PubMed Health⌕ Search

Biomedical subjects

O Bosco

Publications and source records attributed to O Bosco.

24 records · Page 2Linked to original sources

Evidence for interactions between HLA system class I and beta-adrenergic receptors in human mononuclear leukocytes.

In order to determine the possible interactions between histocompatibility leukocyte antigen (HLA) -class I antigens and beta-adrenergic receptors, we evaluated the effects of anti-HLA class I monoclonal antibodies on beta-adrenoceptor-mediated intracellular production of cAMP in human mononuclear leukocytes. Moreover, we studied whether anti-HLA class I monoclonal antibodies inhibit the binding of a specific radioligand to the beta-adrenoceptors, and, conversely, whether both isoproterenol and propranolol interfere with the binding (evaluated by a cytofluorometric assay) of the anti-HLA class I monoclonal antibodies to the cell membrane. Our results showed that anti-HLA class I monoclonal antibodies induced a significant beta-adrenergic-dependent increase in intracellular cAMP whereas anti-HLA class II and antimelanoma monoclonal antibodies were ineffective. Moreover anti-HLA class I monoclonal antibodies inhibited, in part, the specific binding of a beta-adrenergic radioligand, although they did not induce the internalization of the beta-adrenoceptors. On the other hand, both isoproterenol and propranolol induced a significant decrease in the peripheral blood mononuclear cell expression of HLA-class I molecules. Our data suggest that important interactions between major histocompatibility complex gene products and the beta-adrenergic receptors may occur in human cells.

Adult↗

Underestimation of the incidence of measles in a population of French children.

Data on titres of specific antibodies against measles virus and information given by families and physicians were analysed in 133 vaccinated and 117 unvaccinated children. Only 2 of the 133 vaccinated children reported a history of measles, while 131 had detectable levels of antibodies. Measles antibodies were detected in 102 (87.2%) of the unvaccinated children, but a history of measles diagnosed clinically by a physician was reported in only 42 of them. These findings suggest that subclinical cases of measles are possible and contribute to the high circulation of the measles virus in the child population in France.

Adolescent↗

Relation between chloroguanide bioactivation to cycloguanil and the genetically determined metabolism of mephenytoin in humans.

It has been suggested recently that the bioactivation of chloroguanide hydrochloride (proguanil) to its active antimalarial metabolite cycloguanil cosegregates with the genetically determined polymorphism of mephenytoin hydroxylation. We determined the chloroguanide to cycloguanil ratio in urine after oral administration of a single dose of 200 mg proguanil either alone or together with 100 mg racemic mephenytoin or 40 mg dextromethorphan in a randomized crossover study performed in 24 healthy subjects. The mephenytoin hydroxylation index was also determined after administration of 100 mg racemic mephenytoin either alone or together with 200 mg proguanil. Two subjects were poor metabolizers and one subject was an intermediate metabolizer of mephenytoin. These three subjects had chloroguanide to cycloguanil ratios of more than 50. The 21 subjects with the extensive metabolizer phenotype for mephenytoin hydroxylation had chloroguanide to cycloguanil ratios of less than 10. The chloroguanide to cycloguanil ratio was not significantly altered by mephenytoin or dextromethorphan coadministration. The trend toward a correlation between chloroguanide/cycloguanil ratio and log mephenytoin hydroxylation index did not reach statistical significance. Inclusion of the dextromethorphan metabolic ratio into the model did not improve the relationship. These findings confirm that the bioactivation of chloroguanide to cycloguanil cosegregates with the genetically determined activity of the CYP2C family. However, the chloroguanide to cycloguanil ratio and the mephenytoin hydroxylation index do not similarly reflect the variable activity of CYP2C.

Adult↗

[Immunity to and incidence of measles in a population of Parisian children].

BACKGROUND: Measles remains prevalent in France despite the development of nationwide vaccination program. This study evaluates measles immunity and correlates it with active immunization. MATERIAL AND METHODS: A total of 250 (131 boys and 119 girls) French children, aged 2 to 15 years, seen as outpatients in our hospital, were studied from 1.01.90 to 1.06.91; 133 had received live measles vaccine during the 2nd year of life, the 117 others were not vaccine-protected. Evaluation included medical records, specially those concerning past-history of measles or measles-like diseases and immunizations. Measles IgG and IgM antibodies (ELISA) were looked for in all 250 children. RESULTS: 102 of the 117 children who were not vaccine-protected had a detectable antibody titer. 42 of these 102 had a history of measles, before the age of 5 years in 30, between 5 and 10 years in 9 and after the age of 10 years in 3. Only 4 of the 70 children aged over 10 years and not vaccine-protected had no detectable antibodies. 131 of the 133 actively immunized children had detectable antibodies. CONCLUSIONS: Measles is probably more frequently subclinical than was believed until now. Its relative frequency in France in children who had not received the live vaccine explains the high percentage of those aged over 10 years who had detectable antibodies and the relatively low incidence of the disease in teenagers and young adults.

Adolescent↗

Use of an established cell line in the evaluation of the cytotoxic effects of various chemicals.

The HTC hepatoma cell line was used as an "in vitro" model to detect the cytotoxicity of eighteen chemicals, chosen on the basis of different biological activities and physicochemical characteristics. Two different cytotoxicity assays measuring cell lethality (CS) or inhibition of cell growth (CF) were applicated to confluent cell monolayers or to colony-forming cells, respectively. Cells were exposed to the chemicals at doses ranging from 10(-6) M to 10(-2) M for 24 h. The results indicated a wide range of IC 50 (the concentration resulting in 50% inhibition of toxicity parameters) from as low as 1 microM (Potassium dichromate) to as high as 407.5 mM (Ethanol), the sensitivity of the CF test being greater than that of the CS test. A battery of cytotoxicity tests could be established in order to offer simple, rapid and economic methods which can be complementary and, in part, alternative to the use of laboratory animals.

Animal Testing Alternatives↗

Decreased surface antigen density on lymphocytes of elderly humans.

The aim of our study was to analyze some poorly investigated and controversial aspects of senescent lymphocyte phenotype and functions. We examined 100 healthy aging individuals, divided into 4 age groups, and 30 young controls, correlating lymphocyte responsiveness to mitogenic stimulation with membrane phenotypic pattern and surface molecular densities of the main functional lymphoid markers. Stability of values in the period of study was established. No age-related differences in the parameters evaluated were detected among aging subjects. Phytohemagglutinin-induced lymphocyte proliferation was found severely impaired (about halved) in all elderly individuals with respect to controls. There was no significant difference between elderly group and controls in CD2, CD3, CD4, CD8, CD19, CD25 and HLA-DR antigen distribution. CD56 positive cell percentages were slightly decreased in the elderly groups. In apparent correlation with reduced lymphocyte responsiveness, CD2, CD3, CD4 and CD8 molecular densities, to different extents, were found relevantly (about 1 to 3-fold) lower in all aging groups than in controls. We could not ascertain if those antigens were poorly synthesized, defectively transported to membrane or shed in excess. However, we suggest that decreased surface molecular densities of antigens involved in functional processes of immune responses may be responsible for an abnormal costimulatory pattern during lymphocyte activation, leading to apoptotic rather than proliferative signals in a greater proportion of cells than normal.

Age Factors↗