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Biomedical subjects

J Marchal

Publications and source records attributed to J Marchal.

At least 19 recordsLinked to original sources

Chain orientation in natural rubber, Part I: the inverse yielding effect.

Inhomogeneous deformations are observed in stretched natural rubber of different crosslink density; the conditions of observation, nucleation and propagation are given in the first part of the paper. In samples of low crosslink density these inhomogeneities recall necking observed in others materials and in glassy polymers when the materials are drawn above a critical draw ratio. The difference is that in natural rubbers, NR, they nucleate and propagate at constant stress during unloading. This phenomenon, called inverse yielding appears during recovery only if the samples have been drawn previously in the hardening domain. During necking propagation the stress is constant. The mechanical and crystallinity properties of samples with and without inverse yielding are studied as a function of draw ratio, crosslink density and temperature. In the second part of the paper this transition zone (neck) of thickness 2 mm is studied by WAXS at the synchrotron source. From the orientation of NR crystallites and from the orientation of the stearic acid (2%, present in this type of rubber) we conclude that the deformation in the neck follows the flow lines. From the local crystallinity of the NR crystallites one deduces the local draw ratio across this transition zone. We suggest that in all these rubbers, which present a plateau of the recovery stress strain curve, micronecking exists. This effect is discussed in the framework of the Flory theory.

Computer Simulation↗

Expression of apoptosis-regulatory proteins in lesions of pulmonary Langerhans cell histiocytosis.

AIMS: Pulmonary Langerhans cell histiocytosis (PLCH) is characterized by the presence of lesions containing numerous activated Langerhans cells (LCs). An uncontrolled immune response sustained by activated LCs seems to be involved in the pathogenesis of the disease. The aim of this study was to establish whether disruption of LC apoptosis related to the expression of the Bcl-2 family proteins is implicated in the maintenance of PLCH lesions. METHODS: Six patients with PLCH were evaluated by morphological and immunohistochemical techniques to explore the incidence of apoptosis in pathological LCs and to characterize the expression of Bcl-2-related proteins by these cells. RESULTS: Very few LCs present in PLCH lesions exhibited nuclear apoptotic changes or expressed cleaved caspase-3, whereas they all strongly expressed the anti-apoptotic molecule Bcl-x(L). Interestingly, pulmonary LCs present in intervening lung tissue not involved by the pathological process and known to be immature dendritic cells did not express Bcl-2 family proteins. CONCLUSIONS: These findings suggest that activated LCs present within PLCH lesions are poorly susceptible to apoptosis and, thus, are able to sustain the pathological process by causing continuous local stimulation of T cells. Functional studies are needed, however, to demonstrate that they are actually resistant to programmed cell death.

Adult↗

Consequences of transvaginal follicular puncture on well-being in cows.

The purpose of this study was to evaluate the impact of repeated follicular puncture used in the ovum pick-up technique on the welfare of cows. The evaluation relies on the physiological measurement of stress, milk production criteria, immune status, and the histological examination of ovaries. Two groups of five Holstein cows were submitted to epidural anaesthesia and genital palpation with insertion of an intravaginal ultrasound probe for transvaginal puncture (the puncture was not performed in the control group). Animals were manipulated twice a week for 8 weeks (16 manipulation sessions). The blood cortisol concentrations increased after each session; however, the concentrations were the same in both the control and the punctured groups. Two adrenocorticotrophic hormone challenge tests, performed before the first session and after the last session, showed an unchanged adrenal sensitivity through repeated puncture sessions. The transvaginal puncture did not affect milk production, or blood and milk somatic cell counts. Ovariectomies were performed on another group of four Holstein cows at various intervals (0 to 30 days) after five similar puncture sessions. Histological examination of the ovaries 4 days after puncture revealed blood-filled follicles and haemorrhagic foci in ovarian stroma, but the examination 30 days after the last puncture session demonstrated very limited, if any, fibrosis. On the basis of the criteria chosen for this study, repeated transvaginal follicular puncture on its own does not impact adversely on the welfare of cows.

Animals↗

Corticospinal pathway and exercise hyperpnea: lessons from a patient with Arnold Chiari malformation.

The study of a patient with an Arnold Chiari malformation gave us the opportunity to test the hypothesis that the motor cortex contributes significantly to respiratory control during muscular exercise through the corticospinal pathway. The patient was a 25 years old woman who exhibited a severe impairment of the 'automatic' ventilatory control due to a type I Arnold Chiari malformation. Since she never complained of being breathlessness even on exertion, the breath-by-breath ventilatory (VE) and pulmonary gas exchange responses to a three minute bout of constant work rate exercise at 60 W, 90 W and 120 W were studied before then 16 and 23 months after posterior fossa decompression. The VE response to the three different levels of exercise was dramatically blunted so that the expected vertical relationship between PET(CO(2)) and VE during moderate exercise was replaced by an almost horizontal relationship with a slope ranging from 0.15 to 0.17 l/min/Torr. The reduced VE response was associated with a total lack of respiratory sensation during and following the exercise bouts. This abnormal ventilatory response to exercise persisted despite posterior fossa decompression. There was however no evidence of an alteration of the corticospinal pathway. Indeed, not only was there no sign of motor deficit but the patient was able both to mobilize 96% of her expected vital capacity and to voluntarily increase her ventilation to the level expected in a normal subject during exercise. This observation suggests that during exercise, motor control of respiratory muscles via a direct corticospinal pathway does not play a major role in adjusting phrenic motoneuron activity to the magnitude of the motor inputs to the exercising skeletal muscles.

Adult↗

Lymphoid hypoplasia and somatic cloning.

BACKGROUND: Adult somatic cloning by nuclear transfer is associated with high rate of perinatal mortality but there is still no evidence that nuclear transfer itself is responsible for these failures. We report on a longlasting defect linked to somatic cloning. METHODS: Skin cells grown from an ear biopsy specimen from a 15-day-old calf were used as a source of nuclei. The donor animal was a clone of three females obtained from embryonic cells. Clinical examination, haematological, and biochemical profiles, and echocardiography of the somatic clone were done from birth to death. FINDINGS: After 6 weeks of normal development, the somatic cloned calf had a sudden and rapid fall in lymphocyte count and a decrease in haemoglobin. The calf died on day 51 from severe anaemia. Necropsy revealed no abnormality except thymic atrophy and lymphoid hypoplasia. INTERPRETATION: Somatic cloning may be the cause of long-lasting deleterious effects. Our observation should be taken into account in debates on reproductive cloning in human beings.

Anemia↗

Nuclear transfer from sexed parent embryos in cattle: efficiency and birth of offspring.

The objectives of this study were to evaluate the efficiency and reliability of embryo sexing from isolated single blastomeres, and after nuclear transfer to examine the influence of the sex of donor embryos on development in vitro and in vivo up to calving. The sex of the donor embryo was determined by revealing a specific Y DNA sequence by PCR and electrophoresis after isolation of one, two, three, or more than five cells. The efficiency of sex determination was over 90% and reliability was 100% independent of the number of blastomeres used. In a second experiment, sex was determined from a single cell and the other cells were used for nuclear transfer. The effect of sex on in vitro development was studied in 386 male and 314 female reconstructed embryos derived from 19 male and 14 female parent embryos, respectively. Developmental competence in vitro of male and female constructs over 7 days was not statistically different (25.2 and 23.1% blastocysts on day 7, respectively; P > 0.05). After the transfer of predetermined male (n = 30) and female (n = 27) cloned embryos into recipient heifers, no effect of sex was observed on pregnancy rates at day 21, 35 and 90, or on calving rates (P > 0.05). These rates did not differ between single and twin transfer (P > 0.05). The sex of the calves born always corresponded to that determined from a single blastomere. These results show that sex can be determined accurately when using a single blastomere before nuclear transfer and that the sex of the parent embryo does not affect in vitro development or in vivo survival rates of cloned embryos.

Animals↗

Effect of 6(5H)-phenanthridinone, a poly (ADP-ribose)polymerase inhibitor, and ionizing radiation on the growth of cultured lymphoma cells.

The ability of 6(5H)-phenanthridinone (Phen), a new potent poly(ADP-ribose)polymerase (PARP) inhibitor, to potentiate the effect of ionizing radiation on tumour cells was evaluated. RDM4 murine lymphoma cells were irradiated using a 60Co panoramic source and then examined for their growth, cell cycle distribution and apoptosis. Phen (100 microM) was found to inhibit more than 90% of the PARP activity in control and irradiated cells. Cell proliferation was assessed using Alamar Blue, a new fluorometric assay. Phen was found to sharply increase the radiation-induced inhibition of cell proliferation. Indeed, at 2.5 Gy the relative cell number of Phen-treated cells was 60% below control levels. At the same radiation dose, the G2M arrest was also significantly reinforced by the addition of Phen. Furthermore, this PARP inhibitor was shown to significantly increase the amount of DNA fragmentation as revealed by the DNA migration pattern in agarose gel electrophoresis. Comparable results were obtained with 3-aminobenzamide, another PARP inhibitor, but at concentrations 200-fold higher. Taken together, these results indicate the potential interest of Phen as a valuable pharmacological probe for investigating the role of PARP in cellular responses to radiation. They also suggest a possible use of Phen as an adjuvant in radiotherapy.

Animals↗

N-acetylcysteine protects lymphocytes from nitrogen mustard-induced apoptosis.

The ability of the antioxidant N-acetylcysteine to prevent apoptosis induced in lymphocytes by nitrogen mustard (HN2) was investigated. HN2 caused a concentration-dependent induction of apoptosis on C3H murine spleen cells, as identified by two criteria: morphological features revealed by microscopical observations and DNA fragmentation visualized by the characteristic "ladder" pattern observed upon agarose gel electrophoresis, as well as by hypodiploid DNA-containing cells revealed by the flow cytometric analysis of propidium iodide labelled cells. The antioxidant N-acetylcysteine (NAC) was found to markedly reduce the occurrence of HN2-induced apoptosis in these cells. This protective effect will still obtained when NAC was added 30 min after HN2. In contrast, the pretreatment of spleen cells with this antioxidant did not provide any significant protection. We also showed that lymphocytes protected by NAC are still able to respond to a mitogenic stimulation. To gain some insight into the mechanisms underlying the cytoprotective action of NAC against HN2, we tested whether or not poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30), a nuclear enzyme that participates in the triggering of apoptosis induced by alkylating agents, is involved. We report that 6(5H)-phenanthridinone, a potent PARP inhibitor, did not affect the ability of NAC to prevent HN2-induced apoptosis under our experimental conditions. Thus, the exact mechanism by which NAC protects lymphocytes from HN2 cytotoxicity has yet to be determined.

Acetylcysteine↗

Immunosuppressive activities of 6(5H)-phenanthridinone, a new poly(ADP-ribose)polymerase inhibitor.

6(5H)-phenanthridinone, a recently identified poly(ADP-ribose)polymerase (PARP) inhibitor, is able, at micromolar concentrations, to inhibit concanavalin A-induced lymphocyte proliferation and to potentiate the effect of gamma radiation upon murine spleen cells. When added at the onset of a mixed lymphocyte culture, this compound strongly depresses the induction of primary allogeneic (anti-H2k) cytotoxic T-lymphocytes (CTLs). Lymphokine-activated killer (LAK) induction was also found to be impaired by the PARP inhibitor. Taken together, these results clearly indicate that PARP plays a key-role in immune reactions involving cytotoxicity and that 6(5H)-phenanthridinone could be considered as a potent immunomodulator.

Acridines↗

Oxysterol-induced apoptosis in human monocytic cell lines.

Oxysterols constitute a large family of natural compounds, endowed with various biological activities including cholesterol regulation, immunosuppression and antitumoral potency. In the present study, we examine and compare the cytotoxic effects of two representative members of this family: 7 beta-hydroxycholesterol (7 beta-OH) and 25-hydroxycholesterol (25-OH), in two human monocytic cell lines, U-937 and HL-60. In both cell lines 7 beta-OH at 30 mu M induces cell death by apoptosis within the first hours of treatment. Under the same conditions and in contrast with results previously obtained with lymphoma cells, 25-OH is cytostatic only. It is interesting to note that the simultaneous treatment of U-937 cells by equimolar concentrations of 7 beta-OH and 25-OH leads to a considerably decreased induction of apoptosis. Such an effect is not observed with HL-60 cells. Taken together, these results indicate for the first time that: 1) oxysterols hydroxylated on the sterol nucleus are also able to induce apoptosis, 2) apoptosis can be induced by these substances in cells belonging to the myeloid lineage and 3) as far as apoptosis is concerned, a combined treatment with 7 beta-OH and 25-OH can lead to opposite effects depending on the cell type.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Psychoeducational multiple family groups: four-year relapse outcome in schizophrenia.

Earlier studies of family psychoeducation and clinical reports on multiple family groups (MFGs) have reported substantial reductions in relapse rates for patients with schizophrenia. These groups offer an expanded social network and thereby may confer a margin of protection against relapse. However, to date, there has not been an empirical trial of this modality. The advent of family psychoeducational and behavioral management strategies provided the basis for an experimental, three-way comparison of psychoeducational MFGs to psychoeducation in a single-family format and to MFGs without psychoeducation, using symptomatic relapse as the outcome criterion. After 4 years, the psychoeducational MFGs were significantly more effective in extending remission than the single-family format, while the MFGs without psychoeducation approximated outcome in the psychoeducational MFGs. The respective relapse rates at 4 years were 50%, 78%, and 57%; MFGs averaged 12.5% and 14% per year. These results point toward an enhanced and independent, long-term therapeutic effect for multiple family groups, when combined with antipsychotic medication and psychoeducation, with especially promising cost-effectiveness.

Adult↗

Effect of 6(5H)-phenanthridinone, an inhibitor of poly(ADP-ribose) polymerase, on cultured tumor cells.

By catalyzing posttranslational modifications of nuclear proteins, poly(ADP-ribose) polymerase (PARP) controls their functions and therefore constitutes an enzyme of crucial importance in tumor development. In this study, we have investigated the action of 6(5H)-phenanthridinone, an isoquinoline derivative and one of the most potent PARP inhibitors described so far, on RDM4 murine lymphoma cells in culture. We also examined whether this compound could act synergistically with an antineoplastic drug in tumor-cell destruction. Our results demonstrate that a marked inhibition of PARP activity can be obtained in whole cells after a short incubation, and that this compound, when associated with an alkylating agent, dichloro-2,2' N-methyldiethylamine (chloromethine), leads to a marked drop in the RDM4 proliferation, indicative of a synergy between the two compounds.

Animals↗

[Spontaneous rupture of the liver during triplet pregnancy following in vitro fertilization].

The authors present an observation of a spontaneous rupture of the liver happening during the 8th month of gestation of a triple pregnancy obtained by in-vitro fertilization. The diagnosis was done with some delay but evolution was successful for the mother and all her children. It is elective ligation of the right branch of the hepatic artery which produced the hemostasis.

Adult↗

[Benign liver tumor during pregnancy. Review of the literature and management (apropos of a case)].

The authors report a case of a tumour of the liver in a pregnant woman who had taken oral contraception for six years. Since oral contraceptives have become far more widely used the two benign tumours of the liver, namely a hepatocellular adenoma of the liver and focal nodular hyperplasia, have become far more common. The increased blood supply to the liver can make such a tumour symptomatic and increase the risk of it rupturing intraperitoneally, especially at the onset of labour. A course of management has been suggested according to the size of the tumour and the duration of the pregnancy.

Adult↗

[Juvenile fibromatosis with isolated intra-abdominal form. Apropos of 2 cases].

Among infantile fibromatosis, isolated intra-abdominal forms are the most unusual. The authors report two cases, a hepatic fibromatosis in an eleven year old girl, and a desmoïd tumor located in the jejunal mesentery in a ten month old infant. Pre-operative diagnosis is very difficult and histologic findings show a benign fibroblastic proliferation that tends to infiltrate surrounding tissues and often recur after surgical excision.

Child↗