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Biomedical subjects

G Antonelli

Publications and source records attributed to G Antonelli.

At least 37 records · Page 2Linked to original sources
PubMed2000

Recovery of hematopoietic activity in bone marrow from human immunodeficiency virus type 1-infected patients during highly active antiretroviral therapy.

The mechanisms responsible for the hematopoietic failure in human immunodeficiency virus type 1 (HIV-1)-infected patients are still unknown. Several findings indicate that the in vitro proliferative potential of precursor cells from AIDS patients is reduced. The changes seen in bone marrow (BM) morphology and the defective BM functions associated with cytopenias have both been proposed as potential explanations. In patients treated with highly active antiretroviral therapy (HAART) an immune reconstitution associated with increased whole blood cell counts has been described. We have investigated the effects of HAART on the number of colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs), using long-term BM cell cultures (LTBMC) in a group of subjects with HIV-1 infection enrolled in an open study to evaluate the mechanisms of immune reconstitution during HAART. In each patient, the increase in colony growth was homogeneous, regardless of the type of hematopoietic progenitor cells assayed; in four subjects an increase in the most primitive progenitor cells (LTC-ICs) was observed. These findings were associated with the in vivo data showing increased numbers of BM mononuclear cells (BMMCs) after HAART and with a rise in peripheral CD4(+) T cell counts and decreased levels of plasma HIV-1 RNA. A decreased number of hematopoietic progenitor cells and/or a defective modulation of progenitor cell growth might be the cause of the hematological abnormalities in AIDS patients. Controlling HIV-1 replication by HAART could determine a restoration of stem cell activity, probably because of the suppression of factors that inhibit normal hematopoiesis.

Adult↗
PubMed2000

Low-dose IL-2 reduces lymphocyte apoptosis and increases naive CD4 cells in HIV-1 patients treated with HAART.

During HIV disease an increased in vitro apoptosis of peripheral blood mononuclear cells has been demonstrated. This can be reversed in vitro by interleukin (IL)-2. Recent trials with highly active antiretroviral therapy (HAART) and IL-2 in HIV-1-infected patients showed promising immunological and clinical results. Here we investigated the effects of subcutaneous low-dose IL-2 administration in combination with HAART on in vitro apoptosis and the relationship between apoptosis, CD4(+) counts, and HIV replication. Twenty-two asymptomatic HIV patients were randomized for HAART (arm I) and HAART plus IL-2 (arm II). Spontaneous apoptosis was decreased in both arms after 28 weeks of therapy but the reduction was highly significant only in arm II (P = 0.05 vs P = 0.001). As the percentage of apoptosis decreased, there was a significantly higher increase of both CD4(+) and CD4(+) naive T cells in arm II vs arm I. HIV plasma viremia was reduced in all patients after therapy. Our data suggest that intermittent therapy with low-dose subcutaneous IL-2 in addition to HAART induces a positive immunomodulation in asymptomatic HIV-infected patients.

Adult↗
PubMed2000

Synthesis and antiviral properties of novel analogues of monophosphate and diphosphate bioactive forms of acyclovir.

New analogues (compounds 6, 7 and 9) of the mono- (8) and diphosphate (10) bioactive forms of the antiherpes drug acyclovir are described. In compound 6, the monophosphate moiety of 8 was replaced by an aminosulfonyloxy group, while in compounds 7 and 9, a phosphonoacetamidoxy and an O-ethyl phosphonoacetamidoxy moiety are, respectively present instead of the diphosphate one of 10. None of the compounds synthesized proved to possess an appreciable activity on herpes simplex virus (HSV) or human immunodeficiency virus (HIV).

Acyclovir↗
PubMed2000

Synthesis and antiviral properties of 9-[(2-methyleneaminoxyethoxy)methyl]guanine derivatives as novel Acyclovir analogues.

This paper reports the synthesis and the antiviral properties of a series of 9-[(2-methyleneaminoxyethoxy)methyl]guanine derivatives, which can be viewed as analogues of the antiherpes drug Acyclovir (ACV) from which they differ in the replacement of its hydroxy group with variously substituted methyleneaminoxy moieties. Some of the newly synthesized compounds proved to possess a certain activity against HSV-1, albeit lower than that of ACV.

Acyclovir↗
PubMed2000

The number of HIV DNA-infected mononuclear cells is reduced under HAART plus recombinant IL-2. IRHAN Study Group.

It is common opinion that, in addition to potent antiretroviral regimens which effectively reduce plasma viremia, new strategies should be developed to ensure the reduction of cell-associated HIV DNA load together with HIV RNA plasma levels. The present study explored whether the number of provirus-infected cells can be reduced by combined antiviral and immunomodulatory regimens. Thus, 14 naive patients (with CD4 > 400/microl and plasma HIV RNA copies > 5000/ml) were randomly assigned to receive highly active antiretroviral therapy (HAART) alone or HAART plus rIL-2. Plasma viremia (measured by a commercial RT-PCR assay) and the number of provirus-infected cells (measured by an endpoint cell dilution PCR assay) were monitored at the enrollment and after 12 weeks of treatment. The results indicate that while HAART and HAART plus rIL-2 are both able to significantly reduce plasma viremia after 12 weeks of treatment, a significant reduction of the number of provirus-infected cells can be achieved only by treatment with HAART plus rIL-2.

Anti-HIV Agents↗
PubMed2000

Cellular factors involved in the induction of resistance of HIV to antiretroviral agents.

Long-term treatment of HIV-1 infected patients with antiretroviral agents may result in failure of therapy due to the emergence of resistant virus mutants with decreased susceptibility to the therapeutic agents. Several authors have asked whether cellular factors, other than viral mutation may contribute to the declining efficiency of chemotherapy including nucleoside analogues and protease inhibitors (PI). Prolonged treatment with AZT may induce a defect of thymidine kinase activity in vitro and in vivo. Long-term treatment with other nucleoside analogues, such as d4T and 3TC, is also able to induce in host cells, a decreased sensitivity to the antiviral activity of these compounds. It is suggested that antiviral activity of PI could be modified by the expression of a protein P-gp that has been demonstrated to be able to bind PI and is involved in extrusion of anticancer agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Cystic lymphoepithelial lesions of the parotid gland in HIV-1 infection.

The benign cystic lymphoepithelial lesion (BLL) of the parotid gland is a rare disorder affecting HIV-1-infected patients. Here we describe the clinical and histopathological features of 10 cases of BLL, who presented to our observation between November 1992 and December 1996, before the combination antiretroviral therapy was introduced.

Adult↗
PubMed2000

Ambamustine in the second-line treatment of patients with small-cell lung cancer: a phase II Fonicap study.

Despite a high probability of response to first-line chemotherapy, most patients with small-cell lung cancer (SCLC) will eventually have progression of their disease because of the development of resistant disease. Second-line testing of new drugs is an accepted research strategy in SCLC. In this context, the Italian Lung Cancer Task Force (FONICAP) has tested a new synthetic bifunctional alkylating agent, Ambamustine, with preliminary evidence of activity in other solid tumors. Patients with measurable SCLC, progressive after one first-line chemotherapy regimen (either "sensitive" or "refractory"), were eligible for the study. Ambamustine was administered at the dose of 2 mg/kg as a 1-hour intravenous infusion on day 1 every 21 days. The dose was to be increased to 3 mg/kg if no grade IV toxicity and complete hematologic recovery had occurred by day 22. Sample size was calculated according to a two-stage optimal Simon's design. Seventeen patients were entered into the study. Twelve patients were refractory to prior chemotherapy; 12 had extensive disease; the median age was 64 years (range: 46-75 years) and the median performance status was 1. Among 13 patients who received more than one cycle, 9 patients could increase Ambamustine dose from 2 to 3 mg/kg. No objective response was observed: one patient obtained a 50% regression of the primary tumor with contemporary disease progression in the liver and was qualified as having progressive disease. The treatment was well tolerated: grade IV leukopenia occurred in only 1 patient; grade III anemia occurred in 17.6%, grade III leukopenia in 11.8%, and grade III thrombocytopenia in 23.5%. Nonhematologic toxicity was minimal. Ambamustine, at the dose and schedule used in this study, is well tolerated in pretreated patients with SCLC but has no significant antitumor activity in this unfavorable group of patients.

Aged↗
PubMed2000

[Bowenoid papulosis: myth or reality?].

The authors present a review of recent theories about clinical entity of Bowenoid Papulosis (P.B.), considering histological and etiopathogenesis aspects. The starting point of this review was recent observation of some clinical cases of P.B. The HPV is clearly involved in the start and the growth of this pathology. However, we have serious doubts regarding the etiopathology role of such virus of the pathology and the element of the start of a simil-neoplastic shape because the HPV was not found in the clinical shapes that we have examined. The frequent spread of the illness might give an answer to the immunology of the patient even though there was not significant immunity deficit in the previous cases that we have examined. Another remark was noticed by therapy writers. They are wondering whether they should practice a therapy called "wait" rather than treatment which is sometimes harmful and collateral effects. The last patients who have been treated by dtc in the beginning were restricted to local therapies with podofilotoxines in rare cases where they were examined after their treatment.

Bowen's Disease↗
PubMed1999

Reversal of iron deficiency anemia after Helicobacter pylori eradication in patients with asymptomatic gastritis.

BACKGROUND: Iron deficiency anemia is the most common form of anemia worldwide. Recent studies have suggested an association between Helicobacter pylori infection and iron deficiency. OBJECTIVE: To investigate the effects of eradicating H. pylori with combination antibiotic therapy on iron deficiency anemia in patients with H. pylori-associated gastritis. DESIGN: Case series. SETTING: University hospital. PATIENTS: 30 patients with a long history of iron deficiency anemia in whom H. pylori-associated gastritis was the only pathologic gastrointestinal finding detected. INTERVENTION: Eradication therapy with two antibiotics and discontinuation of iron replacement therapy. MEASUREMENTS: Complete blood count, ferritin levels, and gastroscopy with biopsy to evaluate H. pylori status. RESULTS: At 6 months, 75% of patients had recovered from anemia (P<0.001), ferritin values increased from 5.7+/-0.7 microg/L to 24.5+/-5.2 microg/L (95% CI, 8.85 to 29.97). After 12 months, 91.7% of patients had recovered from anemia. CONCLUSIONS: Cure of H. pylori infection is associated with reversal of iron dependence and recovery from iron deficiency anemia.

Adult↗
PubMed1999

Further study on the specificity and incidence of neutralizing antibodies to interferon (IFN) in relapsing remitting multiple sclerosis patients treated with IFN beta-1a or IFN beta-1b.

The development of neutralizing antibodies (NAbs) to interferon (IFN) is a common phenomenon of IFN beta therapy for relapsing-remitting multiple sclerosis (RRMS) patients. Here we examine the specificity of NAbs developed during therapy for RRMS with recombinant interferon (rIFN) beta-1a or rIFN beta-1b, and study the effect of switching from rIFN beta-1a to rIFN beta-1b on the incidence and specificity of NAbs. The relative ability to neutralize rIFN beta-1a and beta-1b was assayed in sera positive for NAbs derived from RRMS patients treated with either rIFN beta-1a (N=9) or rIFN beta-1b (N=16), while the incidence and specificity of NAbs to IFN beta developed during therapy were studied in 50 RRMS patients who were treated for two years with rIFN beta-1a followed by a further year either switching to rIFN beta-1b (N=34) or continuing treatment with rIFN beta-1a (N=16). The results show that all positive sera, independent of the source, may recognize both forms of rIFN beta and that a further year of treatment does not significantly affect the incidence and specificity of the NAbs developed during the first two years of treatment even if treatment is switched to a different type of IFN beta. The data then suggests that it is unlikely that the administration of rIFN beta-1b to anti-rIFN beta-1a NAbs-positive patients can overcome the inhibitory effect exerted by the serum antibodies (and vice versa), and that a further period of treatment with IFN beta-1b in patients previously treated with rIFN beta-1a does not significantly change the pattern of antibody response to IFN beta.

Adjuvants, Immunologic↗
PubMed1999

The benign cystic lymphoepithelial lesion of the parotid gland is a viral reservoir in HIV type 1-infected patients.

The presence of HIV-1 in cystic fluid aspirates from six cases of benign cystic lymphoepithelial lesion (BLL) of the parotid gland, a rare disorder affecting HIV-1-infected patients, has been investigated. HIV-1 p24 protein was present at a concentration ranging from 3 to 15 ng/ml, while it was undetectable in the peripheral blood of the same patients. The number of RNA copies of HIV-1 in the cystic fluids was high, ranging from 0.5 x 10(7) to 7.2 x 10(7) RNA copies/ml. BLL cystic fluid aspirates, despite the high level of HIV-1 RNA, were found to contain only a few infectious virions. The low infectivity correlated with the infrequent detection by electron microscopy of complete HIV-1 particles. The pathogenic mechanism leading to virus accumulation in the cystic fluid was studied by immunohistochemistry of tissue sections. p24 protein was associated with DRC-1+/S-100+ follicular dendritic reticulum cells, which were also present within the cystic cavities. Our findings are consistent with the possibility that the large amounts of virus present in the fluid derive from continuous shedding of HIV-1-infected cells from the surrounding lymphoid tissue.

Adult↗
PubMed1999

Synthesis and HIV-1 inhibitory properties of new tetrahydrobenzoquinazolinedione and tetrahydrobenzocycloheptenuracil derivatives and of their thioxo analogues.

Some new tetrahydrobenzoquinazolinediones 2a-4a, tetrahydrobenzocycloheptenuracils 5a, 6a and their thioxo analogues 2b-6b were synthesized within a project aimed at obtaining new HIV-1 tricyclic inhibitors whose scaffold includes a pyrimidine and a phenyl ring, which are present in various HIV-1 non-nucleoside inhibitors. Among the tetrahydrobenzoquinazolinediones 2a-4a, compounds 3a and 4a, in which the tricyclic system is respectively in an angular or linear arrangement, proved to possess a HIV-1 inhibitory activity which was in the micromolar range, while compound 2a, in which the tricyclic system is in the angular arrangement opposite to that of 3a, was found to be completely inactive. As regards the tetrahydrobenzocycloheptenuracil derivatives (5a and 6a), only 5a showed an inhibitory activity similar to that of 3a and 4a. Furthermore, all thioxo analogues 2b-6b were found to be devoid of any activity.

Anti-HIV Agents↗
PubMed1999

Prenatal diagnosis of fetal cytomegalovirus infection after primary or recurrent maternal infection.

OBJECTIVE: To determine the reliability of prenatal diagnosis of cytomegalovirus infection in women with primary or recurrent infection. METHODS: Amniotic fluid (AF) samples from 117 pregnant women were evaluated for cytomegalovirus culture and cytomegalovirus-DNA detection. Neonatal and postnatal samples also were examined to confirm or exclude transmission of maternal-fetal cytomegalovirus infection. RESULTS: Of 25 women with primary cytomegalovirus infection, 13 (52%) had cytomegalovirus-positive AF samples by polymerase chain reaction (PCR), nine of which also were diagnosed by culture. All eight neonates born to mothers whose AF was cytomegalovirus-positive by PCR and culture were cytomegalovirus infected, and three were symptomatic. One aborted fetus had cytomegalovirus-DNAemia. Of four women with cytomegalovirus-positive AF samples by PCR only, two delivered asymptomatic cytomegalovirus-infected neonates and two aborted (one fetus had cytomegalovirus encephalopathy). Of 45 mothers with recurrent infection, two with AF cytomegalovirus-positive by PCR and culture, and another with cytomegalovirus-positive AF samples by PCR only, aborted cytomegalovirus-DNA-positive fetuses. Of the other seven women with cytomegalovirus-positive AF samples by PCR only, two delivered asymptomatic cytomegalovirus-infected neonates, two delivered neonates cytomegalovirus-positive by PCR only (one was symptomatic), and three delivered infants cytomegalovirus-negative by PCR and culture. All 47 mothers with nonactive cytomegalovirus infection and cytomegalovirus-negative AF samples had uninfected neonates. Polymerase chain reaction was superior to viral culture in sensitivity and negative predictive value (100% compared with 57% and 94%, respectively) but was lower in specificity and positive predictive value (97% and 83%, respectively, compared with 100%). CONCLUSION: Prenatal diagnosis of fetal cytomegalovirus infection should include PCR in addition to viral culture, particularly for congenital cytomegalovirus infections following maternal recurrence.

Adult↗
PubMed1999

Susceptibility of human and non-human cell lines to HCV infection as determined by the centrifugation-facilitated method.

The centrifugation-facilitated inoculation method was used to test 51 human and non-human cell lines for ability to support HCV replication. As determined by nested RT-PCR, one fifth of the cell lines tested were virus positive 15 days post inoculation suggesting that the centrifugation-facilitated inoculation is an efficient method for cell infection with HCV. However, virus production by infected cultures remained of low grade, thus showing that the unknown factors which limit HCV replication in vitro are not overcome by the procedure.

Amino Acid Sequence↗
PubMed1999

Antigenic characterization of recombinant, lymphoblastoid, and leukocyte IFN-alpha by monoclonal antibodies.

To gain more insight into similarities of different interferon-alpha (IFN-alpha) species, we evaluated neutralization and immunoactivity of a variety of IFN preparations with various monoclonal antibodies (IFN-alpha mAb). Nine IFN-alpha mAb obtained through immunization with recombinant IFN-alpha (rmAb), lymphoblastoid IFN-alpha (LY mAb), and leukocyte IFN-alpha (LE mAb) were tested. The IFN-alpha mAb were evaluated for their ability to neutralize the antiviral activity of 11 recombinant IFN-alpha subtypes, two recombinant IFN-alpha hybrids, and lymphoblastoid and leukocyte IFN-alpha preparations. The same IFN-alpha mAb were also used in immunoblotting, and some of them were used in immunoaffinity chromatography. The results of the neutralization assay reveal that the IFN-alpha mAb significantly differ in their ability to neutralize the individual IFN-alpha species. Interestingly, none of the IFN-alpha mAb was able to neutralize all the IFN-alpha species. In particular, rmAb were unable to neutralize LE-IFN-alpha or LY-IFN-alpha, whereas LE mAb and LY mAb efficiently neutralized rIFN-alpha2. In some cases, the epitopes to which IFN-alpha mAb are directed were identified through the use of synthetic fragments of IFN-alpha2 or by evaluating the selectivity in binding to IFN-alpha subtypes.

Animals↗