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Biomedical subjects

J Nilsson

Publications and source records attributed to J Nilsson.

At least 253 records · Page 14Linked to original sources

cDNA cloning of human-milk bile-salt-stimulated lipase and evidence for its identity to pancreatic carboxylic ester hydrolase.

We have isolated and sequenced cDNA clones covering the entire coding sequence of human-milk bile-salt-stimulated lipase, as well as 996 nucleotides of the 3' end of the pancreatic enzyme carboxylic ester hydrolase. The deduced amino acid sequence of the lipase starts with a 23-residue leader peptide. The open reading frame continues with 722 amino acid residues. The sequence contains in the C-terminal part a proline-rich repeat, 16 repeats of 11 amino acid residues each. The mRNA was estimated to be approximately 2500 nucleotides from Northern blot and of similar size in mammary and pancreatic tissues. Data obtained indicate that the lipase and the carboxylesterase are identical and coded for by the same gene. The cDNA is 2428 bases long, which indicates that a near full-length copy of the transcript has been isolated. Comparisons with other enzymes show that the lipase is a new member of the supergene family of serine hydrolases. It is not only closely related (and in its N-terminal half virtually identical) to lysophospholipase from rat pancreas and cholesterol esterase from bovine pancreas, but also shows a high degree of similarity to several esterases, e.g. acetylcholine esterase. In contrast, no such similarity could be found to typical lipases.

Adipose Tissue↗

Clinical and electromyographic studies of postpoliomyelitis muscular atrophy.

Eleven patients with progressive weakness following polio (postpoliomyelitis muscular atrophy syndrome) were compared electromyographically with nine patients who had stable strength following polio. Abnormalities included (1) abnormal motor unit characteristics in many muscles indicating widespread loss of motor neurons and reinnervation in muscles, including many not clinically affected by the polio; (2) prevalent spontaneous denervation potentials; and (3) abnormal single-fiber electromyographic jitter. These electromyographic abnormalities were similar in progressive and stable postpoliomyelitis patients even when muscles were separated by strength, stability, age and duration of the postpoliomyelitis state. Postpoliomyelitis muscular atrophy appears to be the clinically apparent end of the spectrum of abnormalities existing in all postpoliomyelitis patients.

Action Potentials↗

Effects of coil design on delivery of focal magnetic stimulation. Technical considerations.

The localization of effects from magnetic coil stimulation is not immediately obvious. We measured the magnetic fields produced by several different coils and compared the results with theoretical calculations. Magnetic stimuli were delivered from a Cadwell MES-10 magnetic stimulator using 3 circular coils (one 9 cm in diameter; two with an angulated extension, 5 and 9 cm in diameter) and twin oval coils arranged in a butterfly shape (each coil approximately 4 cm in diameter) and from a Novametrix Magstim 200 using two circular flat-spiral coils (6.7 and 14 cm in diameter). Peak-induced strength of the magnetic field was recorded with a measuring loop (1 cm in diameter) at different distances from the center of the coil. When the measuring loop was moved in the same plane laterally from the center of the coil, for all coils except the butterfly-shaped coil, the field was highest in the center and fell off near the circumference of the coil. The field dropped progressively when measurements were made more distant from the plane of the coils. The electric field induced from the magnetic coil could be calculated from the coil geometry. For all coils except the butterfly-shaped coil, the largest electric field was at the circumference of the coils. The 6.7 cm flat-spiral coil induced currents similar to those induced by the larger coils but more focally. The butterfly-shaped coil induced the largest currents under its center, where the circumferences of the two component coils come together. The component of the electric field parallel to the wire in the center of this coil was the largest and most localized.

Electric Stimulation↗

Effect of probucol treatment on the susceptibility of low density lipoprotein isolated from hypercholesterolemic patients to become oxidatively modified in vitro.

Lipid accumulation in monocyte-originated macrophages in the subendothelial space is an important characteristic of atherosclerotic lesions. Several lines of evidence have indicated that this accumulation occurs as a result of lipid peroxidation. In the present study the ability of probucol to prevent oxidation of low density lipoprotein (LDL) was investigated in 20 hypercholesterolemic individuals taking part in the Probucol Quantitative Regression Swedish Trial (PQRST). The effect of Cu2(+)-induced oxidation of LDL on degradation by macrophages, binding to LDL receptors on fibroblasts and LDL TBARS content was analysed. With LDL isolated from patients on diet alone oxidation led to a 44.3% decreased binding to fibroblasts (P less than 0.001), a ninefold increased uptake in macrophages (P less than 0.001) and a twentyfold increase in TBARS content (P less than 0.001) as compared to native LDL. These values were essentially the same during treatment with cholestyramine alone. However, during treatment with probucol plus cholestyramine exposure of LDL to Cu2+ resulted in an increase in TBARS which was less than 50% (P less than 0.02) of that observed during the other two treatment periods. Furthermore, probucol treatment abolished more than 70% of the decrease in B,E receptor binding to fibroblasts (P less than 0.05) and more than 90% of the increased degradation by macrophages (P less than 0.001) of Cu2+ oxidatively modified LDL.

Aged↗

Oxidized low density lipoprotein induces differentiation and adhesion of human monocytes and the monocytic cell line U937.

Hypercholesterolemia is a major risk factor for development of atherosclerosis. In experimental animals fed a high-cholesterol diet, monocytes adhere to the arterial endothelium and penetrate into the intima where they differentiate into macrophages and ingest lipids thus giving rise to fatty streaks, the earliest type of atherosclerotic plaque. Macrophages express few receptors for normal low density lipoprotein (LDL) but can take up oxidized LDL by way of a scavenger receptor. The present study was designed to investigate the possible role of oxidized LDL in recruitment of resident intimal macrophages. We found that oxidized LDL induced enhanced expression of major histocompatibility complex class II molecules on human monocytes and U937 cells, a well-established system for studies of monocytic differentiation. Oxidized LDL also induced enhanced expression of the surface antigen LeuM3 but caused decreased expression of CD4 antigen, a pattern compatible with expression of a more-differentiated macrophage-like phenotype. Oxidized LDL also initiated aggregation of monocytes and U937 cells and stimulated adhesion of U937 cells to cultured endothelial cells. The results indicate that oxidized LDL may contribute to development of atherosclerosis by inducing adhesion of monocytes to the arterial intima and by stimulating intimal monocytes to differentiate into resident macrophages.

Cell Adhesion↗

Calcitonin gene-related peptide stimulates proliferation of human endothelial cells.

The effects of the vasoactive perivascular neuropeptides calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) on proliferation of cultured human umbilical vein endothelial cells (HUVECs) were investigated. CGRP was shown to increase both cell number and DNA synthesis, whereas NKA, NPY, and VIP were ineffective. 125I-labeled CGRP was shown to bind to HUVECs and this binding was displaced by addition of unlabeled CGRP, suggesting the existence of specific CGRP receptors. The effect of CGRP on formation of adenosine 3',5'-cyclic monophosphate (cAMP) and inositol phosphates (InsP), two intracellular messengers known to be involved in regulation of cell proliferation, was investigated. CGRP stimulated cAMP formation but was without effect on the formation of InsP. Proliferation, as well as cAMP formation, was also stimulated by cholera toxin. Basic fibroblast growth factor stimulated growth without affecting cAMP or InsP formation, whereas thrombin, which increased InsP formation, did not stimulate proliferation. We thus suggest that CGRP may act as a local factor stimulating proliferation of endothelial cells; that the mechanism of action is associated with cAMP formation; and that this effect of CGRP may be important for formation of new vessels during physiological and pathophysiological events such as ischemia, inflammation, and wound healing.

Calcitonin↗

Decreased mitogenic activity in hypercholesterolaemic plasma.

The mitogenic activity on rat aortic smooth muscle cells of plasma from patients with hypercholesterolaemia was compared to that of plasma from a normocholesterolaemic control group and to that obtained after lowering plasma cholesterol levels in the hypercholesterolaemic groups with simvastatin. Mean plasma total and low density lipoprotein cholesterol and apolipoprotein B concentrations in the two groups were 8.62 +/- 0.62 mmol l-1, 7.03 +/- 0.56 mmol l-1 and 1.96 +/- 0.14 g l-1, respectively, and 5.05 +/- 0.20 mmol l-1, 3.42 +/- 0.18 mmol l-1 and 0.80 +/- 0.04 g l-1, respectively, all differences significant at P less than 0.001. During simvastatin treatment these parameters decreased to 5.70 +/- 0.35, 4.15 +/- 0.33 mmol l-1 and 1.33 +/- 0.08 g l-1, all changes being significantly (P less than 0.001) lower than before treatment. Hyperlipidaemic plasma in untreated patients had a significantly lower mitogenic activity than normolipidaemic control plasma as measured by autoradiographic labelling of DNA after 3H-thymidine incorporation, 25.7 +/- 1.8% vs. 32.0 +/- 1.9%, P less than 0.05. Lowering plasma cholesterol levels in the hyperlipidaemic patients 'normalized' the mitogenic activity to 32.3 +/- 1.6%, P less than 0.05. The reason for this unexpected finding is not known.

Adult↗

H-reflex recovery curve and reciprocal inhibition of H-reflex in different kinds of dystonia.

We studied the H-reflex recovery curve and reciprocal inhibition of the H-reflex bilaterally in the upper limb of 5 patients with generalized dystonia, 5 patients with blepharospasm, 10 patients with spasmodic torticollis, and 14 patients with writer's cramp. We compared the results with those obtained from a group of healthy volunteers. The recovery curve of the H-reflex was normal in patients with writer's cramp or blepharospasm, but showed an increase of the physiologic recovery at a 200 msec delay in patients with spasmodic torticollis or generalized dystonia. Reciprocal inhibition of the H-reflex showed a decrease in the amount of inhibition in all the patient groups and a facilitation of the H-reflex during the 3rd period of inhibition in the patients with spasmodic torticollis or generalized dystonia.

Adult↗

Low density lipoprotein-induced growth of U937 cells: a novel method to determine the receptor binding of low density lipoprotein.

U937 is a monocytic cell-line originally derived from a histiocytic lymphoma. In serum-free medium the growth of U937 cells was stimulated by addition of low density lipoprotein (LDL). Methylation of LDL impaired its ability to be taken up in U937 cells as well as the capacity to stimulate the growth of these cells. Pretreatment of U937 cells with a monoclonal antibody against the LDL receptor was also found to completely block the growth-promoting effect of LDL. Exposure of U937 cells to liposomes with a lipid composition similar to that of LDL did not stimulate the growth rate. These findings demonstrate that growth of U937 cells under serum-free conditions is related to the amount of LDL ingested by the cells and that this uptake is mediated by binding of LDL to the LDL receptor. To determine if LDL-induced growth of U937 cells can be used to identify LDL with decreased binding to the LDL receptor, U937 cells were incubated with LDL isolated from a patient with familial defective apolipoprotein B-100 and from subjects with various lipoprotein phenotypes. LDL containing defective apolipoprotein B-100 was found to be less than half as effective as LDL from normolipidemic controls in stimulating growth of U937 cells. LDL isolated from patients with hyperlipoproteinemia type IIa and IV did not differ from normal LDL in their ability to promote growth of U937 cells. The present results suggest that LDL-induced growth of U937 cells may be used as an assay to identify defective receptor binding of LDL.

Cell Division↗

Correlation between plasma levels of growth factors and von Willebrand factor.

Intimal proliferation of smooth muscle cells is an important characteristic of developing atherosclerotic lesions and late occlusion of venous bypass grafts. Platelet-derived growth factor, released from aggregating platelets at sites of endothelial injury, has been suggested as a main factor responsible for intimal hyperplasia. The von Willebrand factor is a platelet binding protein secreted by endothelial cells and increased plasma levels of this factor has been identified as a marker of endothelial injury. In the present study we have analysed plasma levels of von Willebrand factor and growth factors in healthy controls, young post-infarction patients and patients with recent coronary bypass surgery. The results demonstrate a significant correlation between plasma growth factor activity and the level of von Willebrand factor (R = 0.52, p less than 0.01) and support the notion of a coupling between endothelial injury and release of platelets mitogens.

Adult↗

Optimal stimulus duration for the H reflex.

Authorities advocate different stimulus durations to produce an H reflex. In order to find the optimal stimulus duration for recording H reflexes, the recruitment curves for H reflexes and M responses were studied in 10 healthy subjects. The H reflex was recorded in the upper and lower extremities, and the durations of the electrical stimulus used ranged from 0.1 to 3 msec. The amplitude of the H reflex and the relation between the H reflex and M response changed with stimulus duration. H reflexes are brought out to advantage using a stimulus duration between 0.5 and 1 msec.

Adult↗

Lack of correlation between the apolipoprotein B XbaI polymorphism and blood lipid levels in a Swedish population.

The possible connections between the apolipoprotein B (apo B) XbaI polymorphism and the serum levels of total cholesterol, triglycerides, LDL, HDL and apo B have been investigated among 187 randomly selected subjects from Gothenburg, Sweden. The interferences of age and sex on the serum lipoproteins and apo B concentrations were considered. Using multiple regression analysis, we compared the different lipid levels and the levels of apo B with the genotypes X1X1, X1X2 and X2X2 (X1 = without the XbaI restriction site, X2 = with the site), with age and with sex and with those factors combined with each other. A significantly higher concentration of serum cholesterol and LDL among men than among women was found and total serum cholesterol, LDL and apo B were positively correlated with age. The allele frequency of the XbaI polymorphism in the sample was 0.45 for the allele without the XbaI restriction site. No correlation was found between the apo B genotypes and the levels of serum lipoproteins or apo B.

Adult↗

Vasoactive intestinal polypeptide stimulates cell proliferation and adenylate cyclase activity of cultured human keratinocytes.

An increasing body of evidence has suggested trophic effects of peripheral nerves. In this study, the growth stimulatory properties of the sensory neuropeptides vasoactive intestinal polypeptide (VIP), substance P (SP), calcitonin generelated peptide (CGRP), and somatostatin (SOM) on cultured human keratinocytes were investigated. It was shown that VIP, in the presence of lethally treated 3T3 fibroblast feeder cells and epidermal growth factor (EGF), stimulated proliferation of keratinocytes in a dose-dependent manner, whereas SP, CGRP, and SOM were ineffective. VIP stimulated adenylate cyclase activity in membranes obtained from cultured keratinocytes in a dose-dependent manner, indicating an involvement of cAMP as second messenger in this reaction. Furthermore, 125I-labeled VIP was shown to bind to cultured keratinocytes and this binding could be displaced by addition of unlabeled VIP, suggesting the presence of specific receptors. It is therefore possible that VIP, released from sensory nerve endings in the skin, may act as a local mitogenic factor for human keratinocytes by stimulating adenylate cyclase activity via specific VIP receptors.

Adenylyl Cyclases↗