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Biomedical subjects

P Mandel

Publications and source records attributed to P Mandel.

At least 127 records · Page 7Linked to original sources
PubMed1985

Time course of polynucleosome relaxation and ADP-ribosylation. Correlation between relaxation and histone H1 hyper-ADP-ribosylation.

Isolated rat pancreatic polynucleosomes were poly(ADP-ribosylated) with purified calf thymus poly(ADP-ribose) polymerase. A time course study was performed using an NAD concentration of 200 microM and changes in nucleosomal structure were investigated by means of electron microscopy visualization and sedimentation velocity determinations. In parallel, analyses of histone H1 poly(ADP-ribosylation) and determinations of DNA polymerase alpha activity on ADP-ribosylated polynucleosomes were done at different time intervals. A direct kinetic correlation between ADP-ribose incorporation, polynucleosome relaxation amd histone H1 hyper-ADP-ribosylation was established. In addition, DNA polymerase alpha activity was highly stimulated on ADP-ribosylated polynucleosomes as compared to control ones, suggesting increased accessibility of DNA to enzymatic action. Because of the strong evidence implicating histone H1 in the maintenance of higher-ordered chromatin structures, the present study may provide a basis for the interpretation of the involvement of the histone H1 ADP-ribosylation reaction in DNA rearrangements during DNA repair, replication or gene expression.

Adenosine Diphosphate Ribose↗
PubMed1985

Glutamine synthetase and energy metabolism enzymes in cultured chick glial cells: modulation by dibutyryl cyclic AMP, hydrocortisone, and trypsinization.

Modifications induced by dibutyryl cyclic AMP (diBcAMP) and hydrocortisone in the energy metabolism of chick astroblasts in culture have been investigated. DiBcAMP does not modify the levels of enolase, malate dehydrogenase (MDH), total lactate dehydrogenase (LDH) and glutamine synthetase (GS) activities in these cultured glial cells. However, these cells can be sensitized to the nucleotide analog by trypsinization before seeding. The phenomenon affects specifically GS activity and the synthesis, with an inhibitory effect, of the H subunit of LDH. Addition of hydrocortisone to the culture medium stimulates MDH and GS activities of the cells; trypsinization accentuates the stimulatory effect on GS. This hormone also modifies the synthesis of H and M subunits of LDH in a positive and negative way respectively. The phenomenon is increased by trypsin treatment. The present studies indicate clearly that hydrocortisone generates in cultured chick glial cells metabolic modifications qualitatively different from those obtained by diBcAMP. It is suggested that trypsin treatment, by altering some protein constituents of the cell surface, modifies the adhesiveness of different cell types present in the cell suspension after dissociation of the brain and thus leads to select, in culture, a specific astroglial subpopulation.

Animals↗
PubMed1985

gamma-Hydroxybutyrate uptake by rat brain striatal slices.

gamma-Hydroxybutyrate uptake by rat brain striatal slices was studied. The uptake was saturable with a Km of 702 +/- 107.10(-6) M. gamma-Hydroxybutyrate uptake was sodium dependent and inhibited by the omission of potassium. In addition, the effect of ouabain suggests that the transport is dependent on a cation gradient. Several analogues of gamma-hydroxybutyrate inhibit the transport system. GABA has no significant effect. This energy and cation dependent transport system is in favor of a transmitter or modulator role of gamma-hydroxybutyrate in the rat brain striatum.

Animals↗
PubMed1985

Effect of ethanol on adenosine triphosphatase and enolase activities in rat brain and in cultured nerve cells.

The effect of alcohol on enzymes involved in energy metabolism of nervous tissue were analyzed, in vivo after acute and chronic ethanol administration to rats and in vitro by addition of 50 mM and 100 mM ethanol to the medium of cultured nerve cells: chick neurons, chick glial cells, a neuronal cell line (MT17) and a glial tumoral cell line (C6). The parameters we measured were (Na+, K+), Mg2+ and ecto Ca2+, Mg2+ ATPase activities involved in transport phenomena and enolase activities (non neuronal NNE and neuron specific enolase NSE) as markers of nerve cell maturation. In vivo, after chronic ethanol administration (Na+, K+) ATPase activity was increased while Mg2+ dependent activity was not affected. Enolase activity was decreased. Acute ethanol administration decreased (Na+, K+) ATPase activity, while Mg2+ dependent activity was not affected. In cultured nerve cells ethanol effect was dose, time and cell type dependent; alterations of the cell membrane by trypsinization of the tissue before seeding modifies the effect of ethanol on the enzymes we analyzed. Our results suggest that alcohol effect on nerve cells depends mainly on the lipoprotein structure of the cell membranes which may have different properties from one cell type to another.

Adenosine Triphosphatases↗
PubMed1985

Calcium-dependent regulation of adenylate cyclase and phosphodiesterase activities in bovine lens: involvement of lens calmodulin.

When calmodulin levels were determined in bovine lens layers at different ages, the values in the epithelial cell layer were strikingly higher than in the cortical layer and higher than in the nucleus. In the epithelial cell layer, except in very old animals, the calmodulin levels were maintained in adult animals. In the lens nucleus the extremely low level of calmodulin decreased during aging. In the cortical layer there were no systematic changes of calmodulin level during aging. In vitro, low calcium concentrations (micromolar) activated and higher calcium concentrations (over 100 microM) inhibited the lens adenylate cyclase activity. cAMP and cGMP degradation by phosphodiesterase was activated by calcium. It is suggested that calmodulin might be involved in the regulation of both adenylate cyclase and phosphodiesterase activities of lens epithelial cells and that free calcium plays a well-defined role in cAMP synthesis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Factors involved in expression of neuron-specific and non-neuronal enolase activity in developing chick brain and in primary cultures of chick neurons.

The effect of various factors affecting non-neuronal enolase (NNE) and neuron-specific enolase (NSE) was investigated in developing brain of two different chick strains, in primary cultures of pure neurons and of mixed cultures of neuronal and glial cells. NNE and NSE activities reached their maximum at an earlier stage of brain development in the fast growing Hybro strain than in the Leghorn strain. In pure neurons cultured during 6 days, NNE was stimulated by hydrocortisone in presence or in absence of serum. Dibutyryl cyclic AMP (diBcAMP) stimulated NNE only in serum-free medium. NSE activity was increased by glial cell-conditioned medium in presence of serum and by removal of serum from the medium. Hydrocortisone and diBcAMP had no effect on NSE. In mixed cultures of neurons and glial cells both enolase activities were raised in absence of serum. Hydrocortisone and diBcAMP had no effect. Steroid hormones, insulin and serum albumin also modify both enolase activities in pure neurons and in mixed cultures of neurons and glial cells. Our results suggest that NNE and NSE are regulated separately by various factors involved in nerve cell maturation.

Animals↗
PubMed1985

Isoproterenol-sensitive adenylate cyclase in glomeruli isolated from young and adult rat renal cortex.

The stimulation of the adenylate cyclase activity of isolated rat renal glomeruli by isoproterenol decreased during kidney maturation. A potentiation of the isoproterenol response by GTP was demonstrated in young and adult animals. Both KF and GPP(NH)P enhanced the enzyme activity under basal conditions in young and adult glomeruli. GTP had no significant effect upon the basal activity of the adenylate cyclase in glomeruli of 14-day old rat kidney while it had one in 21-day old and adult kidneys.

Adenylyl Cyclases↗
PubMed1985

The use of technetium-99m sulfur colloid in the detection of patent processus vaginalis in patients on continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) is commonly used in patients with renal failure as an alternative to hemodialysis. A not infrequent complication is scrotal swelling due to bowel or fluid passing through a patent processus vaginalis secondary to increased abdominal pressure. A radionuclide study using Tc-99m sulfur colloid is a safe and simple method to determine if this complication is present or may be used as a pre-CAPD screening procedure.

Edema↗
PubMed1985

Conversion of gamma-hydroxybutyrate to gamma-aminobutyrate in vitro.

[3H]gamma-Hydroxybutyric acid [( 3H]GHB) at physiological concentration incubated with brain slices in Krebs-Ringer medium produced [3H]gamma-aminobutyric acid [( 3H]GABA). This compound was identified by its Rf values on thin-layer chromatograms and by analysis of the dansyl derivatives of the free amino acid fraction. No labelled glutamate could be detected. Brain slices incubated with labelled glutamate and nonradioactive GHB generated labelled 2-oxoglutarate, suggesting that gamma-aminobutyrate-2-oxoglutarate transaminase (GABA-T) is involved in catalyzing this reaction. Furthermore, specific inhibitors of GABA-T blocked the production of labelled GABA from labelled GHB and of labelled 2-oxoglutarate from labelled glutamate. Transformation of [3H]GHB into [3H]GABA was not inhibited by malonate, demonstrating that the succinate-linked pathway is not involved in the generation of GABA. The kinetic characteristics of the multienzyme system involved in GHB degradation studied in vitro are compatible with the production of GABA in vivo.

4-Aminobutyrate Transaminase↗
PubMed1985

Age-dependent changes in brain GABA turnover rates in two inbred strains of mice.

gamma-Aminobutyric acid (GABA) steady-state levels and turnover rates have been determined in 15 brain areas of 21-day- and 3-month-old DBA/2J (DBA) and C57B1/6J (C57) mice. These two inbred strains differ by their susceptibility to audiogenic seizures; moreover, the involvement of GABAergic neurotransmission has been suggested in the control of this behavior. Turnover rates are generally higher at 21 days than at 3 months of age. There are few significant differences in the GABA steady-state levels between 21-day-old seizure-prone DBA mice when compared with seizure-resistant C57 mice. In the DBA mice, the steady-state level is higher in the olfactory bulbs and lower in the posterior colliculus and the olfactory tubercles than in the C57 mice. Although there are some significant differences in GABA turnover rates and steady-state levels, intra or inter strains, it is difficult to correlate directly these differences with seizure susceptibility.

Animals↗
PubMed1985

Poly(ADP-ribosyl)ation of chromatin: kinetics of relaxation and its effect on chromatin solubility.

We have studied the kinetics of relaxation of poly(ADP-ribosyl)ated polynucleosomes produced by endogenous enzyme activity by comparing the generation of hyper(ADP-ribosyl)ated histone H1 and its effect on the chromatin structure as revealed by electron microscopy. A correlation can be established between the appearance of histone H1 modified forms and the localized relaxation of the chromatin. We have also noticed, in parallel, that poly(ADP-ribosyl)ated chromatin showed increased solubility in the presence of Mg2+ and 0.2 M NaCl. Electron microscopic examination of the solubilized chromatin produced by poly(ADP-ribosyl)ation shows polynucleosomes exhibiting more relaxed conformation, whereas an increasing amount of hyper(ADP-ribosyl)ated histone H1 is found in the pellet, as shown by acid-urea-polyacrylamide electrophoretic separation of histone extracts.

Animals↗
PubMed1985

[PolyADP-ribosyl polymerase (adenosine diphosphate ribosyl transferase) in bovine crystalline lens; modulation of its activity during aging].

PolyADP-ribose polymerase activities were measured in bovine lens. Activities similar to those in brain were found in the epithelial cells; none activity was detected in the fiber cells. During aging ADP-ribosyl transferase activity of epithelial cells raised, the number of polyADP-ribose chains increased while the average chain length decreased. A possible correlation between ADP-ribosylation and cell proliferation or repair is discussed.

Aging↗
PubMed1985

Minaprine, a new drug with antidepressant properties.

Minaprine is a new psychotropic drug which has recently proved to be effective in the treatment of various depressive states. In rodents, minaprine exhibits an atypical spectrum of antidepressant and dopaminomimetic activities. Thus in mice minaprine antagonizes the effects of reserpine, decreases immobility time in the behavioural despair test and potentiates the effects of 5-HTP; in rats it antagonizes muricidal behaviour (blocked by PCPA or raphectomy). However, minaprine does not affect yohimbine lethality and does not induce anticholinergic effects in mice. Minaprine also activates central dopaminergic transmission. Thus at low doses the drug antagonizes neuroleptic-induced catalepsy and induces stereotypies in rats. These stereotypies are blocked by neuroleptics. In addition, minaprine (like apomorphine) induces contralateral turning in mice with a unilateral lesion of the striatum, whereas d-amphetamine induces ipsilateral rotations. Unlike classical dopaminomimetic drugs, minaprine does not stimulate locomotor activity in rats. The mechanisms by which minaprine exerts its effects are still unclear, since in vitro minaprine does not affect monoamine uptake or release and does not interact with monoamine receptors. In vivo, minaprine (acute doses) increases 5-HT, decreases 5-HIAA levels in various brain areas and weakly and reversibly inhibits type A MAO; subacute treatments lead to a decrease in the number of 5-HT1 and 5-HT2 receptors. In addition, in the striatum the drug decreases HVA and DOPAC, and increases 3-MT levels, without affecting DA levels. Minaprine also weakly displaces (3H)-spiperone from striatal D2 receptors and increases striatal ACh levels. Finally, minaprine fails to affect brain NA or MHPG levels in acute doses and does not modify beta receptor density in subacute treatment. Thus minaprine appears to be a chemically and pharmacologically original antidepressant drug which activates both 5-HT- and DA-mediated transmission but which is devoid of NAergic and anticholinergic effects. This latter statement is confirmed by the good cardiovascular tolerance of minaprine in dog, monkey and humans, and by the lack of "tricyclic-like" anticholinergic side-effects in man.

Acetylcholine↗
PubMed1985

[Prevalence of HLA-A and -B antigens, anti-HBc and -HBs antibodies in alcoholic hepatopathies].

The frequency of 26 HLA-A and B antigens and of antibodies to the hepatitis B core antigen (anti-HBc) and surface antigen (anti-HBs) has been studied in 150 alcoholic patients divided into 3 groups: I) n = 50, isolated hepatic steatosis; II) n = 50, acute alcoholic hepatitis +/- cirrhosis; III) n = 50, cirrhosis without acute alcoholic hepatitis. For the control group 184 blood donors were selected. In all these subjects, as in all the alcoholic patients, the Alsatian origin of four grand parents was proved. An increased frequency of HLA-B15 was observed in group III (34 p. 100) compared to the control group (9.8 p. 100) (corrected p less than 0.001). There was no significant difference between the four groups for all the other HLA antigens. In group III, the prevalence of anti-HBc and/or anti-HBs was higher in patients with HLA-B15 (64.7 p. 100) than in patients without this antigen (15.1 p. 100) (p less than 0.001). In groups I and II, there was no significant difference. These results suggest that there is a genetic predisposition to cirrhosis without acute alcoholic hepatitis, dependent on HLA-B15 antigen. This predisposition could involve the hepatitis B virus.

Acute Disease↗
PubMed1985

[Isolation and characterization of a new cell line of spontaneously transformed astrocytes of the rat brain].

A new cell line of transformed astrocytes was obtained from primary new born rat brain cultures. rat brain cultures. These transformed cell line possess a normal karyotype, a doubling time of 17-24 hrs. and astrocyte specific protein marquers: glial fibrillar acidic protein (GFA) and glutamine synthetase. The ganglioside pattern is more differentiated than that of other known astrocyte lines.

Animals↗
PubMed1984

Specific stimulation of phospholipase activities with phosphatidylethanolamine in transformed cells.

Phospholipase A1, A2 and C activities with phosphatidylethanolamine were enhanced in C6 cells relative to primary astrocytic cultures. Enhancement was a function of cell density. Phospholipase activities with phosphatidylcholine were unchanged as a function of cell density, while phospholipase C activity with phosphatidylinositol was reduced. All acid phospholipase activities measured were low or essentially absent in the three transformed cell lines examined. These results suggest that arachidonate release upon confluency is mainly from phosphatidylethanolamine.

Animals↗