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Biomedical subjects

R Merolla

Publications and source records attributed to R Merolla.

13 recordsLinked to original sources
PubMed1995

Respiratory syncytial virus replication in human lung epithelial cells: inhibition by tumor necrosis factor alpha and interferon beta.

Respiratory syncytial virus (RSV) is the major pathogen causing severe lung disease in children. RSV initially replicates efficiently in the respiratory tract but becomes undetectable by 7 to 21 d after infection in normal children, suggesting that intrinsic cellular mechanisms, as yet undefined, may restrict virus replication. To provide an in vitro model to examine mechanisms that restrict RSV replication, three human lung epithelial cell lines were exposed to RSV in vitro and virus replication proceeded in a dose- and time-dependent manner, although less efficiently than the highly permissive CV-1 cell line (monkey kidney epithelial cell). Tumor necrosis factor alpha (TNF alpha) and/or interferon beta (IFN beta) markedly inhibited RSV replication in a dose- and time-dependent manner. TNF alpha combined with IFN beta essentially aborted RSV replication in A549 epithelial cells. TNF alpha and/or IFN beta did not induce cell membrane damage, cause cell lysis, or inhibit cellular protein synthesis. RSV-infected human alveolar macrophages, which produce TNF alpha, failed to productively infect lung epithelial cells in co-culture. Together these studies suggest that endogenous TNF alpha coupled with exogenous IFN beta could restrict RSV replication in lung epithelium.

Animals↗
PubMed1995

Respiratory syncytial virus induces interleukin-10 by human alveolar macrophages. Suppression of early cytokine production and implications for incomplete immunity.

Respiratory syncytial virus (RSV) causes repeated infections thought to be due to an ineffective immune response. We examined the hypothesis that incomplete immunity may result, in part, from RSV-infected alveolar macrophage production of IL-10 which can interfere with the production of immunoregulatory cytokines. We also assessed whether RSV induced the expression of the 2',5' oligoadenylate (2-5A)-dependent RNase L, an endoribonuclease involved in the antiviral activities of interferons. Human alveolar macrophages were exposed to medium (uninfected control), RSV, LPS, and RSV + LPS then were assessed for expression of the cytokines TNF-alpha, IL-1 beta, IL-8, IL-10, as well as 2-5A-dependent RNase L. LPS up-regulated the expression of protein and mRNA for all cytokines. RSV stimulated the protein levels of TNF-alpha, did not alter IL-1 beta, and decreased IL-8. RSV markedly stimulated protein expression of IL-10 and 2-5A-dependent RNase L. RSV had minor effects on the steady state mRNA levels of TNF-alpha, IL-1 beta, and IL-8, yet potently induced IL-10. Cells costimulated with RSV + LPS demonstrated reduced protein and mRNA levels of TNF-alpha, IL-1 beta, IL-8 but synergistically increased IL-10 levels compared to RSV- or LPS-activated cells. Kinetic analysis indicated that RSV induced a delayed and sustained increase in IL-10 transcripts. Furthermore, RSV-infected alveolar macrophage supernatants suppressed IL-1 beta and IL-8 production by LPS-stimulated alveolar macrophages as did recombinant IL-10. Anti-IL-10 neutralized these effects. These studies indicate that RSV is capable of suppressing production of early immunoregulatory cytokines through induction of IL-10 perhaps mediated by 2-5A-dependent RNase L (or other endoribonucleases) accounting for the ineffective immune response to this virus.

Base Sequence↗
PubMed1991

Analysis of expiratory pattern for monitoring bronchial obstruction in school-age children.

This study was designed to assess the validity of the percent of volume expired at tidal peak flow (dV/Vt) as an indicator of bronchial obstruction in school-age children. We analyzed 126 dV/Vt ratios and compared them with spirometric and plethysmographic results measured in 24 healthy (14 males) and 60 asthmatic (41 males) children; 42 of them underwent measurements before and after bronchial challenge with histamine. The two groups differed in resistance, forced expiratory volume in 1 sec (FEV1), and forced expiratory flows, as percents of predicted (FEV1: 94.6 +/- 2.4% in controls vs 86.7 +/- 1.6% in asthmatics; P less than 0.001). They did not differ in peak expiratory flow (PEF), forced vital capacity, functional residual capacity, measured by body plethysmography, and in dV/Vt. The dV/Vt was found to correlate with FEV1 (r = 0.58, P less than 0.001), PEF (r = 0.57, P less than 0.001), and other lung function parameters. Forty-two of the asthmatic children performed a bronchoprovocation histamine test. The fall of dV/Vt after histamine was significantly correlated (r = 0.61, P less than 0.001) with the variation in FEV1 and other lung function parameters. We conclude that dV/Vt is a good indicator of bronchial obstruction, as useful in school-age children as in adults and infants, with no need for the subject's cooperation.

Adolescent↗
PubMed1976

L-Asparaginase: effect on 7S gamma globulin extents and germinal centers in spleen and lymph-nodes.

Administration of L-asparaginase may cause remission in a high percentage of acute lymphocytic leukemias and lymphomas, either in experimental animals or in human beings. This enzyme is able to depress immune reactions like lymphocyte blastogenesis and delayed hypersensitivity, and to impair gamma-globulin synthesis. L-asparaginase also has antigenic properties, and may cause the formation of anti-L-asparaginase antibodies. This study reports observations on the effect of L-asparginase on the 7S gamma-globulin levels and on the behaviour of the germinal centers in spleen and lymph nodes. It has been found that after administration of low or intermediate doses of L-asparginase, a decrease in the size of the follicular marginal zones occurred. This was accompanied by an enlargement of the germinal centers. Furthermore the spleen weight decreased and the concentration of 7S gamma-globulin diminished slightly. In animals given high doses of L-asparaginase, germinal centers were enlarged even more but marginal zones appeared repopulated although not to the degree of the controls. The spleen weight of these enzyme-injected animals reached almost the normal values, while a statistically significant decrease of 7S gamma-globulin concentrations was found.

Animals↗
PubMed1975

Electrophoretic investigation of L-asparaginase influence on blood and spleen blood globulins. Experimental study.

In view of detecting the influence of L-asparaginase on blood and spleen blood globulins, 42 rabbits were daily injected for three weeks with different doses of this drug. Electrophoretic analysis of blood and spleen blood samples from these animals showed no relationship between the doses used and the changes of circulating blood globulins indicating the well known immunodepressing effects of the drug. However, in the spleen blood from the inoculated rabbits (as compared with a control group) a small excess of gamma globulins which appeared especially after 1-2 weeks of daily injections with 2,000 or 10,000 I.U.L-asparaginase/kg b.w. was interpreted as due to the antigenic action of the enzymatic product administered.

Animals↗