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Biomedical subjects

G Rocchi

Publications and source records attributed to G Rocchi.

At least 73 records · Page 4Linked to original sources
PubMed1992

A tetrazolium-based colorimetric assay for quantification of HIV-1-induced cytopathogenicity in monocyte-macrophages exposed to macrophage-colony-stimulating factor.

A sensitive assay was developed for in vitro evaluation of anti-HIV agents in monocyte-macrophage cells (M/M) (a crucial target of HIV in the body). Monocyte-macrophage cells are usually poorly sensitive to the cytopathic effect induced by HIV. However, when fresh adherent monocyte-macrophage cells are cultured at relatively high density in the presence of macrophage-colony stimulating factor (M-CSF), they undergo cytolysis and die in 2-3 weeks. HIV-mediated cell-killing can thus be assessed with a method based on the reduction of the yellow colored 3-(4-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) by metabolically active cells to a blue formazan, which can be measured spectrophotometrically. HIV-mediated cytopathic effect of M-CSF-exposed monocyte-macrophage cells was consistently achieved in all experiments performed under the conditions described herein. Anti-HIV activity of zidovudine (AZT) was also comparatively evaluated in M-CSF- and normal monocyte-macrophage cells both using the MTT assay and by measuring HIV-p24 antigen production in supernatants of monocyte-macrophage cells cultures, and similar results obtained with both methods. These results support the use of this colorimetric assay for broad screening of anti-HIV agents in monocyte-macrophage cells.

Colorimetry↗
PubMed1992

Efficient and reproducible new semimicromethod for the detection and titration of HIV in human plasma.

A semimicromethod was established for isolating human immunodeficiency virus (HIV) in plasma using 48-well plates and a pool of peripheral blood mononuclear cells (PBMC) from several donors as targets for infection, which increases the efficiency of isolation by reducing the effect of variability due to diverse donor cell susceptibility to HIV infection. The addition of H9 cells to the PBMC cultures did not affect measurable titers. Nevertheless, it potentiated strongly virus replication in terms of p24 production in the supernatant of the wells with HIV isolates, thus facilitating interpretation of the results. The titration of a virus strain of a known titre and reverse transcriptase activity in parallel provided a constant parameter of efficiency and reproducibility within each experiment, permitting comparison with results from other laboratories. The reproducibility of the method was highly significant (r = 0.97, P < 0.001); 68% of the 22 plasma samples from HIV-infected individuals tested by this method were positive. The presence of plasma HIV titer correlated well (P < 0.02) with the low count of CD4+ cells of less than 300/mm3, but not with the presence of the p24 antigen in the serum.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Different pattern of activity of inhibitors of the human immunodeficiency virus in lymphocytes and monocyte/macrophages.

Monocyte/macrophages (M/M) are important targets for HIV in the body, and represent the majority of cells infected by the virus in some body compartments such as the central nervous system (CNS). M/M can be different from T-lymphocytes in terms of surface antigens, cell replication and drug metabolism. Thus, we evaluated, in M/M and in T-lymphocytes, the pattern of viral inhibition induced by various anti-HIV drugs, and assessed some of the mechanisms of action related to such antiviral activity. Inhibitors of HIV binding on CD4 receptors have similar activity in M/M and T-lymphocytes, while AZT and other dideoxynucleosides (ddN) are in general more active against HIV in M/M than in T-lymphocytes. This phenomenon can be related to the increased ratio in M/M of ddN-triphosphate/deoxynucleoside-triphosphate, and can at least in part explain the ability of zidovudine and didanosine in improving neurological dysfunctions in AIDS patients. Moreover, the antiviral activity of AZT (but not of other ddN- or HIV-binding inhibitors) is potently enhanced by cytokines like granulocyte-macrophage colony stimulating factor (GM-CSF) in M/M, while anti-HIV activity of TIBO compounds in M/M is not down-modulated by GM-CSF and other cytokines. Finally, non-toxic concentrations of adriamycin, an anticancer drug reported to be active against DNA viruses, can inhibit HIV replication in M/M (but not in T-lymphocytes). Taken together, these results suggest that M/M are selective targets for HIV with peculiarities different from those of T-lymphocytes. Thus, promising anti-HIV compounds should be evaluated both in T-cells and in M/M before reaching clinical trials. This may help in selecting drugs with good chances of being effective in patients with HIV-related disease.

Adenine↗
PubMed1992

Selective inhibition of HIV replication by adriamycin in macrophages but not in lymphocytes.

Adriamycin (ADR) is an anticancer drug commonly used in the treatment of HIV-related cancers. Due to its effect on DNA metabolism, ADR might be able to modulate HIV replication in monocyte-macrophages (M/M), resting cells potentially less sensitive to the toxic effect of this drug. Thus, we assessed the efficacy of ADR against HIV replication in both lymphocytes and M/M. We further investigated the mechanism(s) of action of ADR and its potential synergistic activity with zidovudine (AZT) or alpha-interferon (IFN alpha). ADR consistently inhibited viral replication in M/M: 50% viral inhibition was obtained with 0.005 micrograms/ml ADR, while greater 90% viral inhibition was obtained with 0.05 micrograms/ml ADR. No cell toxicity was seen in M/M at concentrations up to 0.5 micrograms/ml. No anti-HIV activity was shown by ADR in lymphocytes at concentrations up to 0.05 micrograms/ml, that is also the toxic dose 50% (TCID50 for these cells). ADR neither inactivates HIV virions nor affects HIV binding with CD4 receptors. No inhibition of HIV reverse transcriptase by ADR was found at concentrations at least 2,000-fold greater than the 50% HIV inhibitory concentration in M/M. Molecular analysis by polymerase chain reaction (PCR) suggests that ADR substantially affects virus DNA production at concentrations that inhibit viral replication. Finally, late stages of HIV replication were not affected by ADR. At least additive effects of the association ADR + AZT and ADR + IFN alpha were obtained against de novo HIV infection of M/M.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiviral Agents↗
PubMed1992

A double blind, placebo controlled trial of efficacy and safety of oral acyclovir (Zovirax) in the treatment of chickenpox in adults.

A double-blind placebo controlled trial of oral acyclovir in otherwise healthy immune competent young adults with chickenpox was conducted. One hundred males were recruited into the trial, fifty were randomised to receive acyclovir at a dose of 800 mg five times daily for 5 days and fifty to receive matching placebo. Acyclovir recipients experienced itching and required anti-pruritic therapy for a significantly shorter period of time (p less than 0.05); no significant effects of acyclovir therapy on overall rash progression were observed. In patients with a mild rash on entry the maximum daily temperature recorded was significantly lower in the acyclovir group as compared with placebo recipients on day 1 of therapy (p less than 0.01). Acyclovir was extremely well tolerated and no adverse events were reported. Studies with early oral acyclovir therapy in otherwise healthy children with chickenpox has demonstrated significant benefits, particularly in rash progression. It is postulated that the partial benefits shown in this study in adults reflect the high proportion of patients with mild disease and enrollment of the majority of patients more than 24 hours after the rash onset.

Acyclovir↗
PubMed1991

A report on radiation-induced gliomas.

Radiation-induced gliomas are uncommon, with only 73 cases on record to date. The disease that most frequently occasioned radiation therapy has been acute lymphoblastic leukemia (ALL). Three more cases are added here, two after irradiation for ALL and one after irradiation for tinea capitis. In a review of the relevant literature, the authors stress the possibility that the ALL-glioma and the retinoblastoma-glioma links point to syndromes in their own right that may occur without radiation therapy.

Adult↗
PubMed1990

Neurinoma of the oculomotor nerve.

A rare case of neurinoma of cranial nerve III is described. Preoperative diagnosis of such tumors is difficult because they may be mistaken for brainstem tumors.

Brain Stem↗
PubMed1990

Ability of anti-HIV agents to inhibit HIV replication in monocyte/macrophages or U937 monocytoid cells under conditions of enhancement by GM-CSF or anti-HIV antibody.

Monocyte/macrophages (M/M) are an important target cell for human immunodeficiency virus (HIV) infection in the body. The study of HIV infection in these cells, however, is rather complicated because they represent a variable population, and because HIV entry and replication in M/M may be markedly influenced by a number of factors. These must be considered in therapeutic approaches to HIV infection. In the present set of experiments, we studied the interaction between certain agents which increase the infection of monocyte/macrophages (M/M) by HIV and two groups of anti-HIV agents: dideoxynucleosides and specific inhibitors of gp120-CD4 binding. We found that the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which markedly enhances HIV replication in M/M, does not affect the activity of recombinant soluble CD4 (sCD4) or OKT4A, two agents which block gp120-CD4 binding. However, it had varying effects on different dideoxynucleosides: GM-CSF increased the net anti-HIV activity of 3'-azido2',3'-dideoxythymidine (AZT), while at the same time it reduced the activity of 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI). These effects probably represent an interplay between varying effects of GM-CSF on drug entry and phosphorylation. In additional experiments, we showed that very low concentrations of anti-HIV antibodies could enhance HIV infection of the U937 monocytoid cell line. Interestingly, while this effect has been hypothesized to occur through a CD4-independent mechanism, we found that the anti-HIV activities of both sCD4 and OKT4A were unchanged under conditions of enhancement.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiviral Agents↗
PubMed1989

Cerebral meningiomas in children.

Cerebral meningiomas are rare tumors in children that represent 1.4% of CNS tumors and 1.5% of intracranial meningiomas. We have analyzed 197 cases of cerebral meningiomas under 16: 178 cases were taken from the available literature and 19 from our series. When comparing pediatric meningiomas with those of adults, we noted some differences. Before the age of 16 there is a slight preference for males; the intraventricular variety is more frequent; cystic meningiomas and the absence of dural attachment are more frequent findings; the neuroradiological diagnosis is more difficult.

Adolescent↗
PubMed1989

Epstein-Barr virus DNA sequences in precursor monocyte-macrophage cell lines established from the bone marrow of children with maturation defects of haematopoiesis.

Epstein-Barr virus (EBV) DNA sequences were detected in four established monoblast or early monocytic cell lines (CM-S, ROV-S, CV-S and AD-S) obtained from bone marrow of children suffering from maturation defects of haematopoiesis. EBV is present in these cells in a latent state. The viral DNA in these cell lines was analysed by Southern blot hybridization, using a set of cloned EBV DNA fragments from the EBV strain B95-8 as probes. A common spectrum of highly related but distinguishable EBV DNA restriction enzyme sequences was found, suggesting some genomic diversity. Propagation of the cells in long-term culture revealed a gradual decrease of EBV copies per cell in all lines with some minor changes in the restriction pattern of the EBV DNA. These findings demonstrate that human precursor monocyte cells may be susceptible to infection by EBV.

Anemia, Aplastic↗
PubMed1988

Cytomegalovirus infection in day care centers in Rome, Italy: viral excretion in children and occupational risk among workers.

From nine day care centers in Rome, Italy, 253 children of middle to low socioeconomic classes were examined for cytomegalovirus (CMV) excretion in saliva. The overall excretion rate was 13%, with no marked differences between centers. Socioeconomic level, age of enrollment, chronological age, length of attendance, and number of siblings did not have any discernible influence on viral shedding. The most notable result is that during the second year of age, 100% of the excretors had been breast fed, but only 60% in the third year, indicating that maternal transmission is the most likely source of children's infection early in life. Serologic survey of 82 female workers in day care centers, 82 matched housewives, and 229 female students aged 14 to 18 years who were in training to care for children showed that at 14 years of age the CMV seropositivity rate is 85, which suggests that primary infection during childbearing age is an uncommon event in Rome.

Adolescent↗
PubMed1988

A three-year diagnostic and epidemiological study on viral infantile diarrhoea in Rome.

Rotavirus infection was demonstrated in 168 (29.3%) of 573 children hospitalized for acute diarrhoea in Rome between January 1982 and December 1984. Laboratory diagnosis of these infections was made by transmission electron microscopy and enzyme immunoassay techniques with an overall agreement of 91.3%. Astroviruses, adenoviruses and small round viruses were detected in the faeces of 36 patients (6.4%). Whereas in 1982 rotavirus positive patients were clustered in the winter and following spring, in the following years cases were recorded all year round. The median age of patients with rotavirus infections was 17, 10 and 11.5 months in 1982, 1983 and 1984, respectively. In addition, a smaller number of rotavirus positive cases were admitted in 1983 when compared to those admitted during the previous as well as the subsequent years. It is suggested that a herd immunity was induced in the population by epidemic spread of rotavirus in the first half of 1982.

Adenovirus Infections, Human↗
PubMed1987

Immune response to cytomegalovirus in patients with acquired-immunodeficiency syndrome related complex (ARC) and AIDS.

This study was undertaken with the aim of elucidating the mechanisms underlying the cell-mediated immunodeficiency seen in the acquired immunodeficiency syndrome (AIDS). An intrinsic functional defect in the in vitro surviving T lymphocytes from patients with AIDS has been described. This defect is reflected by profound reductions in both the cloning efficiency of these cells and in the number of precursor cells for response to lectins. Since many patients affected by AIDS present active cytomegalovirus (CMV) infections and impairment in CMV-specific cellular immunity, we examined the number of CMV-specific precursor cells in patients affected by the AIDS-related complex (ARC), who had serum antibodies to CMV and to the human-T-lymphotropic retrovirus-type III (HTLV-III), recently termed human immunodeficiency virus (HIV). Their responses were compared to those of patients with AIDS and to those of healthy-CMV-seropositive and HTLV-III seronegative controls. We detected a significant reduction of precursors for cell-mediated immune response to CMV in AIDS, in comparison to normal controls and a reduction in ARC, even if not significant. In parallel, we assayed the response to phytohemagglutinin, which was maintained in ARC and depressed in AIDS. Our results show a defect of specific cell-mediated immunity to CMV in ARC and AIDS patients.

AIDS-Related Complex↗
PubMed1986

Epstein-Barr virus-related ultrastructural modifications of plasma membrane during B-cell transformation.

Ultrastructural modifications are described in the plasma membrane of in vitro established human B cells. By the freeze-fracture technique, intramembrane particles (IMPs) are quantified in B lymphocytes following Epstein-Barr virus (EBV) transformation in vitro, and in B-lymphoma (Burkitt-type) cells, either positive or negative for EBV genome. Analysis shows an overall increase in IMP density as compared to normal controls. Differences are observed between the protoplasmic and exoplasmic faces of fractured membranes as well as among in vitro transformed and clearly neoplastic cells. Results indicate that conformational changes in IMP distribution parallel neoplastic evolution of transformed cells.

B-Lymphocytes↗
PubMed1986

Adriamycin-induced glomerulosclerosis in the rat.

To evaluate long-term effect of sustained proteinuria induced by a single injection of adriamycin (ADR) on occurrence of focal segmental glomerulosclerosis (FSG), we treated 50 Sprague-Dawley (SD) rats, weighing 250 g with 5 mg/kg body weight of ADR. After six months of heavy proteinuria, 40% of ADR-treated rats did not develop FSG. In the remaining 60% of animals, a mild FSG was observed associated with the presence of large tubular casts and interstitial inflammation. Glomerulosclerosis was never observed in absence of tubulointerstitial lesions. Nine months after ADR, all rats exhibited FSG with renal insufficiency but the severest changes were restricted to the tubulointerstitial level. Our results indicate that chronic proteinuria induced by ADR is a relatively good model of glomerular sclerosis, however, the cause of glomerular sclerosis is probably different from that operating in other experimental models of FSG. Both sclerotic changes and progression of disease seem to be dependent on formation of tubular casts with consequent interstitial changes. This study raises the question of the relative role of tubulointerstitial changes in the subsequent development of FSG.

Animals↗