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Biomedical subjects

Y Lefebvre

Publications and source records attributed to Y Lefebvre.

At least 19 recordsLinked to original sources

[Prostatic leiomyoma].

Large leiomyomas of the prostate are rare tumors. The authors report the case of a 78-year-old patient with two large prostatic leiomyomas who presented with chronic obstructive urinary symptoms. The US and CT aspects are illustrated; the signs are not specific but rather suggest a benign process. The tumor, probably of embryologic origin, must be distinguished from neoplasms when presenting in association with the classical benign prostatic hypertrophy. The definite diagnosis is obtained histopathologically. Prognosis is good with no evidence of recurrent disease.

Aged

Reactive oxygen species produced from chromate pigments and ascorbate.

The reactions of various chromate pigments and ascorbate were investigated by an ESR spin trapping technique. Production of Cr(V) was detected directly and productions of very electrophilic reactive oxygen species (ROS) was detected via the oxidation of formate. We demonstrated previously that both dissolved oxygen and Cr (V) were essential in the production of ROS in this system, and that ROS production was inhibited by catalase. We studied here the effect of solubility of different chromate pigments: sodium, calcium, strontium, basic zinc, basic lead supported on silica, and lead and barium chromates on the production of ROS in buffered medium and cell culture medium (Dublecco's Modified Eagle medium + fetal calf serum). Sodium, calcium, basic zinc, and basic lead chromates were active in the production of ROS in presence of cell culture medium, whereas lead and barium chromates were inactive.

Ascorbic Acid

[Paratesticular rhabdomyosarcoma].

The observation presented is based on one patient 18 years old who presents a paratesticular rhabdomyosarcoma stage I. A radical orchidectomy through on inguinal incision with high ligation of the spermatic cord was performed. We have omitted retroperitoneal lymph node dissection. The patient was treated by postoperative chemotherapy with V.A.C. during five weeks. Our patient remains disease free one year post-surgery, but after that, he presents suddenly a symptomatic bone metastasis of the thigh-bone and a massive metastatic pulmonary spreading, without retroperitoneal lymph nodes on the CT-scan. A multidisciplinary approach has considerably improved the prognosis of this tumor. Some reports suggest that routine retroperitoneal lymphadenectomy may be unnecessary for patients with no evidence of nodal involvement on CT-scan. The recent literature insists on problems cause by retroperitoneal lymph node involvement, but our clinical caused must induce us not to underestimate the potential of hematogenous spreading of this tumor.

Adolescent

Effects of growth hormone (GH)-releasing factor and somatostatin on GH secretion from early to midgestation human fetal pituitaries.

Using explant cultures of human anterior pituitary glands (9-19 weeks fetal age) and an acute (3-h) test protocol, we investigated fetal somatotrope responsiveness to human GH-releasing factor [hGRF-(1-44)] and somatostatin [SRIF-(1-14) and SRIF-(1-28)] as a function of age. Ontogenic data were analyzed using three age groups: 9-10, 12-13, and 15-19 weeks fetal age. Both daily (24-h) and acute test (3-h) basal GH secretion increases as a function of fetal age, with the greatest increase occurring after 12-13 weeks; however, the 3 h/24 h secretion ratio remains unchanged, at approximately 12%. GRF (0.1-10 nM) stimulates GH release in a dose-related fashion, regardless of fetal age; there is a significant increase in the response to both 1 nM (P < 0.05) and 10 nM (P < 0.01) GRF between 9-10 and 15-19 weeks fetal age and to 10 nM GRF (P < 0.05) between 12-13 and 15-19 weeks. Pretreatment of cultures (9-19 weeks) with 1 or 10 nM GRF for 24 h does not alter basal 3-h GH secretion, but significantly decreases subsequent responses to 1 or 10 nM GRF, respectively (P < 0.01). Pretreatment with 1 nM GRF does not alter a subsequent 3-h response to 10 nM GRF. SRIF-(1-14) (1-100 nM) causes a dose-related inhibition of basal GH secretion from as early as the ninth week of fetal life; there is a small age-related increase in the somatotrope response to 100 nM SRIF-(1-14) between 12-13 and 15-19 weeks fetal age (P < 0.05). In a group of 11- to 14-week-old fetal pituitaries, SRIF-(1-28) had a significantly (P < 0.05) greater inhibitory effect than SRIF-(1-14) at both 1 and 10 nM; the two peptides decreased basal GH secretion to a similar extent at 100 nM (52.8 +/- 4.0% of control value; P < 0.01). SRIF-(1-14) (10 and 100 nM) does not significantly alter 10 nM GRF-stimulated GH release from 9- to 10-week-old fetal pituitaries. However, by 12-13 weeks, 10 nM SRIF-(1-14) reduces GRF-stimulated GH secretion by 60% (P < 0.01), while 100 nM SRIF-(1-14) decreases it by 80% (P < 0.01); similar inhibitory effects are observed with 15- to 19-week-old fetal somatotropes.(ABSTRACT TRUNCATED AT 400 WORDS)

Cells, Cultured

In vitro modulation of growth hormone (GH) secretion from early to midgestation human fetal pituitaries by GH-releasing factor and somatostatin: role of Gs-adenylate cyclase-Gi complex and Ca2+ channels.

Using explant cultures of human fetal anterior pituitary glands (9-19 weeks fetal age) and an acute (3-h) test protocol, we investigated the role of two signal transduction pathways (Gs-adenylate cyclase-Gi, Ca2+ channels) in GH-releasing factor (GRF)/somatostatin (SRIF) regulation of GH secretion during the first half of gestation. Data have been analyzed for ontogenic changes using three age groups: 9-10, 12-13, and 15-19 weeks fetal age. The fetal somatotrope shows dose-related responses to forskolin (0.1-10 microM), dibutyryl cAMP (dBcAMP; 0.1-1 mM), and theophylline (0.01-1 mM), all factors that increase intracellular concentrations of cAMP; there is a significant age-related increase in the stimulatory effects of 1 mM dBcAMP and 1 mM theophylline. When any one of these three factors is added with 10 nM GRF, there are no significant additive or synergistic effects on GH secretion. Although 10 nM SRIF has no effect at 9-10 weeks, it is inhibitory in the 12-13 and 15-19 week groups, significantly suppressing the stimulatory effect of 1 microM forskolin and completely blocking the effects of 1 mM dBcAMP or theophylline. Pretreatment of cultures with pertussis toxin completely blocks SRIF inhibition of both basal and GRF-stimulated GH release. KCl (5-50 mM) and Bay K 8644 (0.1-10 microM), both activators of Ca2+ channels, have dose-related stimulatory effects on GH release; 50 mM KCl shows an age-related increase in stimulatory activity. If 10 nM GRF, 1 microM forskolin, 1 mM theophylline or 1 mM dBcAMP is added with either 50 mM KCl or 1 microM Bay K 8644, there is an additive response. SRIF (10 nM) completely blocks the stimulatory effects of 1 microM Bay K 8644 and markedly inhibits the effects of 50 mM KCl from as early as the ninth week of fetal age. The Ca2+ channel blocker nifedipine (1-10 microM) significantly inhibits basal as well as stimulated (GRF, forskolin, dBcAMP, theophylline, KCl, and Bay K) GH release from as early as 9 weeks fetal age; in contrast, the calmodulin blocker trifluoperazine (0.01-10 microM) has no effects on basal GH secretion and only slightly inhibits the stimulatory effects of KCl. Pretreatment with 10 nM GRF for 24 h significantly decreases a subsequent 3-h response to 10 nM GRF, but does not alter the subsequent response to 1 mM theophylline or 50 mM KCl.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases

[Infected urachal cyst].

There is a wide variety of pathologies associated with the presence of urachal remnants. We describe a case of infected urachal cyst in a young adult male, with classical symptoms of dysuria, lower abdominal pain, and fever. Ultrasound, cystography and CT are described, ultrasound being often the modality of choice. Differential diagnosis of acute abdominal and pelvic pain or a midline lower abdominal mass at this age should include infection of an urachal remnant.

Adult

[The Entremise crisis center: from autonomy ... to institutional control?].

The L'Entremise crisis centre is located in the Hochelaga-Maisonneuve working class district, on the island of Montreal. Its services include temporary lodging and crisis intervention on its location or within the community. The authors provide an overview of the centre's history, its client population, its development framework and its organization methods. The article then focuses on the first results of an evaluation made in 1988 and on the measures that followed as a result of comments and suggestions. The authors present the changes that were implemented in 1991 following the 1988 review. As such, this article explores the purpose and uses of such an evaluation.

Community Mental Health Centers

A serum-free system for culturing human placental trophoblasts.

We have compared hormone production by early gestation and term human placental trophoblasts cultured in Ham's F10 medium containing 10% fetal bovine serum with that by cells cultured in serum-free HB102 medium. Mean daily production of progesterone on Days 3 to 7 was approximately 25% less by both early gestation and term cells cultured in HB102 as compared to Ham's F10, but production was maintained at a stable level for at least 7 d longer than the cells in Ham's. Estradiol production from 10(-6) M dehydroepiandrosterone by both early gestation and term cells was comparable in both media. Human placental lactogen production on Days 3 to 7 was 40% less by cells cultured in HB102. Human chorionic gonadotropin (hCG) output by early gestation cells was also 50% less in HB102 but term cells in HB102 produced twice as much hCG as those in Ham's F10. 3B-Hydroxysteroid dehydrogenase (3BHSD) activity in early gestation and term cells and 11B-hydroxysteroid dehydrogenase (11BHSD) activity of early gestation cultures was comparable in the two media. 11BHSD activity was decreased in the term cultures, and this decrease was more marked in Ham's than in HB102. Sulfatase and aromatase activities in the early gestation cultures were comparable in both media; sulfatase activity was comparable and aromatase activity only 20% less in the term cells cultured in HB102. These results indicate that serum-free HB102 supports differentiated function of human trophoblast cells and is useful for studies of placental activity for as long as 14 d in culture.

Aromatase

The effects of RU-38486 on cervical ripening. Clinical studies.

One hundred eighty pregnant patients, 17 to 39 years old (mean (+)/- SEM: 25.1 (+)/- 0.39), with an amenorrhea of 7 to 12 weeks (mean (+)/- SEM: 9.4 (+)/- 0.10), and requesting a therapeutic abortion, were selected according to general good health and gave their informed consent to the study. Mifepristone (RU-486; Roussel UCLAF, Paris, France) an antiprogestin steroid, was administered at random in doses of 0, 50, 100, 200, 400, or 600 mg. Clinical evaluations and measurements of cervical dilatation were done before the study and repeated at 24 hours after administration of Mifepristone and at 48 hours, at which time the aspiration was performed. Significant increases in cervical dilatation were observed at 48 hours with all doses of Mifepristone above 50 mg. The increases were significantly greater in patients with a gestational age greater than 10 weeks than in those less than 10 weeks' gestational age. Parity had no influence on cervical dilatation at 48 hours. Bleeding was observed significantly more often with 100 to 600 mg doses of Mifepristone than with 0 to 50 mg. No influence of gestational age or parity on bleeding could be detected. Abdominal cramps were reported more frequently with 200, 400, and 600 mg of Mifepristone at 48 hours and their occurrence appeared to parallel cervical dilatation.

Abortion, Induced

Growth-inhibitory effect of TGF-B on human fetal adrenal cells in primary monolayer culture.

We examined the effects of transforming-growth factor-B (TGF-B) on growth ([3H]-thymidine uptake) and function (dehydroepiandrosterone sulfate [DHAS] and cortisol production) of human fetal zone adrenal cells. Results indicate that TGF-B significantly inhibits, in a dose-related manner, both basal and epidermal growth factor (EGF)-stimulated cell growth: IC50 = 0.1-0.25 ng/ml. EGF is ineffective in overcoming the inhibitory effect of TGF-B, suggesting a noncompetitive antagonism between the two factors. Also, the inhibitory effect of TGF-B is additive to that of adrenocorticotropic hormone (ACTH). On the other hand, TGF-B (1 ng/ml) does not significantly change basal or ACTH-stimulated DHAS or cortisol secretion. We conclude that, unlike its effect on other steroid-producing cells, TGF-B inhibits growth of fetal zone cells and does not appear to have a significant inhibitory effect on steroidogenesis.

Adrenal Glands

Effect of placental factors on growth and function of the human fetal adrenal in vitro.

Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: 1) maximal response to PM was 2-5 times greater; 2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; 3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

Adrenal Cortex

Attachment and multiplication, morphology and protein production of human fetal primary liver cells cultured in hormonally defined media.

We established for human fetal liver cells (cultured for 2 wk) in a hormonally defined medium, optimal conditions for attachment, multiplication, and preservation of epithelial morphology as well as production and secretion of serum proteins characteristic of fetal (alpha l-fetoprotein, AFP) and adult (albumin and hemopexin) life. Conditions were considered optimal when cell number, albumin, and hemopexin levels were maintained throughout the 2-wk culture period. However, the decrease in AFP concentration, which occurred after a few days of culture, could not be reversed. The culture system developed is a suitable model for studying regulatory mechanisms governing structure and function during differentiation and may prove useful for testing the effect of toxic agents during fetal development of the human liver.

Cell Adhesion

Multiple thyroid hormone binding sites on male rat liver nuclear matrices.

Equilibrium binding of T3 to nuclear matrices isolated from male rat liver occurred after incubation for 3h at 20 degrees C. Two binding sites, having KD's of 6 and 95 nM, were revealed by Scatchard analysis. T3 and Triac competed for the binding of [125I]T3 to the high affinity site whereas only T3 competed for binding to the lower affinity site. Reverse T3 (rT3) did not compete for the binding of T3 to either class of binding sites. The binding sites were highly DNAse-sensitive, and less sensitive to protease treatment. The effect of binding of T3 to nuclear matrices by ATP, DTT and EDTA indicated that the sites are dissimilar to previously identified cytosolic binding sites. The higher affinity site resembles the T3 receptor in affinity and thyroid hormone specificity. The second site represents a new class of thyroid hormone binding sites. Its role in the regulation of thyroid hormone action warrants further investigation.

Animals

Regulation of growth hormone secretion from human fetal pituitaries: interactions between growth hormone releasing factor and somatostatin.

Using an explant culture system, we have demonstrated that human somatotropes respond to growth hormone releasing factor (GRF) and somatostatin (SRIF) from as early as 9.5 weeks of fetal age. Responsiveness to GRF increases significantly as a function of age up to midgestation while SRIF inhibition of basal growth hormone (GH) release does not change. SRIF has little effect on GRF-stimulated GH secretion from early gestation pituitaries, but its ability to block GRF stimulation gradually increases with fetal age from 9.5 to 16 weeks. The response to GRF remains predominant throughout this developmental period: 100 times more SRIF than GRF must be added to the cultures in order to block the GRF stimulatory effect and maintain GH secretion at basal (control) levels. Finally, adding SRIF 30 min prior to the GRF does not increase the inhibitory activity of SRIF. Our data suggest that the mechanisms that permit an interaction between GRF and SRIF are developing, but slowly, in the early to midgestation human fetal somatotrope and that GRF stimulatory pathways predominate. This may help to explain the very high levels of GH in fetal serum during the first half of gestation.

Gestational Age

Effect of insulin-like growth factors on human foetal, adult normal and tumour pituitary function in tissue culture.

To determine the direct effects of insulin-like growth factors (IGFs) on hormone release by the human pituitary gland, human foetal, adult normal and tumour pituitary tissues were maintained in culture for 2 to 4 weeks and tested with acute (3 h) exposures to different preparations of IGF peptides. Adult normal pituitaries and adenomas were tested with a semipurified preparation of IGFs, free of immunoreactive insulin, containing IGF-I and IGF-II in a ratio of approximately 1:4. Human foetal pituitaries were tested with the semipurified IGFs as well as more purified preparations of IGF-I and IGF-II. Culture media were assayed for hGH, hPrl, hACTH and hLH using specific radioimmunoassays. Both foetal (n = 16 (No. of pituitaries), 33 (No. of observations] and normal adult (n = 3, 16) human pituitaries cultures responded to the semipurified IGFs (2-25 ngEq/ml for foetal and 2-4 ngEq/ml for adult pituitaries) with a significant decrease in hGH release compared to basal (P less than 0.01) whereas the GH-secreting pituitary tumours showed no effect when tested with from 2 to 25 ngEq/ml (n = 8, 129, NS). The effect of IGFs on human foetal somatotrope activity was dose-related for both the semipurified IGFs (2-25 ngEq/ml, n = 16, 33) and IGF-I or IGF-II (10-100 ng/ml; n = 3, 18).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma

Functional zonation of the midgestation human fetal adrenal cortex: fetal versus definitive zone use of progesterone for cortisol synthesis.

Studies of human fetal adrenal function and its control have revolved mainly around the remarkable capacity of the unique fetal zone of this gland to elaborate dehydroepiandrosterone sulfate. Another important function of the fetal adrenal, however, is its production of cortisol. Because the human fetal adrenal is deficient in 3 beta-hydroxysteroid dehydrogenase activity, cortisol has been thought to be formed from circulating progesterone. To further investigate this hypothesis, cortisol production by separated fetal and definitive zones of the midgestation human fetal adrenal in organ culture has been examined in the absence and presence of varying concentrations of progesterone and adrenocorticotropic hormone. Cortisol was measured by radioimmunoassay. In the absence of progesterone, cortisol production by both zones increased gradually over time in culture in response to adrenocorticotropic hormone. In the presence of progesterone, cortisol production by the definitive zone was unchanged. In contrast, the response of the fetal zone to progesterone was immediate: cortisol production increased significantly and remained high throughout the culture period. These results suggest a greater capacity of the fetal zone to utilize progesterone for cortisol production and are consistent with morphologic evidence that the active zone of the midgestation human fetal adrenal is the fetal zone, possessing not only the enzyme activity necessary for dehydroepiandrosterone sulfate production but, except for 3 beta-hydroxysteroid dehydrogenase, that for cortisol production as well.

Adrenal Cortex