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R Bernard

Publications and source records attributed to R Bernard.

At least 37 records · Page 2Linked to original sources

Physiological and induced neuronal death are not affected in NSE-bax transgenic mice.

Bax, a family member of the survival protein Bcl-2, is expressed in the nervous system during development and throughout adulthood. Bax deficiency has been demonstrated to prevent developmental and trophic factor deprivation-induced neuronal death. To further clarify the role of Bax in naturally occurring neuronal death and in neuronal death following apoptotic stimuli, we generated several lines of transgenic mice expressing the human Bax protein specifically in neurons, under the control of the neuron-specific enolase promoter. Transgene expression was first detected around E10.5 and E12.5, depending on the transgenic line. The total number of ganglion cells in the retina and of pyramidal cells in the hippocampus, both expressing the transgene, was similar in control and transgenic mice. In addition, in our model system, Bax overexpression did not appear to influence the in vitro survival of sensory neurons isolated from dorsal root ganglia after nerve grwoth factor (NFG) deprivation or the apoptotic death of motor neurons following axotomy.

Animals↗

Interaction of age, strain, sex and food restriction on plasma creatine kinase activity in turkeys.

1. Plasma creatine kinase activity was determined at 4, 8, 12, 16, 20, 24, 28, 38 and 48 weeks of age in male and female traditional turkeys fed ad libitum, in male and female turkeys of a sire-line fed ad libitum or restricted to 0.5 during rearing and subsequently to 0.8 of sex-specific ad libitum-fed body weight, and in sire-line males fed ad libitum to 18 weeks and 0.8 of ad libitum body weight thereafter. 2. Plasma creatine kinase activity was low in traditional turkeys and increased rapidly after 12 weeks of age in males and females of the sire-line of turkeys. 3. Food restriction decreased the activity of plasma creatine kinase. 4. There was no difference in plasma creatine kinase activity between the sexes during rearing. After the onset of lay, the activity in plasma from females decreased at 38 weeks of age and rose dramatically in restricted females at 48 weeks when the birds had ceased laying. 5. The changes in plasma creatine kinase activity in females were associated with concomitant changes in ovarian activity as reflected in altered plasma triglyceride concentrations.

Aging↗

Comparative development of the ovary and production, fertility and hatchability of eggs from traditional turkeys and a contemporary male-line fed ad libitum or restricted.

1. Ovarian function was assessed at first egg and at 44 and 54 weeks of age in traditional turkeys and in a male-line fed ad libitum or restricted to 0.5 of ad libitum during rearing. Egg production was recorded daily and fertility and hatchability were determined at 2 ages. 2. Age at sexual maturity did not differ between the 3 treatments. 3. The number of follicles at first egg in the male line averaged 16.3 compared with 8.9 in traditional turkeys. Food restriction in the male line decreased the number of yellow follicles to 14.6 at first egg and restricted birds were largely in a non-reproductive state from 44 to 54 weeks of age. 4. The total number of recorded ovipositions to 54 weeks of age in male line fed ad libitum or restricted and traditional turkeys respectively were 40.1, 25.2 and 70.7; comparable productions of normal shelled eggs were 28, 20 and 66.3. 5. There were no differences between treatments in fertility after a single insemination at 2 different ages. Hatch of fertiles after the first inseminations were 71.4, 45.5 and 90.3 respectively for male line fed ad libitum or restricted and traditional turkeys.

Aging↗

Effects of male body weight, strain and dietary protein content on fertility and musculo-skeletal disease in naturally mated broiler breeder males.

1. The effects of male body weight at mating and different rates of gain on overall fertility were studied in two strains of broiler breeder males fed on a diet containing 160 or 120 g crude protein/kg. Sexual activity, musculo-skeletal disease and culling were also assessed. 2. There were no differences in early fertility between males weighing 3.0 or 3.5 kg at the start of the mating period, or between males gaining 1.0 or 1.5 kg body weight from mating to 60 weeks of age. 3. There were no differences in fertility between males fed on the two diets differing in crude protein content. 4. One strain of male had lower fertility than the other and this was associated with a greater weight of breast muscle, lower frequency of observed copulations and a higher number of incompleted matings. 5. Sexual activity declined and the number of spermatozoa trapped on the perivitelline membrane increased with age. 6. There were no differences among the treatments in the prevalence of musculo-skeletal lesions (destructive cartilage loss). As a proportion destructive cartilage loss occurred in 0.67 of the males at 66 weeks of age. Degeneration of the antitrochanter was present in 3 of 50 females examined and a cartilage flap in the medial condyle of the tibiotarsus occurred in 15 of these birds. 7. Beak lesions were the most important cause of male culling which averaged 0.24 as a proportion of the males at the start of the experiment.

Aging↗

Effects of dietary crude protein content and food intake on the production of semen in two lines of broiler breeder males.

1. The effects of dietary crude protein (CP) concentration and feeding rate on semen production and quality from 21 to 66 weeks of age were assessed in a factorial experiment with 48 caged broiler breeder males from 2 strains. 2. The probability of obtaining semen and semen volume were lower in one of the two strains but the concentration and yield of spermatozoa were similar. 3. There was no evidence that males which were fed on an increasing quantity of food produced more semen or a greater concentration of spermatozoa than males on a fixed allocation of 120 g/d food. 4. The concentration of spermatozoa was lower in males fed on a diet containing 160 compared with 120 g CP/kg. On termination of the experiment, average testes size was small and testicular function was absent in a large proportion of the males on the high protein diet.

Animal Husbandry↗

NSE-bcl-2 transgenic mice, a model system for studying neuronal death and survival.

Bcl-2 is a crucial regulator of cell survival and death. We have recently demonstrated that transgenic mice overexpressing the human Bcl-2 protein specifically in their neurons have an increased number of neuronal cells which can survive in tissue culture in the absence of neurotrophic factors. In order to understand why only some neurons can be rescued from developmental and neurotrophic factor deprivation-induced death, we have studied the expression pattern of the transgene during embryonic development an in adulthood. We have demonstrated that transgene expression starts in embryos at E12.5 and that only half of the sensory neurons of the dorsal root ganglia expressed detectable levels of the human Bcl-2. These results may explain why only 40% of the sensory neurons survived in tissue culture in the absence of neurotrophic factors.

Aging↗

Comparative development of the antitrochanter in three strains of domestic fowl.

Lameness and musculoskeletal disease were more frequent in two strains of broilers (selected [S] and relaxed [R]) than in an unselected layer (J). Defective fibrocartilage accounted for 0.15 of the total area of antitrochanteric cartilage at 29 weeks of age in the S-strain birds. There was more retained hyaline cartilage in the R- and S-strain birds at 15 weeks, and at 22 and 29 weeks there was delayed ossification. Occluded blood vessels, death of chondrocytes and degenerate areas of fibrocartilage occurred only in the broiler strains; they were worse in the S-strain and degenerate fibrocartilage occurred more frequently and in larger amounts. The area, length and depth of cartilage were larger in the heavier strains but the differences were considerably smaller than the difference in their relative bodyweights. The degeneration of the antitrochanter appeared to be associated with a reduction in the blood supply to the underlying hyaline cartilage and with the death of chondrocytes and the degeneration of matrix within the fibrocartilage of the antirochanter.

Acetabulum↗

Nonpeptide angiotensin II receptor antagonists: in vivo inhibition of [125I-Sar1,Ile8]angiotensin II binding by losartan, EXP597 and L-159,282 in rats.

Effects of losartan, L-159,282 and EXP597 on the in vivo binding of [125I-Sar1,Ile8]angiotensin II to kidney cortex and adrenal were examined in rats. Losartan, an AT1 receptor antagonist, completely blocked [125I-Sar1,Ile8]angiotensin II binding to the kidney cortex which contains only AT1 binding sites with an ID50 of 0.06 mg/kg. Losartan partially inhibited [125I-Sar1,Ile8]angiotensin II binding to the adrenal which contains equal amounts of AT1 and AT2 binding sites. Blockade by the AT1 receptor antagonist L-159,282 sufficiently increased the plasma levels of angiotensin II to block the AT2 receptor. EXP597 inhibited [125I-Sar1,Ile8]angiotensin II binding to the kidney cortex and adrenal almost totally with ID50s of 0.05 and 0.06 mg/kg, respectively. This result suggests that EXP597 exhibits almost equal binding affinity for AT1 and AT2 binding sites in vivo in rats.

Angiotensin II↗

Contrast matching techniques for digital subtraction radiography: an objective evaluation.

Digital subtraction radiography (DSR) enables the detection of subtle early detrimental effects of periodontal disease as well as the evaluation of the effects of therapy. However, the differences between two radiographs due to alignment and contrast errors must be kept at minimum. In the present in vitro study we test the efficacy of three basic contrast correction methods in the reduction of contrast mismatches which can adversely affect a subtracted image. The ODTF (Optical Density Thickness Function) method, which is based on a function relating grey level values of the aluminium wedge image and the corresponding thickness of the wedge, induced less contrast correction error than the CDF (Cumulative Density Function) and the LSQA (Least Square Quadratic Approximation) methods. Moreover, CDF, ODTF, and LSQA functions obtained from the reference structure density distribution may be applied for objective contrast enhancements and for standardisation of image quality, while the ODTF function allows also bone change volume estimations.

Animals↗

Pharmacology of XR510, a potent orally active nonpeptide angiotensin II AT1 receptor antagonist with high affinity for the AT2 receptor subtype.

The angiotensin II (Ang II) type 1 receptor (AT1) mediates all known physiological effects of ANG II, whereas functions of the type 2 (AT2) receptor are not clear. Should undesirable AT2 effects be identified, it may be advantageous to combine antagonism of AT1 and AT2 receptors. XR510 was shown to inhibit the specific binding of [125I]Sar1,Ile8-Ang II for AT1 and AT2 subtype binding sites in rat adrenal membranes with IC50 of 0.26 and 0.28 nM, respectively, and in human tissues with subnanomolar binding affinity. In isolated rabbit aorta, XR510 exerted insurmountable Ang II antagonism with a Kb value of 4 nM. In conscious renal hypertensive rats, XR510 decreased blood pressure (BP) with intravenous (i.v.) and oral (p.o.) ED30 of 0.08 and 0.27 mg/kg, respectively. In spontaneously hypertensive rats (SHR), repeated daily oral dosing of XR510, losartan, and enalapril at 30 mg/kg/day decreased BP similarly. In conscious furosemide-treated dogs, XR510, given either intravenously or orally, decreased BP. These results suggest that XR510 is an orally active and selective Ang II receptor antagonist with equal binding affinities for AT1 and AT2 receptor binding sites.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Immortalization of different precursors of glial cells with a targeted and temperature-sensitive oncogene.

Different types of glial precursor cell lines were obtained after stable transfection of brain cells with the pJC-SVLTtsA vector carrying the tsA58 simian virus 40 large T (SVLT) gene driven by the promoter of a gliotropic strain of JC papovavirus. The immortalized cells were conditional for growth: they expressed the SVLT antigen and proliferated at 34 degrees C, but their growth was either reduced or arrested when they were shifted to 39 degrees C. The differentiation characteristics of four representative lines were more extensively studied. The CR15 and CM8 lines displayed properties of bipotential glial progenitors: they were able to express oligodendrocyte markers at both temperatures, but could differentiate into astrocytes only at 39 degrees C. In contrast, the CR19 and CM3r lines corresponded to more committed oligodendrocyte precursors: they expressed various oligodendroglial markers but they could not synthesize the glial fibrillary acidic protein. More particularly, the CM3r mouse cells displayed a typical oligodendrocyte progenitor morphology and expressed the proteolipid protein mRNA.

Animals↗

Plasma growth hormone and insulin-like growth factor-I (IGF-I) concentrations at the onset of lay in ad libitum and restricted broiler breeder fowl.

1. Plasma concentrations of growth hormone (GH) and insulin-like growth factor I(IGF-I) were determined in individually caged broiler breeder females from 17 to 30 weeks of age. The birds were fed ad libitum or restricted during rearing in a randomised block design. Restricted birds were fed ad libitum after laying an egg and egg production was recorded to 54 weeks. 2. GH concentrations were higher in restricted compared with ad libitum-fed birds at 17 to 21 weeks of age and were similar thereafter. Plasma IGF-I concentrations were higher in restricted compared with ad libitum-fed birds throughout the sampling period of the experiment. 3. The age at first egg was delayed by about two weeks in restricted birds. At 54 weeks of age they had laid 114 compared with 67 eggs in birds fed ad libitum throughout and had produced less than half the number of eggs with defective shells. 4. It was suggested that differences in egg production between ad libitum and restricted broiler breeder females could be related to changes in the pattern of GH and/or IGF-I secretion.

Aging↗

Proliferation and differentiation properties of bipotent glial progenitor cell lines immortalized with the adenovirus E1A gene.

Bipotent glial progenitors have been immortalized by the transfer of the adenovirus E1A gene into primary cultured cells from embryonic rat brain. The lines obtained are phenotypically untransformed, retain growth contact-inhibition, and are able to differentiate, unless they are surtransfected with transforming oncogenes. Depending on the growth conditions, these immortalized cells express differentially either oligodendrocyte or astrocyte-specific markers and genes. After being seeded in serum-free medium, they display gangliosides recognized by A2B5 monoclonal antibody, and then they express sequentially O4 epitopes, galactocerebroside, and the myelin protein DM20. When grown in serum-supplemented medium, the cells express at first A2B5 epitopes, and then transiently O4 and galactocerebroside; after reaching confluence, O4 and galactocerebroside become undetectable, whereas the cells begin to coexpress glial fibrillary acidic protein and glutamine synthetase. These results indicate that the cell lines can undergo a differentiation reminiscent both of O-2A progenitors and of plastic process-bearing glial subpopulations. The cells were also genetically marked by the stable introduction of the nlslacZ reporter gene. Thus, the lines could be useful for studying direct interactions in vitro, or for post-grafting investigations. They should also provide a model for studying the mechanisms involved in the commitment and in the control of proliferation and differentiation of this cell lineage. This suggestion is consistent with the data indicating a growth arrest-dependent differential expression of a novel gene encoding a protein with a helix-loop-helix domain.

Adenovirus E1A Proteins↗

Grafting of fast blue labeled glial cells into neonatal rat brain: differential survival and migration among cell types.

Cultures of oligodendrocyte progenitor cells, ERD 1.1 cells, a nontransformed immortalized cell line of oligodendrocyte progenitors and C6 glioma cells were labeled with the fluorescent dye Fast Blue and transplanted into brains of 4 day postnatal Wistar rat pups. The localization of fluorescent cells within host brain was examined at various times post-transplantation to determine patterns of cell migration as well as survival and integration among the host tissue. Oligodendrocyte progenitors migrated mainly along white matter tracks, integrating successfully into the host parenchyma. High survival rates were found between 5 and 27 days post grafting. ERD 1.1 cells survived and migrated between 1 and 5 days after transplantation. However, by 27 days survival had dropped from 60 to 20% of the initial cell population. The surviving cells were mainly localized to subventricular and subependymal regions at 27 days. C6 cells migrated extensively rostrally and caudally from the site of injection in the hippocampus and were tumorogenic. This finding confirmed previous reports on the survival and migration patterns of oligodendrocyte progenitors grafted into neonatal brain. However, they show that two cell lines that share phenotypic properties of oligodendrocyte progenitors markedly differ from these cells with respect to migration patterns and integration within host parenchyma. Fast Blue dye was still detectable after repeated cell division in grafted C6 cells, enabling us to track single cells as well as tumor formation. This dye should be useful not only to address issues of development, but also of tumor biology and therapeutic treatment.

Amidines↗

Effects of TGF beta 1 on the proliferation and differentiation of an immortalized astrocyte cell line: relationship with extracellular matrix.

The astrocyte cell line (C.LT.T.1.1.), which is immortalized and has retained a normal density-dependent regulation of growth, is a suitable model for studying the relationships between proliferation, differentiation, and the production of extracellular matrix. The growth factor TGF beta 1 was used to modulate these processes. When added to proliferative cells, it inhibited growth and caused morphological changes. It also suppressed the growth arrest at confluence, so that the cells formed multilayers of parallel spindle-shaped cells. Whereas untreated control cells expressed progressively the glial fibrillary acidic protein (GFAP) after arrest of multiplication, the addition of TGF beta 1 to proliferative cells prevented GFAP expression and accumulation of its mRNA. Concomitantly, it increased the amounts of laminin, fibronectin, and collagens synthesized during the growth phase and greatly altered the composition and the structure of the matrix deposited at confluence. In contrast, when added after cell differentiation had begun, TGF beta 1 did not alter the appearance of the matrix whereas it still stimulated, but to a lesser extent, extracellular matrix components production. The results show that TGF beta 1 prevents the transition from the proliferating to the differentiating state and correlatively alters the composition and structure of the extracellular matrix.

Animals↗

Effect of blocking angiotensin II receptor subtype on rat sympathetic nerve function.

This study examined effects of nonpeptide angiotensin II (Ang II) receptor subtype antagonists on the interaction of sympathetic function and Ang II in pithed rats. Effects of spinal cord stimulation (0.5-4 Hz) and norepinephrine (0.3-3 micrograms/kg i.v.) on mean arterial pressure (recorded with a carotid arterial catheter), cardiac output (measured with an electromagnetic flowmeter and flow probe around the thoracic ascending aorta), total peripheral resistance, and heart rate were determined. The subtype 1-selective Ang II receptor antagonist losartan (previously known as DuP 753) at 10 mg/kg i.v. blocked the hemodynamic responses to Ang II at 1 microgram/kg i.v. It inhibited mean arterial pressure and total peripheral resistance responses but not cardiac output and heart rate responses to spinal cord stimulation. In contrast, it reduced mean arterial pressure and cardiac output responses but not total peripheral resistance and heart rate responses to intravenous norepinephrine. Given at 100 mg/kg i.v., the subtype 2-selective receptor antagonist PD123177 did not reduce hemodynamic responses to intravenous Ang II, spinal cord stimulation, and intravenous norepinephrine. These results suggest that endogenous Ang II facilitates the release of norepinephrine from sympathetic nerve terminals in the vasculature of pithed rats. Similar to the Ang II receptor in vascular smooth muscle, the prejunctional Ang II receptor in pithed rats appears to be of subtype 1.

Angiotensin Receptor Antagonists↗

Pyruvate dehydrogenase activity is stimulated by growth hormone (GH) in human mononuclear cells: a new tool to measure GH responsiveness in man.

Human peripheral mononuclear cells (PMC) were used to examine the effects of hGH and insulin on the activity of the pyruvate dehydrogenase (PDH) complex. Incubation of PMC with 10(-7) mol/L hGH or insulin increased basal PDH activity. Hormonal effects were maximal (50-60% above control values) at 15 min. Later on, activation progressively decreased and was no longer detectable at 30 min. Total PDH activity was unaffected by hormonal treatment. PMC were subfractionated into lymphocytes and monocytes to assess the sensitivity of each cell types to the hormones. hGH significantly increased basal PDH activity in lymphocytes and monocytes (38% and 70% above control values, respectively), whereas insulin increased basal PDH activity only in monocytes (151% above control value). PMC from healthy subjects aged 1-45 yr were incubated for 15 min with 10(-7) mol/L hGH or insulin before PDH measurement. An increase of enzyme activity higher than 20% was observed in 26 patients out of 29 with hGH, and in 15 out of 18 with insulin. In conclusion, hGH is able to stimulate PDH activity of human mononuclear cells. This hormonal effect allows rapid evaluation of the cellular responsiveness of hGH in various pathophysiologic situations.

Adolescent↗