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  • Anti-phospholipid antibodies  (2)
  • LDL metabolism  (2)
  • 1
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; VLDL metabolism ; LDL metabolism ; human macrophages
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The very low- and low-density lipoprotein fractions were isolated from 16 normolipidaemic Type 2 (non-insulin-dependent) diabetic patients in good to fair glycaemic control and from corresponding age-, sex-, and race-matched, non-diabetic control subjects. Rates of cholesteryl ester synthesis averaged 268±31 vs 289±40 pmol 14C-cholesteryl oleate·-mg cell protein−1·20 h−1 for very low- and 506±34 vs 556±51 pmol 14C-cholesteryl oleate·mg cell protein−1·20 h−1 for low-density lipoproteins isolated from the Type 2 diabetic patients and control subjects, respectively, when they were incubated with human macrophages. A group of approximately one-third of the patients was selected for separate analyses because very low-density lipoproteins isolated from these patients did stimulate more cholesteryl ester synthesis when incubated with macrophages. There were no significant differences in the lipid composition of the lipoproteins isolated from the three groups of subjects. The relative proportion of apoprotein C to apoprotein E was significantly decreased (p〈0.002) in the very low-density lipoproteins from diabetic patients and was further decreased in samples from these selected diabetic patients. The apoprotein C-I content of very low-density lipoproteins isolated from diabetic patients was increased compared to control subjects and was further increased in samples from the selected diabetic patients (p〈0.02). There were no significant differences in the proportions of apoproteins C-III-0, C-III-1, or C-III-2 among the three groups. These studies suggest that in normolipidaemic Type 2 diabetic patients, the apoprotein composition of VLDL is abnormal and this may alter VLDL macrophage interactions and thus contribute to the increased prevalence of atherosclerosis in diabetic patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Eosinophilia myalgia syndrome ; Fibromyalgia syndrome ; Anti-serotonin antibodies ; Anti-ganglioside antibodies ; Anti-phospholipid antibodies ; Anti-nucleolar antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Eosinophilia myalgia syndrome (EMS) has been related to intake of “contaminated” L-tryptophan, and an alteration in tryptophan 5-hydroxytryptamine (5-HT, serotonin) metabolism has been reported in EMS patients. Recently we found that a defined autoantibody pattern consisting of antibodies to nucleoli, gangliosides, and phospholipids is closely related to the fibromyalgia syndrome (FS) which clinically resembles the EMS. We were therefore interested to see whether these antibodies can also be detected in patients with EMS. Studied were 27 patients with acute EMS (13 of whom were also examined 2 years after acute onset), 100 patients with FS, and 40 patients with progressive systemic sclerosis (PSS). As controls, sera from 100 blood donors were analyzed. Antibodies to nucleoli were demonstrated by immunofluorescence test on cell cultures in 52% of patients with acute EMS, 62% of patients with chronic EMS, and 37% of FS patients. Western blotting with a nuclear extract from HeLa cells revealed in both diseases the same epitopes at 63, 57, and 53 kDa. Antibodies to 5-HT, gangliosides (Gm1), and phospholipids were determined by enzyme-linked immunosorbent assay. Among patients with FS 73% had antibodies to 5-HT, in contrast to only 19% of patients with acute EMS. However, 77% of the 13 EMS patients analyzed 2 years later had become anti-5-HT antibody positive during that time. Also the incidence of antibodies to Gm1 increased from 37% at acute onset to 69% in patients with chronic EMS (30%). The various antibodies were detected in only 18% of healthy controls. Serum 5-HT levels were decreased in patients with acute EMS compared to those with chronic EMS or FS. In patients with PSS they were significantly increased. It is concluded that EMS may have been developed in patients with FS who may have reacted in an allergic manner to a more immunogenic (“contaminated”) L-tryptophan.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Diabetes ; LDL metabolism ; glycosylated LDL ; cholesteryl ester synthesis ; human macrophages
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetes mellitus is an independent risk factor in the development of atherosclerosis. In this study we aimed to demonstrate whether there is an abnormal interaction between low-density lipoproteins from diabetic patients and human macrophages. We measured cholesteryl ester synthesis and cholesteryl ester accumulation in human monocytederived macrophages (obtained from non-diabetic donors) incubated with low density lipoproteins from Type 1 (insulin-dependent) diabetic patients in good or fair glycaemic control. Low density lipoproteins from the diabetic patients stimulated more cholesteryl ester synthesis than low density lipoproteins from non-diabetic control subjects (7.19±1.19 vs 6.11±0.94 nmol/mg cell protein/20 h, mean±SEM, p〈0.05). The stimulation of cholesteryl ester synthesis by low density lipoproteins isolated from diabetic patients was paralleled by a significant increase in intracellular cholesteryl ester accumulation (p〈0.02). There were no significant differences in the lipid composition of low density lipoproteins between the diabetic and control groups. Non-enzymatic glycosylation of low density lipoproteins was higher in the diabetic group (p〈0.01) and correlated significantly with cholesteryl ester synthesis (r=0.58). Similarly, low-density lipoproteins obtained from non-diabetic subjects and glycosylated in vitro stimulated more cholesteryl ester synthesis in macrophages than control low density lipoproteins. The increase in cholesteryl ester synthesis and accumulation by cells exposed to low density lipoproteins from diabetic patients seems to be mediated by an increased uptake of these lipoproteins by macrophages. This study suggests that glycosylation of low density lipoproteins to the extent occurring in diabetes may alter their interaction with human monocyte-derived macrophages and may lead to increased intracellular cholesteryl ester accumulation. The results suggest a possible mechanism by which hyperglycaemia may contribute to the acceleration of atherosclerosis in diabetes.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1434-9949
    Keywords: Anti-ganglioside antibodies ; Anti-phospholipid antibodies ; Anti-serotonin antibodies ; Fibromyalgia syndrome ; 5-HT-receptor blocker ; Ritanserin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the study was to evaluate in a double-blind manner the effect of the long-acting 5-hydroxytryptamine 2 (5-HT2)-receptor blocker Ritanserin on clinical symptoms in patients with fibromyalgia syndrome (FM) and on production of antibodies to serotonin, gangliosides and phospholipids, recently shown to have a high incidence in this disease. Fifty-one female patients with typical FM were included in the 16-week study: 24 received Ritanserin and 27 received a placebo. Antibodies to 5-HT, gangliosides (Gm1) and phospholipids (thromboplastin) were determined by enzyme-linked immunosorbent assay at day 0 and at the end of week 16. The psychological and physical status, including tender points, of the patients was evaluated at day 0 and at the end of weeks 4 and 16. At the end of the study, there was an improvement (p〈0.05) in feeling refreshed in the morning in the Ritanserin-treated group and headache was also significantly improved compared with the placebo group. There was no difference in pain, fatigue, sleep, morning stiffness, anxiety and tender point counts in the Ritanserin and placebo groups. Fifty-one per cent of the 51 patients had at least one of the three antibodies to 5-HT, Gm1 and phospholipids. The incidence and activity of these antibodies were not influenced by Ritanserin or placebo. The observation that Ritanserin has only a small effect on clinical symptoms indicates that disturbances in serotonin metabolism or uptake may be only one factor in the pathogenesis of the disease. The high incidence of a defined autoantibody pattern in FM could again be confirmed in this study. However, it remains speculative whether immunological reactions are, indeed, involved.
    Type of Medium: Electronic Resource
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