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F Paris

Publications and source records attributed to F Paris.

At least 37 records · Page 2Linked to original sources

Natural ceramide reverses Fas resistance of acid sphingomyelinase(-/-) hepatocytes.

The role of the second messenger ceramide in Fas-mediated death requires clarification. To address this issue, we generated hepatocytes from paired acid sphingomyelinase (ASMase; asmase)(+/+) and asmase(-/-) mice. asmase(-/-) hepatocytes, derived from 8-week-old mice, manifested normal sphingomyelin content and normal morphological, biochemical, and biologic features. Nonetheless, ASMase-deficient hepatocytes did not display rapid ceramide elevation or apoptosis in response to Jo2 anti-Fas antibody. asmase(-/-) hepatocytes were not inherently resistant to apoptosis because staurosporine, which did not induce early ceramide elevation, stimulated a normal apoptotic response. The addition of low nanomolar quantities of natural C16-ceramide, which by itself did not induce apoptosis, completely restored the apoptotic response to anti-Fas in asmase(-/-) hepatocytes. Other sphingolipids did not replace natural ceramide and restore Fas sensitivity. Overcoming resistance to Fas in asmase(-/-) hepatocytes by natural ceramide is evidence that it is the lack of ceramide and not ASMase which determines the apoptotic phenotype. The ability of natural ceramide to rescue the phenotype without reversing the genotype provides evidence that ceramide is obligate for Fas induction of apoptosis in hepatocytes.

Animals↗

CD95-mediated apoptosis in vivo involves acid sphingomyelinase.

Acid sphingomyelinase (ASM) is reported to have an essential function in stress-induced apoptosis although the physiological function of ASM in receptor-triggered apoptosis is unknown. Here, we delineate a pivotal role for ASM in CD95-triggered apoptosis of peripheral lymphocytes or hepatocytes in vivo. We employed intravenous injection of anti-CD4 antibodies or phytohemagglutinin that was previously shown to result in apoptosis of peripheral blood lymphocytes or hepatocytes via the endogenous CD95/CD95 ligand system. Our results demonstrate a high susceptibility in normal mice whereas ASM knock-out mice fail to immunodeplete T cells or develop autoimmune-like hepatitis. Likewise, ASM-deficient mice or hepatocytes and splenocytes ex vivo manifest resistance to anti-CD95 treatment. These results provide in vivo evidence for an important physiological function of ASM in CD95-induced apoptosis.

Animals↗

Role of acidic sphingomyelinase in Fas/CD95-mediated cell death.

Engagement of the Fas receptor has been reported to induce ceramide generation via activation of acidic sphingomyelinase (aSMase). However, the role of aSMase in Fas-mediated cell death is controversial. Using genetically engineered mice deficient in the aSMase gene (aSMase(-/-)), we found that thymocytes, concanavalin A-activated T cells, and lipopolysaccharide-activated B cells derived from both aSMase(-/-) and aSMase(+/+) mice were equally sensitive to Fas-mediated cell death, triggered by either anti-Fas antibody or Fas ligand in vitro. Similarly, activation-induced apoptosis of T lymphocytes was unaffected by the status of aSMase, and aSMase(-/-) mice failed to show immunological symptoms seen in animals with defects in Fas function. In vivo, intravenous injection of 3 microg/25 g mouse body weight of anti-Fas Jo2 antibody into aSMase(-/-) mice failed to affect hepatocyte apoptosis or mortality, whereas massive hepatocyte apoptosis and animal death occurred in wild type littermates. Animals heterozygous for aSMase deficiency were also significantly protected. Susceptibility of aSMase(-/-) mice to anti-Fas antibody was demonstrated with higher antibody doses (>/=4 microg/25 g mouse). These data indicate a role for aSMase in Fas-mediated cell death in some but not all tissues.

Animals↗

Ordovician palynology: balance and future prospects at the beginning of the third millennium.

Ordovician palynologic studies started in the 1930s when Eisenack first described Palaeozoic "hystrichospheres" (later named acritarchs), and defined the chitinozoans and melanosclerites. During the ensuing two decades, Ordovician palynologic investigations were mostly descriptive. It was the rise of the oil industry in the 1950s and 1960s, which accelerated palynologic research, particularly with the recognition that acritarchs and chitinozoans were biostratigraphically important groups for Ordovician stratigraphy. Today, more than 700 publications deal with Ordovician acritarchs, and about 400 papers concern Ordovician chitinozoans. In addition to these two palynomorph groups, other less important organic-walled microorganisms have been studied. These include plant remains (spores, cuticles), scolecodonts and such enigmatic groups as the melanosclerites and the mazuelloids. This paper summarises the research on Ordovician palynomorphs during the 20th century and looks ahead to the types of research that may be important and most fruitful for Ordovician palynology at the beginning of the new millenium. Particular attention is paid to the C.I.M.P./I.G.C.P. no. 410 joint meeting "Ordovician Palynology and Palaeobotany," held in Prague during the 8th International Symposium on the Ordovician System. A brief account is given concerning the global Ordovician chronostratigraphy and the correlation of the main regional series and stages.

Journal Article↗

The effects of the final stages of the Late Ordovician glaciation on marine palynomorphs (chitinozoans, acritarchs, leiospheres) in well Nl-2 (NE Algerian Sahara).

Palynomorph assemblages, especially chitinozoans and acritarchs, from the Upper Ordovician of well Nl-2 (north-east of the Algerian Sahara) are studied in order to precisely date the ultimate effects of the Late Ordovician glaciation and to document the impact of this major climatic stress on the diversity of the palynoplankton. References are made to stable isotope excursions and to global eustatic sea level variations in order to improve the local age determination. The Hassi el Hadjar Formation, i.e. glacio-marine diamictites, is interpreted as a transgressive event resulting from the melting of the northern Gondwana ice cap. It yields poorly preserved and moderately diverse chitinozoans of late Hirnantian age. Acritarchs are more abundant in the lower part of these "microconglomeratic clays", but display a low diversity and are badly preserved throughout the whole formation. Reworked individuals are recorded in both groups. The marine sediments of the M'Kratta Formation of latest Hirnantian age contain better preserved, more abundant and more diverse palynomorph assemblages, especially in the Upper Member. The composition of this palynoplankton indicates a fairly good faunal and phytoplankton recovery after the early Hirnantian climatic stress.The extinction of the Ordovician forms, and the appearance of Silurian type taxa occur only in the uppermost Hirnantian, i.e. following with a slight delay the glacial event. The overlying black shales of Wenlock age (lower part of the Oued Mehaiguène Formation) are indicative of marine anoxic environments. They yield a virtually exclusive, but enormous number of Tasmanacea. The very peculiar composition of this palynoplankton seems to be independent of the Late Ordovician glaciation and is most likely related to the factors that, later, generated and maintained anoxic conditions in this area.A new species of chitinozoan, Spinachitina oulebsiri sp. nov. from the latest Hirnantian M'Kratta Formation, is described and illustrated.

Journal Article↗

The C.E.B.A.S.-Minimodule: behaviour of an artificial aquatic ecological system during spaceflight.

The C.E.B.A.S.-Minimodule, a closed aquatic ecosystem integrated into a middeck locker and consisting of a Zoological (animal tanks), a Botanical (plant bioreactor), a Microbial (bacteria filter) and an Electronic Component (data acquisition/control system) was flown on the STS-89 spaceshuttle mission in January 1998 for 9 days. Preflight the plant bioreactor was loaded with 53 g of Ceratophyllum demersum (coontail) and the animal tanks with 4 adult pregnant females of the fish, Xiphophorus helleri (sword-tails), 200 juveniles of the same species less than 1 week of age, 38 large and 30 juvenile Biomphalaria glabrata water snails. The filter compartment was filled with 200 g of lava grain inoculated with laboratory strains of ammonia-oxidizing bacteria. A ground reference was undertaken with the same biological setup with a delay of 4 d. After an adaptation period of 5 d the system was closed and integrated into the spaceshuttle one day before launch. Video recordings of the animals were automatically taken for 10 minutes in 2-hour periods; the tapes were changed daily by the astronauts. The chemical and physical data for the aquatic system were within the expected range and were closely comparable in comparison to the ground reference. After 9 d under space conditions, the plant biomass increased to 117 g. The plants were all found in very good condition. All 4 adult female fish were retrieved in a good physiological condition. The juvenile fishes had a survival rate of about 33%. Almost 97% of the snails had survived and produced more than 250 neonates and 40 spawning packs. All samples were distributed according to a defined schedule and satisfied all scientific needs of the involved 12 principal investigators. This was the first successful spaceflight of an artificial aquatic ecosystem containing vertebrates, invertebrates, higher plants and microorganisms self-sustained by its inhabitants only. C.E.B.A.S. in a modified form and biological setup is a promising candidate for the early space station utilization as a first midterm experiment.

Aggression↗

Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy.

The time at which ovarian failure (menopause) occurs in females is determined by the size of the oocyte reserve provided at birth, as well as by the rate at which this endowment is depleted throughout post-natal life. Here we show that disruption of the gene for acid sphingomyelinase in female mice suppressed the normal apoptotic deletion of fetal oocytes, leading to neonatal ovarian hyperplasia. Ex vivo, oocytes lacking the gene for acid sphingomyelinase or wild-type oocytes treated with sphingosine-1-phosphate resisted developmental apoptosis and apoptosis induced by anti-cancer therapy, confirming cell autonomy of the death defect. Moreover, radiation-induced oocyte loss in adult wild-type female mice, the event that drives premature ovarian failure and infertility in female cancer patients, was completely prevented by in vivo therapy with sphingosine-1-phosphate. Thus, the sphingomyelin pathway regulates developmental death of oocytes, and sphingosine-1-phosphate provides a new approach to preserve ovarian function in vivo.

Animals↗

Syndrome of body fat redistribution in HIV-1-infected patients: relationships to cortisol and catecholamines.

OBJECTIVE: Alterations of body fat distribution have been recently reported in HIV-infected patients. We aimed to investigate whether the hormones modulating adipose tissue metabolism could be implicated. SUBJECTS: We investigated twenty-eight HIV-infected patients who had developed abdominal fat, combined with peripheral lipodystrophy in 25 cases and 'buffalo hump' in 2 cases, but who had otherwise improved on antiretroviral therapies. Twelve patients with no change in body fat, matched for age, disease control and treatment, were studied as controls. MEASUREMENTS: Body composition was assessed by bioelectrical impedance analysis. Subcutaneous (SAT) and visceral (VAT) compartments of total abdominal adipose tissue (TAT) were measured by computed tomography. Resting metabolic rate (RMR) was assessed by indirect calorimetry. Endocrine investigations included plasma thyroid hormones, cortisol, testosterone, oestradiol and 24-hour urinary free cortisol (UFC) and catecholamines. RESULTS: Despite similar body mass index, the patients with body fat alterations showed significantly larger VAT and higher VAT:TAT ratio than controls (P = 0.002 and 0.0001, respectively). In these patients, RMR was significantly higher than estimated according to the Harris-Benedict formula (+ 19.7 +/- 11.6 %, P = 0.0001) and correlated with VAT (r = 0.58, P = 0.003) and 24-hour urinary output of catecholamines (r = 0.67, P = 0.002), that was significantly increased in comparison with controls (1737 +/- 1228 vs 476 +/- 292 nmol, P = 0.013). We also found a significant correlation between VAT and UFC (r = 0.41, P = 0.042) that was absent in controls, although levels of UFC were similar in the two groups. CONCLUSIONS: Our data suggest that body fat redistribution may involve cortisol and catecholamine actions. While high release of catecholamines may enhance RMR through increased lipolysis, cortisol may promote central fat storage. These effects might be related both to persistent hormonal responses to stress becoming inappropriate while disease control improved and to an increased sensitivity of visceral adipose tissue to cortisol in affected patients.

Adipose Tissue↗

Enhanced expression of the Kin17 protein immediately after low doses of ionizing radiation.

Kin17 is a mammalian nuclear protein sharing a slight sequence homology with the bacterial RecA protein. Kin17 has a zinc-finger motif and binds efficiently to curved DNA, a genomic topology associated with illegitimate recombination junctions. We investigated the relationship between the level of Kin17 protein and genomic alteration due to either impaired wild-type p53 functions or exposure to gamma rays. We used BP cells, a rodent epithelial cell system. The cell lines used were syngeneic and harbored wild-type or mutant p53 alleles and exhibited different sensitivities to gamma irradiation. In radioresistant cells (wild-type p53 genotype), the level of Kin17 protein peaked 30 min after a low dose of radiation (2 Gy), whereas maximum accumulation of p53 protein was observed 3 h postirradiation. Radiosensitive cells carrying the same mutation in both alleles of the p53 gene showed elevated basal levels of both Kin17 and p53 proteins and failed to accumulate Kin17 and p53 proteins after exposure to ionizing radiation. These cells exhibited enhanced cell death by apoptosis after gamma irradiation. Our results indicate that Kin17 protein accumulated immediately after DNA damage in cells carrying a wild-type p53 genotype, and that levels of constitutive Kin17 protein increased in highly proliferating tumorigenic cells when wild-type p53 functions were abrogated.

Animals↗

The effect of androgens and antiandrogens on the immunohistochemical localization of the androgen receptor in accessory reproductive organs of male rats.

The androgen receptor (AR) was localized immunohistochemically after different hormonal treatments in the ventral prostate, coagulating gland, seminal vesicle and epididymis of the adult rat. In the untreated controls AR-immunoreactivity was confined to the cell nuclei. One week after castration or treatment with the gonadotropin-releasing hormone antagonist Cetrorelix (150 micrograms/animal per day) a cytoplasmic staining occurred in the epithelial cells of the ventral prostate and in part of the coagulating gland and seminal vesicle. In contrast, the AR remained exclusively in the nuclei in the epididymal epithelium and the glandular smooth muscle layer even after 2 weeks of androgen depletion. Bolus injections of either dihydrotestosterone (1 mg/kg), the antiandrogen flutamide (40 mg/kg), or the novel non-steroidal antiandrogen casodex (40 mg/kg) to androgen-depleted animals eliminated cytoplasmic AR-immunoreactivity and restored the nuclear staining pattern in the ventral prostate. A sustained 2-week treatment with the antiandrogens resulted in a loss of weight in all organs but did not alter the distribution of AR-immunoreactivity. The data show an apparent cytoplasmic/nuclear ligand-dependent translocation of the AR in the ventral prostate, coagulating gland and seminal vesicle but not in the epididymis of the adult rat.

Amino Acid Sequence↗

Survival benefit of repeat liver resections for recurrent colorectal metastases: 143 cases. Association Francaise de Chirurgie.

PURPOSE: Resection is the only chance for cure in patients with colorectal liver metastases (LM). Five-year survival rates are close to 25%. Unfortunately, recurrences occur in most patients. Some recurrent LM are technically resectable. The aim of this study was to determine the risks and benefits of repeat resections for recurrent LM. PATIENTS AND METHODS: Data from 130 patients who received 143 repeat liver resections for recurrent LM were collected. In 116 patients, only the liver was involved, while 14 had both liver and extrahepatic recurrences. RESULTS: In the first group, the operative mortality and morbidity rates were 0.9% and 24.7%, respectively. Two- and 3-year survival rates were 57% and 33%, respectively. Recurrences were observed in 66% of patients. Twelve patients underwent a third hepatectomy for recurrence. The mortality rate was nil, and the mean survival time was 12.5 months. In the group with liver and extrahepatic metastases, the operative mortality and morbidity rates were 0% and 25%. The mean survival time was 16 months. Eleven patients died and 13 had recurrences during the follow-up period. CONCLUSION: Some hepatic recurrences after surgical excision of colorectal metastases can be resected with a low operative risk and with a long-term survival rate similar to that obtained after first resections. This emphasizes the need for a careful follow-up after hepatectomy for colorectal metastases to detect resectable recurrences.

Adult↗

The relaxant effects of cromakalim (BRL 34915) on human isolated airway smooth muscle.

Cromakalim (BRL 34915) is a potassium channel opener with therapeutic potential as a bronchodilator in asthma. Cromakalim (0.1-30 mumol/l) inhibited the spontaneous tone of human isolated bronchi in a concentration-related manner being nearly as effective as isoprenaline or theophylline. The order of relaxant potencies (expressed as -log10 IC50 mol/l; mean +/- SEM) was isoprenaline (7.29 +/- 0.27; n = 8) > cromakalim (5.89 +/- 0.12; n = 7) > theophylline (4.07 +/- 0.13; n = 10). In human bronchi where tone had been raised by addition of histamine (0.1 mmol/l), acetylcholine (0.1 mmol/l) or leukotriene D4 (LTD4, 0.1 mumol/l), the relaxant effect of cromakalim was substantially reduced. Cromakalim suppressed the contraction produced by KCl (25 mmol/l) but not that produced by KCl (120 mmol/l). Tetraethylammonium (8 mmol/l) was without effect against the relaxant action of cromakalim but procaine (0.5-5 mmol/l) and glibenclamide (0.3 mumol/l) antagonised it. Cromakalim (10 mumol/l) produced an upward displacement of concentration-effect curves for KCl (1-100 mmol/l), acetylcholine (1 nmol/l-1 mmol/l) and histamine (1 nmol/l-1 mmol/l) but it did not alter the concentration-effect curve for LTD4 (0.1 nmol/l-0.1 mumol/l). When tissues were challenged in the presence of cromakalim (10 mumol/l) with KCl (100 mmol/l), acetylcholine (1 mmol/l) or histamine (1 mmol/l), an enhanced contraction was observed compared to control tissues. This enhancement by cromakalim was absent when tissues were challenged with acetylcholine or histamine in either a Ca(2+)-free medium (plus EGTA 0.1 mmol/l) or in the presence of verapamil (10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

[Anorectal manometry and ileo-anal anastomosis].

Seventeen patients (12 ulcerative colitis, 5 familial adenomatous polyposis) underwent proctocolectomy and ileal J pouch anastomosis. Anal manometry with determination of maximum tolerable volume and a liquid continence test were perform before ileo-anal anastomosis, before closure of the loop ileostomy and 12 months after closure of the loop ileostomy. All patients were continent during the daytime less 12 months after proctocolectomy. The mean stool frequency was 5 stools per day in our 17 patients. A significant increase in maximum tolerable volume and in the liquid continence test was observed during the first year after closure of the ileostomy. Anal manometry is unnecessary after ileoanal anastomosis, but preoperatively, this test is able to exclude some patients with low anal pressure.

Adenomatous Polyposis Coli↗

[Synchronous colorectal cancers].

The frequency of synchronous colorectal cancers ranges from 1.7 to 9.3% according to the series. The incidence of these cancers has been appreciated in various ways, according to variable diagnostic criteria, especially because some authors have included in situ carcinomas developing on degenerated polyps. A retrospective study of the synchronous cancers operated in our department from January, 1980 to August, 1990 allowed us to assess their frequency and location and to discuss the therapeutic choices. Two hundred and forty-nine patients with cancers of the colon or of the rectum have been operated during that period. Twelve (4.8%) presented with more than one colorectal cancer, all discovered simultaneously. The average age of the patients operated for synchronous cancer was higher that that of those operated of isolate cancer (68.8 years versus 63.3). Two thirds of the synchronous cancers were located in the sigmoid loop or the colon and, in one third of all cases, on non-adjacent segments of the colon. The frequent association of colic adenomatous polyps and of synchronous cancers--in one half of the patients in our series--must raise a discussion on the merits of systematic subtotal, or even total, colectomy in the treatment of synchronous colorectal cancers. This is also true for tumoral sites in 2 different segments of the colon. Segmental colectomy may be advocated in the other cases: cancers located on one segment, polyps located only on the resected segment of the colon, or polyps that can be resected via endoscopy.

Aged↗