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M Bernard

Publications and source records attributed to M Bernard.

At least 91 records · Page 5Linked to original sources
PubMed1998

Circadian expression of tryptophan hydroxylase mRNA in the chicken retina.

Many aspects of retinal physiology are controlled by a circadian clock located within the eye. This clock controls the rhythmic synthesis of melatonin, which results in elevated levels during the night and low levels during the day. The rate-limiting enzyme in melatonin biosynthesis in retina appears to be tryptophan hydroxylase (TPH)[G.M. Cahill and J.C. Besharse, Circadian regulation of melatonin in the retina of Xenopus laevis: Limitation by serotonin availability, J. Neurochem. 54 (1990) 716-719]. In this report, we found that TPH mRNA is strongly expressed in the photoreceptor layer and the vitread portion of the inner nuclear layer; the message is also expressed, but to a lesser extent, in the ganglion cell layer. The abundance of retinal TPH mRNA exhibits a circadian rhythm which persists in constant light or constant darkness. The phase of the rhythm can be reversed by reversing the light:dark cycle. In parallel experiments we found a similar pattern of expression in the chicken pineal gland. However, whereas a pulse of light at midnight suppressed retinal TPH mRNA by 25%, it did not alter pineal TPH mRNA, suggesting that there are tissue-specific differences in photic regulation of TPH mRNA. In retinas treated with kainic acid to destroy serotonin-containing amacrine and bipolar cells, a high amplitude rhythm of TPH mRNA was observed indicating that melatonin-synthesizing photoreceptors are the primary source of the rhythmic message. These observations provide the first evidence that chick retinal TPH mRNA is under control of a circadian clock.

Animals↗
PubMed1998

Ionic and metabolic imbalance as potential factors of ischemia reperfusion injury.

This study examined the influence of metabolic substrates on the effects of trimetazidine on functional and metabolic aspects of the ischemic reperfused heart. Isovolumic rat hearts were submitted to a 30-minute period of global mild ischemia (coronary flow decreased by an average of 70%) and then reperfused at constant preischemic coronary flow rate. Either glucose (11 mM) or glucose and palmitic acid (0.1 mM) were used as metabolic substrates. Trimetazidine (6 x 10(-7)M) markedly reduced the increase in diastolic pressure that occurred on reperfusion after the ischemic episode, whatever the exogenous substrate used. However, in those hearts that received fatty acid, the postischemic increase in diastolic pressure was abolished. Ischemia-induced increase in acyl carnitine levels-determined as indicators of fatty acid utilization by myocardial cells-was significantly decreased by trimetazidine in those hearts receiving fatty acid. Also, similar effects to those of trimetazidine on the postischemic increase in diastolic pressure and on tissue levels of acyl carnitine were obtained in the presence of dichloroacetate. Moreover, the presence of trimetazidine was associated with a reduction in the intracellular pH decrease during ischemia in those hearts receiving fatty acid. Combined with previous studies, these results suggest that an improved metabolic balance by trimetazidine may well consequently decrease the ionic imbalance after a transient period of ischemia.

Acetylcarnitine↗
PubMed1998

Antiapoptotic effect of ectopic TAL1/SCL expression in a human leukemic T-cell line.

Aberrant expression of TAL1 occurs frequently in human T-cell acute lymphoblastic leukemia. The effect of TAL1 expression in the T-cell lymphoid precursor, however, remains unclear. In the current study, we have developed TAL1 stable transfectants in a human immature T-cell lymphoid cell line. Whereas no effect on proliferation, cell culture density, or cell cycle was detected, the transfectants were more resistant than the parental cell line to apoptosis induced by chemotherapeutic agents including etoposide, daunorubicin, doxorubicin, cytosine arabinoside, methotrexate and vincristine and also to apoptosis induced by Fas/CD95 cross-linking. This effect was independent of the cytostatic effects of the drugs. The basic domain-deleted transfectants did not demonstrate altered sensitivity, suggesting that DNA binding was necessary for resistance to apoptosis. The ability to alter the response to a wide range of cell death-inducing stimuli suggests that TAL1 acts at a late stage of the apoptotic cascade. These data therefore provide direct evidence of an antiapoptotic effect of ectopic TAL1 expression in response to cytotoxic agents, thus providing insight into its oncogenic function in T-cell acute lymphoblastic leukemia and a novel experimental model to further investigate the underlying mechanisms. These data also have potential practical significance for cytotoxic therapy of this disorder.

Antineoplastic Agents, Phytogenic↗
PubMed1998

BCR-ABL and constitutively active erythropoietin receptor (cEpoR) activate distinct mechanisms for growth factor-independence and inhibition of apoptosis in Ba/F3 cell line.

The interleukin-3 dependent murine Ba/F3 cell line has been widely used as an experimental model of cell transformation by BCR-ABL oncogenes as assessed by induction of growth-factor-independence and inhibition of apoptosis in vitro. The signaling pathways used by BCR-ABL oncogenes to exert these effects are unknown. To gain insights into this phenomenon, we have introduced the p190- and p210-encoding BCR-ABL oncogenes as well as the constitutively activated oncogenic murine erythropoietin receptor (cEpoR) into Ba/F3 and compared the behavior of individual clones in response to apoptotic stimuli. Both p210 and p190 BCR-ABL vectors induced IL-3-independent growth and the same result was obtained with the cEpo-R vector. Individual clones of Ba/F3 cells expressing BCR-ABL exhibited significant resistance to apoptosis induced by either etoposide, serum deprivation or growth-factor withdrawal. In contrast, Ba/F3 cells expressing the constitutively active cEpoR behaved like parental Ba/F3 cells undergoing apoptosis when similarly treated with etoposide or upon serum deprivation. Bc12 and Bax levels were similar in all BCR-ABL and cEpoR-transfected clones. However, in band-shift assays, nuclear extracts from growth-factor-independent Ba/F3 clones expressing cEpoR had no detectable STAT activity as opposed to the constitutive STAT activation detected in all Ba/F3 clones expressing p210 or p190 BCR-ABL. Our results indicate that although both constitutively activated cEpoR and BCR-ABL oncogenes induce growth-factor independence in Ba/F3 cells, only BCR-ABL is able to protect cells from etoposide and serum-deprivation-induced apoptosis and induce a strong constitutive activation of STAT factors, suggesting a role for these molecules in the anti-apoptotic activity of BCR-ABL.

Animals↗
PubMed1998

The influence of temperature on metabolic and cellular protection of the heart during long-term ischemia: a study using P-31 magnetic resonance spectroscopy and biochemical analyses.

We have compared the influence of two different cold temperatures (below 10 degreesC) for cardiac ischemia by measuring a large variety of hemodynamic and metabolic parameters during ischemia and reflow. Isolated isovolumic rat hearts were arrested with a preservation solution which was developed in our laboratory and then submitted to 5 h of cold storage (4 degreesC, group I; and 7.5 degreesC, group II) in the same solution. After an additional period of 50 min of ischemia at 15 degreesC with intermittent cardioplegic infusion, hearts were reperfused for 60 min at 37 degreesC. Function was assessed during the control period and reflow. High-energy phosphates and intracellular pH were followed by 31P magnetic resonance spectroscopy. Analyses of metabolites and enzymes were performed by biochemical assays and HPLC in coronary effluents and in freeze-clamped hearts to assess cellular integrity. The energetic pool was better preserved at 4 degreesC during ischemia (ATP at the end of 4 degreesC ischemia, 59 +/- 7% in group I vs 31 +/- 5% in group II, P < 0.01) and reflow (P < 0.05) but membrane protection was higher when increasing the temperature to 7.5 degreesC (reduction of creatine kinase leakage, 89 +/- 16 IU/min in group I vs 51 +/- 5 IU/min in group II, P < 0.05). As a result, functional recovery, represented by the rate pressure product, was higher in hearts preserved at 7.5 degreesC (52 +/- 6% recovery in group I vs 77 +/- 7% in group II at the end of reflow, P < 0.05). Altogether, cold storage at 7.5 degreesC provides a better protection than storage at 4 degreesC.

Animals↗
PubMed1998

Acute respiratory failure caused by secondary alveolar proteinosis in a patient with acute myeloid leukemia: a case report.

Pulmonary alvelolar proteinosis (PAP) is a rare cause of chronic respiratory failure due to progressive alveolar accumulation of a periodic acid-schiff (PAS) positive proteinaceous material. In some cases, the rapid accumulation of intra-alveolar material leads to acute respiratory failure (ARF). We report the causative role of secondary PAP in the case of a 26-year-old man with acute myeloid leukemia who developed fever, increased serum lactate dehydrogenase level and ARF, and required mechanical ventilation. The diagnosis of PAP was established by the examination of material obtained by bronchoalveolar lavage (BAL). Respiratory improvement occurred several days after the patient had recovered from neutropenia. This report underlines the importance of the early diagnosis of PAP as a potential cause of ARF in leukemic patients. Adequate stain on BAL fluid provides the diagnosis and avoids repeated invasive procedures and inappropriate treatments.

Acute Disease↗
PubMed1998

ESR spectroscopy applied to the study of pharmaceuticals radiosterilization: cefoperazone.

As an alternative to heat and gas exposure sterilization, ionizing radiation is gaining interest as a sterilization process for medicinal products. Nevertheless, essentially for economic profits, an unauthorized and uncontrolled use of radiation process may be expected. In this context, it is necessary to find methods distinguishing between irradiated and unirradiated pharmaceuticals and, in the absence of suitable detection methods, our attention was focused on ESR spectrometry. In this paper, we examine the potential of ESR as an analytical tool in cefoperazone radiosterilization; this cephalosporin is a potential candidate for radiation treatment due to its thermosensitivity. While the ESR spectra of unirradiated sample present no intensity, a signal, dependent of the irradiation dose, is found exclusively in irradiated samples. The number of free radicals (2 x 10(17) radicals per g at 25 kGy) was estimated by comparison of the second integral from radiosterilized samples and DPPH. From this, the G-value could be estimated to 0.3. Limit of detection and limit of quantification are 0.5 kGy and 1 kGy, respectively. Aside from qualitative detection, ESR can be used for dose estimation. The dose-ESR response curves can be simulated by bi-exponential or power functions and the linear function can't be used for simulation even for low doses. Decay of radicals upon storage were simulated using bi-exponential function. The limit of detection of free radicals after irradiation at 25 kGy is 140 days.

Cefoperazone↗
PubMed1998

Electron spin resonance detection of radiosterilization of pharmaceuticals: application to four nitrofurans.

The detection and dosimetry of radiosterilization of pharmaceuticals is a growing concern to numerous government regulatory agencies worldwide. In the absence of suitable detection methods, attention was focused on electron spin resonance (ESR) spectrometry. This paper reports experimental data on ESR dosimetry of irradiated nitrofurans (nitrofurantoin, nifuroxazide, nifurzide and nifurtoinol). Whereas the ESR spectrum of a non-irradiated sample shows no signal, a signal, that is dependent on the irradiation dose is observed with irradiated samples. The number of free radicals was calculated by comparing the second integral from radiosterilized samples and a Bruker strong pitch reference; the values were in the range 1.1 x 10(18)-1.5 x 10(19) radicals mol-1 (G = 0.003-0.03). In addition to qualitative detection, ESR spectrometry can be used for dose determination. When a bi-exponential function is applied to the variation of the peak-to-peak amplitude versus dose, the function correlates well with the data. However, an exponential function, easier to use than a bi-exponential function, will probably be sufficient for dose determination by retrospective dosimetry. Decay of radicals upon storage was modelled using a bi-exponential function. From this, the time limit from the irradiation (25 kGy) for identification of irradiated nitrofurans by ESR can be evaluated. With regard to the commercial aspects of drugs, radicals should be detected up to 2 years after irradiation. The kinetic decrease makes discrimination between irradiated and non-irradiated nitrofurans possible even after storage for up to 2 years, except for nifurtoinol.

Electron Spin Resonance Spectroscopy↗
PubMed1998

TAL1 expression does not occur in the majority of T-ALL blasts.

The TAL1 gene is disrupted by translocation or deletion (tal(d)) in up to 30% of T-cell acute lymphoblastic leukaemia (T-ALL), leading to aberrant transcriptional activation, as a SIL-TAL1 fused transcript in tal(d). It has been suggested that TAL1 transcription occurs in approximately 50% of a T-ALLs without apparent rearrangement. SIL-TAL1 was positive in 15/60 (25%) of T-ALL, whereas wild-type TAL1 transcripts were detected in all 13 SIL-TAL1 and in 19/43 (44%) T-ALL without SIL-TAL1. To investigate the cellular origin of TAL1 we exploited the fact that GATA1 and TAL1 are co-ordinately expressed in non-lymphoid haemopoietic cells, whereas only the latter is found in T-ALL. GATA1 was detected in 10/23 (43%) TAL1-negative T-ALLs but in 17/19 (89%) 'unexplained' TAL1-positive cases, suggesting a common non-lymphoid cellular origin. Immunocytochemical analysis with a TAL1-specific monoclonal antibody showed nuclear expression in the blasts of 10/34 (29%) cases, including 8/10 SIL-TAL1+ and two RT-PCR TAL1+, SIL-TAL1- cases. In the remaining cases TAL1 expression was restricted to a minor population (< 5%) of larger, strongly TAL1-positive cells which comprised erythroid cells, CD34+ CD3- precursors and an unidentified TAL1+ CD45- population which morphologically resembled monocytes/macrophages. We therefore suggest that appropriate diagnostic evaluation of T-ALL should include molecular detection of SIL-TAL1 transcripts and in situ immunocytochemical detection of TAL1 protein expression by leukaemic blasts. This approach will enable accurate analysis of the prognostic significance of TAL1 deregulation in T-ALL.

Adolescent↗
PubMed1998

Backs to the future? Reflections on women, ageing and nursing.

There is now a certain amount of evidence to support the contention that ageism is not only rife amongst the population at large, but also amongst many of those who care for older people in a professional capacity. Given that many of these professionals are women caring for other women -- and nursing is a prime example -- this should at the very least give us serious cause for concern. This paper explores the relationship between 'ageing women' and 'old women' from the point of view of personal and professional attitudes and practices. It examines the proposition that until we, as women, fully explore and understand our own attitudes towards ageing and old age, we cannot work in ways which are truly beneficial and empowering for the older women in our care. The purpose of the paper is threefold. First, it reviews what is a relatively limited body of literature and research on this topic. Second, it reports on the preliminary findings from an exploratory study examining the attitudes of female nurses to their own ageing. Finally, it reflects further on the issues raised and considers some of the ways in which we can begin to address and confront the challenges which being 'ageing women' and 'aged women' in late 20th century Britain presents.

Adult↗
PubMed1998

Radiosterilization dosimetry of vitamins: an ESR study.

PURPOSE: As an alternative to heat and gas exposure sterilization, ionizing radiation is gaining interest as a sterilization process for medicinal products. Detection and dosimetry of pharmaceutical radiosterilization is a growing concern for numerous government regulatory agencies world-wide. MATERIALS AND METHODS: Equations to describe the ESR curves versus the dose and storage time were developed using mathematical procedures. For this investigation six vitamins (riboflavin, biotin, thiamine mononitrate, thiamine hydrochloride, folic acid and pyridoxine) were chosen as models. RESULTS: The yield of free radicals is in the range 1.7 10(18)-7.3 10(19) radicals mol(-1) (G values from 0.0003 to 0.025 mol J(-1)). Apart from qualitative detection, ESR spectrometry can be used for dose estimation; when an exponential function is applied to the variation of peak-to-peak amplitude on dose, the function correlates well with the data. Tests were carried out to investigate whether storage has an effect on the concentration of free radicals. In order to estimate the time limit of detection, decay curves were modelled using a bi-exponential function. From this, the time limit from the irradiation (25 kGy) for identification of irradiated vitamins by ESR was evaluated. In the commercial drug market, radicals should be detected for up to 2 years after irradiation; this probably will be the case for the vitamins studied, with the exception of folic acid and pyridoxine. CONCLUSION: The detection method based on ESR dosimetry seems promising. ESR dosimetry requires only small samples, and minimal time and effort for sample preparation; the measurement is non-destructive.

Dose-Response Relationship, Radiation↗
PubMed1998

Radiation-induced effects on cefotaxime: ESR study.

As an alternative to heat and gas exposure sterilization, ionizing radiation is gaining interest as sterilization process for medicinal products. Detection and dosimetry of pharmaceuticals radiosterilization is a growing concern to numerous government regulatory agencies worldwide. In this context, it is necessary to find methods distinguishing between irradiated and nonirradiated pharmaceuticals. In the absence of suitable detection methods, our attention was focused on electron spin resonance (ESR) spectrometry. A third generation cephalosporin, cefotaxime, was chosen as model; this antibiotic is a potential candidate for radiation treatment due to its thermosensitivity. While the ESR spectra of a nonirradiated sample presents no signal, a signal, dependent of the irradiation dose, is found in irradiated samples. The number of free radicals was estimated by comparing the second integral from radiosterilized samples and a diphenyl-picrylhydrazyl reference. Estimation of the number of free radicals gives 1.9 x 10(20) radicals mol(-1) at 20 kGy. From this result, the G-value (number of radicals (100eV)(-1)) could be estimated to 0.3. Aside from qualitative detection, ESR spectrometry can be used for dose estimation. When quadratic, exponential or bi-exponential functions are applied to the variation of peak to peak amplitude vs. dose, these functions correlate well with the data. However, it is important to notice that linear function correlates well with the data for doses lower than 20 kGy. Since the radiation dose selected must be always based upon the bioburden of the products and the degree of sterility required (EN 552 and ISO 11137) 25kGy could no longer be accepted as a "routine dose" for sterilizing a pharmaceutical. Doses from 6kGy (ISO 11137) could be investigated and linear regression would appear to be the least expensive route to follow. The free radicals concentration appeared to not decrease during the 57 days of storage; the number generated during the irradiation allows the detection of radiosterilized cefotaxime up to two years after irradiation.

Cefotaxime↗
PubMed1998

Helix-loop-helix (E2-5, HEB, TAL1 and Id1) protein interaction with the TCRalphadelta enhancers.

In order to dissect the correlation between aberrant TAL1 basic-helix-loop-helix (b-HLH) expression and the exclusive development of T cell acute lymphoblastic leukemias (T-ALL) of the TCRalphabeta lineage, we have assessed the ability of class A b-HLH proteins to regulate the TCRalpha and delta enhancers. We demonstrate that E47S binds to TCRalpha but not to TCRdelta E-boxes in vitro. Despite this, neither E2-5 nor HEB transactivate the TCRalpha enhancer in NIH 3T3, nor did Id1 modify endogenously driven TCRalpha [alphaE1-4] activity in a TCRalphabeta cell line. We also demonstrate that TAL1 inhibits both binding of E47S to aE3 and aE4 and endogenous transactivation of the TCRalpha enhancer. Comparison of the activity of the minimal [alphaE1-2] fragment, which contains no E-boxes, with the accessory [aE3-4] fragment, which contains two, suggested some contribution from the latter to TCRalpha enhancer activity in HPB-ALL. TCR [alphaE1-2] activity was partially (40%) inhibited by TAL1 but not at all by Id1. In contrast, [alphaE3-4] activity was almost completely inhibited by TAL1 (80%) and slightly reduced by Id1 (15%). These data demonstrate that class A b-HLH regulation of the TCRalpha enhancer E-boxes differs from their B lymphoid Igmicro counterparts and suggest a novel mechanism of transcriptional inhibition by TAL1, which may be, at least partly, independent of E-box-mediated activation, as we currently recognize it. They also clearly demonstrate that the restriction of TAL1 deregulation to T-ALL of the TCRalphabeta lineage is not due to induction of TCRalpha enhancer activity by the TAL1 protein.

3T3 Cells↗
PubMed1998

The effect of aging on bone mineral metabolism and bone mass in Native American women.

OBJECTIVE: To examine the effect of age on mineral metabolism and bone mineral density (BMD) of the hip and spine in Native American women. DESIGN: A cross-sectional study. SETTING: The Sac and Fox Nation in rural Oklahoma MEASUREMENTS: Serum measurements were made of 25 hydroxyvitamin D (25OHD), osteocalcin, and immunoreactive parathyroid hormone. Bone mineral density of the hip and spine was assessed by dual energy X-ray absorptiometry. PARTICIPANTS: A total of 77 Native American women aged 19 to 85 years. RESULTS: Serum 25 hydroxyvitamin D was related inversely to age (r = -0.32; P < .05) and was less than 15 ng/mL in 7% of the subjects. Serum osteocalcin was higher (P < .001) in postmenopausal than in premenopausal subjects. In postmenopausal subjects, serum osteocalcin was related to age (r = .59, P < .001). BMD was lower (P < .001) in postmenopausal than in premenopausal subjects. There was no evidence of bone loss before age 50 in either the femur or the spine. Age (r > or = -0.48, P < .001) and body mass index (BMI) (r > or = 0.41, P < .005) were independent determinants of both femoral and lumbar BMD. Serum 25OHD was a significant independent determinant of both lumbar (r = .26, P < .05) and femoral (r = .41, P < .01) BMD. Age, BMI, and serum 25OHD together accounted for 70% of the variance in BMD at these sites. The use of t scores indicated femoral bone density was higher (P < .05) in premenopausal Native American women, and lower (P < 0.05) in postmenopausal subjects, compared with white women. CONCLUSIONS: In Native American women, there is a reduction in bone density and a sustained increase in bone turnover postmenopausally. BMI and serum 25OHD are significant determinants of BMD. Peak BMD may be higher, and the postmenopausal rate of bone loss greater, than that in white women.

Adult↗
PubMed1998

Prophylactic use of itraconazole for the prevention of invasive pulmonary aspergillosis in high risk neutropenic patients.

Invasive pulmonary aspergillosis (IPA) is an increasing cause of morbidity and mortality in patients with hematologic malignancies. A major program of construction work close to our unit prompted us to evaluate the efficacy of itraconazole prophylaxis in preventing IPA in these patients. During September 1994 to December 1995, 77 patients undergoing 96 neutropenic episodes (mean duration, 19.3 days +/- 9.1) received itraconazole as antifungal prophylaxis. All patients were treated in laminar air flow rooms. Itraconazole was administered at a loading dose of 600mg/d, (day 1 to day 3) and 400mg/d on the following days, in 87 instances. In the remaining episodes, the daily dose was 200 or 400mg. Oral doses were adjusted to reach a plasma itraconazole level (PIL) above 1000ng/l. In cases of inadequate PIL or poor oral intake, IV AmphoB was started at a 20 mg daily dose. Five cases of IPA (proven n = 2, probable n = 3) were observed. This represents an incidence of 5.2% of the total number of episodes. One out of 67 (2%) treatment episodes with adequate PIL were associated with IPA as compared to 4 of 29 (14%) episodes with inadequate PIL, (p < 0.02). AmphoB was added in 28 cases because of low PIL (n = 25), and/or antibiotic-resistant fever persistent pulmonary infiltrate (n = 8). These results need to be interpreted with caution, because of the absence of randomization or a control group. The efficacy of Itraconazole in neutropenic patients with high risk IPA has to be confirmed on larger and prospective studies.

Adult↗
PubMed1998

[Evaluation of the association of a serum marker and second trimester ultrasonography for the screening of trisomy 21 in women of less than 38 years. Prospective study of 5,163 patients].

OBJECTIVES: Use of serum markers alone for trisomy 21 screening programs leads to a high rate of amniocentesis. Adding a second parameter (ultrasonography during the second trimester) might reduce this rate yet retain satisfactory sensitivity. This work was conducted to evaluate the pertinence of associating serum hCG level between 16 and 17 weeks gestation and morphological ultrasonography between 18 ans 20 weeks gestation. METHOD: A prospective study was conducted in 5,163 pregnant women aged over 38 years. A morphological ultrasonography was performed in all patients whose hCG level > 1/150 indicated a risk. An amniocentesis was proposed if an anomaly was detected at ultrasonography. RESULTS: Serum hCG was above the risk threshold retained in 11.9% of the patients and among these patients at least one anomaly was detected at ultrasonography in 12%. An amniocentesis was performed in 1.4% of all patients. The positive predictive value of the screening test was 20%. CONCLUSION: Combining a serum marker and ultrasonography during the second trimester allows a reduction in the rate of amniocentesis compared with screening with serum markers alone. Sensitivity for detecting trisomy 21 remains satisfactory.

Adult↗