger than 45 years at the time of the event. METHODS: 92 patients completed an initial 3-month period of dietary intervention and were randomly assigned to treatment with bezafibrate or placebo. Dietary intervention continued throughout the trial. Coronary angiography was done at baseline and after 2 and 5 years. 81 patients (42 bezafibrate treated and 39 placebo treated) who underwent baseline angiography and at least one post-treatment angiogram were included in the efficacy analysis. The primary endpoint was change in mean minimum lumen diameter. FINDINGS: The mean minimum lumen diameter decreased from baseline to the last angiographic assessment (2 or 5 years) by 0.06 mm (95% CI 0.15 reduction to 0.01 increase) in the bezafibrate group and by 0.17 mm (0.33 reduction to 0.09 increase) in the placebo group. The treatment effect was therefore 0.13 mm (95% CI 0.10 to 0.15; p=0.049). Parallel treatment effects, although not statistically significant, were observed for the secondary angiographic endpoints (mean segment diameter 0.02 mm [0.01-0.04] and percentage stenosis -3.41% [-4.00 to -2.98]). The cumulative coronary event rate was significantly lower among bezafibrate-treated than among placebo-treated patients (three vs 11 patients; p=0.02). There were significant treatment effects of bezafibrate for serum concentrations of cholesterol (-9%; p<0.001), very-low-density-lipoprotein (VLDL) cholesterol (-35%; p<0.001), serum triglycerides (-31%; p<0.001), VLDL triglycerides (-37%; p<0.001), and plasma fibrinogen (-12%; p=0.001), whereas low-density (LDL) cholesterol concentrations did not change. High density lipoprotein (HDL) cholesterol increased significantly with bezafibrate (9%; p=0.02). INTERPRETATION: The results show that bezfibrate improves dyslipidaemia, lowers plasma fibrinogen, slows the progression of focal coronary atherosclerosis, and reduces coronary events in young survivors of myocardial infarction.

Adult↗
PubMed1996

Single-step trypsin cleavage of a fusion protein to obtain human insulin and its C peptide.

The kinetics for trypsin cleavage of different fusion proteins, consisting of human proinsulin and two IgG-binding domains (ZZ), were investigated. To achieve simultaneous removal of the fusion tag and processing of proinsulin to insulin and free C peptide, three versions of the ZZ-proinsulin fusion protein were generated, having different trypsin-sensitive cleavage sites, Arg, Lys-Arg or Lys. The ZZ-proinsulin fusion proteins which accumulated as inclusion bodies in Escherichia coli cells were solubilized, refolded and purified by IgG affinity chromatography. The yield of ZZ-proinsulin monomers exceeded 90%. The kinetics for the trypsin cleavage revealed unexpected differences when comparing the three linkers and it was found that the single arginine linker was most efficiently processed. Characterization of the cleavage products by reverse-phase chromatography, mass spectrometry and N-terminal sequencing verified that human insulin and C peptide were generated. The results demonstrate that high yields of native insulin, C peptide and affinity tag can be achieved by simultaneous cleavage of a fusion protein at three different trypsin-sensitive sites in a single step. The implications for production and recovery of various recombinant proteins are discussed.

Amino Acid Sequence↗
PubMed1996

Electrophysiological tests of autonomic function in patients with idiopathic autonomic failure syndromes.

Three electrophysiological tests of autonomic function were performed in patients with autonomic nervous system dysfunction to define test sensitivities and specificities. The skin sympathetic response, Valsalva ratio, and heart rate variation with deep breathing were studied in 10 patients with multiple system atrophy (MSA) and in 7 patients with pure (also called progressive or primary) autonomic failure (PAF); control subjects were 17 normal individuals of similar age. Thirteen patients had abnormal skin sympathetic responses, and 16 had abnormal Valsalva ratios. Fourteen patients had an abnormal variation of the heart rate with deep breathing. Taking the three tests together, binary logistic regression for distinguishing between patients and normal subjects correctly classified 91% of the 33 individuals for whom there were complete data with sensitivity of 88% and specificity of 94%. However, only 69% of the patients could be correctly classified by a logistic regression for discriminating between MSA and PAF. Electromyography (EMG) studies showed that 7 of 8 patients with MSA but only 2 of 7 patients with PAF (both multiparous women) had denervation of the rectal sphincter muscle. The EMG study is, therefore, valuable in men, but has a high false positive rate in women, probably because of pudendal nerve injury from parturition.

Aged↗
PubMed1996

Different cytogenetic patterns in skeletal breast cancer metastases.

Short-term cultures of breast cancer metastases to bone from two patients were analyzed cytogenetically. One metastasis had a complex hypotriploid karyotype with numerous marker chromosomes, whereas the other had simple karyotypic changes in three unrelated clones, 46,XX,t(4;11 )(p14;p 13)/45,XX,- 19/46,XX,del(3)(p 13p23), suggesting that the metastasis had originated from a simultaneous invasion of multiple cells from the primary tumor. The metastasis with complex chromosomal aberrations developed quickly as part of a clinically aggressive disease, whereas that with simple changes developed more than 20 years after the initial breast cancer diagnosis. Our findings therefore indicate that the tumor karyotype may play a role in determining the clinical course in patients with breast cancer.

Bone Neoplasms↗
PubMed1996

EMG activities of the quadratus lumborum and erector spinae muscles during flexion-relaxation and other motor tasks.

OBJECTIVE: The aim of this study was to provide new information on the myoelectrical activation of the quadratus lumborum, the deep lateral and the superficial medial lumbar erector spinae, the psoas, and the iliacus muscles in various motor tasks. DESIGN: An intramuscular electromyographic study was performed. BACKGROUND: The contribution of individual deep trunk muscles to the stability of the lumbar spine is relatively unknown in different tasks, including the flexion-relaxation phenomenon. METHODS: Seven healthy subjects participated. Fine-wire electrodes were inserted with a needle guided by ultrasound. RESULTS: The highest activity observed for quadratus lumborum and deep lateral erector spinae occurred in ipsilateral trunk flexion in a side-lying position and for superficial medial erector spinae during bilateral leg lift in a prone position. Quadratus lumborum and deep lateral erector spinae were activated when the flexion-relaxation phenomenon was present for superficial medial erector spinae, i.e. when its activity ceased in the latter part of full forward flexion of the trunk, held relaxed and kyphotic. CONCLUSIONS: In general, the activation of the investigated muscles showed a high degree of task specificity, where activation of a certain muscle was not always predictable from its anatomical arrangement and mechanical advantage.

Journal Article↗
PubMed1996

Transverse-field activation mechanism in magnetic stimulation of peripheral nerves.

The activating function of peripheral nerves in magnetic stimulation is thought to be the gradient of the induced electric field component parallel to the nerve. This implies that there are several orientations of the coil that should not excite nerves. We show that these orientations, however, often yield high-amplitude and even supramaximal muscle response, indicating that the model of the activating function has to be modified. We propose that the electric field component perpendicular to the nerve is responsible for these unexpected muscle responses. Our conclusion is based on practical experiments with different coils and on computer simulations of the induced electric field and its gradient.

Electric Stimulation↗
PubMed1996

Inverse relation between the concentration of low-density-lipoprotein vitamin E and severity of coronary artery disease.

Oxidation of low-density lipoprotein (LDL) is believed to play an important role in atherogenesis, and antioxidant vitamins are thought to protect against coronary artery disease (CAD). We investigated whether the vitamin E concentrations in serum and LDL were associated with the severity of CAD as assessed by a semiquantitative scoring system in which coronary angiograms are analyzed for the number and size of distinct stenotic lesions (global stenosis score). The study group consisted of 64 consecutive male survivors of myocardial infarction aged < 45 y. Lipid-adjusted serum and LDL vitamin E concentrations were significantly lower in the patients than in 35 age-matched male control subjects, whereas the absolute serum and LDL vitamin E concentrations did not differ significantly. No associations were found between the serum concentration or lipid-adjusted serum values of vitamin E and the stenosis score. In contrast, significant inverse correlation was found between the LDL vitamin E concentration, whether adjusted to the lipid (r=-0.477,P<0.001) or protein (r=-0.375, P<0.01) content of LDL, and the global coronary stenosis score. We conclude that a low LDL vitamin E concentration might play a role in the development of stenoses in coronary arteries and may contribute to clinically manifest CAD.

Adult↗
PubMed1996

Secondary preventive potential of lipid-lowering drugs. The Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).

Current experience from coronary angiographic trials using different treatment regimens such as lifestyle changes, resins, nicotinic acid and statins, shows that progression of atheroma can be retarded, and that regression can sometimes be induced, by a marked lowering of LDL-cholesterol. Young post-myocardial infarction patients, however, usually exhibit a multiplicity of metabolic risk factors with dyslipidaemias, predominantly hypertriglyceridaemia, and disturbances of glucose-insulin homeostasis and of the haemostatic system. These factors, together coupled with coronary angiographic data showing that the degree of dyslipidaemia is related to the extent and degree of coronary atherosclerosis, and the fact that rapid progression of coronary atherosclerosis was foreseen in this group of patients, resulted in the initiation of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) in 1985. BECAIT was a 5-year, double-blind, placebo-controlled study of bezafibrate (200 mg three times daily) and dietary intervention in dyslipidaemic male survivors of myocardial infarction below 45 years of age. The angiographic analysis included 81 patients (42 bezafibrate and 39 placebo) who underwent baseline and at least one post-treatment angiogram, at 2 and 5 years. Changes in mean minimum lumen diameter indicated that there was 0.13 mm less (95% Cl: 0.10; 0.15) disease progression in focal lesions in the bezafibrate group than in the placebo group (P = 0.049). Parallel, but non-statistically significant, treatment effects were observed for mean segment diameter and percent stenosis. Three patients treated with bezafibrate and 11 patients in the placebo group suffered coronary events during the course of the trial (P = 0.02 logrank test). The angiographic effects of bezafibrate were accompanied by statistically significant reductions in serum cholesterol and triglycerides. Furthermore, plasma fibrinogen levels were significantly reduced and HDL-cholesterol concentration increased but there was no net change in LDL-cholesterol. These findings show that bezafibrate slowed the progression of focal coronary atherosclerosis to a degree that is comparable to that achieved with the statins in angiographic trials such as MAAS and REGRESS. Bezafibrate also reduced the occurrence of coronary events in young post-infarction victims. Like BECAIT, analyses of data from the NHLBI type II study, CLAS, POSCH and MARS provide evidence for the role of triglyceride-rich lipoproteins in the progression of coronary artery disease. Retardation of progression of atherosclerosis and a reduction in coronary events is, therefore, possible without reducing LDL-cholesterol.

Adult↗
PubMed1996

A volume-conduction analysis of magnetic stimulation of peripheral nerves.

Magnetic stimulation is a method to study several nervous disorders as well as the intact nervous system in humans. Interest in magnetic stimulation of peripheral nerves has grown rapidly, but difficulties in locating the site of excitation have prevented it from becoming a routine clinical tool. It has been reasoned that the activating function of long and straight nerves is the first spatial derivative of the electric field component parallel to the nerves. Therefore, to predict the site of activation, one has to compute this field feature. We describe here an analytical mathematical model and investigate the influence of volume-conductor shape on the induced field. Predictions of the site of activation are given for typical stimulation coil arrangements and these results are compared with experimental and literature data. Comparisons suggest that the activating function is not simply the spatial gradient of the induced electric field, but that other mechanisms are also involved. The model can be easily utilized in the search for more efficient coil constructions and improved placements with respect to the target nerves.

Computer Simulation↗
PubMed1996

Paroxetine and amitriptyline in the treatment of depression in general practice.

A total of 144 outpatients in general practice in Denmark, aged 18-65 years and diagnosed as suffering from depression with a HAMD-17 score of 15 or more, were included in this 8-week double-blind, randomised, multicentre, controlled, parallel group comparison of paroxetine versus amitriptyline. The purpose of the study was primarily to evaluate efficacy and tolerance of treatment. In addition, focus was added on weight change and subjective well-being. The efficacy results showed equal effect of both drugs. However, paroxetine was tolerated better than amitriptyline, and this difference reached the level of significance when four non-evaluable patients were taken out of the analysis. Moreover, there was a significant weight increase in the amitriptyline group and no significant weight change in the paroxetine group. There was no difference between the groups as regards subjective well-being as measured by the VAS. In conclusion, paroxetine is an effective and well-tolerated antidepressant, and well-suited for the treatment of depression in general practice.

Adolescent↗
PubMed1996

Human monocytes/macrophages release TNF-alpha in response to Ox-LDL.

The uptake of oxidatively modified low density lipoprotein (Ox-LDL) by intimal macrophages is believed to play a key role in the development of atherosclerosis. The present study demonstrates that Ox-LDL in low concentrations activates monocyte/macrophage release of factors that stimulate smooth muscle cell growth, whereas higher concentrations are inhibitory. Exposure of monocytes/macrophages to 8 micrograms/mL Ox-LDL increased expression of tumor necrosis factor-alpha (TNF-alpha) mRNA but had no effect on interleukin-1 beta, platelet-derived growth factor B and heparin-binding epidermal growth factor-like mitogen mRNA levels. Ox-LDL also stimulated monocyte/macrophage release of TNF-alpha in a dose-dependent manner, with maximal effect at an LDL concentration of 8 micrograms/mL. Addition of TNF-alpha-blocking antibodies to conditioned medium from monocytes/ macrophages already exposed to Ox-LDL reduced mitogenic activity by 44.7 +/- 8.4% (P < .005). Stimulation of TNF-alpha release by Ox-LDL was associated with activation of transcription factor AP-1, whereas the activity of transcription factor nuclear factor-kB remained unchanged. These findings suggest that enhanced secretion of TNF-alpha by macrophages exposed to Ox-LDL may be involved in the formation of atherosclerotic lesions.

Cell Division↗