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Biomedical subjects

J Lefebvre

Publications and source records attributed to J Lefebvre.

At least 37 records · Page 2Linked to original sources
PubMed1991

[Pseudo-hyperkalemia. Apropos of a familial case].

One case of pseudo-hyperkalaemia is reported in a women who suffered of labile hypertension and was previously treated by fluorohydrocortisone because of hyperkalaemia. Clinical examination and ECG were normal. An incubation test performed at different temperatures confirmed the diagnosis. There was no haematological abnormality. Familial screening prompted us to discover 2 affected subjects among four studied, according to autosomal dominant inheritance. This abnormality was due to increased passive membrane permeability to potassium at low temperature out of any hematological syndrome. The diagnostic is important to avoid inappropriate medications.

Aged↗
PubMed1990

Insulin-like growth factor 1 receptors (IGF1-R) and IGF1 in human breast tumors.

To appreciate the IGF1 sensitivity of breast tumors we detected IGF1-R with a biochemical assay (RRA). We then localized and quantified IGF1-R on frozen tissue sections by histo-autoradiographic analysis (HAA). In some cases, the IGF1 and IGF1-R mRNA expression were studied by Northern blot analysis. We also studied the IGF1 plasma concentration in primary breast cancers compared to controls. IGF1-R (RRA) were found in 87% (n = 297) of the breast cancers. The mean geometric value was 3.87% (specific binding as percentage of total radioactivity); we found a highly significant correlation between IGF1-R and ER on the one hand (P = 0.0001) and PgR on the other (P = 0.0001) (Spearman test). The presence of IGF1-R was associated with a better prognosis, either on relapse-free survival (actuarial analysis: P = 0.004; Cox analysis: P = 0.005) or overall survival (respectively P = 0.003; P = 0.005). The median duration of follow-up was 30 months. By Cox analysis IGF1-R was a better prognostic factor than ER and PgR. In a series of 77 cases of benign breast disease only 47% (36/77) were positive; the mean geometric level was 1.8%. The HAA IGF1-R quantification in 20 breast carcinomas and 12 cases of benign breast disease confirmed the RRA results and demonstrated that the labeling was localized on the epithelial component. In four breast cancers, we did not detect IGF1 mRNA; IGF1-R probe demonstrated two major mRNAs of 11 and 7 kB. Finally we found that IGF1 plasma level was higher in breast cancer patients than in healthy controls of the same age. These results show that IGF1 is implicated in breast cancer growth and suggest that anti-IGF1 treatment might be useful in human breast cancer: for this reason, we and others carried out a phase II clinical trial with somatostatin.

Autoradiography↗
PubMed1990

Bifunctional thrombin inhibitors based on the sequence of hirudin45-65.

The interaction of alpha-thrombin with the hirudin (HV1) fragment N alpha-acetyl desulfo hirudin45-65 (P51) was investigated. Kinetic analysis revealed that P51 inhibits the proteolysis of a tripeptidyl substrate with Ki = 0.72 +/- 0.13 and 0.11 +/- 0.03 microM for bovine and human alpha-thrombins, respectively. The inhibition was partially competitive, affecting substrate binding to the enzyme-inhibitor complex by a factor alpha = 2 (bovine) and alpha = 4 (human) characteristic of hyperbolic inhibitors. P51 also inhibited thrombin-induced fibrin clot formation with IC50 values of 0.94 +/- 0.20 and 0.058 +/- 0.006 microM for bovine and human alpha-thrombins, respectively. The enhanced antithrombin activity for human thrombin could be attributed to species variations in the putative auxiliary "anion" exosite since N alpha-acetyl desulfo hirudin55-65 displayed the same rank order of potency shift in a clotting assay without inhibiting the amidolytic activity of either enzyme. From these observations, a potent thrombin inhibitor was designed having modified residues corresponding to the P1 and P3 recognition sites. N alpha-Acetyl[D-Phe45, Arg47] hirudin45-65 (P53) emerged as a pure competitive inhibitor with a Ki = 2.8 +/- 0.9 nM and IC50 = 4.0 +/- 0.8 nM (human alpha-thrombin) and is designated as a "bifunctional" inhibitor. Its enhanced potency could be explained by a cooperative intramolecular interaction between the COOH-terminal domain of the inhibitor and the auxiliary exosite of thrombin on the one hand, and the modified NH2-terminal residues with the catalytic site on the other.

Amino Acid Sequence↗
PubMed1990

Functional beta-adrenergic receptors in breast cancer cells.

Using L-[3H]dihydroalprenolol [( 3H]DHA), a potent beta-adrenergic antagonist, we demonstrated in breast cancer cells the presence of beta-adrenergic receptors with high affinity (Kd 1-9 nM) as shown by Scatchard analyses. Natural and synthetic agonists inhibited the [3H]DHA binding in the following order of potency: L-isoproterenol = L epinephrine much much greater L-norepinephrine, identical to the well-established order of potency for these compounds in producing beta-adrenergic responses. We verified that these compounds actually stimulated cAMP production in breast cancer cells. At the present time, the pathophysiological significance of beta-adrenergic receptors remains unclear. In view of the importance of cAMP in lactose production and in tumor growth mechanisms, it seems to be important to characterize the beta-adrenergic receptors in breast cancer cells in more detail and study their possible involvement in breast tumor growth.

Breast Neoplasms↗
PubMed1989

Secretion of transferrin by human breast cancer cells.

Transferrin (Tf), the major iron-binding protein in the plasma of vertebrate species is an essential growth factor for cells in serum-free media and appears to be involved in the regulation of growth and differentiation of human tissues. We report here that human breast cancer cells secrete a factor immunologically similar to Tf. The secretion of Tf by the hormone-responsive cell-line MCF-7 is stimulated by 17 beta-estradiol and reduced by the antiestrogen 4-hydroxy tamoxifen. These data suggest that Tf secreted by breast cancer cells may be an additional autocrine growth factor confering selective advantages to rapidly proliferating breast cancer cells and perhaps permit tumor cell growth in poorly vascularized areas.

Breast Neoplasms↗
PubMed1989

Structure of citrus pectins and viscometric study of their solution properties.

Citrus pectins with degrees of methylation between 30 and 72% were carefully characterized in order to determine their charge density and molecular weight distribution, the content in galacturonic acid and in neutral sugars, the degree of methylation and acetylation. Using enzymic degradation it has been found that pectin molecules consist mainly of long homogalacturonan regions with some regions of neutral sugars as side chains attached on rhamnose residues. The viscometric behaviour of the different samples indicates that 0.1 M NaCl, at 25 degrees C, is a good solvent of sodium pectinates. From the evolution of the Huggins parameter, it appears that pectins with 50% of methylated galacturonic groups exhibit a maximum flexibility. A Mark-Houwink exponent of 0.8 has been found in good agreement with theoretical predictions for flexible polymers in a good solvent.

Acetylation↗
PubMed1989

Opposite effects of estrogen and catecholestrogen on hormone-sensitive breast cancer cell growth and differentiation.

Catecholestrogens and especially 2-hydroxyestrone (2OH-E1) are estradiol metabolites locally formed in breast cancer cells. The present study demonstrates that the two parent compounds, estradiol (E2) and its metabolite 2OH-E1, exert opposite effects on hormone-sensitive breast cancer cell growth assessed by cell counts and transferrin receptor levels, and also on cell differentiation assessed by secreted proteins such as alpha-lactalbumin and gross cystic disease fluid protein (GCDFP-15). The present findings may highlight estradiol regulation in hormone-sensitive breast cancer cells.

Breast Neoplasms↗
PubMed1989

Altered erythrocyte cation permeability in familial pseudohyperkalaemia.

1. Erythrocyte cation transport pathways have been investigated in a family with pseudohyperkalaemia. 2. Ouabain- and bumetanide-resistant Na+ and K+ effluxes in three pseudohyperkalaemic patients were not different from those of control subjects when assessed at 37 degrees C. 3. When the temperature was decreased to 20 degrees C and 9 degrees C, K+ passive permeability markedly increased and Na+ permeability remained unchanged in these patients. In contrast, in control subjects a reduction in temperature caused a marked reduction in Na+ and K+ passive permeability. 4. These findings could account for the marked increase in plasma K+ concentration observed at subphysiological temperatures. 5. The Na+-K+ co-transport pathway was reduced in all members of the family, but the Na+-K+ pump was reduced in only two of them. These alterations were independent from the pseudohyperkalaemic state.

Aged↗
PubMed1989

Possibilities and limits of the medical treatment for primary hyperparathyroidism.

Clinically obvious primary hyperparathyroidism is only curable by surgery. Medical treatment is debatable under other circumstances: mild chronic hypercalcemia, patients who refuse surgery, serious coexisting medical problems and recurrence or persistence of PHPT after surgical treatment. Prior to medical treatment, the usual common management of any mild hypercalcemia must be taken. The potential medical treatments are: (1) the inhibition of parathyroid hormone (PTH) secretion, and (2) the inhibition of the effects of PTH. The substances of these two main types are successively described. Nevertheless, no ideal medical treatment of PHPT is actually available.

Amifostine↗
PubMed1989

[Changes in the glucose tolerance parameters in non-diabetic hypertensive patients treated with cicletanine].

The effects of cicletanine hydrochloride on glucose tolerance parameters were studied in a two-phase trial in which patients received a placebo for 2 weeks, followed by cicletanine 50 mg/day for 3 months. Ten patients with mild to moderate hypertension, who were neither obese nor diabetic and had no disorder of glucose tolerance entered the study. None of the patients was withdrawn. Glucose tolerance was evaluated by two oral glucose tolerance tests performed at 90 days' interval, each with half hourly blood glucose and insulin assays. The clinical effectiveness of the drug was assessed by monthly blood pressure measurements. No significant change in glycaemia and insulinaemia was observed. There was a significant decrease of supine SBP from 170.7 +/- 9.1 mmHg to 150.3 +/- 6.7 mmHg (p less than 0.0001) and of supine DBP from 101.3 +/- 4.1 to 80.3 +/- 7.7 mmHg (p less than 0.0001). At the end of the study, 9 of the 10 patients had normal blood pressure values. No undesirable clinical or biochemical effect was noted. thus, cicletanine, an antihypertensive drug derived from furopyridine, proved to be devoid of adverse effects on glycoregulation and clinically effective on hypertension.

Adult↗
PubMed1989

[Enkephalin-like immunoreactivity in Leydig cell tumor].

So far, the presence of an enkephalin-like immunoreactivity has never been reported in Leydig cell tumors at our knowledge. A 39 years old man having a painful gynecomastia and an impotency changing in time has been studied. At clinical examination, he was normal, without palpable testis tumor. The sperm count analysis showed an oligoastheno-spermia. Plasma testosterone (T) was low and plasma estradiol (E2) was high, varying from day to day. T/E2 ratio was always low (20 to 72 - N:220-240) and fell after HCG administration. Plasma LH was normal and plasma FSH was low. 17 hydroxyprogesterone (17 OH-P)/T ratio was increased (0.7 - N:0.23). A small tumor was localized in the left testis by ultrasonography. The spermatic vein catheterization, which was only possible on the left side, showed a decreased T, a high E2 and a low T/E2 ratio (19 - N:304). After unilateral orchidectomy, the histological study confirmed the diagnosis of Leydig cell tumor. With antibodies raised against synthetic Met-en-kephalin, it has been possible to detect an enkephalin-like immunoreactivity in the tumoral cells as well as in the surrounding normal cells.

Adult↗
PubMed1988

Assay of GCDFP-15 by ELISA: an available method for in vitro studies of functional differentiation in human breast cancer.

An enzyme-linked immunosorbent assay (ELISA) was applied to a light protein, isolated from human breast cyst fluid (BCF) termed "gross cystic disease fluid protein - 15 Kda" (GCDFP-15), a potential differentiation marker in in vitro human breast cancer studies. The detection limits of this procedure, performed in microtiter plates, were 0.5 to 250 ng/well corresponding to 10 ng/ml to 5 micrograms/ml of sample or antigen solution. Possible cross-reaction with various antigens, especially those found in culture media, were investigated. The correlation coefficient between enzymoassay and radioimmunoassay was 0.978. The results showed that quantification of GCDFP-15 by ELISA is a specific and highly sensitive method. This procedure may be of interest in in vitro studies on the functional differentiation of breast cancer cells.

Apolipoproteins↗
PubMed1988

Comparison of three techniques for detection of Chlamydia trachomatis in endocervical specimens from asymptomatic women.

Culture in DEAE-dextran-treated HeLa 229 cells, a solid-phase enzyme immunoassay (EIA) (Chlamydiazyme; Abbott Laboratories, North Chicago, Ill.), and a direct immunofluorescence test (DFA) (MicroTrak; Syva Co., Palo Alto, Calif.) were compared for the detection of Chlamydia trachomatis in endocervical specimens from 715 asymptomatic women. Response to antibiotic therapy was also monitored at least 4 weeks after completion of therapy. An additional sample was collected at a control visit, and a second culture was performed if discrepancies were observed between the three tests. A total of 48 infections were diagnosed, for a prevalence of 6.7%. At the first visit, 37 specimens were positive by culture. The respective sensitivities of EIA and DFA were 78.4 and 81.1% and the respective specificities were 96.8 and 97.9% when compared with the cell culture technique. The positive predictive values were 56.9 and 68.2%, respectively. When the additional 11 infections detected by the second culture were included to establish a new standard of positivity, the sensitivity of the first culture was estimated at 77.1%. The positive predictive values of EIA and DFA increased to 77.6 and 83.7%, respectively. EIA and DFA performed as well as culture for control of therapy; a 100% agreement among the three techniques was observed.

Adolescent↗