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Biomedical subjects

V Roman

Publications and source records attributed to V Roman.

At least 19 recordsLinked to original sources
PubMed2005

TGFalpha and AVP in the mouse suprachiasmatic nucleus: anatomical relationship and daily profiles.

Daily rhythms in behavior and physiology are under control of the suprachiasmatic nucleus (SCN), the main mammalian circadian pacemaker located in the hypothalamus. The SCN communicates with the rest of the brain via various output systems. The aim of the present study was to determine the neuroanatomical and temporal relationship between two output systems, arginine-vasopressin (AVP) and transforming growth factor alpha (TGFalpha), in the mouse SCN. TGFalpha-positive cells were found throughout the SCN, but more abundantly in the core than the shell area, while AVP was predominantly found in the shell. Fluorescent double labeling revealed a total lack of co-expression for the two proteins in SCN cells. The circadian profile, studied by way of optical density in immunostaining at 3 h intervals, showed peak values for AVP shortly after the LD transitions. Immunoreactivity for TGFalpha was highly variable, especially at time points before the LD transitions. In addition, strong lateralization in TGFalpha immunostaining in the SCN was found in some individuals. Daily fluctuations in the paraventricular nucleus were absent for TGFalpha, and only weakly present for AVP. The main conclusion derived from this study is that these two output systems of the biological clock are anatomically separated with different daily profiles in expression.

Animals↗
PubMed2001

Detection of pesticide model compounds in ethanolic and aqueous microdroplets by nonlinear Raman spectroscopy.

Pesticide model compounds are detected in microdroplets by means of in situ nonlinear Raman spectroscopy. The chloro- and nitro-substituted aromatics are dissolved in ethanol as well as in water. Their vibrational spectroscopic fingerprint, that is, Raman bands characteristic of the functional groups attached to the aromatic system, is determined in bulk medium by linear Raman spectroscopy. As a result of the concept of group vibrations, the chosen compounds can be regarded as representatives for a whole class of pesticides containing these residues. External seeding of stimulated Raman scattering (SRS) is applied for the detection of these group vibrations of the pesticide model compounds. This technique can be utilized for in situ diagnostics and a noninvasive vibrational spectroscopic analysis of the chemical composition of microdroplets with natural or anthropogenic origin.

Journal Article↗
PubMed2001

Contribution of nitric oxide to the apoptotic process in human B cell chronic lymphocytic leukaemia.

B cell chronic lymphocytic leukaemia (B-CLL) is characterised by defective apoptosis that cannot be explained solely on the basis of the known chromosomal abnormalities. We and other have now reported that the leukemic cells spontaneously display the inducible isoform of nitric oxide synthase, iNOS. Inhibition of the iNOS pathway leads to increased apoptosis of the tumoral cells in vitro, indicating that the endogenous release of NO contributes to their resistance to the normal apoptotic process. The factors that induce the expression of iNOS in vivo in the leukemic cells are not yet identified. Yet, as interaction of B-CLL leukemic cells with bone marrow stromal cells promotes their survival, the involvement of adhesion molecules and integrins may be suspected. The engagement of CD23 stimulates iNOS activation in the tumoral cells, suggesting that in vivo interaction of CD23 with one of its recognised ligands may contribute to iNOS induction. A role for CD40-CD40 ligand interaction may also be hypothesised. The mechanisms involved in the anti-apoptotic role of NO are not fully understood, but may implicate the inhibition of caspase activity, hence the impairment of the Fas pathway. In addition, the mitochondrial membrane potential disruption appears to be a NO-sensitive step in the apoptosis cascade. The presence of a NOS displaying anti-apoptotic properties has now been recognised in different cell types, including various leukaemia. A better knowledge of the mechanisms governing the ultimate fate of NO, anti- versus pro-apoptotic would allow the development of new therapeutic approaches for the treatment of these diseases.

Apoptosis↗
PubMed2000

Expression of a functional inducible nitric oxide synthase in hairy cell leukaemia and ESKOL cell line.

The expression of nitric oxide synthase (NOS) isoforms was investigated in the established ESKOL hairy cell line and in leukemic cells of patients with hairy cell leukemia (HCL). By reverse transcription-polymerase chain reaction (RT-PCR), these cells were found to spontaneously express inducible NOS (iNOS)-specific mRNA, but not endothelial constitutive NOS (ecNOS) mRNA. The iNOS protein was detected by immunofluorescence in the cytoplasm of permeabilized leukemic cells and ESKOL cells, using different anti-iNOS monoclonal antibodies. A protein of 135 kDa was identified by Western blotting in ESKOL and HCL lysates, confirming the presence of an iNOS in these cells. Cytosolic homogenates displayed NOS catalytic activity, as measured by the conversion of 14C-labelled L-arginine into 14C L-citrulline and by detection in situ using the DAF-2DA (diaminofluorescein diacetate) NO-sensitive fluorescent probe. Ligation of CD23 (low affinity IgE receptor) was found to increase iNOS expression in ESKOL and conversely to decrease the percentage of cells undergoing apoptosis, as measured by the percentage of cells expressing annexin V. These results indicate that, as in chronic B cell lymphocytic leukemia cells (B-CLL) a functional iNOS is expressed constitutively in hairy cells that contributes to protecting these tumoral cells from apoptosis.

Amidines↗
PubMed1998

Anti-emetic effect of ondansetron and granisetron after exposure to mixed neutron and gamma irradiation.

The anti-emetic efficiency of orally administered ondansetron and granisetron has been tested in macaques exposed to a mixed y and neutron radiation (6 Gy) with a high neutron/gamma-ray ratio. Our experiments reveal that a single delivery of ondansetron (1 or 2 mg kg(-1)) or of granisetron (0.25 mg kg(-1)) 45-90 min before irradiation or 35-45 min after irradiation was not totally effective. Conversely, the delivery of two doses with the same delay prior to and after exposure led to a complete prevention of vomiting and retching. These observations can be explained by the dual mechanism of radiation-induced emesis: an early peripheral mechanism and a later central mechanism. Two deliveries of 5-HT3 receptor antagonists seem to disrupt serotonergic transmission at the brain stem structures and to affect the peripheral release of serotonin from the gut, thus completely preventing radiation-induced vomiting. This study confirms that the 5-HT3-dependent mechanisms that mediate emesis are similar for both neutron and gamma radiation.

Animals↗
PubMed1997

Characterization of a constitutive type III nitric oxide synthase in human U937 monocytic cells: stimulation by soluble CD23.

The soluble cleavage fragment of the low-affinity immunoglobulin E (IgE) receptor/CD23 (sCD23 25000 MW) and antibodies directed against their receptors on monocytes, CD11b and CD11c, stimulate the production of nitric oxide (NO) by these cells and we have suggested that the enzyme involved could be related to the endothelial constitutive type III nitric oxide synthase (ecNOS). In the present work, we have analysed the characteristic properties of this NOS isoform in the model of the human promonocytic cells U937 By reverse-transcription polymerase chain reaction (RT-PCR), the presence of an mRNA coding for type III NOS was found in U937 cells and the corresponding protein was detected by immunofluorescence in permeabilized cells with a specific anti-ecNOS monoclonal antibody (mAb). Membrane extracts displayed a NOS activity dependent on the presence of calcium and calmodulin in the reaction medium and that was abrogated in the presence of EGTA. Recombinant soluble CD23 (25000 MW) was found to trigger an NO-dependent cGMP accumulation in these cells, which was abrogated by calcium chelators and inhibitors of the calcium/calmodulin complex. Moreover, sCD23 elicited a transient augmentation of intracytoplasmic free calcium concentration [Ca2+]i that was dependent on the presence of calcium in the external buffer and was prevented in the presence of EGTA, indicating that it was due to a calcium influx. In conclusion, human promonocytic cells such as U937 exhibit a functional type III NOS that can be stimulated by calcium-raising agents, such as sCD23.

Calcium↗
PubMed1996

Mouse multivalent IgG(2a, b) antibody--ricin A-chain immunotoxins combined with homologous or heterologous interleukin 2 in the treatment of a murine malignant lymphoproliferation (EL4).

Two immunotoxins containing ricin A-chain, staphylococcal protein A and mouse anti-Thy 1.2 antibodies of IgG(2a,b) subclass, were prepared. The two multivalent immunotoxins of 750 and 370 kDa and molar ratio A-chain: IgG of 1:2, were used for the treatment of mice bearing ascitic EL4 lymphoma. The immunotoxin-treatment, performed intraperitoneally, was combined or not with homologous or heterologous interleukin 2. The antitumor effects expressed by increase of mice survival time (p < 0.001 as compared with nontreated animals) corresponded to a proportion of 88-90% lymphoma cell-kill by immunotoxin and 93-95% by combination treatment (immunotoxin + interleukin 2), as calculated from the relationship between the survival time of nontreated mice and the number of tumor cells inoculated.

Animals↗
PubMed1992

Some recent data on chemical protection against ionizing radiation.

Once introduced in the organism, the radioprotectors are fastly degraded and that increases their toxicity, shortens their duration of action and renders them inactive after oral delivery. So, it was tried to protect them by their incorporation in vectors. When a cysteamine-liposomal suspension was orally delivered, it showed a radioprotective activity for about 4 hours. By using 35S cysteamine, it was noted that its plasmatic concentration was increased. Freeze-drying of these preparations was a good mean of conservation if the samples were stored at 4 degrees C. A good and sustained activity was also obtained after oral delivery of WR-2721 entrapped in microspheres. Otherwise, it was shown that after interacting with the polar heads of phospholipids, under determined conditions of pH and in fluid phase, aminothiols can penetrate inside the membrane and be entrapped in the internal medium of liposomes and as they penetrate, they can lessen the diffusion of oxygen in the lipidic bilayers.

Administration, Oral↗
PubMed1987

Radioprotective activity of ethylcellulose microspheres containing WR 2721, after oral administration.

Ethylcellulose microspheres containing WR 2721 were prepared by the emulsion-solvent evaporation technique. No significant loss or degradation of this phosphorothioate was noted during preparation. Oral administration of these microspheres to mice gave an important lowering of WR 2721 toxicity and an enhancement of its radioprotective activity with a D.R.F. of about 1.7-1.8 over 2-3 h. This action is explained by the protection of WR 2721 from acid hydrolysis and degradation in the gastro-intestinal tract. The adsorption of a fraction of WR 2721 onto the surface of microspheres constitutes an inconvenience. This study confirms the interest of such carriers for providing important sustained radioprotection after oral administration.

Administration, Oral↗
PubMed1987

A radioprotector: cysteamine, inhibits oxygen transport in lipidic membranes.

Spin labeling techniques make possible the observation of oxygen diffusion or concentrations in phospholipid membranes. In such a system, cysteamine, depending upon the molecular cysteamine/DPPC ratio and the pH conditions, inhibits oxygen transport, and this result provides an original explanation for cellular hypoxia after cysteamine administration.

Biological Transport↗
PubMed1985

The binding of the radioprotective agent cysteamine with the phospholipidic membrane headgroup-interface region.

The interaction of the aminothiol radioprotector cysteamine (beta-mercaptoethylamine) (CYST) with dipalmitoylphosphatidylcholine (DPPC) artificial membranes has been studied by differential scanning calorimetry (DSC), turbidimetry and spin labeling. This hydrophilic molecule displays a biphasic, concentration-dependent binding to the phospholipidic head groups at neutral pH. In the CYST/DPPC molar ratio 1:160-1:2 (mole/mole) an increasing ordering effect is observed. At high concentrations (over 3:1 ratio), this ordering effect decreases. With the symmetric disulfide dimer cystamine, the biphasic effect is not shown and the membrane rigidity decrease is obtained only at concentration ratio higher than 1:1. The charge repartition of the cysteamine molecule has been shown to be disymmetric, +0.52 e on the NH3 group and +0.19 e on the SH extremity, [38] whereas the cystamine molecule is electrostatically symmetrical. These properties could be related to their membrane effects. With cysteamine, at a low concentration, an electrostatic bridging between the negatively charged phosphate groups of the polar heads induces the increase in membrane stability: the molecules behave like a divalent cation. At high concentrations a displacement of the slightly charged SH extremity by the amine disrupts the bridges and induces the decrease in rigidity: the drug behaves like a monovalent cation. Due to its symmetric charge and its double length, such an effect is not observed with cystamine. This study could bring further information about the interactions between cysteamine and polyelectrolytic structures (ADN for example) and about the radioprotective properties of this drug.

Binding Sites↗
PubMed1985

Interaction of vinblastine sulfate with artificial phospholipid membranes. A study by differential scanning calorimetry and spin labeling.

The effect of the antimitotic drug vinblastine sulfate has been studied on fully hydrated dipalmitoylphosphatidylcholine (DPPC) liposomes in the temperature range 0 degrees to 60 degrees using differential scanning calorimetry and electron spin resonance spectroscopy with two fatty acid spin labels. In the gel phase, vinblastine interacts essentially with the DPPC polar heads and induces an important disorganization of the phospholipidic bilayer. The co-operativity of the main thermal transition is decreased. In the crystal-liquid phase, the drug penetrates inside the artificial membrane and induces the formation of domains which increased thermal stability. These effects are opposite to those observed with the drug isaxonine which is used to reduce the axonal degenerating effects due to vinblastine.

Binding Sites↗
PubMed1985

Oral administration of liposome-entrapped cysteamine and the distribution pattern in blood, liver and spleen.

Oral administration of liposome-entrapped cysteamine induces an increase in the concentration of exogenous sulphur compounds in blood (plasma), liver and spleen. Among those sulphur compounds, an important amount of plasma thiols can be related to a protection of cysteamine in the digestive tract. This can account for the radioprotective effect of a liposomal-cysteamine suspension in rodents, and clearly demonstrates the interest of such a preparation in radioprotection.

Administration, Oral↗
PubMed1984

Isaxonine base is a strong perturber of phospholipid bilayer order and fluidity--a differential scanning calorimetry and spin labeling study.

The effects of the neurotropic drug isaxonine on fully hydrated dipalmitoyl-phosphatidyl-choline (DPPC) bilayers has been studied in the temperature range 0 degree-60 degrees, using differential scanning calorimetry and electron spin resonance spectroscopy, with two stearic acid spin labels. At low concentration (1% mol/mol), isaxonine is trapped in the polar interface and enhances the phospholipid multibilayers organization in the gel state. In contrast, at high concentration (30% mol/mol), the drug disorganizes the phospholipidic structures and may induce domain formation by phase separation. The strong interactions of isaxonine at the lipid-water interface change the ionization state of the stearic acid spin labels which become totally ionized. Then isaxonine acts as a modifier of the surface pH of the bilayer. The strong membrane effects of isaxonine may explain in part its pharmacological properties in vivo.

Calorimetry, Differential Scanning↗