M. Gidlund - Academia.edu (original) (raw)
Papers by M. Gidlund
Cellular Immunology, 1979
Injection of mice with several interferon inducers, Newcastle Disease virus, polyinosinic-polycyt... more Injection of mice with several interferon inducers, Newcastle Disease virus, polyinosinic-polycytidylic acid and tilorone resulted in an increase in spleen cell cytotoxicity for 5'chromium-labeled mouse YAC tumor target cells in 4-hr in vitro assays. This increase in spleen cell cytotoxicity was abrogated by injection of mice with potent anti-mouse interferon globulin. Inoculation of mice with mouse interferon (but not human leucocyte or mock interferon preparations) also resulted in a marked enhancement of spleen cell cytotoxicity. The extent of enhancement of spleen cell cytotoxicity was directly proportional to the amount of interferon injected and a significant increase was observed after inoculation of as little as IO3 to IO4 units of interferon. An effect could be detected as soon as 1 hr after injection of interferon. The increase of spleen cell cytotoxicity after inoculation of an interferon inducer was not due to a localization and accumulation of cytotoxic cells in the spleen but reflected a general increase in cytotoxic cell activity in various lymphoid tissues (except the thymus). The splenic cytotoxic cells from interferon or interferon-inducer-injected mice had the characteristics of natural killer (NK) cells since (i) interferon enhanced spleen cell cytotoxicity in athymic (nuinu) nude mice, (ii) classical spleen cell fractionation procedures by nylon wool columns, anti-Thy 1.2 serum plus complement, anti-Ig columns, and depletion of FcR+ rosette-forming cells, failed to remove the effector cells generated in vivo or in vitro. Therefore like NK cells, interferon-induced cytotoxic cells lack the surface markers of mature T and B lymphocytes, are not adherent, and are devoid of avid Fc receptors. Furthermore like NK cells, the spleen cells from interferon-treated mice lysed various target cells (known for their sensitivity to NK cells) without H-2 or species restriction. Incubation in vitro of normal spleen cells with interferon also resulted in an increase in cytotoxicity for YAC tumor cells. We conclude that interferon acts directly on NK cells and enhances the inherent cytotoxic activity ofthese cells.
the metabolism of s-adenosylmethionine (SAM) cycle, the major methyl donor source for transmethyl... more the metabolism of s-adenosylmethionine (SAM) cycle, the major methyl donor source for transmethylation reaction, can suppress T cell immunity. By giving excess SAM, both TCR-mediated T cell proliferation and B cell proliferation were inhibited in dose-dependent manner. Methylthioadenosine (MTA) is a byproduct of SAM metabolism and serves as a methyl-transferase inhibitor. We demonstrate that MTA inhibits TCR-mediated and antigenic specific-T cell responses including T cell activation markers, Th1/Th2 cytokines and TCR-related signaling events. Interestingly, we found that MTA phosphorylase activity, the major enzyme to metabolize MTA, was significant higher in B cells than in T cells. It is consistence with our results that B cell immunity was not suppressed by MTA. These studies demonstrate the central role of SAM-dependent methylation in immune responses and provide a simple approach to altering lymphocyte metabolism and potentially T cell mediated autoimmune diseases such as SLE and MS.
Journal of Fluorescence, 2010
Low-Density Lipoprotein (LDL), often known as "bad cholesterol" is one of the responsible to incr... more Low-Density Lipoprotein (LDL), often known as "bad cholesterol" is one of the responsible to increase the risk of coronary arterial diseases. For this reason, the cholesterol present in the LDL particle has become one of the main parameters to be quantified in routine clinical diagnosis. A number of tools are available to assess LDL particles and estimate the cholesterol concentration in the blood. The most common methods to quantify the LDL in the plasma are the density gradient ultracentrifugation and nuclear magnetic resonance (NMR). However, these techniques require special equipments and can take a long time to provide the results. In this paper, we report on the increase of the Europium emission in Europium-oxytetracycline complex aqueous solutions in the presence of LDL. This increase is proportional to the LDL concentration in the solution. This phenomenum can be used to develop a method to quantify the number of LDL particles in a sample. A comparison between the performances of the oxytetracycline and the tetracycline in the complexes is also made.
Clinics, 2010
OBJECTIVES: To investigate whether oxidized low-density lipoprotein is a suitable predictor of pe... more OBJECTIVES: To investigate whether oxidized low-density lipoprotein is a suitable predictor of peripheral arterial disease severity. The role of oxidized low-density lipoprotein in the pathogenesis of atherosclerosis has already been investigated. Its relevance as a predictor of the appearance and worsening of coronary arterial disease is also well known. However, the same is not true regarding peripheral arterial disease. METHOD: Eighty-five consecutive patients with an ankle-brachial pressure index (ABPI) < 0.9 and the presence of either intermittent claudication or critical lower leg ischemia were included. The plasma level of IgG autoantibodies against oxidized low-density lipoprotein was evaluated through an enzyme-linked immunosorbent assay. The results were categorized into quartiles according to the ankle-brachial pressure index (a marker of peripheral arterial disease severity), and significant differences were investigated with the Kruskal-Wallis test. RESULTS: There was no significant difference between the quartiles for this population (p = 0.33). No correlation was found between the ankle-brachial pressure index and oxidized low-density lipoprotein levels in subjects with clinically evident peripheral arterial disease with a wide range of clinical manifestations. CONCLUSIONS: Oxidized low-density lipoprotein is not a good predictor of peripheral arterial disease severity.
Archives of Internal Medicine, 1994
Oxidation of low-density lipoprotein is believed to be an important step in the pathogenesis of a... more Oxidation of low-density lipoprotein is believed to be an important step in the pathogenesis of atherosclerosis. The purpose of the present study was to determine whether antibody against oxidized low-density lipoprotein, reported to be associated with the progression of carotid atherosclerosis, is predictive of cardiac death and nonfatal myocardial infarction. Serum samples from 135 cases and their controls, drawn at entry from middle-aged dyslipidemic men participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil, were tested for immunoglobulin G class antibodies against oxidized low-density lipoprotein by enzyme-linked immunosorbent assay. The mean antibody level, expressed in optical density units, was significantly higher in cases than in controls (0.412 vs 0.356, P = .002). After adjustment for age, smoking, blood pressure, and high-density lipoprotein cholesterol level, there was a 2.5-fold increased risk (95% confidence interval, 1.3 to 4.9) of a cardiac end point in the highest tertile of antibody level vs the lowest tertile (P = .005 for trend). Elevated levels of antibodies against oxidized low-density lipoprotein were predictive of myocardial infarction. The effect was independent of low-density lipoprotein cholesterol levels, and the joint effect was additive. Elevated antibody levels modified the effects of classic coronary risk factors.
The American Journal of Cardiology, 2002
ABSTRACT Oxidative low-density lipoprotein (LDL) damage caused by oxidants present in cigarette s... more ABSTRACT Oxidative low-density lipoprotein (LDL) damage caused by oxidants present in cigarette smoke may be involved in the pathogenesis of coronary heart disease,(1) but there is a controversy in published reports on this subject. Gouaze et al(2) demonstrated increased oxidizability in smokers, Siekmeier et al(3) could not confirm these results, and Chen and Loo(4) found an antioxidant property of cigarette smoke extract by measuring its effect on LDL oxidizability in vitro. We evaluated the contribution of cigarette smoking on LDL oxidizability and,plasma levels of antioxidized LDL in a well-defined healthy population of normolipidemic smokers. Blood samples were drawn a few minutes after subjects smoked 1 cigarette to ensure higher blood levels of oxidative products from cigarette smoke.(5).
Latin America Optics and Photonics Conference, 2010
Abstract: Low Density Lipoprotein (LDL) or bad cholesterol, becomes even more dangerous when it i... more Abstract: Low Density Lipoprotein (LDL) or bad cholesterol, becomes even more dangerous when it is oxidized. In this paper we report an increase of the Europium Chlortetracycline complex emission in the presence of oxidized LDL. ©2010 Optical Society of America OCIS ...
Scandinavian Journal of Immunology, 1987
Several sets of data indicate the possibility that carbohydrate moieties on the target cell arc i... more Several sets of data indicate the possibility that carbohydrate moieties on the target cell arc important structures in natural killer (NK) cell-mediated lysis. Striking changes in the NK susceptibility of targets can be induced in several systems involving in vitro differentiation of tumour eell lines. The effect on target cells of tbe glycosylation inhibitor tunicamyein. which acts by blocking the dolichol-dependeni asparagine-linked glyeosylation pathway was investigated. Using several different tumour cell lines we can conclude that: (a) asparagine-linked carbohydrate chains do noi contribute directly to NK susceptibility, (b) induced differentiation may or may not be linked with a change in NK susceptibility, and (c) secondary changes caused by tunicamycin treatment may lead to alterations in the gangliosides. a finding that is positively correlated with decreased NK susceptibility.
Atherosclerosis Supplements, 2009
Atherosclerosis Supplements, 2009
Atherosclerosis Supplements, 2006
Haematology and blood transfusion, 1981
Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2003
Oxidized low-density lipoproteins (oxLDL) and protein fractions obtained by size exclusion chroma... more Oxidized low-density lipoproteins (oxLDL) and protein fractions obtained by size exclusion chromatography of oxLDL were tested for vascular permeability effects on topical application to the hamster cheek pouch. The hamster cheek pouch was prepared for intravital microscopy observations of macromolecular leakage at post capillary venules (=leaks) with FITC-dextran as tracer. OxLDL (0.1 mg/ml), PAF (platelet activation factor, 50-100 nM) and protein fractions of oxLDL (10 microg/ml) were applied topically to hamster cheek pouches. Application of oxLDL and PAF resulted in reversible increases in the number of leaks. The PAF-antagonist WEB 2170, L-NAME and a beta(2)-adrenoceptor agonist inhibited (P<0.01) almost completely the macromolecular leakage induced with oxLDL or PAF. Protein fractions were found to be more effective than unfractionated oxLDL in inducing plasma leakage as calculated on mg/ml-basis. Hamster oxLDL is a potent inducer of macromolecular leakage increase in the h...
Journal of lipid research, 1994
Estrogen treatment raises plasma high density lipoprotein (HDL) levels, which may reduce cardiova... more Estrogen treatment raises plasma high density lipoprotein (HDL) levels, which may reduce cardiovascular risk. To identify the responsible mechanisms as well as the importance of the route of administration, we treated eight healthy postmenopausal women in a double-blind crossover study with three treatments for 6 weeks each: oral estradiol, 2 mg daily; transdermal estradiol, 0.1 mg twice weekly; and placebo. At the end of each treatment, apoA-I of HDL2 (d 1.063-1.125 g/ml) and HDL3 (d 1.125-1.210 g/ml) was endogenously labeled by a constant intravenous infusion of trideuterated leucine. HDL2 and HDL3 were separated by preparative ultracentrifugation. The pool sizes and enrichment curves of HDL apoA-I were used to calculate production rates and fractional catabolic rates (FCR). Oral estradiol increased the levels of HDL2 apoA-I by 37% (P < 0.005) and of HDL3 apoA-I by 11% (P < 0.05). These increased apoA-I levels resulted entirely from increased production, by 36% for HDL2 (P &...
Haematology and blood transfusion, 1983
Cellular Immunology, 1979
Injection of mice with several interferon inducers, Newcastle Disease virus, polyinosinic-polycyt... more Injection of mice with several interferon inducers, Newcastle Disease virus, polyinosinic-polycytidylic acid and tilorone resulted in an increase in spleen cell cytotoxicity for 5'chromium-labeled mouse YAC tumor target cells in 4-hr in vitro assays. This increase in spleen cell cytotoxicity was abrogated by injection of mice with potent anti-mouse interferon globulin. Inoculation of mice with mouse interferon (but not human leucocyte or mock interferon preparations) also resulted in a marked enhancement of spleen cell cytotoxicity. The extent of enhancement of spleen cell cytotoxicity was directly proportional to the amount of interferon injected and a significant increase was observed after inoculation of as little as IO3 to IO4 units of interferon. An effect could be detected as soon as 1 hr after injection of interferon. The increase of spleen cell cytotoxicity after inoculation of an interferon inducer was not due to a localization and accumulation of cytotoxic cells in the spleen but reflected a general increase in cytotoxic cell activity in various lymphoid tissues (except the thymus). The splenic cytotoxic cells from interferon or interferon-inducer-injected mice had the characteristics of natural killer (NK) cells since (i) interferon enhanced spleen cell cytotoxicity in athymic (nuinu) nude mice, (ii) classical spleen cell fractionation procedures by nylon wool columns, anti-Thy 1.2 serum plus complement, anti-Ig columns, and depletion of FcR+ rosette-forming cells, failed to remove the effector cells generated in vivo or in vitro. Therefore like NK cells, interferon-induced cytotoxic cells lack the surface markers of mature T and B lymphocytes, are not adherent, and are devoid of avid Fc receptors. Furthermore like NK cells, the spleen cells from interferon-treated mice lysed various target cells (known for their sensitivity to NK cells) without H-2 or species restriction. Incubation in vitro of normal spleen cells with interferon also resulted in an increase in cytotoxicity for YAC tumor cells. We conclude that interferon acts directly on NK cells and enhances the inherent cytotoxic activity ofthese cells.
the metabolism of s-adenosylmethionine (SAM) cycle, the major methyl donor source for transmethyl... more the metabolism of s-adenosylmethionine (SAM) cycle, the major methyl donor source for transmethylation reaction, can suppress T cell immunity. By giving excess SAM, both TCR-mediated T cell proliferation and B cell proliferation were inhibited in dose-dependent manner. Methylthioadenosine (MTA) is a byproduct of SAM metabolism and serves as a methyl-transferase inhibitor. We demonstrate that MTA inhibits TCR-mediated and antigenic specific-T cell responses including T cell activation markers, Th1/Th2 cytokines and TCR-related signaling events. Interestingly, we found that MTA phosphorylase activity, the major enzyme to metabolize MTA, was significant higher in B cells than in T cells. It is consistence with our results that B cell immunity was not suppressed by MTA. These studies demonstrate the central role of SAM-dependent methylation in immune responses and provide a simple approach to altering lymphocyte metabolism and potentially T cell mediated autoimmune diseases such as SLE and MS.
Journal of Fluorescence, 2010
Low-Density Lipoprotein (LDL), often known as "bad cholesterol" is one of the responsible to incr... more Low-Density Lipoprotein (LDL), often known as "bad cholesterol" is one of the responsible to increase the risk of coronary arterial diseases. For this reason, the cholesterol present in the LDL particle has become one of the main parameters to be quantified in routine clinical diagnosis. A number of tools are available to assess LDL particles and estimate the cholesterol concentration in the blood. The most common methods to quantify the LDL in the plasma are the density gradient ultracentrifugation and nuclear magnetic resonance (NMR). However, these techniques require special equipments and can take a long time to provide the results. In this paper, we report on the increase of the Europium emission in Europium-oxytetracycline complex aqueous solutions in the presence of LDL. This increase is proportional to the LDL concentration in the solution. This phenomenum can be used to develop a method to quantify the number of LDL particles in a sample. A comparison between the performances of the oxytetracycline and the tetracycline in the complexes is also made.
Clinics, 2010
OBJECTIVES: To investigate whether oxidized low-density lipoprotein is a suitable predictor of pe... more OBJECTIVES: To investigate whether oxidized low-density lipoprotein is a suitable predictor of peripheral arterial disease severity. The role of oxidized low-density lipoprotein in the pathogenesis of atherosclerosis has already been investigated. Its relevance as a predictor of the appearance and worsening of coronary arterial disease is also well known. However, the same is not true regarding peripheral arterial disease. METHOD: Eighty-five consecutive patients with an ankle-brachial pressure index (ABPI) < 0.9 and the presence of either intermittent claudication or critical lower leg ischemia were included. The plasma level of IgG autoantibodies against oxidized low-density lipoprotein was evaluated through an enzyme-linked immunosorbent assay. The results were categorized into quartiles according to the ankle-brachial pressure index (a marker of peripheral arterial disease severity), and significant differences were investigated with the Kruskal-Wallis test. RESULTS: There was no significant difference between the quartiles for this population (p = 0.33). No correlation was found between the ankle-brachial pressure index and oxidized low-density lipoprotein levels in subjects with clinically evident peripheral arterial disease with a wide range of clinical manifestations. CONCLUSIONS: Oxidized low-density lipoprotein is not a good predictor of peripheral arterial disease severity.
Archives of Internal Medicine, 1994
Oxidation of low-density lipoprotein is believed to be an important step in the pathogenesis of a... more Oxidation of low-density lipoprotein is believed to be an important step in the pathogenesis of atherosclerosis. The purpose of the present study was to determine whether antibody against oxidized low-density lipoprotein, reported to be associated with the progression of carotid atherosclerosis, is predictive of cardiac death and nonfatal myocardial infarction. Serum samples from 135 cases and their controls, drawn at entry from middle-aged dyslipidemic men participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil, were tested for immunoglobulin G class antibodies against oxidized low-density lipoprotein by enzyme-linked immunosorbent assay. The mean antibody level, expressed in optical density units, was significantly higher in cases than in controls (0.412 vs 0.356, P = .002). After adjustment for age, smoking, blood pressure, and high-density lipoprotein cholesterol level, there was a 2.5-fold increased risk (95% confidence interval, 1.3 to 4.9) of a cardiac end point in the highest tertile of antibody level vs the lowest tertile (P = .005 for trend). Elevated levels of antibodies against oxidized low-density lipoprotein were predictive of myocardial infarction. The effect was independent of low-density lipoprotein cholesterol levels, and the joint effect was additive. Elevated antibody levels modified the effects of classic coronary risk factors.
The American Journal of Cardiology, 2002
ABSTRACT Oxidative low-density lipoprotein (LDL) damage caused by oxidants present in cigarette s... more ABSTRACT Oxidative low-density lipoprotein (LDL) damage caused by oxidants present in cigarette smoke may be involved in the pathogenesis of coronary heart disease,(1) but there is a controversy in published reports on this subject. Gouaze et al(2) demonstrated increased oxidizability in smokers, Siekmeier et al(3) could not confirm these results, and Chen and Loo(4) found an antioxidant property of cigarette smoke extract by measuring its effect on LDL oxidizability in vitro. We evaluated the contribution of cigarette smoking on LDL oxidizability and,plasma levels of antioxidized LDL in a well-defined healthy population of normolipidemic smokers. Blood samples were drawn a few minutes after subjects smoked 1 cigarette to ensure higher blood levels of oxidative products from cigarette smoke.(5).
Latin America Optics and Photonics Conference, 2010
Abstract: Low Density Lipoprotein (LDL) or bad cholesterol, becomes even more dangerous when it i... more Abstract: Low Density Lipoprotein (LDL) or bad cholesterol, becomes even more dangerous when it is oxidized. In this paper we report an increase of the Europium Chlortetracycline complex emission in the presence of oxidized LDL. ©2010 Optical Society of America OCIS ...
Scandinavian Journal of Immunology, 1987
Several sets of data indicate the possibility that carbohydrate moieties on the target cell arc i... more Several sets of data indicate the possibility that carbohydrate moieties on the target cell arc important structures in natural killer (NK) cell-mediated lysis. Striking changes in the NK susceptibility of targets can be induced in several systems involving in vitro differentiation of tumour eell lines. The effect on target cells of tbe glycosylation inhibitor tunicamyein. which acts by blocking the dolichol-dependeni asparagine-linked glyeosylation pathway was investigated. Using several different tumour cell lines we can conclude that: (a) asparagine-linked carbohydrate chains do noi contribute directly to NK susceptibility, (b) induced differentiation may or may not be linked with a change in NK susceptibility, and (c) secondary changes caused by tunicamycin treatment may lead to alterations in the gangliosides. a finding that is positively correlated with decreased NK susceptibility.
Atherosclerosis Supplements, 2009
Atherosclerosis Supplements, 2009
Atherosclerosis Supplements, 2006
Haematology and blood transfusion, 1981
Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2003
Oxidized low-density lipoproteins (oxLDL) and protein fractions obtained by size exclusion chroma... more Oxidized low-density lipoproteins (oxLDL) and protein fractions obtained by size exclusion chromatography of oxLDL were tested for vascular permeability effects on topical application to the hamster cheek pouch. The hamster cheek pouch was prepared for intravital microscopy observations of macromolecular leakage at post capillary venules (=leaks) with FITC-dextran as tracer. OxLDL (0.1 mg/ml), PAF (platelet activation factor, 50-100 nM) and protein fractions of oxLDL (10 microg/ml) were applied topically to hamster cheek pouches. Application of oxLDL and PAF resulted in reversible increases in the number of leaks. The PAF-antagonist WEB 2170, L-NAME and a beta(2)-adrenoceptor agonist inhibited (P<0.01) almost completely the macromolecular leakage induced with oxLDL or PAF. Protein fractions were found to be more effective than unfractionated oxLDL in inducing plasma leakage as calculated on mg/ml-basis. Hamster oxLDL is a potent inducer of macromolecular leakage increase in the h...
Journal of lipid research, 1994
Estrogen treatment raises plasma high density lipoprotein (HDL) levels, which may reduce cardiova... more Estrogen treatment raises plasma high density lipoprotein (HDL) levels, which may reduce cardiovascular risk. To identify the responsible mechanisms as well as the importance of the route of administration, we treated eight healthy postmenopausal women in a double-blind crossover study with three treatments for 6 weeks each: oral estradiol, 2 mg daily; transdermal estradiol, 0.1 mg twice weekly; and placebo. At the end of each treatment, apoA-I of HDL2 (d 1.063-1.125 g/ml) and HDL3 (d 1.125-1.210 g/ml) was endogenously labeled by a constant intravenous infusion of trideuterated leucine. HDL2 and HDL3 were separated by preparative ultracentrifugation. The pool sizes and enrichment curves of HDL apoA-I were used to calculate production rates and fractional catabolic rates (FCR). Oral estradiol increased the levels of HDL2 apoA-I by 37% (P < 0.005) and of HDL3 apoA-I by 11% (P < 0.05). These increased apoA-I levels resulted entirely from increased production, by 36% for HDL2 (P &...
Haematology and blood transfusion, 1983