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Biomedical subjects

G Antonelli

Publications and source records attributed to G Antonelli.

At least 91 records · Page 5Linked to original sources

CD4-positive lymphoid cells rescue HIV-1 replication from abortively infected human primary endothelial cells.

Human primary endothelial cell cultures, derived from umbilical vein (HUVEC), can be infected by different strains of HIV-1, but mature virus production remains undetectable both in supernatants and in cellular extracts. Yet viral DNA is transiently detectable during the first days of infection, but progressively declines during the subsequent days. This finding is characteristic of abortive infections. Co-culture of HUVEC carrying HIV DNA with activated peripheral blood mononuclear cells or with CD4-positive lymphoid cells elicited a massive cpe (syncytia formation and cell degeneration) in the latter cells, caused by the establishment of productive HIV-1 infection. HUVEC infected in the presence of AZT were significantly impaired in the ability to transmit the infection of CD4-positive cells, indicating that active DNA synthesis is required in HUVEC before rescue by CD4-positive cells. These results are of interest in view of the possibility that endothelial cells can play a role in the transmission of HIV-1 infection from infected pregnant women to the foetuses, and, more generally, suggest a potential role of endothelial cells as a transient reservoir of HIV-1.

Antibodies, Monoclonal↗

2',5'-Oligoadenylate synthetase activity as a responsive marker during interferon therapy for chronic hepatitis C.

The 2',5'-oligoadenylate (2-5A) synthetase is an intracellular enzyme induced by interferon (IFN). We evaluated the serum level of this enzyme in 25 patients affected by chronic hepatitis C and treated with recombinant IFN-alpha 2b. At the end of treatment, 14 patients were classified as responders and 11 as nonresponders. Before therapy initiation no significant differences in 2-5A synthetase levels among the patients were detected, while during therapy responders showed higher mean levels of 2-5A synthetase than nonresponders. An increase in the enzyme activity was observed after 1 month of therapy, and this trend was maintained in the following 2 months. The peak of 2-5A synthetase activity was found at the end of therapy. 2-5A synthetase levels were negatively correlated with serum alanine aminotransferase (ALT). This study suggests that 2-5A synthetase may be a useful marker to monitor IFN efficacy during treatment and to predict the clinical response.

2',5'-Oligoadenylate Synthetase↗

Neutralizing antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection.

Forty-seven patients with chronic hepatitis C were treated with recombinant interferon alpha-2a (rIFN alpha 2a) given subcutaneously in a standard dose of 3 MU thrice weekly for 12 months. Stored baseline sera and monthly samples during treatment were assayed for anti-interferon neutralizing antibodies using the antiviral neutralization bioassay against 5 IU of rIFN alpha 2a. During therapy, 15 of 47 patients (31.9%) developed detectable levels of neutralizing antibodies within 2-8 months after starting treatment. After 12 months of therapy, 26 of 32 antibody-negative patients (81.3%) showed normalization or marked reduction of ALT levels compared to 4 of 15 (26.6%) who developed anti-IFN neutralizing antibodies (p = 0.0009). Four patients demonstrated antiviral response during treatment even in the presence of low levels or late occurrence of neutralizing antibodies. Six of the seven patients who had disease reactivation after an initial response developed high titers of neutralizing antibodies. Our results suggest that reactivation of chronic hepatitis C before completion of therapy seems to be an obvious consequence of anti-IFN neutralizing antibody formation.

Alanine Transaminase↗

90K protein: a new predictor marker of disease progression in human immunodeficiency virus infection.

A 90,000-Da molecular mass tumor-associated protein has recently been identified in the sera of patients infected by HIV. In this study, we have evaluated the serum levels of 90K for its ability to predict the progression to ARC or AIDS retrospectively in 49 HIV-seropositive subjects who were initially symptom-free. 90K levels were higher in those HIV-seropositive subjects who progressed to ARC or AIDS than in those who had not progressed both at entry into the study and at the latest visit. CD4+ cell number was not different in the two groups at entry but was lower in the progressors at the latest visit. Evaluation of the patterns of change over time showed that 90K increased and CD4+ cells decreased more in progressors than in nonprogressors. During the 3 years preceding the onset of ARC or AIDS, 90K increased regularly while CD4+ cell decrease was later. Elevated levels of 90K (p = 0.007) and lower numbers of CD4+ cells (p = 0.001) were significantly associated with a higher cumulative incidence of ARC or AIDS. These findings suggest that 90K is an early indicator of progression to ARC and AIDS.

AIDS-Related Complex↗

[The noninvasive assessment of coronary flow during isometric exercise by Doppler ultrasonography of the internal mammary artery anastomosed to the left coronary].

Isometric contraction of small group of muscles is believed to increase heart rate and contractility and arterial pressure without significant changes in systemic arterial resistance. Such a manoeuvre has been employed in this work to study dynamic changes induced in blood flow into coronary bed, in subjects in which an anastomosis of the internal mammary artery to anterior descending coronary artery was performed. Ten patients with no clinical signs of myocardial ischaemia at rest and during exercise, were requested to perform an endurance left handgrip manoeuvre, at 50% of maximal voluntary contraction. Doppler blood velocity curve in the anastomosed mammary artery; non-invasive blood pressure curve at a finger of the right hand by Finapres; the electrocardiogram, were recorded. A significative increase in heart rate and mean and diastolic blood pressure was found. Blood flow significantly increased, approximately in the same percentage as double product was increased. A calculated index of coronary resistance did not show significant changes. In this group of patients, the handgrip manoeuvre may display the ability of the cardiac pump to match its metabolic needs due to increased pressure load, by employing the same developed pressure load as an adequate coronary perfusion pressure. It is suggested to employ this simple test in the routine monitoring of patients with internal mammary artery bypass grafts.

Aged↗

In vitro selection of human immunodeficiency virus type 1 resistant to 3'-azido-3'-deoxythymidine.

3'-Azido-3'-deoxythymidine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) was obtained by growing HTLV-IIIB in C8166 cell cultures in the presence of inhibitory concentrations of AZT. The AZT-resistant HIV-1 was capable of replicating, as measured by infectious virus yield, and inducing cytopathic effect in the presence of AZT concentrations able to completely suppress the replication of parental HTLV-IIIB. Cloning of the AZT-resistant HIV-1 revealed that a number of different variants of HIV-1 with various degrees of sensitivity to AZT emerged during propagation of HTLV-IIIB in C8166 cells in the presence of the drug. PCR experiments performed on DNA extracted from C8166 cells infected with a resistant strain revealed that viral DNA was produced in the presence of inhibitory concentrations of AZT, while viral DNA in C8166 cells infected with the parental virus was drastically inhibited. Reverse transcriptase isolated from the AZT-resistant HIV-1 variant failed to show resistance to AZT 5'-triphosphate.

Antiviral Agents↗

Resistance of HIV-1 to AZT might also involve the cellular expression of multidrug resistance P-glycoprotein.

Resistance of tumor cells to the antigrowth activity of several cytotoxic compounds has been associated with the expression of the so-called multidrug resistance protein or P-glycoprotein. This article addresses the question whether the expression of such protein could also affect the sensitivity of HIV to AZT. Our data indicate that this possibility does exist. In fact, multidrug-resistant CEM VBL100 cells, which express high levels of P-glycoprotein, are less sensitive to both the antiproliferative activity and the antiviral action of AZT. Additionally, our data suggest that this phenomenon is specifically mediated by P-glycoprotein since trifluoroperazine, which is known to circumvent multidrug resistance due to the action on P-glycoprotein, increases the intracellular accumulation of AZT and affects the sensitivity of HIV to AZT. Although the biological and clinical significance of these observations has still to be established, this study suggests that cellular factors, other than virus itself, should be taken into account to address the phenomenon of drug resistance of HIV.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Changes in left ventricular filling after acute increase of afterload in essential arterial hypertension with or without left ventricular hypertrophy].

It is debatable whether a direct causal link exists between left ventricular hypertrophy (LVH) and abnormal left ventricular filling (LVF) in arterial hypertension (AH). To assess if LVH is responsible for peculiar patterns of LVF, we examined 30 selected subjects, similar in age and body surface area, by Doppler echocardiography: 10 hypertensives (SBP: 158 +/- 15; DBP: 105 +/- 7 mmHg) with LVH (IM: 154 +/- 19 mg/m2) (Group 1); 10 hypertensives (SBP: 157 +/- 9; DBP: 101 +/- 5 mmHg) without LVH (IM: 105 +/- 17 mg/m2; Group 2); 10 normotensives without familiar history of AH (Group 3). LVF was analyzed in baseline conditions and during transient afterload increase, obtained by isometric exercise (handgrip, HG, for 5 min at 30% of maximal effort). At rest: 1) A wave peak velocity resulted significantly higher (p less than 0.01) in Group 1 (61 +/- 3 cm/s) versus Group 3 (52 +/- 7 cm/s), and E wave peak velocity was significantly lower in Group 1 (58 +/- 13 cm/s) versus Group 3 (74 +/- 10 cm/s); 2) Group 2 values (E wave: 66 +/- 12; A wave: 58 +/- 15 cm/s) were intermediate between those of groups 1 and 3, and with no significant differences; 3) E/A ratio resulted significantly lower both in Group 1 (1.04 +/- 0.2) and Group 2 (1.21 +/- 0.2) versus Group 3 (1.6 +/- 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

[Acquired immunodeficiency virus (HIV-1). Biological aspects and virological diagnosis].

The etiologic agent of the acquired immunodeficiency syndrome is a retrovirus included in the subclass of lentiviruses in view of certain characteristics common to these viruses. Their similarity is mainly represented by the extreme slowness of disease manifestation and by the fact that HIV, like other lentiviruses, spreads within the organism in spite of an immune reaction. The mechanism of replication is not dissimilar to that of other retroviruses except for the expression of a particularly large number of regulating genes the most important of which are called tat, rev, and nef. Further genes with a probable regulating function are nef, vpr, and vpx. In the field of diagnostic virology, together with normal isolation tests, a technique that has become particularly important is PCR (polymerase chain reaction) which allows to obtain a relevant amount of specific viral DNA sequences by the use of a DNA polymerase and specific primers.

AIDS Serodiagnosis↗

Long-term results of therapy with interferon-alpha for type II essential mixed cryoglobulinemia.

Severe type II essential mixed cryoglobulinemia (EMC) bears a poor prognosis. Treatment with corticosteroids and/or cytotoxic drugs infrequently results in long-term remissions, and is associated with significant toxicity. We conducted a prospective study with interferon (IFN) in 21 patients with severe type II EMC unresponsive to immunosuppressive regimens. They were treated with recombinant IFN-alpha 2a (18 patients) or with natural IFN-beta (three patients), alone, at a dosage of 3 megaunits (MU)/d for 3 months, followed by 3 MU every other day as maintenance. We observed 11 complete remissions, five partial remissions, and five minor responses. Of 16 patients observed for more than 1 year, 11 remained in remission for 14 to 40 months; five of them remained in complete remission for 18 to 40 months after withdrawal of treatment. Four patients discontinued treatment because of side effects. In four patients who relapsed while on maintenance therapy with recombinant IFN-alpha 2a, remission could be reinduced by treatment with natural IFN-alpha. The response rate of 77% achieved in this study prompts the use of IFN-alpha as a first-choice drug for type II EMC.

Adult↗

The combined treatment of human peripheral blood mononuclear cells with thymolymphotropin and interleukin 2 increases PPD-driven T-cell proliferation and IL-2 induced cellular cytotoxicity against HIV-infected cells.

Two in vitro systems (the DNA synthetic response to mycobacterial antigens and cytotoxicity against lymphoid cells) were used to analyse the effect of thymolymphotropin (TLT) on peripheral blood mononuclear cells (PBMC). Purified protein derivative of mycobacteria (PPD)-driven T-cell proliferation in low-responder donors was increased by the combined treatment with TLT and suboptimal doses of recombinant interleukin 2 (IL-2). Similarly, the activities of natural killer (NK) cells and lymphokine-activated killer (LAK) cells have been enhanced in PBMC cultures pretreated with TLT. Also, TLT showed an enhancing effect on the development of LAK cells capable of lysing Epstein-Barr virus (EBV)-transformed B-lymphocytes infected or uninfected with the human immunodeficiency virus (HIV).

Cytotoxicity, Immunologic↗

Cell mediated cytotoxicity and cytokine production in peripheral blood mononuclear cells of glioma patients.

A mannoprotein preparation (MP) from Candida albicans induced MHC-unrestricted cytotoxicity in peripheral blood mononuclear cells (PBMC) from healthy subjects, but not in those from glioma-bearing subjects. The two groups of subjects did not significantly differ in the number of cells bearing typical natural killer (NK) markers (both in resting and MP stimulated PBMC) and NK activity. However, interferon gamma (IFN-gamma) production was in tumour patients minimal or significantly reduced, as compared to healthy subjects, following PBMC stimulation by MP or phytohaemoagglutinin, respectively. In addition, minimal, if any, stimulation of interleukin-2 (IL-2) production was achieved in MP stimulated PBMC from glioma patients. Considering the pivotal role of the above cytokines in immune responses, particularly in those concerning generation of antitumour effectors, our results consistently suggest that defective cytokine production is one possible mechanism of immunological impairment in glioma patients. They also provide indirect support for a possible clinical use of IFN-gamma as an immunopotentiating agent in gliomatous subjects.

Adult↗

Neutralizing antibodies to interferon-alpha: relative frequency in patients treated with different interferon preparations.

The frequencies of antibody development so far reported in patients treated with different interferons (IFNs) are not readily comparable because of differences in treatment regimens and assay methods. Thus the frequency of neutralizing antibody development was analyzed in a large sample of sera derived from a relatively homogeneous group of patients treated with different IFN-alpha preparations. The frequency of developing neutralizing antibody to IFN varied according to the IFN given. Particularly, the seroconversion frequency was significantly higher in patients treated with recombinant IFN-alpha 2a (20.2%) than in patients treated with either recombinant IFN-alpha 2b (6.9%) or IFN-alpha N1 (1.2%), a lymphoblastoid IFN-alpha. Furthermore, sera obtained from patients treated with either recombinant IFN neutralized both types of recombinant IFNs but failed to neutralize IFN-alpha N1.

Antibodies↗

Prostaglandin A inhibits replication of human immunodeficiency virus during acute infection.

An antiviral effect of prostaglandins (PGs) of the A series on the replication of human immunodeficiency virus (HIV) has been determined. In the T cell line C8166 under single growth cycle conditions, PGA1 reduced the number of infectious progeny 1000-fold in the absence of cytotoxicity. Thus, inhibition of HIV replication by PGA1 represents a true antiviral phenomenon. The number and size of virus-induced syncytia, and the amount of viral antigen were also drastically reduced. The effect was specific for PGAs because PGA2 was also inhibitory, whereas PGB1, PGE1 and PGE2 were inactive. Virus adsorption and penetration do not appear to be targets of antiviral action because PGA1 substantially reduced virus replication, even when added 5 h post-infection. PGA1 did not inhibit viral reverse transcriptase, as determined by in vitro assays, suggesting that its antiviral action is not the consequence of a direct inhibitory effect on this enzyme. PGA1 also inhibited the replication of HIV-1 in CEM x 174 cells, but with less potency. Previously, intravenous infusion of PGA1 into human volunteers has shown no significant deleterious side-effects and thus these observations suggest that PGAs might have potential as antiviral agents in humans.

Antiviral Agents↗

High-performance liquid chromatographic approach to the separation of antiviral and immunostimulant fractions in Neuramide.

Neuramide, a tissue extract having antiviral action against influenza A virus and immunostimulant action, was analyzed by preparative size-exclusion high-performance liquid chromatography (HPLC) and a low-molecular-weight fraction responsible for the antiviral action was isolated after reversed-phase HPLC. Four fractions having immunostimulant activity were also isolated, as evidenced by their potentiating action in the human lymphocyte proliferation induced by phytohaemagglutinin.

Adjuvants, Immunologic↗