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Biomedical subjects

M Dufour

Publications and source records attributed to M Dufour.

At least 19 recordsLinked to original sources
PubMed1992

Endosulfine, an endogenous peptidic ligand for the sulfonylurea receptor: purification and partial characterization from ovine brain.

Antidiabetic sulfonylureas act through receptors coupled to ATP-dependent potassium channels. Using the binding of [3H]glibenclamide, a highly potent sulfonylurea, to rat brain membranes to follow the purification procedure, we extracted from ovine brain, purified, and partially characterized two peptides that are endogenous ligands for the central nervous system sulfonylurea receptors. These peptides, referred to as alpha and beta endosulfine, differ by their isoelectric points, the beta form being more basic. Each form of endosulfine is recognized equally by the sulfonylurea receptors from the central nervous system and from insulin-secreting beta cells. In the same concentration range that is active on the receptors, beta endosulfine releases insulin from a beta-cell line. Endosulfine is a good candidate for being implicated in the physiology of beta cells and their disorders (e.g., type II diabetes) and in certain pathologies related to modifications of ion fluxes.

ATP-Binding Cassette Transporters↗
PubMed1992

Role of G protein beta gamma subunits in the regulation of the plasma membrane Ca2+ pump.

In Zajdela hepatoma cells (ZHC) the plasma membrane Ca2+ pump displayed no sensitivity to glucagon (19-29) (mini-glucagon), whereas in hepatocyte this metabolite of glucagon evoked a biphasic regulation of the Ca2+ pump system via a cholera toxin-sensitive G protein. Analysis of G protein subunits in ZHC membranes indicated the presence of cholera toxin-sensitive Gs alpha and G beta gamma proteins, whose functionality was manifested by GTP and NaF stimulation of adenylylcyclase activity, and pertussis toxin-catalyzed ADP-ribosylation of Gi alpha, respectively. However, immunoblotting experiments suggested a lower content in beta gamma subunits in ZHC as compared with hepatocyte plasma membranes. Complementation of ZHC or hepatocyte plasma membranes with purified beta gamma subunits from transducin (T beta gamma) caused inhibition of the basal activity of the Ca2+ pump at 10 and 300 ng/ml, respectively, and revealed (in ZHC) or increased (in hepatocytes) sensitivity of the system to mini-glucagon. After cholera toxin treatment of ZHC, T beta gamma no longer reconstituted the response of the Ca2+ pump to mini-glucagon, suggesting that the mechanism of beta gamma action is dependent on an association with the alpha subunit of a cholera toxin-sensitive G protein. It is concluded that G beta gamma subunits control both the basal activity of the plasma membrane Ca2+ pump and its inhibition by mini-glucagon.

Adenosine Diphosphate Ribose↗
PubMed1992

Rabbit embryo-fetal fluid decreases the cell cycle activities of DU-145 cells.

Successful reproduction requires tight control of cell proliferation and differentiation. Rabbit blastocoelic fluid contains such regulatory factors. For instance, it inhibits tumour or transformed cell proliferation. In this study, DU-145 cells have been used to characterize further this inhibitory activity. Maximal inhibition of cell proliferation is observed at day 12 of embryo-fetal development and this is accompanied by a strong reduction of [3H]-thymidine incorporation. DNA specific staining and analysis by flow cytometry show that cells are not stopped at any specific stage of the cell cycle. Using bromodeoxyuridine incorporation in combination with propidium iodide labelling, it has been possible to estimate the percentage of labelled cells, the duration of the S phase of the cell cycle derived from their relative movement and also the proportion of cells participating to the cell cycle. In the presence of embryonic and fetal fluids collected on day 12 (EFF D-12) the duration of the S phase and the doubling time are considerably increased and the percentage of cells participating in the cell cycle is decreased. The results also show that treatment with EFF D-12 induces the release of the cells from the monolayer. Taken altogether, these results suggest that EFF D-12 increases the duration of the cell cycle. This reduction of the mitotic activities lead up to cell death with subsequent release of cells into the culture medium.

Animals↗
PubMed1992

[Post-traumatic osteolysis of the distal extremity of the clavicle. Anatomopathological study of 2 cases].

Two patients with post-traumatic osteolysis of the distal end of the clavicle undergoing surgery 5 months and 22 months respectively after the initial trauma were evaluated histopathologically. The lysed zone was replaced by tissue of fibrous appearance, with little blood supply and non-inflammatory, the presence of which could be suspected by magnetic resonance. The synovial membrane, non-inflammatory but hypervascularised, participated in the process but did not appear to be directly responsible for the osteolysis. The osseous tissue of the patient, operated upon early, showed signs of osteoclastic resorption but there was neither stasis, vasodilatation nor signs of osteogenesis. These various findings suggest that post-traumatic osteolysis of the distal end of the clavicle does not result from local ischemic events. These appearances seem identical to those described in multifocal primary osteolysis, the cause of which also remains unknown.

Adult↗
PubMed1991

Characteristics of the biphasic action of androgens and of the potent antiproliferative effects of the new pure antiestrogen EM-139 on cell cycle kinetic parameters in LNCaP human prostatic cancer cells.

The most potent steroid in human prostatic carcinoma LNCaP cells, i.e., dihydrotestosterone (DHT), has a biphasic stimulatory effect on cell proliferation. At the maximal stimulatory concentration of 0.1 nM DHT, analysis of cell kinetic parameters shows a decrease of the G0-G1 fraction with a corresponding increase of the S and G2 + M fractions. In contrast, concentrations of 1 nM DHT or higher induce a return of cell proliferation to control levels, reflected by an increase in the G0-G1 fraction at the expense of the S and especially the G2 + M fractions. Continuous labeling for 144 h with the nucleotide analogue 5'-bromodeoxyuridine shows that the percentage of cycling LNCaP cells rises more than 90% after treatment with stimulatory concentrations of DHT, whereas in control cells as well as in cells treated with high concentrations of the androgen, this value remains below 50%. Although LNCaP cells do not contain detectable estrogen receptors, the new pure steroidal antiestrogen EM-139 not only reversed the stimulation of cell proliferation and cell kinetics induced by stimulatory doses of DHT but also inhibited basal cell proliferation.

Androgens↗
PubMed1991

Inhibition of cell cycle kinetics and proliferation by the androgen 5 alpha-dihydrotestosterone and antiestrogen N,n-butyl-N-methyl-11-[16' alpha-chloro-3',17 beta-dihydroxy-estra-1',3',5'-(10')triene-7' alpha-yl] undecanamide in human breast cancer ZR-75-1 cells.

We have investigated the effects of the pure antiestrogen EM-139 and the nonaromatizable androgen dihydrotestosterone (DHT) alone or in combination with estradiol (E2) on cell proliferation and cell kinetic parameters in human ZR-75-1 breast cancer cells. Following a 24- to 30-h exposure to E2, a decrease in the proportion of G0-G1 cells was observed, this effect being accompanied by the well-known stimulatory effect of the estrogen on cell proliferation at later time intervals. By contrast, DHT or EM-139 alone inhibited basal cell proliferation without a significant influence on cell cycle distribution. Moreover, pretreatment with DHT for 8 days, while decreasing ZR-75-1 cell number, did not cause a loss in E2 sensitivity. In fact, as early as after 24 h of E2 treatment, a decrease in the G0-G1 cell fraction accompanied by a corresponding increase of the S-phase was observed in both control and DHT-pretreated cells. When added concomitantly with E2, DHT or EM-139 inhibited the E2 stimulatory effect on cell proliferation, but only EM-139 significantly reversed the G0-G1 decrease induced by E2. Although DHT and EM-139 did not affect the distribution of ZR-75-1 cells between the different phases of the cell cycle, continuous labeling with 5'-bromodeoxyuridine showed that EM-139 and DHT had a global slowing effect on the duration of the cell cycle, thus explaining the potent inhibitory effect of these compounds on cell proliferation. The present data demonstrate that DHT and EM-139 are both potent inhibitors of the stimulatory effect on E2 on cell proliferation, their main action being related to a general increase in the duration of the cell cycle.

Breast Neoplasms↗
PubMed1991

The evolution of oxidative stress indicators in the course of myocardial ischemia.

Two studies were carried out in patients suffering from Unstable Angina (UA) and Myocardial Infarction (MI). The first study investigated the variations of the Malondialdehyde (MDA) rate at 1st, 5th, 12th day of treatment in 27 patients (15 UA and 12 MI), compared to 15 controls. This rate varied in a different way, with a first peak and a rapid decrease in UA, where it regularly decreases in MI. The second study focused on the variations of MDA, Superoxide Dismutase (SOD), Glutathion Peroxydase (GPX) rates at 2nd, 12th days in 53 patients (19 UA and 34 MI), compared to 35 controls. Here again, the rate of MDA was high on day 2 and decreased on day 12. The rate of GPX showed similar evolution while the SOD rate had an opposite evolution. These two studies confirm the evidence of oxidative stress in acute coronary deficiency.

Aged↗
PubMed1991

[Post-traumatic osteolysis of the distal end of the clavicle. Contribution of MRI].

The authors describe a case of post-traumatic osteolysis of the clavicle. The clinical and roentgenographic aspects are well known. But regarding the lytic X ray aspect, another diagnosis, particularly a tumor may be evoked. Scintigraphy and computed tomograms can take a part in the diagnosis. But scanograms are uneasy to do in this region. The MRI allows to delimit the lesion, and the hypointense signal in T1 and T2 weighted sequences directs to a fibrosis in the area between the end of the clavicle and the acromion. In this case report, the relation between the MRI findings and the pathological aspects was good.

Adult↗
PubMed1991

[Pigmented villonodular synovitis of joints. Apropos of 16 cases. Surgical aspects. Contribution of nuclear magnetic resonance imaging].

This study of 16 cases of pigmented villonodular synovitis of joints treated by the same surgical team involved 6 cases of the localized or nodular form and 10 cases of the diffuse form. The knee was the commonest joint involved (12 cases), with involvement of the hip (3 cases) and foot (1 case) being rarer. Bone invasion is usual when the joint is narrow (hip, foot) but is rarer in the knee where joint capacity is greater (5 cases out of 12). Clinical symptomatology is rarely typical. Hemarthrosis, the most suggestive sign, was found in only two cases out of twelve. While the final diagnosis must always be based upon histology, great help may be provided by modern techniques such as arthroscopy, computed tomography and above all MRI, the presence of hemosiderin being shown by a low signal in T1 which decreases even further in T2. Treatment is based upon surgical synovectomy, with advanced osteoarticular lesions requiring joint replacement.

Adult↗
PubMed1990

Glucagon-(19-29), a Ca2+ pump inhibitory peptide, is processed from glucagon in the rat liver plasma membrane by a thiol endopeptidase.

Glucagon-(19-29) is 1000-fold more potent that glucagon as an inhibitor of the liver plasma membrane calcium pump, which suggests that this peptide fragment is naturally occurring. Since glucagon-(19-29) is undetectable in plasma, the processing of glucagon into its (19-29) fragment may occur upon interaction of glucagon with its target tissues. The use of a specific radioimmunoassay for glucagon-(19-29) in association with the separation and identification of peptides by high performance liquid chromatography revealed that, upon incubation at 37 degrees C with hepatic plasma membranes, glucagon is processed into its (19-29) C-terminal fragment. The identity of the fragment was confirmed by amino acid sequencing. The processing activity was inhibited by reagents of the thiol group and by 1,10-phenanthroline, suggesting that a thiol endopeptidase containing a catalytically active metal is involved in this processing. Following its production, glucagon-(19-29) was degraded with a half-life of less than 10 s. This degradation was inhibited by bacitracin and by the aminopeptidase inhibitors bestatin and amastatin. When glucagon was incubated with liver plasma membranes in the absence of inhibitors, the accumulation of glucagon-(19-29) reached a maximum at 2 min (1% of initial glucagon), followed by a slow decline. In the presence of bacitracin and bestatin, the amounts of glucagon-(19-29) obtained from glucagon increased continuously, 1 and 2% of glucagon being transformed after 10 and 30 min, respectively. The production of glucagon-(19-29) did not appear to be associated with the binding of glucagon to its receptors, since (i) guanosine 5'-(3-O-thio)triphosphate, a compound which decreases the glucagon-receptor interaction, could not decrease the conversion of glucagon into glucagon-(19-29); (ii) a glucagon analogue which displays a strongly decreased affinity for the hepatic glucagon receptors was processed similarly to glucagon. The conversion also occurs upon incubation with intact hepatoma cells in monolayer culture. These observations suggest that, under physiological conditions, glucagon is processed in liver by cleavage of the Arg17-Arg18 basic doublet, leading to the production of a fragment which is known to display an original biological specificity, namely the modulation of the hepatocyte plasma membrane calcium pump.

Adenosine Triphosphate↗
PubMed1990

Glucagon-(19-29) exerts a biphasic action on the liver plasma membrane Ca2+ pump which is mediated by G proteins.

We have recently shown that nanomolar concentrations of glucagon-(19-29), which can derive from native glucagon by proteolytic cleavage of the dibasic doublet Arg17-Arg18, inhibit the Ca2+ pump in liver plasma membrane vesicles independently of adenylyl cyclase activation (Mallat, A., Pavoine, C., Dufour, M., Lotersztajn, S., Bataille, D., and Pecker, F. (1987) Nature 325, 620-622). We report here that the regulation of the Ca2+ pump by glucagon-(19-29) is dependent on guanine nucleotides. In the presence of 10 microM guanosine 5'-3-O-(thio) triphosphate (GTP gamma S) or 75 microM GTP, glucagon-(19-29) caused a biphasic regulation of the Ca2+ pump. ATP-dependent Ca2+ transport was inhibited in the presence of 10 pM to 1 nM glucagon-(19-29), while higher concentrations of the peptide (1-100 nM) reversed the inhibition caused by lower ones. GTP gamma S alone, at high concentrations (100 microM), reproduced the inhibitory effect of glucagon-(19-29) and induced a 40% inhibition of the basal activity of the Ca2+ pump which was reversed by low concentrations of glucagon-(19-29) (10 pM to 1 nM). Treatment of rats with cholera toxin resulted in a 70% increase in the basal activity of the Ca2+ pump, a loss of sensitivity to GTP gamma S and to the biphasic regulation by glucagon-(19-29). Treatment with pertussis toxin did not affect the response of the Ca2+ pump to GTP gamma S and glucagon-(19-29). We conclude that glucagon-(19-29) can exert a biphasic effect on the Ca2+ pump which is mediated by G protein(s) sensitive to cholera toxin.

Adenylate Cyclase Toxin↗
PubMed1990

Specific properties of smooth muscle cells from different layers of rabbit myometrium.

Myometrial cells were isolated from rabbit uterine horns previously stripped of endometrium and oriented to submit the inner circular (CIRC) or the outer longitudinal (LONG) layer to enzyme dispersal. Cells from both layers attached to the culture dishes within 72 h, reached confluency around day 7, and exhibited different morphological patterns. Indirect immunofluorescence with antidesmin antibody revealed that both preparations were at least 80% smooth muscle. Similarly, electron microscopy confirmed the presence of microfilaments in both cell types and revealed characteristic ultrastructural features of smooth muscle cells. Cultured cells from CIRC appeared larger on the phase-contrast microscope, with a mean apparent surface area of 0.105 mm2 for circular and 0.067 mm2 for longitudinal cells. Adenylate cyclase activity in general was higher in circular than in longitudinal cells (P less than or equal to 0.05), but a significant beta-adrenergic response to isoproterenol was observed only for longitudinal cells. This cell culture model is thus useful in defining the specific properties and functions of the different myometrial layers in the regulation of uterine contractility.

Adenylyl Cyclases↗
PubMed1990

Biointegration of massive bone allografts: imaging and histological studies in cat.

A study was carried out in a cat model to compare three imaging methods (X-ray, bone scintigraphy (BS) and magnetic resonance imaging (MRI] in order to assess the healing of bone allografts. X-ray remains the first technique to proceed, for morphological information and control of devices. BS is very sensitive although unspecific and difficult to quantify in exploration of bone reconstruction. It may be a useful complement of X-ray methods in some pathological circumstances (stress fracture, infection, non union). MRI is a very sensitive exploration of the bone marrow, but not of the cortical bone. In its present state it is of little value in bone graft imaging because of its low specificity and because of metallic artefacts (material, micro particles).

Animals↗
PubMed1989

Differential alcohol-related mortality among American Indian tribes in Oklahoma, 1968-1978.

Tribal differences in alcohol-related mortality were examined among 11 Indian tribes living in Oklahoma. Data on alcohol-related deaths from 1968 to 1978 were compiled and assigned to various tribes on the basis of population distributions by county. Results showed significant differences in alcohol-related mortality among the various tribes. Of the 267,238 total deaths in Oklahoma during the study period, 9.3% of Indian deaths were alcohol-related while only 3.2% of those among blacks and 2.4% of those among whites were classified as such. Indian males and females are far more likely to die of alcohol-related deaths than their black and white counterparts. Cheyenne-Arapaho, Comanche and Kiowa areas (located in the western++ part of the state) have higher alcohol-related deaths than Cherokee, Choctaw, Creek, Seminole and Pawnee areas (located in eastern Oklahoma). Indian residents of the Seminole area have the lowest percentage of deaths identified as alcohol-related. The patterns which emerge may be due to different cultural and historical factors among the Indian tribes.

Adult↗
PubMed1989

[Glucagon is processed to the (19-29) fragment at the level of the hepatocyte membrane].

Upon incubation with hepatic plasma membranes, glucagon is processed into its (19-29) C-terminal fragment. This suggests that, in physiological conditions, glucagon is processed in a target tissue at the level of its Arg17-Arg18 basic doublet, leading to the production of a fragment which is known to display an original biological specificity, namely the modulation of the calcium pump present in hepatocyte plasma membrane.

Animals↗
PubMed1988

An endogenous ligand for the central sulfonylurea receptor.

An endogenous ligand for the rat central sulfonylurea receptor has been evidenced in the rat central nervous system. The characteristics of this ligand (extractibility, non-dialysability, chromatographic behaviour on different media, sensitivity to proteases) indicate that it is a neutral to slightly basic peptide.

ATP-Binding Cassette Transporters↗