Biomedical subjects
Publications and source records attributed to C Delage.
We are reporting a case of arterial hypertension in a young woman who had an atrophic kidney with a cortical groove and histological features of the Ask-Upmark kidney. Her hypertension was renin dependent and the patient was cured following nephrectomy. Controversy on the pathogenesis of this clinical entity is briefly reviewed.
Several classes of flavonoids (flavones, flavanones, 2'-hydroxychalcones and flavan-4-ols) having a variety of substituents on A ring were investigated for their antiproliferative activity against MCF-7 human breast cancer cells. Structure-activity relationships of these compounds were discussed. 2'-hydroxychalcones and methoxylated flavanones were found to be potent inhibitors of MCF-7 cells growth whereas flavones and flavan-4-ols appeared to be weak inhibitory agents except 7,8-dihydroxyflavone.
Ursolic acid (UA) is a pentacyclic triterpenoid compound which occurs naturally in a large variety of vegetarian foods, medicinal herbs and plants. In the present study, ursolic acid was found to decrease cell viability in human lymphoma Daudi cells in a dose-dependent manner. UA also induced morphological changes in cells as well as loss of membrane asymmetry, DNA fragmentation and nuclei condensation, indicating that the mechanism by which UA induced cell death was through apoptosis. Treatment with UA increased intracellular Ca2+ levels. Use of Ca2+ channel inhibitors like verapamil blocked this Ca2+ influx and also the triggering of apoptosis. We hypothesized that the binding of UA to glucocorticoid receptors and the Ca2+ currents induced constituted the first steps of apoptosis.
Curcumin, demethoxycurcumin and bisdemethoxycurcumin are the yellow coloring phenolic compounds isolated from the spice turmeric. This study was part of a program correlating the biological activity and molecular structure of antitumor agents; the effect of these curcuminoids and cyclocurcumin (Cyclocur) was examined on the proliferation of MCF-7 human breast tumor cells. Curcuminoids appeared to be potent inhibitors, whereas Cyclocur was less inhibitory. To contribute to our understanding of the mechanism of antiproliferative activity of curcumin, cell cycle analysis was performed by propidium iodide staining and a flow cytometry technique. Curcumin exerts a cytostatic effect at G2/M which explains its antiproliferative activity. The presence of the diketone moiety in the curcumin molecule seems to be essential for the inhibitory activity.
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The effects of ursolic acid on the proliferation of B16, a mouse melanoma cell line, were studied. During investigations of the anti-proliferative effects of this triterpene, we observed that MTT colorimetric and colony forming assays show that ursolic acid is a potent inhibitor of B16 cell growth. Cell cycle analysis was performed by propidium iodide staining and flow cytometry technique. This triterpene exerts an early effect on cell cycle at G1, which explains its anti-proliferative activity. These results suggest that alterations in cell cycle phase redistribution of B16, by ursolic acid, may significantly influence the proliferation of B16, melanoma cells.
HGT cells are a human gastric tumor cell line. Preliminary data have shown that HGT cells incorporate exogenous arachidonic acid (AA) in their membrane lipids. However, we found that HGT cells are unable to produce significant amounts of AA metabolites after stimulation with calcium ionophore A23187. Furthermore, no lipoxygenase activity was detected in crude HGT cell extracts by employing an assay monitoring the in vitro utilization of linoleic acid. The meaning of these results is discussed in respect of the role of eicosanoids during cell proliferation.
The new quercetin 3-[2,3,4-triacetyl-alpha-L-arabinopyranosyl (1-->6)-beta-D-galactoside] has been isolated along with 5,7-dihydroxychromone and 5,7-dihydroxychromone 7-beta-D-glucoside from fresh flowers of Calluna vulgaris. Structural elucidation of these natural products was achieved mainly by 1H and 13C NMR.
A compound was isolated and purified from heather flowers (Calluna vulgaris) based on its ability to inhibit lipoxygenase activity. This molecule was characterized as ursolic acid by GC-MS. Ursolic acid was found to be an inhibitor of both potato tuber 5-lipoxygenase and soybean 15-lipoxygenase with IC50 values of 0.3 mM. Ursolic acid also inhibits lipoxygenase activity in mouse peritoneal macrophages at 1 microM and HL60 leukemic cells growth (IC50 = 0.85 microM) as well as their DNA synthesis (IC50 = 1 microM). The possible role of lipoxygenase inhibition in the proliferation of leukemic cells is discussed.
A new property of ursolic acid, lipoxygenase and cyclooxygenase inhibition, has been described in an acetone-extract of heather flowers (Calluna vulgaris) which could help explain the anti-inflammatory characteristics of this plant. In mouse peritoneal macrophages, human platelets and differentiated HL60 leukemic cells, ursolic acid, at 1 microM, blocks arachidonate metabolism.
A water-Calluna vulgaris extract (water-CVE) was found to be a relatively specific arachidonate 5-lipoxygenase inhibitor and showed potent anti-proliferative effects on human leukemic HL60 cells. Water-CVE completely inhibited potato 5-lipoxygenase activity at 250 micrograms/ml, partially inhibited soybean 15-lipoxygenase at pH 7.4 and had no effect either on this 15-lipoxygenase at its optimal activity pH (pH 9) or on Lupinus albus 5-, 8-, 15-lipoxygenase. In culture, the proliferation and DNA synthesis of HL60 cells were decreased by water-CVE in a dose-dependent manner with an IC50 of 200 micrograms/ml at day 4. This effect of water-CVE is related to the starting density of HL60 cells. These results suggest that arachidonate 5-lipoxygenase metabolites and/or leukotrienes could play an essential role in cellular functions of leukemic cells and may explain the success of the use of Calluna vulgaris as tea and baths in folk medicine.
Eight clomiphene citrate (150 mg/day for 5 days)-resistant anovulatory women with polycystic ovary were included in this study. A luteinizing hormone-releasing hormone (LH-RH) analog, D-Trp-6-LH-RH, 100 micrograms subcutaneous-per day, induced a hypogonadotropic state within varying periods but at most within 3 weeks, after an initial flare-up effect characterized by slight increase in ovarian size in four patients and in the other four by cysts that disappeared rapidly. On the 28th day or 15 to 20 days after menstruation for subsequent cycles, during maintenance of D-Trp-6-LH-RH therapy, a usual gonadotropin regimen was carried out in 33 cycles. Human menopausal gonadotropins obtained follicular maturation in all cycles. However, there was never the growth of a single dominant follicle but always of several follicles. Human chorionic gonadotropin then induced ovulation in 31 cycles (94%). Luteal phase was normal in 28 and inadequate in 3 of the 31 ovulatory cycles. Hyperstimulation, generally mild to moderate but rather severe in 2 cycles, was constant. Five pregnancies were obtained. The overall pregnancy rate was 15% per cycle and 17.8% per normoovulatory cycle. This study showed that an associated treatment with an LH-RH analog enables gonadotropins to achieve ovulation regularly with an encouraging number of pregnancies but at a risk of hyperstimulation.
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Determination of the bactericidal concentration of antiseptics in vitro is now standardized, allowing interesting comparisons. Conversely, measurement of this activity in vivo in man is difficult since results are dependent upon skin sampling techniques and variations in bacterial growth from individual to individual and from one site to the next. Skin sampling can be standardized by using the hologenic Hairless mouse as an experimental model (skin needle biopsy and crushing). However, variations from one animal to the next remain a problem, even though results are very similar to those found in man. We therefore used monoxenic Hairless mice contaminated with S. aureus, S. epidermidis and P. aeruginosa. All experiments on these animals demonstrated consistency of bacterial cutaneous and digestive growth over time and smallness of variations in bacterial flora from animal to animal. We advocate use of this second model for standardization of evaluation of bactericidal activity of antiseptics.
The ultrastructural findings in 4 cases of the myxoid variant of malignant fibrous histiocytoma (MFH) are described. Although this neoplasm is characterized by a high rate of local recurrence, the overall prognosis is considerably better than the usual nonmyxoid MFH. The neoplasm is composed of an admixture of round, stellate and multinucleated giant cells within a myxoid and well-vascularized stroma. Electron microscopy demonstrated four principal cell types: a primitive mesenchymal cell, spindle cells of fibroblastic and histiocytic nature, and multinucleated giant cells. These observations complement the light microscopic features but probably are insufficient to differentiate critically this entity from other myxomatous lesions of mesenchymal soft tissue such as myxoma, pseudosarcomatous fasciitis, myxoid liposarcoma. The polymorphic cellular composition lends support to the concept that the neoplasm is probably derived from a primitive multipotent mesenchymal cell capable of structural and functional modulation toward more cytodifferentiated forms.
The ultrastructure of three cases of desmoplastic fibroma of bone is presented. The lesion is principally characterized by myofibroblasts admixed with lesser numbers of fibroblasts and primitive mesenchymal cells. Thus, the cellular composition is similar to that described in a variety of nonneoplastic proliferative processes of soft tissue. It is postulated that the myofibroblastic proliferation develops in response to unknown factors acting on marrow fibroblasts or primitive mesenchymal cells.