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Biomedical subjects

M Federico

Publications and source records attributed to M Federico.

At least 91 records · Page 5Linked to original sources
PubMed1993

Homologous superinfection of both producer and nonproducer HIV-infected cells is blocked at a late retrotranscription step.

An HUT-78 cell clone (F12) chronically infected by a nonproducer HIV-1 variant (Federico et al., (1989) AIDS Res. Hum. Retroviruses 5, 385-396) is fully resistant to superinfection with HIV-1 or HIV-2. We demonstrate that, in spite of the down-regulation of CD4 receptors, superinfecting-HIV-1 and -HIV-2 cross the F12 plasma membrane (even in the presence of OKT4A monoclonal antibodies) but fail to complete retrotranscription. We utilized a series of polymerase chain reaction primers designed to detect certain steps in the reverse transcription process. Superinfecting-HIV-1 (an African strain) and -HIV-2 are detectable using primers specific for env (for HIV-1), 5' LTR (the R and U5 regions), and vpx (for HIV-2). No amplification is visible when primers amplifying either HIV-2 gag or the "primer binding site" region of 5' LTR of HIV-2 are used. DNA-PCR performed on DNAse-pretreated HIV-1 and HIV-2 stocks failed to show any amplification. This rules out that any extra- or intravirion viral DNA contamination may have interfered with our results. In addition, no DNA amplification was observed in F12 and HUT-78 cells exposed to heat-inactivated HIV-2. Finally, when the nonproducer F12 cells as well as control CEMss cells are transfected with the HIV-1 infectious molecular clone pNL4-3, progeny infectious virus is obtained. These findings indicate that reverse transcription of HIVs superinfecting F12 cells is prevented from completing viral DNA synthesis. A similar block occurs in HIV-1-infected producer cells. When integration of the HIV genome into the F12 genome is achieved via transfection of a molecular clone, the virus life cycle can proceed as in control CEMss cells.

Base Sequence↗
PubMed1993

HIV variability and perspectives for a vaccine.

An overview of efforts to induce neutralizing antibodies in order to develop an effective vaccine against AIDS is presented. The principal Neutralizing Determinant (PND) on the HIV-1 envelope is described. PND variability and the induction of neutralizing antibodies by synthetic peptides representing PND are discussed. The use of a cocktail of different peptides representing the PND sequences of the majority of HIV-1 isolates, as well as the construction of hybrid immunogens containing PND of several viral isolates, could overcome the problems related to PND variability. A different approach based on the possibility of inducing a type of intracellular immunity is also discussed: a cellular clone (F12) obtained in our laboratory from Hut-78 cells infected with supernatant of cultured lymphocytes from an HIV-infected patient, does not release viral particles despite the presence of a full-length HIV-1 provirus. Moreover, F12 cells are fully resistant against superinfection with any HIV-1 or HIV-2 isolates. We are now attempting to reproduce the homologous viral interference by transferring the F12/HIV genome of the clone into HIV-susceptible cells in order to render these cells resistant to HIV infection.

AIDS Vaccines↗
PubMed1993

A recombinant retrovirus carrying a non-producer human immunodeficiency virus (HIV) type 1 variant induces resistance to superinfecting HIV.

A human immunodeficiency virus (HIV) type 1-infected Hut-78 cell clone (F12) shows a peculiar phenotype: it exhibits an altered viral protein pattern, is a nonproducer and is resistant to homologous superinfection. To determine whether this phenotype is dependent upon the expression of the HIV-1 genome integrated therein, the SstI/SstI F12 provirus [deprived of HIV long terminal repeats (LTRs)] was cloned and inserted in the pLj retroviral vector bearing the neomycin (neo) and Geneticin resistance gene. CD4+ HIV-susceptible CEMss cells (a CEM clone able to form large syncytia 2 to 3 days post-HIV infection) were infected with the recombinant retroviruses rescued from the F12/HIV-pLj-transfected (in either sense or antisense orientation) amphotropic packaging cells PA 317. Neo sense resistant gene clones showed approximately 10 copies of viral DNA/cell (without detectable major deletions) only in episomal form, low viral RNA expression and a viral protein pattern characterized by an uncleaved gp160, no gp41 and little, if any, p55 gag precursor (as in F12 cells). Superinfection of these F12/HIV DNA-engineered clones with HIV-1 resulted in a significant reduction in the yield of superinfecting HIV. This effect (more pronounced when the clones were maintained under neo selective pressure) was observed in all five retrovirus-infected clones exhibiting the presence and expression of sense episomal F12/HIV DNA but not in two clones bearing an antisense F12/HIV DNA or in one clone bearing only the pLj vector. These results indicate that bio-engineered human CD4+ cells expressing the F12/HIV genome exhibit a significant resistance to HIV superinfection.

Antigens, Viral↗
PubMed1993

MOPP/EBV/CAD hybrid chemotherapy with or without limited radiotherapy in advanced or unfavorably presenting Hodgkin's disease: a report from the Italian Lymphoma Study Group.

PURPOSE: We explored the feasibility, toxicity, and preliminary results of a chemotherapy (CT) regimen, mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/epidoxirubicin, bleomycin, and vinblastine (EBV)/lomustine (CCNU), doxorubicin, and vindesine (CAD), derived through hybridization, shortening, and intensification of a corresponding 10-drug alternating combination CAD/MOPP/doxorubicin, bleomycin, and vinblastine (ABV), effective in treatment of advanced Hodgkin's disease (HD). PATIENTS AND METHODS: Hybridization involved all drugs except CCNU and mechlorethamine, which were administered in alternating cycles; the length of therapy was reduced from nine to six cycles. The average projected drug doses during the six cycles were increased by 42%, with an overall 1.54 dose-intensification; epidoxorubicin was substituted for doxorubicin at equivalent tumoricidal doses. Radiotherapy (RT) was optional and its indications were limited. RESULTS: Eighty assessable patients with previously untreated, advanced or unfavorably presenting HD were treated in nine cooperating institutions between 1988 and 1991. RT was delivered to 22 patients. Remissions were complete (CR) in 75 patients (93%), partial in three (4%), and null in two (3%). The median relative dose-intensity was 0.71 for the overall regimen. Three of five patients who failed to achieve CR, and two of the four who relapsed, received lower relative dose-intensive cycles. Nonhematologic toxicity was acceptable, but there was considerable hematologic toxicity. Fatal gastrointestinal bleeding was seen in one patient. CONCLUSION: Caution is advised due to the short median follow-up period. Nevertheless, in addition to the excellent response rate, (1) the results were reached through abbreviation, intensification, and hybridization of an existing alternating regimen; (2) RT had limited use in this program, which may have contributed to lowering the risk of second tumors; and (3) the results were obtained in a multicenter study (a condition that often impairs results from clinical trials).

Adolescent↗
PubMed1993

Soluble interleukin-2 receptor and urinary neopterin concentrations in malignant lymphoma.

The serum concentrations of soluble interleukin-2 receptors and urine neopterin were studied in 82 patients with malignant lymphomas (25 patients with Hodgkin's disease and 57 patients with non-Hodgkin's lymphoma. Increases in soluble interleukin-2 receptors and in urinary neopterin were significantly correlated with the clinical phase of the disease. The average values in both Hodgkin's disease and non-Hodgkin's lymphoma patients suffering from the disease in its active phase were significantly higher than those of patients in complete remission. Neopterin concentrations (but not soluble interleukin-2 receptor concentrations) were also elevated in clinical stages III-IV of each disease. Urinary neopterin correlated directly and significantly with the erythrocyte sedimentation rate and inversely with haemoglobin. Finally, a longitudinal analysis showed a general tendency for the markers to return to normal values, in accordance with the favourable outcome of therapy; this was more evident for urinary neopterin than for soluble interleukin-2 receptors. These findings seem to confirm that soluble interleukin-2 receptors and especially urinary neopterin can be useful markers for monitoring and prognosis of malignant lymphomas.

Adult↗
PubMed1992

Detection and quantitation in rat tissues of the superparamagnetic magnetic resonance contrast agent dextran magnetite as demonstrated by electron spin resonance spectroscopy.

RATIONALE AND OBJECTIVES: The compound studies in this article is a superparamagnetic macromolecular complex of magnetite cores coated with hydrophilic dextran, which is under active investigation as a contrast agent for magnetic resonance imaging (MRI) in liver and spleen. The biodistribution of paramagnetic compounds is problematic and is usually studied by histochemical reactions or by radiolabeling the compound under study. The purpose of this article is to show how electron spin resonance (ESR) spectroscopy detects dextran magnetite (DM) particles in tissues. METHODS: DM injected intravenously in the experimental animal was detected in some reticulo-endothelial organs by ESR. The spectroscopic study was validated using electron microscopy and electron-probe microanalysis. RESULTS: DM exhibits an ESR spectrum; ESR delineated the distribution of DM distribution in liver, spleen, bone marrow, and blood as a function of time. The blood clearance was biphasic, dependent on the size of particles. CONCLUSIONS: ESR spectroscopy is a highly sensitive and reproducible method of studying DM distribution.

Animals↗
PubMed1992

Extrachromosomal human immunodeficiency virus type 1 DNA forms in fresh peripheral blood lymphocytes and in two interleukin-2-independent T cell lines derived from peripheral blood lymphocytes of an asymptomatic seropositive subject.

Two immature T cell lines (FT1 and FT4) were established after in vitro cloning of peripheral blood lymphocytes (PBLs) from an asymptomatic human immunodeficiency virus type 1 (HIV-1) seropositive, human T cell-lymphotropic virus type 1 seronegative homosexual subject. Although derived from a limiting dilution cell cloning assay, these cell lines were not recloned for this study. Their growth was independent of exogenous interleukin-2. Both cell lines were able to form colonies when cloned in agar, but failed to form solid tumours when injected into nude mice. FT lines belong to the very immature T cell lineage as they exhibit rearranged TCR genes but no expression of T cell membrane antigens, including CD2, CD3, CD4, CD6, CD7 and CD8. They also contain an HIV-1 genome that was detected only in an extra-chromosomal DNA form, even after several passages in vitro. The presence of unintegrated viral DNA was also detected by polymerase chain reaction analysis in the same sample of fresh uncultured PBLs. Furthermore, despite the absence of CD4 expression, both T cell lines were susceptible to CD4-independent HIV-1 superinfection (lack of superinfection inhibition in the presence of OKT4A monoclonal antibodies).

Adult↗
PubMed1991

Interaction of HIV-1 with susceptible lymphoblastoid cells. 1H NMR studies.

Different strains of HIV susceptible lymphoblastoid cells have been infected by HIV-1 and examined by means of 1H NMR spectroscopy at different times after infection, taking advantage of the presence of high resolution lipid signals from the plasma membrane of tumor cells. A transient decrease in intensity of fatty acid signals, originated by changes in membrane structure, has been observed early after viral infection. Marked alterations in membrane-dependent steps of phospholipid synthesis can also be inferred by the observed transient depression in peaks from choline-based metabolites. Spectral modifications deriving from changes in lipid metabolism are also produced both in infected cells a few days after infection and in permanently infected cells. 1H NMR can, therefore, monitor structural and metabolic effects induced by HIV infection.

Cell Membrane↗
PubMed1991

Human herpesvirus-6 in human lymphomas: identification of specific sequences in Hodgkin's lymphomas by polymerase chain reaction.

In search of a possible involvement of the human herpesvirus type 6 (HHV-6) in human Hodgkin's and non-Hodgkin's lymphomas, we studied the levels of anti-HHV-6 antibodies in the sera of 94 cases by an immunofluorescence assay, as well as the presence of HHV-6 sequences in the affected tissues of 66 cases by polymerase chain reaction, using one set of primer oligonucleotides. Our results showed higher anti-HHV-6 antibody titers in human lymphomas than in normal blood donors, but the difference is statistically significant only when normal donors are compared with Hodgkin's lymphoma cases. HHV-6 sequences were detected in 3 of 25 Hodgkin's lymphomas and 0 of the 41 cases of non-Hodgkin's lymphomas studied. The three cases positive for HHV-6 sequences belong to the nodular sclerosis-lymphocyte depletion histologic subtype and share remarkable similarities in their clinical features. Furthermore, Southern blot analysis of total genomic DNA obtained from the neoplastic tissues of two of the three patients showed the same restriction fragment length polymorphism. Our results suggest that: (1) the high level of anti-HHV-6 antibodies in Hodgkin's disease is due to an activation of the immune system not related to the presence of HHV-6 sequences in affected lymph nodes; (2) the presence of HHV-6 sequences in human lymphoid tissues is not a frequent event, rather it is in fact a very rare event in non-Hodgkin's lymphomas, while in Hodgkin's cases it is more frequent than previously reported on the basis of Southern blot analysis; and (3) the presence of HHV-6 sequences in Hodgkin's lymphomas may have a relation with the clinical presentation of the disease.

Adult↗
PubMed1991

Blood clearance of dextran magnetite particles determined by a noninvasive in vivo ESR method.

Dextran magnetite (DM) is a potential MR contrast agent with superparamagnetic properties. Its fast clearance from the blood and selective uptake by tissue macrophages provide advantages for imaging tumors in the liver and spleen. DM consists of a suspension of solid particles with a wide distribution of sizes. In this study we have used ESR spectroscopy to determine the blood clearance of DM injected iv in mice. The spectra are obtained on living animals by inserting the tail of a mice into the waveguide cavity of the ESR spectrometer and recording the ESR spectrum continuously. This procedure allows the direct measurement of the plasma clearance of DM from individual animals, without blood sampling. We applied this method to study the clearance of suspensions of DM particles with different average sizes.

Animals↗
PubMed1991

Methotrexate, vinblastine, epidoxorubicin and cisplatin (M-VEC) in patients with locally advanced transitional bladder cancer.

M-VEC (methotrexate, vinblastine, epidoxorubicin and cisplatin), a new combined drug regimen in which epidoxorubicin has been substituted to adriamycin to reduce the toxicity of the original M-VAC chemotherapy, has been tested in 23 patients with locally advanced transitional cell bladder cancer (TCBC) (stage T2-T4 No Mo). After two to four courses, an objective response was observed in 19 patients, with 13 clinical complete responses. Seven patients underwent cystectomy after chemotherapy: one patient had no residual tumor on bladder specimens, five patients had a surgical eradication of the disease, while one patient had only a partial resection. Eight relapses of bladder carcinoma were observed, three among the surgically treated patients and five among patients who did not undergo cystectomy, with a median time-to-relapse of 9.7 months. Progression-free survival at 24 months was 52.3%. M-VEC regimen appears to be effective in locally advanced TCBC, with acceptable toxicity.

Adult↗
PubMed1991

Should alpha interferon be used as primary treatment for hairy cell leukemia? Italian Cooperative Group for Hairy Cell Leukemia.

To answer the question of whether interferon (IFN) should replace splenectomy, we reviewed the Italian HCL Registry: the records of 450 patients with hairy cell leukemia (HCL), seen from 1975 to 1988 were analysed. Of these, 321 were considered for the study: 231 had been splenectomized, 46 of them receiving subsequently IFN and 90 patients had IFN as initial therapy. Patients treated with splenectomy showed different survival according to Jansen and Hermans' staging system, which identified two risk groups: stage 1 and stages 2 and 3, p = 0.0329. On the contrary, patients treated with IFN did not show significantly different survival according to stage. By the comparison of stage 1 patients, either treated with splenectomy or with IFN, no statistical difference in survival was registered. Different survivals emerged for patients stage 2 + 3, which improved when treated with IFN, p = 0.0324. The median failure free survival (FFS) after splenectomy resulted in 89 months versus 33 months after IFN. In conclusion, splenectomy still remains the primary therapy for HCL patients stage 1. For high risk patients, stages 2 and 3, IFN should be adopted as first line therapy, improving substantially the survival. The short duration of response to IFN suggests a sequential combination of the two treatments for this group of patients, IFN reducing tumor mass quite safely and splenectomy assuring long lasting stable disease.

Humans↗
PubMed1991

ProMACE-cytaBOM versus MACOP-B in intermediate and high grade NHL. Preliminary results of a prospective randomized trial.

One hundred seventy-nine patients with intermediate or high-grade non-Hodgkin's lymphoma were randomized to receive either ProMACE-CytaBOM (P-C) or MACOP-B (M-B). At last follow-up 71 patients in the P-C arm and 78 in the M-B arm were assessable for response. Forty-one patients treated with P-C (58%) and 49 patients treated with M-B (63%) achieved a CR. Moreover 18 and 22 patients achieved PR with P-C and M-B, respectively. Twenty-five patients relapsed, 12 in the P-C arm and 13 in the M-B arm. Thirty-nine patients died, 32 from disease progression, 5 from treatment related causes, and 2 from other causes. No differences between the two treatment groups were observed as regard to relapse or death-rate. At 27 months the survival rate was of 71.9% for patients treated with P-C and 70.7% for those treated with M-B. At 2 years the RFD rate was 64% and 60% for patients in P-C and M-B arm, respectively. Patients treated with M-B experienced an high rate of methotrexate-related toxicity. ProMACE-CytaBOM and M-B seem provided with similar activity. However P-C seem less toxic and more manageable in an outpatient setting.

Adolescent↗
PubMed1991

Metabolic and structural effects of HIV infection in human peripheral blood mononuclear cells can be monitored with 1H NMR spectroscopy.

Infection of human peripheral blood lymphocytes by human immunodeficiency virus type 1 (HIV-1) was investigated by means of 1H nuclear magnetic resonance spectroscopy, taking advantage of the presence of signals from fluid lipid domains in the membrane of stimulated lymphocytes. A transient decrease of the lipid methylene signal intensity was observed at the time of HIV internalization, monitoring a general rearrangement of membrane structure associated with virus entry. A similar effect was also observed a few days after infection, when HIV particles are released by infected cells as demonstrated by high reverse transcriptase activity in cell supernatant. Signals arising from choline-based metabolites were also affected by HIV infection, indicating a possible slowing down of phospholipid synthesis.

Cell-Free System↗
PubMed1990

Prevention of cisplatin-induced vomiting in patients with cancer. A pilot study with a multiagent protocol.

Forty patients receiving a total of 102 courses of cisplatin (CDDP)-based treatment were observed in the present study. The patients received an antiemetic prophylaxis with metoclopramide (6 mg/kg), dexamethasone (12 mg/m2), lorazepam (2.5 mg), promethazine (50 mg), and diazepam (10 mg). Complete protection from acute vomiting was obtained in 77.5% of patients during the first course, and partial protection (1 to 3 episodes of vomiting) was observed in 10.1% additional cases. Complete protection was achieved in 84.6% of males vs 57.1% of females. Patients at their first course of chemotherapy had 80% complete protection compared to 66.7% in those who received prior chemotherapy. No differences in the response rate between patients treated with high versus patients receiving low doses of CDDP were noted. The same pattern of response was observed in subsequent courses of therapy. Side effects were minimal (mild sedation in almost all the cases and hiccups in a few cases). No major extrapyramidal reaction was observed. The regimen used in the study showed good efficacy in preventing acute CDDP-induced nausea and vomiting. Moreover, the very low incidence of major side effects makes this protocol safe and recommendable in patients undergoing CDDP chemotherapy.

Cisplatin↗