Inactivation of C3H 10T1/2 cells by monoenergetic high LET alpha-particles.

Inactivation of mouse C3H 10T1/2 cells in plateau-phase (7.8 x 10(4) cells/cm2) was studied by using alpha-particles from the irradiation facility installed for radiobiological experiments at the 3 MV Tandem accelerator, University of Naples. Silicon detectors and CR39 plastic track detectors were employed for dosimetric purposes. The cells were exposed to high LET monoenergetic alpha-particles (energy of 1.8 MeV at the centre of the cell nucleus, track-averaged LET of 177 keV/micron and dose-rate of 1.1 Gy/min) and low-LET 80 kVp X-rays. The X-ray survival curve showed a significant shoulder (alpha/beta = 9 Gy) while the survival curve for alpha-particles was close to exponential. The mean lethal dose of alpha-particles was 0.77 +/- 0.02 Gy and the RBE was 5.2 at 80% survival and 3.0 at 5% survival. Survival of exponentially growing cells (2 x 10(4) cells/cm2) following irradiation with the alpha-particle beam is also reported. The nuclear areas of 10T1/2 cells were measured as 299 +/- 9 micron 2 and 250 +/- 8 micron 2 for cells in log phase and plateau phase, respectively. The inactivation cross-section, obtained from the mean lethal dose, was 34 micron 2 and 37 micron 2 for cells in log phase and plateau phase, respectively. These values appear to be the maximum measured values for the inactivation cross-section of 10T1/2 cells as a function of the alpha-particle LET. This saturation cross-section is very similar to the saturation values reported in the literature for other mammalian cell lines.     

Effect of erythromycin on the immune response and interferon production

The influence of erythromycin on some aspects of humoral and cell-mediated immunity has been examined employing human as well as murine models, both in vivo and in vitro. No significant differences in antibody synthesis, alpha- and gamma-interferon yield, cutaneous delayed hypersensitivity or lymphocyte blastogenic response to mitogens have been detected between erythromycin-treated subjects and controls. Similarly, in vitro tests on interferon production and blastogenic response to mitogens showed no significant differences when performed with and without erythromycin. Therefore, in contrast with many other antibacterial drugs, erythromycin seems to be devoid of any adverse effects on the immune system.     

Nonsteroidal anti-inflammatory drugs (NSAIDs) and the kidney

In patients with PG-dependent renal function, NSAID administration constantly reduces GFR and RBF in a dose-dependent fashion. In this situation, the risk of overt acute renal failure is high and should be taken into proper account. In contrast, the incidence of NSAID-related renal structural alterations appears to be very low, yet the absolute number of patients may be significant considering the wide use of such drugs. Concerning the antiproteinuric effect of NSAIDs, the unfavourable ratio risk/benefit does not seem to support their indication in proteinuric nephropathies. The development of PGHS-2 selective inhibitors is promising, and may open new therapeutical strategies in the treatment of the progression of renal disease.      

Serological Survey of Toscana Virus Infections in a High-Risk Population in Italy

Toscana virus is the most important agent responsible for meningitis in central Italy. We report a serosurveillance study, using an immunoenzymatic assay, of 360 serum samples harvested from a high-risk population occupationally exposed to Toscana virus in two regions of Italy, Tuscany and Piedmont. The results indicates a seroprevalence of Toscana virus of 77.2% in the forestry workers, particularly in the Tuscany region. This fact is strictly correlated with the ecological niches specific for the survival of Toscana virus arthropod vector.     

T-cell and antibody response to Parietaria Judaica allergenic fractions in atopic and nonatopic individuals

The in vitro proliferative response to separated immunologically relevant components of Parietaria judaica pollen extract (PjE) was investigated by proliferation assay and limiting dilution analysis, in peripheral blood mononuclear cells from Parietaria-allergic subjects and nonallergic controls. In the same subjects, the profile of the antibody response to the PjE fractions was also studied by immunoblotting to evaluate the functional significance of allergen-induced T-cell activation in the two groups. The estimated frequency of PjE-reactive T cells in peripheral-blood mononuclear cells was low in both groups. No difference was found between the Parietaria-allergic subjects and nonallergic controls. To assess the overall contribution to the cellular response of PjE components of different molecular weights, we separated the extract by the SDS-PAGE technique, and the fractions were blotted onto nitrocellulose and solubilized. Almost all the 14 fractions tested induced T-cell proliferation, at different degrees of magnitude. Responses were similar in the allergic subjects and nonallergic controls. Immunoblotting demonstrated specific IgG antibodies to the 14 PjE fractions not only in the allergic subjects, but also in the healthy controls, whereas IgE antibodies were found, as expected, only in the sera from atopic subjects. These findings indicate that PjE fractions elicit similar T-cell activation and IgG production in allergic and normal subjects.     

Impaired macrophage phagocytosis of apoptotic neutrophils in patients with human immunodeficiency virus type 1 infection

Dysfunction of neutrophils (polymorphonuclear leukocytes [PMNL]) and macrophagic cells occurs as a consequence of human immunodeficiency virus type 1 (HIV-1) infection. Macrophages contribute to the resolution of early inflammation ingesting PMNL apoptotic bodies. This study investigated macrophage ability to phagocytose PMNL apoptotic bodies in patients with HIV-1 infection in comparison with uninfected individuals and the effect of HIV Nef protein on apoptotic body phagocytosis to determine if phagocytic activity is impaired by HIV infection. Monocytes/macrophages were isolated from 10 HIV-1-infected patients and from five healthy volunteers, whereas PMNL were isolated from healthy volunteers. Macrophage phagocytosis of apoptotic PMNL was determined by staining of apoptotic bodies with fluorescein-conjugated concanavalin A or with fluorescein-labeled phalloidin. Our data show significant impairment of PMNL apoptotic body macrophage phagocytosis in subjects with HIV-1 infection presenting a concentration of CD4(+) T lymphocytes of >200/mm(3) and in particular in those with <200 CD4(+) T lymphocyte cells/mm(3). In addition, HIV-1 recombinant Nef protein is able to decrease phagocytosis of apoptotic PMNL from normal human macrophages in a dose-dependent manner. The results of our study suggest that impaired macrophage phagocytosis of PMNL apoptotic bodies may contribute to the persistence of the inflammatory state in HIV-infected subjects, especially during opportunistic infections that are often favored by defective phagocytic activity.     

Outcome of follow-up programs in patients previously resected for colorectal cancer

The survival of a group of 115 patients (group A) who entered a follow-up program after apparently "curative" surgery for colorectal cancer was compared with that of 62 similar patients (group B) who did not join such a program. No significant difference was found. Clinical benefits to single patients in group A, in terms of anticipated diagnosis and effective treatment of recurrences and of metachronous neoplasias, appeared to be, if any, extremely limited. In light of the high costs of intensive follow-up programs, it is concluded that their use can be justified only within controlled perspective trials aimed to evaluate their usefulness.