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P Cadrobbi

Publications and source records attributed to P Cadrobbi.

At least 19 recordsLinked to original sources
PubMed1992

Release of granulocyte-macrophage colony-stimulating factor by alveolar macrophages in the lung of HIV-1-infected patients. A mechanism accounting for macrophage and neutrophil accumulation.

In this paper, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lung of patients with HIV-1 infection was evaluated. This cytokine has well recognized effects on granulocyte and macrophage growth and differentiation and plays some role in the mechanisms leading to the accumulation of alveolar macrophages (AM) in patients with interstitial lung disease. Detectable levels of GM-CSF (up to 10 pg/ml) were demonstrated in unconcentrated bronchoalveolar lavage fluid retrieved from HIV-1-seropositive patients, thus suggesting that the GM-CSF is released in vivo in the lung during HIV-1 infection. A statistically significant correlation was demonstrated between the bronchoalveolar lavage concentrations of GM-CSF and the absolute numbers of AM and lung neutrophils. Cell-free supernatants obtained from unstimulated 24-h cultured AM isolated from HIV-1-infected patients contained discrete amounts of GM-CSF, as demonstrated by an immunoenzymatic assay. AM lost the capability of releasing GM-CSF after 72 h of culture, thus suggesting that the production of GM-CSF is not constitutive in AM. After exposition of AM with LPS, the release of GM-CSF and the expression of its mRNA significantly increased with respect to the baseline values; interestingly, the amount of GM-CSF released by LPS-stimulated AM was more than 10-fold higher in HIV-1-infected patients than in healthy subjects. As demonstrated by flow cytometry analysis, more than 70% of freshly isolated AM efficiently bound phycoerythrin-GM-CSF, thus indicating that they express the receptor for GM-CSF. Determination of AM in G1, S, and G2+M by flow cytometry showed that, after 48 h of culture with GM-CSF, 5.5 to 7% of AM entered the proliferative phase of the cell cycle. Taken together, these findings suggest that AM might represent an important source of GM-CSF production in HIV-1 infection. In particular, the hypothesis is formulated that pulmonary opportunists might trigger AM to synthesize GM-CSF in situ. The local overproduction of this cytokine is likely to play a role in the pathogenic events leading to the local proliferation of AM and recruitment of neutrophils in AIDS-associated interstitial lung disease.

AIDS-Related Complex↗
PubMed1992

Expression of a functional p75 interleukin-2 receptor on lung lymphocytes from patients with human immunodeficiency virus type 1 (HIV-1) infection.

Lung involvement in patients affected by HIV-1 infection is characterized by an alveolitis sustained by the accumulation of CD8+ T lymphocytes. To investigate whether in situ T cell growth plays a relevant role in the pooling of CD8+ lymphocytes, we have analyzed the activity of two lymphokines involved in the mechanisms of T cell proliferation, i.e., interleukin-2 (IL-2) and interleukin-4. To this aim, following appropriate triggering and blocking, the expression and the functional role of IL-2 receptors (IL-2R) (both p55 and p75 chains) and IL-4 receptors have been analyzed on T lymphocytes obtained from the bronchoalveolar lavage (BAL) of 16 HIV-1+ patients. Molecular and phenotypic studies we performed demonstrated that CD8+ lymphocytes from the BAL of HIV-1 + patients strongly expressed the p75 chain of IL-2 receptor, while neither p55 mRNA nor its surface membrane product (Tac antigen) was detectable; in addition, there was no expression of IL-4 receptors. IL-2 stimulation was able to induce T cell growth in a dose-dependent manner, whereas IL-4 did not. Finally, using mAbs which specifically block the p55 or p75 IL-2R, we showed that both subunits of IL-2R were involved in the proliferative activity of lung lymphocytes. The results obtained in the present study directly demonstrate that BAL T lymphocytes of HIV-1 + patients express a fully functional IL-2 receptor apparatus, pointing to the role for this lymphokine in maintaining the alveolitis taking place in the lungs of AIDS patients.

Adult↗
PubMed1992

Cryptogenic chronic liver disease and hepatitis C virus infection in children.

The clinical features of 'cryptogenic' chronic liver disease and the prevalence of antibody to hepatitis C virus (HCV) in serum have been investigated in 33 Italian children (mean age 5 years). The diagnosis was based on the persistence of increased alanineaminotransferase values for longer than 6 months after the exclusion of biliary diseases, of extra-hepatic causes of hypertransaminasemia, of infection with known hepatotropic viruses and of autoimmune or metabolic disorders. Five patients had been transfused early in life, three had undergone surgery and one girl's mother had had acute non-A, non-B hepatitis during pregnancy. The remaining patients had no history of overt parenteral exposure. At presentation only 11 patients were symptomatic, the others had been referred after a check-up for intercurrent diseases. Liver histology performed in 21 cases showed persistent or mild active hepatitis in 18 cases and severe hepatitis or cirrhosis in three cases. Anti-HCV antibodies were found in 48% of the cases, including 88% with obvious exposure and 33% of the remaining cases. During a mean follow-up period of 5 years (range 1-14 years) only 11% of the cases achieved sustained biochemical remission, although none developed signs of liver failure. There was no significant difference in the clinical features and outcome of the disease between anti-HCV-positive and -negative patients. The results of this study suggest that HCV is implicated in most cases of 'cryptogenic' chronic liver disease observed in Italian children with a history of parenteral exposure and in at least one-third of the cases without overt exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1992

Chronic hepatitis B surface antigen-negative hepatitis after treatment of malignancy.

We reviewed the records of all patients with a diagnosis of malignancy who were treated at our center and who had not had chemotherapy for at least 18 months, to assess the prevalence of chronic hepatitis B surface antigen (HBsAg)-negative hepatitis, to assess the prevalence of a marker of hepatitis C virus infection, and to determine the severity of chronic liver disease. Of 557 eligible patients, 38 (6.8%) had chronic HBsAg-negative hepatitis. Of these 38 patients, 20 (52.6%) had a marker of hepatitis C virus infection. The prevalence of chronic HBsAg-negative hepatitis was higher in patients previously treated for leukemia than in patients treated for another malignancy (11.8% vs 4.6%; p = 0.004). The liver biopsy revealed chronic active hepatitis or cirrhosis or both in 8 (28%) of 28 patients with clinical chronic HBsAg-negative hepatitis. Four patients without hepatitis C virus infection who underwent liver biopsy had hepatitis B virus antigen in the liver, confirmed by immunohistochemistry studies. One patient uninfected with hepatitis C virus had hemochromatosis. We conclude that infection with hepatitis C virus was the major cause of chronic HBsAg-negative hepatitis in pediatric patients previously treated for malignancy; the cause remained unidentified in 30% of the patients.

Alanine Transaminase↗
PubMed1991

Histology and virus expression in the liver: a prognostic puzzle in chronic hepatitis B.

Forty chronic untreated paediatric carriers of hepatitis B virus (HBV) infection, with no other causes of liver disease, were biopsied on presentation, when the disease was in the active viral replication phase. After a period ranging from 1 to 13 years, all patients underwent a control biopsy. At the time of the last biopsy, 31 of the patients were anti-HBe positive, whereas 9 persisted in the active replication phase. In this latter phase, necrotic and inflammatory lesions and the presence of nuclear HBcAg were found significantly more frequently than when replication had terminated. The necrotic and inflammatory lesions detected in the first biopsy of patients who subsequently underwent anti-HBe seroconversion were significantly more severe than in patients failing to reach seroconversion. All patients who maintained viral replication showed generalized nuclear reactivity for HBcAg on presentation; such reactivity was also found in 16 of 31 (52%) patients who reached anti-HBeAg seroconversion. All these cases had piecemeal necrosis (PMN) in the biopsy. PMN may therefore be considered as a positive prognostic factor in that it identifies those patients who may seroconvert with significant remission of liver disease.

Adolescent↗
PubMed1991

Antibodies to hepatitis C virus in community-acquired acute non-A, non-B hepatitis.

Circulating antibodies to the recently identified hepatitis C virus (anti-HCV) have been investigated by ELISA in a series of 129 adult Italian patients with acute, community-acquired non-A, non-B hepatitis. Anti-HCV was detected in 50 (38%) cases with a prevalence rate which increased from 19%, in sera taken during the first 2 weeks of illness to 52% in samples obtained 5-6 weeks after onset, indicating a rather late appearance of the antibody. Anti-HCV positivity was independent of risk factors in the clinical history, but correlated with the outcome of the disease. Eighteen (26%) of 68 patients who recovered were anti-HCV positive compared to 10 of 14 (71%) who progressed to chronicity (p less than 0.01). In this latter group the antibody persisted for more than 12 months after the onset of the illness. Conversely, in 12 (85%) of 14 serially tested patients who recovered, anti-HCV positivity was transient, lasting from a few weeks to a few months. These findings indicate that HCV is implicated in a consistent proportion of acute community-acquired non-A, non-B hepatitis cases, particularly cases which progress to chronicity. A large proportion of cases remained unclassified, however, and it will be important to define whether they represent cases of HCV infection with poor serologic response, or are due instead to other, as yet unidentified, non-A, non-B agents.

Adolescent↗
PubMed1991

Shedding of the soluble form of the CD8 complex by CD8+/HLA-DR+ cells in HIV-1-infected patients.

High levels of the soluble form of the CD8 molecule (sCD8) are detectable in the serum of HIV-1-infected patients. To investigate the mechanisms accountable for the release of this molecule we evaluated the presence of sCD8 in the supernatants obtained from in vitro cultures of highly purified CD8 cells isolated from 20 HIV-1-infected patients. At resting conditions cultured CD8 cells from HIV-1-infected patients released low amounts of sCD8; no statistically significant differences were observed between unstimulated cultures from HIV-1-seropositive patients and from HIV-1-seronegative subjects at risk for HIV-1 infection or normal healthy controls. Following in vitro activation of highly purified CD8 cells with a series of stimulatory agents, including phorbol myristate acetate, phytohemagglutinin (PHA) and recombinant interleukin-2, CD8 cells of HIV-1-infected patients significantly increased the shedding of sCD8. By expressing the results of activation-related release index (ARRI = sCD8 levels detected in the cultures with stimulatory agent/sCD8 levels detected in the unstimulated cultures), significantly higher values were observed upon PHA stimulation in HIV-1-infected patients than in control subjects. In order to identify the cell subset responsible for the enhanced release of sCD8 by PHA-stimulated cultures, we correlated the amounts of sCD8 detected in the supernatants with the phenotypic profile of CD8+ cells recovered from the cultures. A significant relationship was demonstrated between the percentage of CD8+/HLA-DR+ lymphocytes and sCD8 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Interferon therapy of chronic delta hepatitis in patients cured of pediatric malignancies: possible harmful effect.

In our Pediatric Haemato-Oncology Unit, 42 young patients cured of their malignancy were left with chronic delta hepatitis. The severity of liver disease in many of these patients prompted us to start a pilot study on the effect of recombinant alpha 2b interferon, given at a dose of 5 MU/square meter thrice weekly. All nine patients included in the study (five males, mean age: 15 years) had well-compensated liver disease, including five cases with active hepatitis and cirrhosis. At the end of the 3rd month of therapy, two patients with cirrhosis developed a biochemical exacerbation leading to hepatic decompensation, which was fatal in one case. The reasons for this unfavourable outcome remain unclear. Basic immunological tests were normal, but one of the two patients was the single case with anti-liver-kidney microsome antibodies. On the other hand, both patients seroconverted from hepatitis B e antigen to antibody at the time of exacerbation, suggesting that liver damage could have been the result of cell-mediated cytotoxicity to hepatitis B virus antigens. The results of this study, which has been interrupted at the 4th month, suggest that interferon therapy for chronic delta hepatitis has to be considered cautiously in young patients cured of pediatric malignancies. In fact, no beneficial effect was seen and the treatment appeared to be harmful in at least two out of nine patients treated.

Adolescent↗
PubMed1991

Prognostic significance of the evaluation of bronchoalveolar lavage cell populations in patients with HIV-1 infection and pulmonary involvement.

To investigate the prognostic utility of the morphologic and immunologic evaluation of BAL cell populations in determining mortality risk, we analyzed BAL data obtained from 115 patients infected with HIV-1. Forty fatal outcomes occurred within 73 patients with OI. The OI patients who died showed a significant increase in neutrophils with respect to surviving patients. Furthermore, the finding of a BAL neutrophilia in HIV-1-infected patients with OI strongly correlated with a high risk of death. Among 42 cases without OI, 11 patients died. Patients without OI who had a fatal outcome showed an increase in CD3+ and CD8+ BAL lymphocytes with respect to the survivors. The presence of a lymphocytic alveolitis was associated with a significant increase in the mortality rate. Taken together our data suggest that the evaluation of the BAL cell populations might be useful in predicting the risk of fatal outcome in patients with HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood.

Seventy-six children aged 1-13 years who were known to be positive for hepatitis B surface antigen and hepatitis B e antigen in serum for at least 6 months and who had biopsy-proven chronic hepatitis have been followed longitudinally for 1-12 years (mean, 5 years). Twenty-three of them are now young adults. Eight patients had acute type B hepatitis 12-24 months before entering the study, while 68 patients came to observation during a chronic phase. At the beginning of follow-up, all 76 children were positive in serum for hepatitis B virus DNA, and 44 (58%) had chronic active hepatitis, associated with cirrhosis in two cases. During follow-up, 23 (30%) patients remained hepatitis B e antigen-positive, most with unchanged biochemical and histological features. The other 53 (70%) cases seroconverted to hepatitis B e antibody and cleared hepatitis B virus DNA from serum, including 7 of 8 (87%) patients with acute hepatitis at presentation. After seroconversion, alanine aminotransferase levels normalized in all patients and remained normal in 49 patients (92.5%) throughout a mean observation period of 3 years. Five of these children, including 2 of 7 (29%) with previous acute hepatitis, eventually cleared hepatitis B surface antigen from their sera. Finally, 4 (7.5%) patients experienced a mild increase of alanine aminotransferase levels several months after seroconversion in the absence of hepatitis B virus replication or of delta virus superinfection. Clinical and virological parameters did not significantly differ between patients with or without acute onset; however, seroconversion occurred earlier, and the rate of hepatitis B surface antigen clearance was greater in the former than in the latter group. The present data indicate that approximately two thirds of children with hepatitis B e antigen- and hepatitis B virus DNA-positive chronic hepatitis clear hepatitis B virus DNA from their sera before reaching adulthood. After termination of viral replication, most patients achieve a sustained biochemical remission, suggesting the disappearance of disease activity. Reactivation of virus replication after hepatitis B e antibody seroconversion has never been observed in this series, although mild alanine aminotransferase level abnormalities could be detected in a minority of cases.

Adolescent↗
PubMed1990

Long-term evolution of chronic hepatitis B in children with antibody to hepatitis B e antigen.

The aim of this study was to evaluate the long-term outcome of chronic hepatitis B in 27 children who had increased alanine aminotransferase activity and antibody to hepatitis B e antigen in serum from the time of their first clinical observation. Initial histologic changes were consistent with chronic active hepatitis in 13 cases (three with associated cirrhosis) and with persistent or lobular hepatitis in the remaining cases. On the basis of virologic testing, three groups of patients were identified: (1) two children had hepatitis delta antigen in the liver and anti-delta antibody in serum, and both had severe hepatitis; (2) 10 children had hepatitis B virus DNA in serum, and 60% of them had active hepatitis; (3) 15 patients had no hepatitis B virus DNA, and 33% of them had active hepatitis. During a follow-up period of 12 months to 12 years (mean +/- SD: 6.1 +/- 2.4 years), the disease remained active in both children with anti-delta antibody, but they had no major complaints. In all eight patients who could be followed in group 2, test results became negative for hepatitis B virus DNA and alanine aminotransferase activity normalized within 4 years; biochemical remission was delayed in three patients with higher hepatitis B virus DNA levels on entry, and one of these patients had a severe exacerbation of disease activity before remission. In group 3, a total of 10 patients (71%) achieved biochemical remission within 1 year, and two within 26 months; only two patients, who were transfused at birth, had long-lasting liver damage. These results indicate a trend to early remission of liver disease in children with chronic hepatitis B with antibody to hepatitis B e antigen without delta virus infection. Antiviral therapy aimed at accelerating the termination of hepatitis B virus replication may be indicated only in those with higher levels of hepatitis B virus DNA.

Adolescent↗