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Biomedical subjects

U Tirelli

Publications and source records attributed to U Tirelli.

At least 127 records · Page 7Linked to original sources
PubMed1996

Human herpesvirus 6 in human immunodeficiency virus-infected individuals: association with early histologic phases of lymphadenopathy syndrome but not with malignant lymphoproliferative disorders.

Preliminary evidence suggested that human herpesvirus-6 (HHV-6) may act as a cofactor in acquired immunodeficiency syndrome (AIDS) and may contribute to the pathogenesis of lymphoproliferative disorders occurring in individuals infected with the human immunodeficiency virus (HIV). To understand better the biological and clinical significance of HHV-6 infection in the context of HIV-related immunosuppression, the polymerase chain reaction was used to study the frequency and variant distribution of HHV-6 in peripheral blood mononucleated cells (PBMCs) from HIV-seropositive individuals, either asymptomatic or with lymphadenopathy syndrome (LAS) or with overt AIDS. Non-neoplastic and malignant lymphoproliferative disorders from both HIV-infected and HIV-seronegative patients were also investigated using the same series of samples for the presence of Epstein-Barr virus (EBV). When compared with healthy blood donors (12/42, 29%), HHV-6 prevalence in PBMCs showed a progressive decline in HIV-seropositive individuals with asymptomatic HIV infection (3/26, 11%) and in patients with LAS (1/13, 8%) and a significant reduction in patients with overt AIDS (1/20, 20%; P = 0.02). The decrease correlated with the number of CD4+ cells at the time of examination. In addition, HHV-6 DNA sequences were significantly more prevalent in LAS biopsies (13/20, 65%) than in HIV-unrelated reactive lymphadenopathies (2/10, 20%; P = 0.02) and the presence of HHV-6 sequences correlated closely with a histologic pattern of follicular hyperplasia (13/16, 81%; P = 0.003). Strikingly, HHV-6 prevalence decreased in PBMCs of LAS patients, suggesting that the likelihood of interactions between HHV-6 and HIV varies in different body districts. In particular, the demonstration that all HHV-6-carrying LAS samples were also positive for HIV infection suggests that LAS lymph nodes constitute one of the sites where biologically relevant interactions between the two viruses might occur. Also, the prevalence of EBV was higher in LAS (14/20, 70%) than in non-neoplastic lymph nodes from HIV-seronegative individuals (4/10, 40%), although the difference was not statistically significant. EBV was associated strongly with HIV-related malignant lymphoproliferative disorders, being detected in 100% of patients with Hodgkin's disease (HD) and 53% of B-cell non-Hodgkin's lymphomas (NHL). In contrast, the prevalence of HHV-6 DNA in HD and B-cell NHL arisen in HIV-infected patients (30% and 6% respectively) was remarkably lower and similar to that observed in lymphoproliferative disorders from HIV-seronegative patients. Finally, as observed in healthy individuals, HHV-6 variant B was more prevalent than variant A in benign and malignant lymphoproliferative disorders from bot HIV-infected and HIV-seronegative patients. These results suggest that the interactions between HHV-6 and HIV could be different in the various phases of HIV disease and in different districts; HHV-6 has probably no direct role in the pathogenesis of HIV-associated B-cell NHL and HD cases, and behave differently from EBV; and HIV-related immunosuppression does not alter the distribution of HHV-6 variants in these tissues, as observed in the case of EBV.

AIDS-Related Complex↗
PubMed1996

Long-term survival of patients with HIV-related systemic non-Hodgkin's lymphomas.

BACKGROUND: the overall outcome of patients with HIV-related non-Hodgkin's lymphomas (HIV-NHL) is poor because of the adverse clinico-pathological features of HIV-NHL and the underlying HIV infection. However, the experience of physicians in the management of HIV-NHL has increased, in particular in the use of intensive chemotherapy regimens, leading to an improvement in the prognosis of some of these neoplasms. Because some patients with AIDS may survive up to 5 years, it is possible to evaluate the long-term efficacy of the treatment of patients with HIV-NHL. In the general population, aggressive NHL, that are those occurring in HIV patients, may be considered cured after 2 years of lasting complete remission (CR) after chemotherapy. PATIENTS AND METHODS: we reviewed our monoinstitutional case-series of 73 HIV-infected patients with systemic NHL, observed between April 1985 and February 1993. Two groups of patients were arbitrarily identified, the first one (group A) including patients with a CR lasting for at least 2 years (N = 13) and the other including all remaining patients (group B) (N = 60). RESULTS: the 13 patients of group A differed significantly from the other patients in terms of higher CD4+ cell count and performance status (PS) at the time of diagnosis of NHL. There was no significant difference in the histological subtypes of the HIV-NHLs. The overall survival of the 73 patients was 8 months. In a separate analysis on all patients, age less than 30 years, PS less or equal to 1, a CD4+ cell count equal to or higher than 100/mm3 and the absence of B symptoms were significantly associated with a longer survival. The median survival in patients of group A was 42 months, however none of these patients relapsed during a median observation time of 42 months (range, 24-90). CONCLUSIONS: long-term survival and possibly cure can be obtained in some patients with HIV-NHL, in particular in those with a better PS and a less advanced immune dysfunction. In fact some of these patients are alive without evidence of disease 4 to 7 years after therapy, and others died of causes related to underlying HIV infection, in particular opportunistic infections, rather than relapse of NHL.

Adult↗
PubMed1996

Immunophenotypic and molecular analyses of acquired immune deficiency syndrome-related and Epstein-Barr virus-associated lymphomas: a comparative study.

Limited information is current available on the molecular and immunophenogenotypic characteristics of CD30-positive anaplastic large cell (ALC) lymphomas occurring in human immunodeficiency virus (HIV)-infected individuals. To address this issue, the authors have undertaken a combined analysis of these lymphomas in a comparison with other Epstein-Barr virus (EBV)-associated tumors in the setting of HIV infection. Twenty-one AIDS-related lymphomas, including five CD30-positive ALC and 11 small noncleaved cell (SNCC) lymphomas, and five Hodgkin's disease (HD) specimens were characterized regarding the immunophenogenotypic features, the frequency and subtype distribution of EBV (as defined by in situ hybridization [ISH], Southern blot, and a polymerase chain reaction [PCR] amplification of the EBV nuclear antigen-2 [EBNA-2] region) antigen expression (latent membrane protein-1 [LMP-1], EBNA-2, and for alterations of the tumor suppressor gene p53. Combined immunophenotypic and immunogenotypic analyses showed a derivation from anomalously matured B cells in four of five CD30-positive ALC lymphomas, whereas SNCC showed features of mature B cells; no evidence of immunoglobulin or TCR gene rearrangement could be obtained in HD cases. Combined ISH and Southern blot analyses revealed that EBV was more strictly associated with HD (five of five) and CD30-positive ALC lymphomas (four of five) than with SNCC lymphomas (four of 11). EBV-positive samples from CD30-positive ALC lymphomas carried type 1 EBV (two of two specimens tested), whereas both EBV subtypes were observed in SNCC lymphomas and HD samples. All three forms of viral latent gene expression were found in the EBV positive CD30-positive ALC lymphomas. SNCC specimens did not express LMP-1 or EBNA-2, whereas HD specimens expressed LMP-1 (four of five tested) but no EBNA-2. Immunostaining for ZEBRA was consistently negative. HHV-6 DNA sequences were detected by PCR in one SNCC of the 19 specimens analyzed. Three out of five CD30-positive ALC lymphoma specimens and six of 10 SNCC showed nuclear staining for p53. No mutation was detected in any of the three CD30-positive Alc lymphoma analyzed, whereas an aberrant SSCP pattern was found in all the four SNCC samples tested. At variance with SNCC lymphomas, AIDS-related B-cell CD30- positive ALC lymphomas are strictly associated with EBV infection and may also express the broad lymphoblastoid cell line-like (LMP-1-positive, EBNA-2-positive) pattern, and lack p53 genetic lesions. Unlike EBV, HHV-6 probably does not represent a relevant factor involved in the pathogenesis of CD30-positive ALC and other HIV related lymphomas.

Adult↗
PubMed1996

CD8+ cells in HIV infection produce macrophage inflammatory protein-1 alpha and RANTES: a comparative study in long-term survivors and progressor patients.

Evidence suggests that CD8+ lymphocytes are involved in the control of Human Immunodeficiency virus type 1 (HIV-1) infection by the release of HIV-suppressive factors. The human chemokines RANTES and the macrophage inflammatory protein 1 alpha (MIP-1 alpha) have been identified to be potent inhibitors of HIV in vitro. The aim of this study was to determine whether high levels of these chemokines are associated with a delayed progression of HIV disease. We have therefore analysed the in vitro production of RANTES and MIP-1 alpha from purified stimulated CD8+ cells from HIV+ long term survivors (LTS) and, as a comparison, from HIV+ patients with progressive disease. RANTES production was similar in LTS and progressors (14.06 +/- 3, 13.36 +/- 4.1 ng/ml, not statistically significant); the same cells from healthy controls show a RANTES production of 20 +/- 3.5 ng/ml (P = 0.034 versus LTS and P = 0.038 versus progressors). MIP-1 alpha production was slightly reduced in LTS (96.8 +/- 12 ng/ml) and progressors (91.6 + 17, not statistically significant between the two groups) when compared to healthy controls (109 +/- 7 ng/ml, P = 0.03). Our study suggests that resistance to HIV-1 progression in LTS may not be associated with high levels of RANTES and MIP-1 alpha production.

Adult↗
PubMed1996

Intra-epithelial and invasive cervical neoplasia during HIV infection.

Patients affected by human immunodeficiency virus (HIV) infection present an elevated risk of developing cancer. In the last 10 years, the relationship between human papilloma virus (HPV) infection and female cervical intra-epithelial neoplasia (CIN) has been established. Several studies have described an increased prevalence of both cervical HPV infection and CIN among HIV-positive women compared to HIV-negative ones. A high recurrence rate of CIN after standard treatment has been noted in HIV-infected women and the severity of these lesions seems to be inversely correlated to immune function. Taking into account these data, the Centers for Disease Control (CDC) since 1993 have included invasive cervical carcinoma among the AIDS-defining conditions. Once cervical cancer develops in HIV-positive women, the disease may be aggressive and less responsive to treatment. A primary means by which HIV infection may influence the pathogenesis of HPV-associated cervical pathology is by molecular interaction between HIV and HPV genes. Although these have not been well defined, an upregulation of HPV E6 and E7 genes expression by HIV proteins (such as tat) has been postulated by some authors. Cervical cytology appears to be adequate as a screening tool for the cervical intra-epithelial neoplasia in HIV-positive women, but the high recurrence rate and multifocality of this disease reinforces the need for careful evaluation and follow-up of the entire anogenital tract in these women. Probably in the next few years, cervical tumours will represent one of the most frequent complications of HIV infection, a part of progression through AIDS. This points to a need for greater interdisciplinary co-operation for a best disease definition and for the development of effective prevention measures.

Female↗
PubMed1996

Kaposi's sarcoma-associated herpesvirus DNA sequences in AIDS-related and AIDS-unrelated lymphomatous effusions.

Primary effusions presenting as the sole lymphoma localization are also known as body-cavity-based-lymphoma (BCBL), and have been shown to carry Kaposi's sarcoma herpesvirus (KSHV) DNA sequences. The aim of this study was a comparative analysis of the clinical, pathologic and molecular features of BCBL and lymphomatous effusions secondary to tissue-based lymphomas occurring both in the general population and in HIV-1-infected individuals. All the lymphomatous effusion samples (seven AIDS-related and nine AIDS-unrelated) were subjected to an identical multiparameter investigation, including collection of clinical data, analysis of morphology and immunophenotype, as well as the study of viral sequences and genetic lesions. In six cases defined as BCBL (four AIDS-related and two AIDS-unrelated), the patients exhibited exclusive or predominant involvement of the body cavities. BCBL tended to display indeterminate phenotypes (4/6), whereas all AIDS-related and AIDS-unrelated lymphomatous effusions secondary to tissue-based lymphomas consistently expressed B-cell phenotype. Detection of KSHV DNA sequences was restricted to cases of BCBL (3/4 AIDS-related and 1/2 AIDS-unrelated), whereas EBV association (3/4) and expression of EBV-encoded antigens (LMP-1, 2/3; EBNA-2, 1/3) were confined to the AIDS-related BCBL. Overall, our results confirm that both AIDS-related and AIDS-unrelated BCBL preferentially associate with peculiar clinical, immunophenotypic and molecular features among lymphomatous effusions and therefore should be singled out as a specific clinico-pathologic entity.

Adult↗
PubMed1996

CD8+ lymphocyte phenotype and cytokine production in long-term non-progressor and in progressor patients with HIV-1 infection.

In most HIV-1-infected patients, clinical and immunological progression develops within a few years. Few infected people, termed long-term non-progressors (LTNP), remain healthy and immunologically stable for a long time. The factors governing the maintenance of this condition are not well known, but it is conceivable that CD8+ lymphocytes, cells that play a central role in controlling in vitro HIV replication, may have a part in vivo in this process. The aim of this study was to characterize the phenotypic profile and the cytokine production of CD8+ cells in a group of LTNP patients who had stable CD4+ cell counts (> 500/mm3) for at least 7 years. Their CD8+ absolute numbers were similar to a control group composed of HIV-1+ patients who have a progressive decline of their CD4+ cell counts. However, our multiparameter immunofluorescence studies show that a clinical and immunologically stable condition is associated with the presence of a CD28+, CD95 strongly positive CD8+ population, while disease progression is marked by the CD28-CD95+CD8+ subset. Purified CD8+ cells from LTNP retain their ability to produce IL-2, interferon-gamma (IFN-gamma) and, to a lesser degree, to produce IL-10 and IL-4. In contrast, CD8+ cells from progressors are unable to secrete IL-2 and IL-10. Although CD8+ cytokine profile does not fit with the proposed T helper (Th)1/Th2 switch in progressive HIV infection, LTNP CD8+ T cells maintain their capacity to produce IL-2 and IL-10 (Th0-like), a pattern very similar to that observed in normal HIV healthy controls. We suggest that CD8+ cells expressing CD28, CD95 and having a Th0-like profile may be considered to be associated with long-term survival.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Treatment of human immunodeficiency virus infection with hydroxyurea: virologic and clinical evaluation.

To assess the efficacy of the therapeutic use of inhibitors of ribonucleotide reductase for the treatment of human immunodeficiency virus (HIV) type 1 infection, 7 consecutive patients were enrolled in a clinical trial involving monotherapy with hydroxyurea for 8-19 weeks. During therapy, patients were evaluated for clinical status and immunologic, hematologic, and quantitative virologic parameters, including determinations of viremia and the number of provirus-containing cells by competitive polymerase chain reaction. In all patients, these parameters were not modified during the course of therapy. The number of CD4 cells remained generally unchanged or showed a tendency to further decline. No sign of improvement in HIV disease was detected in any patient. These observations indicate that monotherapy with hydroxyurea does not provide therapeutic benefit to HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Distribution of human herpesvirus-8 sequences throughout the spectrum of AIDS-related neoplasia.

OBJECTIVE: AIDS frequently associates with certain malignancies, including Kaposi's sarcoma, non-Hodgkin's lymphoma (NHL), and anogenital neoplasia. In this study we aimed to define the frequency of infection by human herpesvirus (HHV)-8 throughout the spectrum of AIDS-related neoplasia in Europe. DESIGN: A tumour panel representative of the distinct types of AIDS-related neoplasms was tested for the presence of HHV-8 DNA sequences. Autologous uninvolved tissues were also tested in selected cases. METHODS: The presence of HHV-8 DNA sequences was assayed by a combination of polymerase chain reaction followed by oligohybridization and Southern blot hybridization of genomic DNA with an HHV-8-specific probe. RESULTS: HHV-8 sequences were detected in 100% of AIDS-related Kaposi's sarcoma (all 35 cases). Among AIDS-related NHL, HHV-8 sequences selectively clustered with body-cavity-based lymphomas (BCBL; all three cases), although they were consistently negative in small non-cleaved cell lymphomas (none in 18 cases), diffuse large cell lymphomas (none in seven), or anaplastic large cell lymphomas (none in three). No HHV-8 sequences were found in cases of anogenital neoplasia (out of 14) or Hodgkin's disease (out of three). HHV-8 DNA sequences were also positive in the uninvolved skin of all six AIDS-related Kaposi's sarcoma patients, but not in the circulating lymphocytes of a BCBL patient. Positivity for HHV-8 sequences occurred in patients belonging to all major AIDS risk categories. CONCLUSIONS: These data confirm that HHV-8 sequences associate at high frequency with selected types of AIDS-related neoplasia, namely Kaposi's sarcoma and BCBL, although they are consistently absent in other types of AIDS-NHL and AIDS-related anogenital neoplasia.

AIDS-Related Opportunistic Infections↗