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Biomedical subjects

J L Beaumont

Publications and source records attributed to J L Beaumont.

At least 37 records · Page 2Linked to original sources
PubMed1990

Circulating IgA-Lp complexes in Watanabe heritable hyperlipidemic and cholesterol fed NZW rabbits.

Auto-immune immunoglobulin-lipoprotein complexes (Ig-Lp), as well as other modified lipoproteins, are activators of the transformation of macrophages into foam cells which may be the first step in atherogenesis. In humans circulating Ig-Lp have been demonstrated in autoimmune hyper- or dyslipidemia (AIH, DIH) and found to be associated with conditions related to atherosclerosis. Thus Ig-Lps may be significant and potentially primary atherogenic factors. In order to test this hypothesis we compared the distribution of Ig-Lps in 14 WHHL homozygote rabbits and in 15 normal fed and 8 cholesterol-fed NZW rabbits, all males aged 4-6 months. The Ig-Lps were detected by ELISA using 2 different capture anti-Lp and 4 indicator antibodies specific for either total Igs or the IgA, IgM or IgG classes. Some Ig-Lp of all classes were found in normal fed NZW. As compared with these normal levels, IgA-Lp are increased 2.5-fold in both the WHHL and the cholesterol-fed NZW rabbits (P = 0.0002). During cholesterol feeding the increase of IgA-Lp and total cholesterol and their decrease after returning to a normal diet were parallel in NZW rabbits, but their variation was mainly independent. IgM-Lp was also increased, but to a much lesser extent, in WHHL and in cholesterol-fed NZW. IgG-Lp was not increased in WHHL and only moderately increased in some of the cholesterol-fed NZW. The WHHL and the cholesterol-fed NZW rabbits did not differ by the IgA-Lp content of the serum, but the level of IgM-Lp was higher in the former.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Retinyl palmitate labeled intestinally derived lipoproteins accumulate in the circulation of WHHL rabbits.

The behavior of native retinyl palmitate labeled intestinally derived lipoproteins and their remnants was studied in 8 NZW and 8 WHHL (5 homo- and 3 heterozygote) normal-fed rabbits and in 3 cholesterol-fed NZW, after 1 month of cholesterol feeding, and 3 and 5 months after resuming normal feeding. Palmitate labeled lipoproteins were produced by the intestine after administration of 50,000 IU of Vitamin A, together with olive oil via gastric intubation. Blood was drawn before and 3,6,9,12,24, and in some instances, 48 h later. Retinol (R) and retinyl palmitate (RP) were measured in whole serum and in the chylomicron, d less than 1006, d greater than 1006 less than 1019, d greater than 1019 less than 1063, d greater than 1063 less than 1210 g/ml lipoprotein fractions and in the infranatant. The R content of the serum was almost all concentrated in the infranatant, it did not change during the vitamin A test and was similar in WHHL, and normal- or cholesterol-fed NZW rabbits. In the normal-fed NZW the RP content of the serum increased within 6 h after giving the vitamin A fat meal (peak value less than 200 microgram/100 ml) and then decreased. In the WHHL homozygotes, the RP increased to a much greater degree (peak value 600-1820 micrograms) and for a much longer time, as it was still increased in the 5 cases studied after 24 h, and in 3 cases studied after 48 h. Similar RP curves were obtained in NZW rabbits, after 1 month of cholesterol feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Vascular risk of oral contraceptive agents: realities and mechanisms. II. Mechanisms of vascular accidents: their prevention].

The mechanism of the vascular complications related to oral contraception is still unclear. In the present paper are discussed: (a) the possibility of accelerated atherosclerosis, suggested by the presence of a number of risk factors, a hypothesis which is not confirmed by pathological findings; (b) the possibility of a coagulation disease leading to thrombosis; (c) the arguments in favor of an immunological mechanism. This hypothesis is supported by the strong correlation between vascular complications and presence of antibodies against the synthetic hormones contained in the drug. It is also consistent with the aspect of the lesions, which might be induced by circulating immune complexes and antibodies. It is proposed that women at risk should be detected by systematic determination of antiethinylestradiol antibodies.

Adult↗
PubMed1989

[Vascular risk of oral contraceptive agents: realities and mechanisms. I. Risk evaluation].

The suspected risk of oral contraception was confirmed when large scale epidemiological studies became available. The present work recalls the methodology of a good evaluation, the pros and cons of retrospective and prospective studies, the different appreciations provided by measuring "relative risk" or "attributable risk". In terms of public health, the data obtained supported the necessity to include mortality related to oral contraception in an evaluation of reproductive mortality. This work compares the incidence of vascular complications evaluated through different studies, according to the criteria selected and the type of vascular disease. The advantage of lowering estrogen content is considered.

Abortion, Spontaneous↗
PubMed1989

Antiestrogen antibodies, oral contraception and systemic lupus erythematosus.

Oral contraceptives (OC) are suspect to play a role in systemic lupus erythematosus (SLE). It has previously been shown that OC can induce immune reactions in a number of normal women. Antiethinylestradiol antibodies (anti-EE Ab) have been detected with a radioimmunoassay method in 25-30% of healthy OC users. In the present paper, a comparative study of 123 controls and 55 SLE patients, with or without OC use, indicates (1) that in the disease-free group, anti-EE Ab were detected in 30% of OC users, and only in OC users; (2) that in the SLE group, anti-EE Ab were observed in 57% of female OC users, and, surprisingly, in 13% of men also, a finding already reported by other authors.

Adolescent↗
PubMed1988

Immunoglobulin-bound lipoproteins (Ig-Lp) as markers of familial hypercholesterolemia, xanthomatosis and atherosclerosis.

In autoimmune hyper- or dislipidemia secondary to a monoclonal antilipoprotein gammapathy, immunoglobulin-lipoprotein (Ig-Lp) complexes are found in the circulating blood. In order to determine their possible significance in common types of hyperlipidemia we compared the Ig-Lp content of sera from 98 healthy blood donors and 155 outpatients from a Lipid Clinic, including 91 cases of hypercholesterolemia (55 familial and 36 non-familial), 15 cases of hypertriglyceridemia, 20 cases of mixed hyperlipidemia and 29 miscellaneous cases. Detection of the Ig-Lp was performed by an ELISA technique with polyclonal affinity purified anti-LDL + HDL as capture antibodies and peroxidase-labeled anti-Ig antibodies specific for IgA, IgG, IgM heavy chains as indicators. Two cases of monoclonal gammapathy (one IgA K and one IgG L) with dislipidemia served as positive controls for the test. IgG, IgA and IgM Lp were found in the sera of the blood donors, in very small quantities when compared with the monoclonal gammapathy cases. All three types of Ig-Lp were also found in the different hyperlipidemic populations studied. When blood donors were compared to hyperlipidemic patients, no difference was observed for IgG Lp. A significant increase in IgM Lp was found in patients with familial hypercholesterolemia (P less than 0.01). An increase in IgA Lp was also found in hypercholesterolemia, familial or not (P less than 0.01), and in patients with corneal arcus (P less than 0.0001), ischaemic disease (P less than 0.01), tendon xanthomas (P less than 0.05) or xanthelasma (P less than 0.05). Furthermore, in a group of 18 paired parents from 9 different families, positive interparent correlations were found for IgM Lp (r = 0.78; P = 0.013) and IgG Lp (r = 0.69; P = 0.038). Therefore IgM Lp may be markers for subpopulations of familial hypercholesterolemia, and IgA Lp markers for the risk of atherosclerotic ischemic disease and deposition of lipids in the cornea. It may be (1) that natural clones of autoanti-lipoprotein antibodies are responsible for the minute quantities of Ig-Lp found in normal people; (2) that the marked development of one of these clones is the cause of autoimmune hyper- or dyslipidemia and xanthomatosis associated with monoclonal gammapathy; (3) that the limited development of a clone produces the Ig-Lp particles found in hypercholesterolemic patients; (4) that there are types of Ig-Lp particles (IgA Lp) that may be harmful for tissues independently of hypercholesterolemia.

Adult↗
PubMed1986

Cytotoxic effect of serum on fibroblasts in one case of normolipidemic plane xanthoma and myeloma IgG lambda.

Serum was examined for a cytotoxic effect on cultured human fibroblasts, using 8 normal controls and 4 patients. Three of the patients had secondary lipidoses associated with monoclonal gammapathies of IgA kappa, IgG kappa and IgG lambda types. The fourth had systemic lupus erythematosus (SLE) with hyperlipidemia. Only serum containing the monoclonal IgG lambda was found to be cytotoxic. This circulating IgG lambda was strongly bound to HDL and behaved like an antilipoprotein antibody. The circulating immune complexes may be the serum factor responsible for the cytotoxicity and the cutaneous plane xanthomas, thus giving another example of 'antibody-dependent' cellular cytotoxicity previously described for endothelial cells in other diseases.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Tumor immunoglobulin with antibody activity against blood coagulation factors.

A cultured tumor cell line from the Greene lymphoma was shown in vitro to secrete immunoglobins of the IgG2 subclass (TcIg), which possessed a direct inhibiting effect on blood coagulation. TcIg prolonged the thrombin time (TT) of normal hamster plasma in vitro. Moreover, the effect of heparin which prolonged the plasma thrombin time was reinforced when TcIg was added to the test. This property was not neutralized by protamine sulfate. In the plasma kaolin clotting time test (KCT), the addition of TcIg lead to an anticoagulant effect, but weaker than in TT. The mixing pattern of normal plasma with tumor-bearing hamster plasma did not reveal the presence of circulating inhibitor in tumor plasma. It was suggested that TcIg had heparin-like activity.

Animals↗
PubMed1985

Residual vascular risk of discontinued oral contraception. Role of antibodies to synthetic sex hormones.

Recent epidemiological data indicate that the risk of thromboembolic disease associated with oral contraception (OC) may persist after discontinuation of the drug. It was demonstrated on the other hand that antibodies to sex steroid hormones which develop in OC users, were significantly correlated with the incidence of thrombosis. It is well known that antibodies may persist years after the antigenic stimulation. So it was of interest to see if the eventual occurrence of thrombosis in ex-users might be correlated with the presence of anti-sex steroid antibodies remaining after stopping OC. Thirty-eight women with thrombosis on OC and positive antibody levels, who were required to stop the pill, were followed for periods ranging from 1 to 10 years. No disappearance of anti-ethinyl-estradiol antibodies (anti-EE ab) was observed except for 2 cases. On the other hand, 109 patients with thrombosis either current- (50), past- (29), or never-users (30) of OC were compared to 102 controls of similar groups. Results indicate that the levels of anti-EE ab, and the percentage of women who had anti-EE ab, were similar in those who experienced thrombosis either in the course of OC or after discontinuation. A significant difference was observed between both cases who were current- or ex-users and their controls.

Adult↗
PubMed1985

Immunogenicity and the vascular risk of oral contraceptives.

Data concerning circulating immune complexes were obtained for women who had had a pulmonary embolism, myocardial infarction, or cerebral thrombosis, and for 224 healthy controls. In women with pulmonary embolism who had used oral contraceptives concentrations of circulating immune complexes were significantly higher than in healthy controls (regardless of oral contraceptive use), or in those with pulmonary embolism who had never used these preparations. Concentrations of circulating immune complexes were not raised in myocardial infarction, but these women had major risk factors for ischaemic heart disease. The group of patients with cerebral thrombosis without risk factors tended to have high concentrations of circulating immune complexes. The data provide some confirmation that immunological mechanisms may play a role in thrombotic episodes associated with oral contraceptives, especially when they occur in the absence of risk factors for vascular disease.

Adolescent↗
PubMed1985

[Immunogenicity of synthetic sex hormones and thrombogenesis].

The ingestion of synthetic steroidal and non-steroidal estrogens may induce antiestrogen antibodies in women on oral contraceptives, and in prostatic patients treated with diethylstilbestrol (DES). Natural sex hormones have no such effect. A radioimmunoassay with tritiated ethinylestradiol or DES was applied to study the prevalence of synthetic sex hormone antibodies in 2 populations: 100 women on estroprogestative hormones and 93 cases of DES treated prostatic cancers. Homologous non-treated controls were compared. Results allowed to identify among treated and asymptomatic subjects an immunoreactive population of 30% women and 47% men. Furthermore, the antibodies were found with a much higher frequency (p less than 0.001) in patients who had experienced a thromboembolic disease while on treatment: 90% of women and 74% of men. The importance of these antibodies as a risk factor, their possible role in promoting vascular lesions, the interest of their detection for the prevention of the vascular risk induced by synthetic sex hormones, are considered.

Adolescent↗
PubMed1985

Quantitative determination of free cholesterol and cholesteryl esters in skin biopsies.

A new technique is described for the determination of cholesterol in skin biopsies which is sensitive, practical and reproducible. The determination of cutaneous cholesterol is of clinical interest, because of its correlation with the degree of atherosclerosis. There was no correlation found between the blood total cholesterol and total triglycerides, and cholesterol and triglycerides determined in the skin biopsies. Determinations were carried out on several normal subjects, 7 long-distance runners, 34 hyperlipidemic patients. There was a significant increase with age of total skin cholesterol in the normal subjects, the values obtained with the long-distance runners had a tendency to be somewhat lower. All the patients investigated had higher cholesterol values than the normal controls or the sportsmen. This technique can be used therefore as a diagnostic tool to detect pathologies of skin lipids, or of tissue lipid metabolism, as for example in normolipidemic patients presenting corneal arcus or xanthelasmas.

Adult↗
PubMed1983

[Vascular complications of oral contraception. In whom and how to prevent them?].

Oral contraception entails an increased risk of arterial and venous thrombosis which can only be prevented by detecting women at risk. The relative importance of various predisposing or precipitating factors was evaluated by comparing 3 groups of women: 50 oral contraceptive (OC) users with thrombosis; 50 healthy OC users and 30 controls who had never used OC's. The factors investigated were: duration of use and dose of oestrogens, age, blood pressure, serum lipid levels and tobacco smoking. In addition, all women were tested for the presence of anti-ethinylestradiol antibodies (anti-EE ab) which we had previously shown to be induced by OC's in a number of women. Our results indicated that the most frequently encountered risk factor associated with vascular thrombosis was the presence of anti-EE ab and that the risk was further increased by smoking in women with these antibodies.

Adult↗
PubMed1983

Evaluation of risk factors associated with vascular thrombosis in women on oral contraceptives. Possible role of anti-sex steroid hormone antibodies.

Women on oral contraceptives have an increased risk of thrombosis. The prevention of the vascular complications relies on the detection of women who are at risk. In order to find out which characteristics correlate with the occurrence of the vascular disease, 3 groups of women were compared; 50 oral contraceptive users with thrombosis, 50 healthy users, and 30 controls. Apart from the modality of oral contraception (duration of use, dose of estrogens), the following parameters were tested as possible risk factors: age, serum lipid levels, tobacco smoking, and especially presence of antiethinylestradiol antibodies (anti-EE ab) which we had previously shown to be induced by oral contraceptives in a number of women. Results indicated that the major risk factor associated with vascular thrombosis was the presence of anti-EE ab. Furthermore, the risk was highly increased by the association of tobacco smoking to anti-EE ab.

Adolescent↗
PubMed1982

Blood changes in sex steroid hormone users. Circulating immune complexes induced by estrogens and progestogens and their relation to vascular thrombosis.

Oral contraceptives (OC) have been shown to induce in some women antiethinylestradiol antibodies which may be detected as circulating immune complexes by precipitation in ammonium sulphate at 25% saturation (CIC.AS). A reevaluation of the presence of CIC.AS in 644 women either receiving sex steroid hormones or not was made, and the respective role of estrogens and progestogens investigated, together with the influence of the dose. The study confirmed that CIC.AS levels were significantly different in controls (442 +/- 246 micrograms/ml serum), healthy gonadal hormone users (754 +/- 700 micrograms) and users with thrombosis (1331 +/- 1099 micrograms/ml). These results indicated that: 1. CIC.AS could be induced by synthetic estrogens as well as progestogens, but not by non-synthetic hormones; 2. the induction of CIC.AS seemed poorly dose-related, and 3. was not correlated with the duration of use; 4. in reactive women, high CIC.AS levels occurred as soon as 3 weeks after the beginning of synthetic gonadal hormones use, persisted throughout treatment and decreased slowly when discontinued; 5. in women with thrombosis CIC.AS were more frequently detected (64.7%) than in healthy users (32.2%) P less than 0.001. The importance of the immunologic changes as a risk factor in thrombosis in OC users was evaluated in comparison with other predisposing factors and tobacco smoking.

Adolescent↗
PubMed1982

Oral contraception, circulating immune complexes, antiethinylestradiol antibodies, and thrombosis.

Circulating immune complexes were detected in women on oral contraceptives (OC) by a simple antigen nonspecific method using precipitation of serum in 25% saturated ammonium sulfate (CIC-AS). A significant correlation was found between the presence of CIC-AS and the OC vascular risk. A radioimmunoassay with tritiated ethinylestradiol indicated that CIC-AS contained antiethinylestradiol antibodies (anti-EE Ab) in a number of OC users, but indicated also that 1) anti-EE Ab may be found in cases with no detectable CIC-AS, 2) CIC-AS containing no anti-EE Ab are found in nonusers, and 3) even in OC users the CIC-AS may contain antibodies to other ligands than EE. The study demonstrated also that, in OC users with a vascular complication, anti-EE Ab were more frequently detected (78% of cases) than CIC-AS (60%). Moreover, among OC users with CIC-AS, anti-EE Ab were found in 95% of women with a vascular complication and only 37% of current healthy users. The detection of anti-EE Ab appears to be more predictive, with regard to the vascular risk of OC, than the detection of CIC-AS.

Adult↗