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Biomedical subjects

V Beaumont

Publications and source records attributed to V Beaumont.

At least 19 recordsLinked to original sources
PubMed2000

Enhancement of synaptic transmission by cyclic AMP modulation of presynaptic Ih channels.

Presynaptic activation of adenylyl cyclase and subsequent generation of cAMP represent an important mechanism in the modulation of synaptic transmission. In many cases, short- to medium-term modulation of synaptic strength by cAMP is due to activation of protein kinase A and subsequent covalent modification of presynaptic ion channels or synaptic proteins. Here we show that presynaptic cAMP generation via serotonin receptor activation directly modulated hyperpolarization-activated cation channels (Ih channels) in axons. This modulation of Ih produced an increase in synaptic strength that could not be explained solely by depolarization of the presynaptic membrane. These studies identify a mechanism by which cAMP and Ih regulate synaptic plasticity.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Somatostatin receptor desensitization in NG108-15 cells. A consequence of receptor sequestration.

In NG108-15 cells inhibition of both N-type calcium channel current and adenylyl cyclase by somatostatin (SRIF) was not sustained but rapidly desensitized in the continued presence of the drug. The degree and rate of desensitization were concentration-dependent, and the desensitization was homologous with respect to the delta-opioid receptor. We have been unable to obtain evidence for the involvement of G protein-coupled receptor kinases (GRKs) in this desensitization. SRIF-induced desensitization of N-type calcium channel currents was not reduced in cells stably overexpressing a dominant negative mutant of GRK2 or following intracellular dialysis with GRK2- and GRK3-blocking peptides or with heparin. Inhibitors of protein kinase A, protein kinase C, and protein kinase G were also without effect. In contrast, both the rate and degree of SRIF-induced desensitization were reduced by pretreatment with phenylarsine oxide or concanavalin A, both inhibitors of receptor endocytosis. Furthermore, SRIF-induced desensitization was enhanced by monensin, which prevents receptor recycling back to the plasma membrane. Similarly, SRIF-induced desensitization of adenylyl cyclase inhibition was not reduced in cells stably overexpressing dominant negative mutant GRK2 but was reduced in cells pretreated with the receptor endocytosis inhibitor hyperosmotic sucrose or concanavalin A. These data are consistent with the view that SRIF-induced desensitization in NG108-15 cells results from receptor internalization.

Adenylyl Cyclase Inhibitors↗
PubMed1993

Whole chromosome 17 loss in ovarian cancer.

Chromosomal deletions, associated with the loss of normal function of tumour suppressor genes, have been identified in a variety of both familial and sporadic human cancers. Although the molecular pathology of ovarian cancer is not understood, several studies have reported deletions in chromosome 17 in ovarian tumours. We have used 13 restriction site polymorphic, microsatellite, and variable number tandem repeat markers to make a detailed analysis of chromosome 17 deletions in 12 benign and 19 malignant ovarian tumours. Two benign and 11 malignant tumours were informative for at least one marker on each arm of the chromosome. Loss of heterozygosity (LOH) was detected in both arms (by all informative markers) in 5 malignant tumours from four women (three with the disease at FIGO stage Ia). In a further bilateral ovarian tumour a partial LOH affecting 17q22-q25 was present in one ovary only. By contrast to a number of previous studies, none of the 19 malignant and 12 benign tumours showed ERBB2 (17q12-22) amplification. The data presented show that the loss of a whole copy of chromosome 17 is a frequent and relatively early event in the development of some ovarian cancers. This suggests the possible involvement of multiple chromosome 17 loci in the pathogenesis of ovarian cancer. Equally plausible is that the loss of a whole chromosome copy could be the product of chromosomal instabilities induced by loss of the normal allele of tumour suppressors, such as TP53, located on this chromosome.

Adenofibroma↗
PubMed1993

Lp(a) levels and antiestrogen antibodies in women with and without thrombosis in the course of oral contraception.

Several reports have shown that lipoprotein(a) is associated with ischemic diseases. Two characteristics might explain this association. Firstly, Lp(a) is an LDL-like lipoprotein which may be implicated in the atherosclerotic process and secondly, Lp(a) possesses an additional apolipoprotein(a) whose structure is close to that of plasminogen and might confer to the molecule prothrombotic properties. It seemed of interest to see whether Lp(a) was a risk factor in oral contraceptive users with thrombotic complications, a group of young women with presumably little or no atherosclerosis. Three groups of women were compared: 25 of them served as controls and did not use oral contraceptives (OC) (group 1); 25 women were healthy current users of OC (group 2); 35 women suffered thrombotic complications in the course of OC (group 3). Mean levels of Lp(a), estimated by RID, were not found to be significantly different in the 3 groups: 19 +/- 18, 20 +/- 23 and 16 +/- 22 mg/dl, respectively. Levels above 30 mg/dl were similarly distributed. Among the other risk factors studied, antiestrogen antibodies were absent in group 1, present in 24% of group 2 and 71.4% of group 3 (P < 0.01). Serum cholesterol levels were similar in the 3 groups: 209 +/- 33, 220 +/- 41, 213 +/- 45 mg/dl respectively. Mean serum triglyceride levels were higher in group 2 than in group 1 (61 +/- 18 and 83 +/- 32, P < 0.01), and higher in group 3 than in group 2 (116 +/- 66 and 83 +/- 32, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Hyperhomocyst(e)inemia, anti-estrogen antibodies and other risk factors for thrombosis in women on oral contraceptives.

Hyperhomocyst(e)inemia was shown to be associated with vascular occlusion in atherosclerotic patients. We have conducted a study to determine if hyperhomocyst(e)inemia was also related to the vascular events observed in women on oral contraceptives, presumably having little or no atherosclerosis. Two hundred women receiving oral contraceptives were included in the study: 100 were healthy controls and 100 had documented vascular occlusion. Determination of serum homocyst(e)ine and anti-estrogen antibody levels wore performed under blind conditions. They were evaluated in logistic regression models in which age and smoking were also included. Women with vascular occlusion had higher levels of homocyst(e)ine (P less than 0.001) and of anti-estrogen antibodies (P less than 0.001) when compared to controls. They were also older (P less than 0.001) and more frequently smokers (P less than 0.05). The above mentioned variables were, in isolation, independent predictors of vascular occlusion. Moreover, a model assessing those variables and their interactions indicated that the levels of anti-estrogen antibodies and smoking increased the predictability in older women, as well as the levels of age-adjusted homocyst(e)ine. The study suggests that the above factors can identify women at risk and that determination of anti-estrogen antibodies and homocyst(e)ine levels may help to detect women predisposed to vascular occlusions when taking oral contraceptives.

Adult↗
PubMed1991

Oral contraceptives, sex steroid-induced antibodies and vascular thrombosis: results from 1318 cases.

The role of antiethinyl estradiol antibodies (anti EE Ab) and associated risk factors was evaluated in 1318 cases of venous or arterial thrombosis in oral contraceptives (OC) users, and compared to 61 non-users and 124 healthy current users. Anti EE Ab were absent in non-users and present in 33% of healthy users and 72% of those with thrombosis, either arterial or venous. Age, duration of use, hyperlipidaemia and smoking were factors associated with thrombosis only in women with an arterial disease. While the two predominant factors, anti EE Ab and smoking may be risk factors in their own right, the combination of both was found in 47.7% of women with thrombosis. It is proposed that thrombosis associated with OC use may be explained by an immunological disease in which anti EE Ab and their complexes with the circulating synthetic hormones may be harmful to the vessels, as also suggested by the type of lesions already described in OC users. The determination of anti EE Ab in healthy users may identify a group at risk of thrombosis.

Adult↗
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↗
PubMed1986

[Demonstration of specific antibodies against diethylstilbestrol during treatment of prostatic cancer].

Antibodies against diethylstilboestrol were detected in prostatic cancer patients treated with diethylstilboestrol (DES). Direct radioimmunoassay (DRIA) was performed in 109 patients divided into three groups: a control group of 33 patients (group I), a group of 38 patients treated by DES and free of cardiovascular complications (group II), and a group of 38 patients treated by DES with cardiovascular complications (group III). Antibody count was significantly higher in group III than in the two other groups (p less than 0.05). These results suggest that DES antibodies may play a role in estrogen-associated cardiovascular toxicity. For this reason, DES should not be used in patients with a positive assay.

Adenocarcinoma↗
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↗
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↗