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Biomedical subjects

A Fournier

Publications and source records attributed to A Fournier.

At least 451 records · Page 25Linked to original sources
PubMed1989

Indirect clinical evidence that 1 alpha OH vitamin D3 increases the intestinal absorption of aluminum.

In a previous study we showed that 1 alpha OH vitamin D3 [1 alpha (OH)3] given to 16 hemodialyzed patients taking Al(OH)3 at a constant dose increased their plasma concentrations of aluminum [Demontis et al. 1986]. In order to choose between 2 possible mechanisms explaining this increase (increased intestinal absorption or decreased tissue storage of aluminum), we gave, in the present study, 1 alpha (OH)3 the same dose (6 micrograms per week) for the same period (4 weeks) to 15 stable hemodialyzed patients after their Al(OH)3 had been discontinued for 6 weeks. Under Al(OH)3 treatment they had a mean plasma aluminum (2.33 +/- 2.36 mumol/l) which was not significantly different from that of the patients in our former study (1.23 +/- 0.25 mumol/l). After Al(OH)3 discontinuation, plasma aluminum (measured by inductively coupled plasma emission spectrometry) decreased significantly as early as the 2nd week of the control period (1.39 mumol/l). The decrease was maintained at a plateau throughout the 5 weeks of the control period (1.38 mumol/l), the 4 weeks of 1 alpha OH vitamin (vit) D3 administration (1.40 mumol/l) and the 8 weeks of the post 1 alpha (OH)3 period (1.22 mumol/l). Plasma calcium and phosphate concentrations increased significantly with 1 alpha (OH)3 and decreased thereafter whereas plasma PTH concentrations decreased during 1 alpha (OH)2 D3 and increased after its discontinuation suggesting biological activity of 1 alpha (OH)3. Since 1 alpha (OH)3 increases plasma aluminum in hemodialyzed patients only when they are simultaneously taking Al(OH)3, it is suggested that this increase is explained by an increase of intestinal absorption of aluminum and not by a tissue redistribution of aluminum.

Adolescent↗
PubMed1989

[Infections caused by central venous catheterization at intensive care units].

All different types of catheters can induce localized (subcutaneous) or systemic sepsis. Infection rates of 7 to 20% have been reported in the literature; catheter infection results from bacterial colonization of the skin, colonization of the line or may be secondary to blood born seeding. In a one year prospective study of 56 catheters in our unit, the rate of systemic infection was 5.3%, insertion site infection 3.6%, and contamination without infection 25%. No catheter with less than 10(2) colonies on a semi-quantitative culture method was infected. Prevention of catheter related sepsis needs strict aseptic protocols, and short duration of catheterization, antiseptic wrapping of the line; antimicrobial filtersets may further reduce the infection risk.

Bacterial Infections↗
PubMed1988

DNA-binding proteins in protein kinase C preparations.

Human DNA enriched in repetitive sequences specifically bound to a component(s) in purified preparations of rat brain protein kinase C (PKC). DNA which bound to protein was cloned in pUC-19 and one clone characterized as containing an approx. 140 bp insert. The band containing this insert (separated by acrylamide gel electrophoresis) was lost when the DNA was incubated with purified PKC preparations. Thus a protein in relatively pure PKC preparations is a sequence-selective DNA-binding protein. The results raise the possibility that PKC or a fragment of PKC binds selectively to specific DNA sequences.

Animals↗
PubMed1988

Low androgen levels induce the development of androgen-hypersensitive cell clones in Shionogi mouse mammary carcinoma cells in culture.

The influence of the concentration of androgen present on the development of heterogeneous growth responsiveness to androgens was studied in an androgen-sensitive clone (SEM-1) of the Shionogi mammary carcinoma cell line incubated for up to 6 months in the presence of 0, 0.01, 0.3, or 100 nM dihydrotestosterone (DHT). In the absence of added androgen, there was a rapid increase in spontaneous cell growth, the increase being delayed by 2, 4, and 6 months when the cells were incubated with 0.01, 0.3, and 100 nM DHT, respectively. Conversely, the mitogenic effect of DHT decreased rapidly when originally androgen-sensitive cells were incubated with less than maximal concentrations of DHT. The most significant finding was the marked heterogeneity in the androgen sensitivity of the clones obtained after incubation for 2 months in the presence of less than maximal concentrations of DHT. In cells exposed to a maximal concentration of DHT (100 nM), only 2 of 22 clones were more sensitive to DHT (lower Km value) than the original clone, while 8 subclones were hyposensitive to DHT. On the other hand, when the cells were incubated for 2 months with a low (0.3 nM) concentration of DHT, 29% (7 of 24) of the clones were hypersensitive to DHT. Clones derived from cells treated with 0 or 0.1 nM DHT lost most of their responsiveness to DHT during the same time interval, with a simultaneous increase in spontaneous growth rate. The present data show that incubation of a clone of androgen-sensitive Shionogi carcinoma cells in the presence of a low DHT concentration, comparable to the circulating levels of DHT in castrated men, induces the development of androgen-hypersensitive cell clones that are able to grow on minute amounts of androgens. Such androgen-hypersensitive cells are likely to be unresponsive or resistant to antihormonal therapy. The present data emphasize the major importance of the hormonal environment on the maintenance, loss, and increase of tumor cell responsiveness to androgens.

Androgen Antagonists↗
PubMed1988

Maintenance of androgen responsiveness by glucocorticoids in Shionogi mammary carcinoma cells in culture.

The possibility that glucocorticoids can delay or prevent loss of responsiveness to androgens in androgen-deprived cells was investigated. While a complete loss of responsiveness to dihydrotestosterone (DHT) was observed within 60 days of androgen deprivation, addition of the synthetic glucocorticoid dexamethasone (DEX) delayed both the loss of growth responsiveness to DHT and the increase in spontaneous growth rate by approximately equal to 60 days. When the growth response to DEX was studied, the changes found were similar to those described above for DHT, namely loss of response following steroid deprivation and preservation of response in cells preincubated with DHT or DEX. In addition, long-term incubation in the presence of DEX was accompanied by low-amplitude stimulation of cell growth at extremely low concentrations of DHT and DEX, suggesting that androgen- and glucocorticoid-hypersensitive cell clones developed during androgen deprivation. The present data show that long-term incubation of androgen-sensitive Shionogi cells leads not only to an increase in the spontaneous growth rate, but also to the appearance of androgen- and glucocorticoid-hypersensitive cells, which may well play an important role in the development of resistance to endocrine therapy in human hormone-sensitive cancers. Although it is not as efficient as DHT, the glucocorticoid DEX can delay the loss of androgen sensitivity in this cell line.

Androgens↗
PubMed1988

Preparation and characterization of biotinylated probes for the beta-interferon receptor.

1. Recently we described the isolation of the beta-interferon receptor [Zhang et al. (1986) J. biol. Chem. 261, 8017-8021]. A highly purified product was obtained but in low quantities. 2. The use of biotinylated beta-interferon as a ligand represents an alternate approach to receptor isolation. 3. We have prepared and characterized the derivatives N-(biotinyl)- and N-(biotinyl-epsilon-aminocaproyl)-recombinant human [Ser17]-interferon beta (B- and BC-recHuIFN beta). 4. Biotin incorporation does not result in any loss of antiviral activity, demonstrating the recognition of the derivative by the cell receptor. 5. The biotinylated recHuIFN beta binds specifically and reversibly to succinoylavidin or guanidine thiocyanate-stripped succinoylavidin linked to a Sepharose matrix. 6. Comparison of the competition curves obtained with [14C]biotin and [3H]biotinyl recHuIFN, in the presence of increasing concentrations of biotin suggests that the IFN moiety of the derivative has little effect on the affinity of biotin for avidin. 7. Biotinylated recHuIFN beta derivatives represent useful probes for the beta-IFN receptor.

Avidin↗
PubMed1988

Glucocorticoids stimulate the growth of mouse mammary carcinoma Shionogi cells in culture.

The relative potency of a series of glucocorticoids to stimulate the growth of a cloned cell line (SEM-1) derived from the androgen-sensitive Shionogi mouse mammary carcinoma is proportional to their known affinity for the glucocorticoid receptor. The stimulatory action of glucocorticoids is not inhibited by the pure antiandrogen hydroxyflutamide while the antiglucocorticoids RU25593 and RU38486 cause 100% and 80% inhibitions of the activity of triamcinolone acetonide, respectively, thus indicating that the stimulatory effect of glucocorticoids on Shionogi cell growth is mediated by the glucocorticoid receptor. Such data indicate that not only androgens but also glucocorticoids should be taken into account when assessing the endocrine control of the growth of these mammary carcinoma cells.

Adrenocorticotropic Hormone↗
PubMed1988

Atrial natriuretic factor in pregnancy-induced hypertension and preeclampsia: increased plasma concentrations possibly explaining these hypovolemic states with paradoxical hyporeninism.

Plasma immunoreactive atrial natriuretic factor 99-126 (ir ANF), plasma volume, plasma renin activity, and plasma aldosterone were measured during pregnancy in 14 normotensive nonpregnant women, 15 normotensive pregnant women, 35 patients with pregnancy-induced hypertension (PIH), and in ten patients with preeclampsia (PE). Repeated measurements were carried out 2 months after delivery in a subgroup of the same patients. The plasma levels of ANF were found to be higher in pregnant normotensive women than in nonpregnant normotensive women, but the decrease of plasma ANF 2 months after delivery was not significant on the basis of seven paired data, so that it cannot presently be stated with certainty that pregnancy per se stimulates ANF secretion. Still higher levels of ANF were found in PIH and, especially, in PE. A positive correlation was found in the pooled population of normotensive and hypertensive pregnant women between plasma ANF and mean arterial pressure. A greater decrease of plasma ANF was found after delivery in the hypertensive patients than in the normotensive controls. This excludes an absolute deficiency of ANF secretion in the pathogenesis of hypertension. These findings suggest a compensatory role of ANF in the prevention of blood pressure increase. Plasma renin activity (PRA) and plasma aldosterone concentrations were higher in normotensive pregnant women than in normotensive nonpregnant women. Compared to normal pregnancy, plasma volume was decreased in PIH (-17%) and in PE (-25%), whereas PRA was less increased in both groups and plasma aldosterone concentration was less increased only in the PE group. The simultaneous high levels of plasma ANF may explain this inappropriate hypostimulation of renin secretion by hypovolemia in these hypertensive states.

Adult↗
PubMed1988

Applications of BOP reagent in solid phase synthesis. Advantages of BOP reagent for difficult couplings exemplified by a synthesis of [Ala 15]-GRF(1-29)-NH2.

The BOP reagent [benzotriazol-l-yl-oxy-tris-(dimethylamino)phosphonium hexa-fluorophosphate] introduced by Castro et al. [Tetrahedron Lett. (1975) 14, 1219-1222] is ideally suited for solid phase peptide synthesis. The rate of coupling using BOP compared favorably to DCC and other methods of activation including the symmetrical anhydride and DCC/HOBt procedures. BOP couplings using the solid phase procedure proceeded more rapidly and to a greater degree of completion for peptide bond formations that were previously determined to be very slow using the conventional DCC method. Stepwise solid phase peptide synthesis using BOP was successfully utilized for the preparation of the (22-29) and (13-29) fragments of [Ala15]-GRF(1-29)-NH2. Single couplings with 3 equiv. BOP and Boc-amino acids and 5.3 equiv. of diisopropylethylamine in DMF were used for each cycle. The yields of the fragments were superior and the purities comparable using the BOP procedure (single couplings) to those observed using multiple couplings via the DCC coupling method. A total synthesis of [Ala15]-GRF(1-29)-NH2 was also carried out using the BOP procedure (single couplings and 3 equiv. BOP and Boc-amino acids and 5.3 equiv. diisopropylethylamine in DMF for each cycle). Multiple couplings were only required for Boc-Asn-OH due to the proposed formation of Boc-aminosuccinimide during activation. The resultant GRF(1-29) analog was comparable to a control prepared with multiple DCC couplings under optimized conditions. In a parallel study, unprotected Boc-(hydroxy)-amino acids were successfully coupled with the BOP reagent. However, the number of coupling cycles after the introduction of unprotected hydroxy-amino acid must be minimal (less than 10). The use of the BOP reagent with unprotected Tyr in solid phase peptide synthesis was also clearly established.

Growth Hormone-Releasing Hormone↗
PubMed1988

Synthesis, biological activity and conformational analysis of cyclic GRF analogs.

A novel cyclic GRF analog, cyclo(Asp8-Lys12)-[Asp8,Ala15]-GRF(1-29)-NH2, i.e. cyclo8,12[Asp8,Ala15]-GRF(1-29)-NH2, was synthesized by the solid phase procedure and found to retain significant biological activity. Solid phase cyclization of Asp8 to Lys12 proceeded rapidly (approximately 2 h) using the BOP reagent. Substitution of Ala2 with D-Ala2 and/or NH2-terminal replacement (desNH2-Tyr1 or N-MeTyr1) in the cyclo8,12[Asp8,Ala15]-GRF(1-29)-NH2 system resulted in highly potent analogs that were also active in vivo. Conformational analysis (circular dichroism and molecular dynamics calculations based on NOE-derived distance constraints) demonstrated that cyclo8,12[Asp8,Ala15]-GRF(1-29)-NH2 contains a long alpha-helical segment even in aqueous solution. A series of cyclo8,12 stereoisomers containing D-Asp8 and/or D-Lys12 were prepared and also found to be highly potent and to retain significant alpha-helical conformation. The high biological activity of cyclo8,12[N-MeTyr1,D-Ala2,Asp8,Ala15]-GRF(1-29)- NH2 may be explained on the basis of retention of a preferred bioactive conformation.

Animals↗