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Biomedical subjects

F Begon

Publications and source records attributed to F Begon.

At least 19 recordsLinked to original sources

Effect of bromolevamisole and other imidazo [2,1-b] thiazole derivatives on adenylate cyclase activity.

We studied the effect of bromolevamisole (BL) and other imidazo [2,1-b] thiazole derivatives--bromodexamisole (BD) and levamisole (LV)--on adenylate cyclase (AC) activity. BL and BD both inhibited forskolin-activated human thyroid AC, while LV had no effect. This inhibition was non-stereospecific and the IC50 values, as measured with 1 mM ATP and 40 microM forskolin, were 0.95 and 0.80 mM for BL and BD, respectively. In contrast, human thyroid alkaline phosphatase (ALP) inhibition was stereospecific, with IC50 values of 0.0012 mM for BL and 0.9 mM for BD. LV was a 10-fold weaker inhibitor of ALP than BL. These results show that ALP inhibition is not correlated with forskolin-activated AC inhibition. Furthermore, in the presence of a competitive inhibitor of GTP (0.1 mM guanosine 5'-O-(2-thiodiphosphate), BL retained its antagonizing effect on forskolin-activated AC which suggests a direct action on the catalytic subunit. The inhibition was of the mixed type, indicating a complex interaction between BL and AC. Glucagon-activated AC activity in rat liver membranes was also inhibited by BL, although to a slightly lesser degree than thyroid stimulating hormone (TSH)-activated AC from human thyroid for a given BL concentration. In cultured human thyroid cells, BL (0.25 mM) induced a potent decrease in cAMP accumulation after 2 hr of stimulation by TSH. Taken together, these results show that BL inhibits AC and that this inhibition is not organ-specific.

Adenylyl Cyclase Inhibitors

Multicentre evaluation of a two-step automated enzyme immunoassay of free thyroxine.

The two-step enzymatic immunoassay of free thyroxine (IMx FT4, Abbott Laboratories, Chicago, IL) was studied in three centres. The assay involved a fluorimetric measurement and took 45 minutes using a completely automated procedure. The results were compared with those from the free thyroxine two-step radioimmunoassay and with the "calculation" of free thyroxine. The analytical precision was found to be excellent if the analyser was correctly set. The IMx FT4 assay seemed unaffected by increased concentrations of albumin and of non-esterified fatty acids (oleic acid) up to 5 mmol/l. The euthyroid reference interval, defined as that including 95% of 194 control subjects, was 12-21 pmol/l. A limited overlap existed between euthyroid and hyperthyroid patients, but a larger one was seen between the euthyroid and hypothyroid population, the latter including subclinical hypothyroidism. IMx FT4 results agreed well when compared with those from two-step radioimmunoassays. The IMx FT4 technique gave rise to a low percentage of elevated results in patients being treated with heparin, but was undisturbed by autoantibodies to thyroxine and triiodothyronine which were present in one hypothyroid patient.

Adolescent

Comparative measurement of progesterone receptors in breast cancer by biochemical and immunoenzymatic assays.

The measurement of progesterone receptors (PR) by enzyme immunoassay (Abbott Laboratories, EIA monoclonal) and biochemical assay using a tritiated ligand (promegestone, R5020) was studied and compared by using the statistical method of Passing and Bablok. In order to improve the reliability of the biochemical method, data were analysed using a hyperbolic model which avoids the need to determine non-specific binding experimentally. The comparison of hyperbolic (Y) and Scatchard (X) plots gave a regression curve of Y = 0.93 x + 1.34 fmol/mg of protein. Cytosols from 70 human breast cancers homogenized in the absence of KCl were assayed for PR by both the EIA (Y) and biochemical (X) methods. The linear regression obtained gave Y = 1.21 X + 1.97 fmol/mg of protein. In the presence of 0.4 M KCl-Tris buffer, the corresponding result for 80 human breast cancers was Y = 3.11 X + 1.91 fmol/mg of protein. The slopes of the two regression lines obtained in the presence or absence of KCl were significantly different. Results of the biochemical and EIA methods were similar in the absence of KCl, whereas EIA gave higher values when KCl was used. This discrepancy probably stem from the methodological differences between the two methods: the biochemical assay measures active steroid binding sites while EIA measures antigenic activity. The authors conclude that clinical studies are required before using high-salt extraction buffer in routine PR determination by the EIA method; this will result in improvements in the determination of the hormone dependence and/or the prognosis of human breast cancers.

Breast Neoplasms

[Evolution of salivary estradiol levels during the spontaneous menstrual cycle. Correlation between saliva and plasma].

The measurement of steroid concentrations is recommended in the exploration of the different endocrine functions. The salivary concentrations are the reflect of the free biologically active fraction in the plasma. In this study we have used a sensitive and specific method that can be routinely applied in salivary extradiol (SE2) RIA, using a 3 CMO 125I histamine derivative as a tracer. This study related to 12 normal spontaneous menstrual cycles and two abnormal spontaneous cycles. Saliva samples were collected daily throughout the menstrual cycle. Plasma samples were collected simultaneously to compare the salivary and plasma patterns. In the follicular phase SE2 was low: M +/- SD = 9.4 +/- 2.4 pmol/l. During the periovulatory period, the mean level of SE2 the day of the preovulatory peak was 27.6 +/- 8.6 pmol/l. In the luteal phase the SE2 levels fluctuated in a serrated manner with a mean of 11.7 +/- 3.4 pmol/l. The difference between the different phases is significant at the probability threshold 0.01. We have compared the salivary and plasma patterns during the different phases. At the beginning the salivary/plasma ratio was 3.4 +/- 0.9%. During the periovulatory period this ratio was only 2.5 +/- 0.6% and the end of the cycle 2.8 +/- 1%. The statistic study showed that these differences were significant at the probability threshold 0.01.

Adult

Breast cancer estrogen receptor assays: assessment of a direct hyperbolic fitting to analyse multipoint binding data.

Analysis of breast cancer estrogen receptor multipoint binding assay is performed by fitting experimental data to a hyperbolic model derived from the law of mass action. The calculations performed on a microcomputer are carried out from the total bound and free ligand concentrations. The parameters estimated by hyperbolic fitting, receptor concentration N and constant of dissociation K, well agree with those obtained by Scatchard's transformation. N and K derived from hyperbolic analysis are much less susceptible to the influence of experimental errors. The method is more reliable at low receptor concentrations. The main advantage of the hyperbolic fitting is to simplify the technical methodology in clinical laboratory practice; there is no need to determine the non-specific bindings experimentally. Calculations can be easily automated on any laboratory microcomputer. Assays of any kind of receptor could be analysed by the hyperbolic fitting when the physical-chemical equilibrium between receptor, nonsaturable component and ligand can be approximated by a two-component model.

Breast Neoplasms

One-step chemiluminescent immunoassay of free thyroxin with acridinium-ester-labeled thyroxin evaluated and compared with a two-step radioimmunoassay.

This new one-step chemiluminescent immunoassay of free thyroxin (FT4) involving a thyroxin-immunoglobulin conjugate labeled with acridinium ester (Magic Lite System; Ciba Corning Diagnostics Corp., Medfield, MA) is rapid (one 1-h incubation), requires two calibrators per run, and takes 10 s per sample for the quantification step. Analytical performances were excellent: within- and between-run CVs of less than 10% in the working range, no significant effect of hemolysis, bilirubin, or lipemia, and no significant interaction between the conjugate and the thyroxin-binding proteins. Magic Lite results (y) correlated well with those obtained by the Sclavo (x) two-step radioimmunoassay (Sclavo, Siena, Italy): y = 1.35x + 1.32 (r = 0.94, n = 267, P less than 0.001, Sxy = 6.29). Clinical sensitivities (diagnostic efficiencies) for hypothyroidism and hyperthyroidism were 0.91 and 0.98 for normal interval limits of 12 and 21.5 pmol/L (95% confidence interval). Magic Lite results in situations where patient therapy, treatment, or unusual conditions can result in a lack of correlation between the clinical status and the FT4 values were qualitatively the same as those obtained by the Sclavo assay.

Adult

Chemiluminescence immunoassay of thyrotropin with acridinium-ester-labeled antibody evaluated and compared with two other immunoassays.

A new chemiluminometric immunoassay of thyrotropin (TSH) involves antibody labeled with acridinium ester ("Magic Lite System," Ciba Corning Diagnostic Corp.). The assay is rapid, with two incubations totaling 2.5 h, requires two standards per run, and takes 10 s per sample for the quantification step. Analytical performance, within- and between-run reproducibilities, and linearity were excellent. The detection limit is 0.04 milli-int. unit/L. Results correlated well with those obtained by immunoradiometric assay (RIA-gnost hTSH, Hoechst-Behring) and immunofluorometric assay (hTSH Delfia, LKB): r = 0.975. TSH measurements in 32 euthyroid subjects ranged from 0.4 to 4.8 milli-int. units/L (mean 1.35 milli-int. units/L). TSH values for 51 hypothyroid and subclinically hypothyroid patients ranged from 2 to 65 milli-int. units/L. TSH values for 33 hyperthyroid patients (less than 0.14 milli-int. unit/L, less than 0.04 milli-int. unit/L in 16 of the 33) were clearly lower than for most untreated euthyroid subjects. For 169 other individuals whose thyroid function was being routinely assessed. TSH ranged from 0.4 to 4.8 milli-int. units/L, three had TSH less than 0.14 milli-int. unit/L, and four had TSH between 0.14 and 0.4 milli-int. unit/L. This system is as efficient and reliable for screening for thyroid function as the two comparison systems.

Acridines

[Effects of nifedipine on carotid blood flow and baroreflex response in essential arterial hypertension. Preliminary results].

The objective of this prospective study was to evaluate the effect of nifedipine administered at usual daily doses of 30 to 40 mg on the carotid flow in arterial hypertension. The study included 15 patients (8 men and 7 women), 50 to 79 (mean 59.5) years old suffering from long-standing, fixed essential hypertension becoming instable under central antihypertensive drug therapy. For calculating the carotid blood flow, vascular echotomography combined with Doppler ultrasonography and spectral analysis (Duplex probe) determining the vascular section and flow velocity were used. Arterial pressure using a mercury tonometer, flow velocity, common carotid artery diameter, carotid blood flow, Pourcelot's index, parietal tension and heart rate were measured before treatment and at the 8th day of nifedipine administration. It could be shown that the drug produced a significantly (p less than 0.001) increased carotid blood flow, in spite of a marked (p less than 0.001) decrease in systolic (p less than 0.001) and diastolic (p less than 0.005) blood pressure. The increase in carotid blood flow was directly related to the increase in flow velocity (p less than 0.001) and in the diameter of common carotid artery (p less than 0.01) and was associated with a significant decrease in the Pourcelot's index. Analysis of two groups of patients isolated from the total group according to the elevation of carotid blood flow, showed that the degree of hypotensive effect of nifedipine is negatively correlated with the baroreflex response determined by the variation of parietal tension.(ABSTRACT TRUNCATED AT 250 WORDS)

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