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M Luppi

Publications and source records attributed to M Luppi.

At least 55 records · Page 3Linked to original sources
PubMed1998

Expression of human herpesvirus-6 antigens in benign and malignant lymphoproliferative diseases.

Immunohistochemistry was used to look for the expression of human herpesvirus-6 (HHV-6) antigens in a well characterized series of benign, atypical, and malignant lymphoid lesions, which tested positive for the presence of HHV-6 DNA. A panel of specific antibodies against HHV-6 antigens, characteristic either of the early (p41) or late (p101K, gp106, and gp116) phases of the viral cycle, was applied to the lymphoid tissues from 15 non-Hodgkin's lymphomas, 14 Hodgkin's disease cases, 5 angioimmunoblastic lymphadenopathies with dysproteinemia, 14 reactive lymphadenopathies, and 2 cases of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). In lymphomatous tissues, the expression of late antigens was documented only in reactive cells, and mainly in plasma cells. Of interest, the expression of the early p41 antigen was detected in the so-called "mummified" Reed-Sternberg cells, in two Hodgkin's disease cases. In reactive lymphadenopathies, the HHV-6 late antigen-expressing cells were plasma cells, histiocytes, and rare granulocytes distributed in interfollicular areas. In both cases of Rosai-Dorfman disease, the p101K showed an intense staining in follicular dendritic cells of germinal centers, whereas the gp106 exhibited an intense cytoplasmic reaction in the abnormal histiocytes, which represent the histological hallmark of the disease. The expression of HHV-6 antigens is tightly controlled in lymphoid tissues. The lack of HHV-6 antigen expression in neoplastic cells and the limited expression in degenerating Reed-Sternberg cells argue against a major pathogenetic role of the virus in human lymphomagenesis. The detection of a rather unique pattern of viral late antigen expression in Rosai-Dorfman disease suggests a possible pathogenetic involvement of HHV-6 in some cases of this rare lymphoproliferative disorder.

Antigens, Viral↗
PubMed1998

Occurrence of a novel t(11;19)(q13;q13.3) in complete remission of acute promyelocytic leukemia.

A woman with t(15;17) and PML/RAR alpha positive acute promyelocytic leukemia (APL-M3v) achieved a complete remission (CR) with cytogenetic and molecular conversion, after one-month ATRA plus idarubicin treatment. During CR, less than one-month after consolidation therapy with topoisomerase II inhibitors, a novel t(11;19) (q13;q13.3) was detected in peripheral blood stem cells and later in harvest bone marrow cells. Persisting CR and the negativity for BCL1 and PRAD1 genes rearrangement, the autotransplantation was performed, with good outcome. The patient is still in CR eighteen months post-transplant, in spite of the persistence of a small t(11;19) clone in BM cells. The emergence of a novel chromosomal change during CR of acute leukemia is a rare phenomenon. This is the first t(11;19)(q13;q13.3) described in APL. This finding raises the issue of whether the abnormal karyotypes at remission might represent a risk of tumor recurrence. The meaning of this genomic instability is yet unknown.

Antineoplastic Agents↗
PubMed1998

Chronic myeloid leukemia with thrombocythemic onset may be associated with different BCR/ABL variant transcripts.

Ph-positive chronic myeloid leukemia (CML) mimicking essential thrombocythemia (ET) at onset seems to be a distinct clinical entity. Whether this rare clinical form of CML is associated with single, specific variants of BCR/ABL transcripts is a matter of debate. Among 82 consecutive patients with Ph-positive CML, we identified 3 patients in which the disease mimicked ET at presentation, because of marked thrombocytosis and moderate leukocytosis, with few immature myeloid cells in peripheral blood and blood basophilia in 2 of them. Molecular analysis with the reverse transcriptase-polymerase chain reaction technique showed the presence of b2a2, b3a2, and b3a2-b2a2 transcript variants in the three patients, respectively. The results of our study together with a review of literature data suggest that different BCR/ABL transcript variants may occur in CML mimicking ET, without an apparently significant prevalence of one type.

Adult↗
PubMed1998

Clinico-pathological characterization of hepatitis C virus-related B-cell non-Hodgkin's lymphomas without symptomatic cryoglobulinemia.

BACKGROUND: Epidemiological evidence has suggested an association between hepatitis C virus (HCV) infection and B-cell lymphoproliferation. We studied the prevalence of HCV infection in a series of de novo B-cell non-Hodgkin's lymphoma (B-NHL) cases and correlated virological findings with clinico-histological features. PATIENTS AND METHODS: One hundred fifty-seven patients with de novo B-NHL were included in the study. Their serum was examined by ELISA and RIBA for the presence of anti-HCV antibodies, and either the peripheral blood mononuclear cells or the pathology tissues of all of the patients were examined by reverse transcriptase polymerase chain reaction for the presence of HCV RNA sequences. RESULTS: HCV infection occurred in 22.3% of B-NHL patients and was documented before the diagnosis in about half of the positive cases. Of interest, HCV infection was more frequently found in follicular center, marginal zone and diffuse large-cell lymphoma types, but was not associated with symptomatic cryoglobulinemia. The median survival time was 48 months in HCV-positive and 52 months in HCV-negative B-NHL patients. CONCLUSIONS: Our findings strengthen the pathogenetic link between HCV and B-NHL and show that HCV infection may be associated with the malignant proliferation of defined B-cell subsets other than the immunoglobulin Mk B-cell subset involved in the pathogenesis of mixed cryoglobulinemia type II and associated lymphoplasmacytoid lymphoma type. HCV-related liver disease did not affect the survival of our B-NHL patients.

Adult↗
PubMed1998

[Toxic shock syndrome by group A beta-hemolytic streptococcus. Study of clonal relationship between a case and its contacts].

Group A Streptococcal infections have increased in severity and frequency worldwide. We report a female patient that was admitted by Group A Streptococcal lethal toxic shock syndrome due to pharyngitis as the primary focus and without cutaneous involvement. Streptococcus pyogenes was isolated from blood cultures and case definition fulfilled standard recommendations. Epidemiological studies among family members showed, that two children (aged 5 and 12 years) harbored the same strain in their pharynxes as confirmed by arbitrarily primed PCR (AP-PCR) using primers ERIC and Pn-1. Control strains were included in the analysis. None of three health care workers involved in intubation and laryngoscopic procedures with the patient carried S pyogenes. AP-PCR appears to be a useful and rapid procedure to demonstrate clonal relatedness among S pyogenes strains.

Adult↗
PubMed1997

Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant transforming activity and its protein binds to p53.

The 357 amino acid open reading frame 1 (ORF-1), also designated DR7, within the SalI-L fragment of human herpesvirus 6 (HHV-6) exhibited transactivation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter and increased HIV-1 replication (Kashanchi et al., Virology, 201, 95-106, 1994). In the current study, the SalI-L transforming region was localized to the SalI-L-SH subfragment. Several ORFs identified in SalI-L-SH by sequence analysis were cloned into a selectable mammalian expression vector, pBK-CMV. Only pBK/ORF1 transformed NIH3T3 cells. Furthermore, cells expressing ORF-1 protein produced fibrosarcomas when injected into nude mice, whereas control cells, expressing either no ORF-1 protein or C-terminal truncated (after residue 172) ORF-1 protein, were not tumorigenic. Western blot analysis of proteins extracted from the tumors revealed ORF-1 protein. Additional studies indicated that ORF-1 was expressed in HHV-6-infected human T-cells by 18 h. Co-immunoprecipitation experiments showed that ORF-1 protein bound to tumor suppressor protein p53, and the ORF-1 binding domain on p53 was located between residues 28 and 187 of p53, overlapping with the specific DNA binding domain. Functional studies showed that p53-activated transcription was inhibited in ORF-1, but not in truncated ORF-1, expressing cells. Importantly, the truncated ORF-1 mutant also failed to cause transformation. Analysis of several human tumors by PCR revealed ORF-1 DNA sequences in some angioimmunoblastic lymphadenopathies, Hodgkin's and non-Hodgkin's lymphomas and glioblastomas. The detection of ORF-1 sequences in human tumors, while not proof per se, is a prerequisite for establishing its role in tumor development. Taken together, the results demonstrate that ORF-1 is an HHV-6 oncogene that binds to and affects p53. The identification of both transforming and transactivating activities within ORF-1 is a characteristic of other viral oncogenes and is the first reported for HHV-6.

3T3 Cells↗
PubMed1997

Hepatitis C virus-induced leuko-thrombocytopenia and haemolysis.

Hepatitis C virus (HCV) has been recognized as the cause of thrombocytopenia occurring in patients with chronic hepatitis C, possibly through autoimmune mechanisms. A patient is described with B cell chronic lymphocytic leukaemia, presenting with a marked leuko-thrombocytopenia and an associated mild haemolysis secondary to HCV infection, in the absence of clinical and biochemical signs of hepatitis. Anti-HCV antibodies were detected in the serum both by ELISA and RIBA but not 2 months before the onset of cytopenia. The presence of HCV RNA was documented both in the peripheral blood mononuclear cells and in the bone marrow by reverse transcriptase polymerase chain reaction of the 5' untranslated region of the viral genome. Of interest, HCV RNA was also found in the serum, showing that viraemia was associated with the presence of circulating anti-HCV antibodies. HCV genotyping, performed by PCR amplification of the core region, revealed the presence of an unclassifiable genotype. The hypothetical mechanisms leading to HCV-induced cytopenia in this patient are briefly discussed. Treatment with corticosteroids was effective in controlling blood cell counts, without increasing viraemia and deterioration of liver disease. HCV infection should be considered in the differential diagnosis of possible causes of cytopenia, mainly in immunosuppressed patients, even in absence of clinical and biochemical signs of hepatitis.

Aged↗
PubMed1997

Detection of human herpes virus type 8 DNA sequences as a valuable aid in the differential diagnosis of Kaposi's sarcoma.

The occurrence of human herpes virus type 8 (HHV-8) DNA sequences was evaluated by polymerase chain reaction in 36 cases of cutaneous Kaposi's sarcoma (KS) (classic and associated with the acquired immunodeficiency syndrome) and in 88 pathologic entities that can histologically mimic KS, such as reactive and neoplastic vascular processes and lesions featuring focal or extensive spindle cell pattern. A positive reaction was detected in 16 (70%) of 23 samples of classic KS and 10 (77%) of 13 KS cases related to the acquired immunodeficiency syndrome. In particular, 4 (50%) of 8 samples in the patch stage were found to be positive, whereas in the plaque and nodular stages, HHV-8 DNA sequences were observed in 8 (67%) of 12 and 14 (87%) of 16 cases, respectively. KS cases that had yielded previous negative results were found to be positive for HHV-8 on nested polymerase chain reaction, except two cases of classic KS in the patch stage (6% of the total number of KS, 25% of cases in the patch stage). Reactive and neoplastic vascular processes and cutaneous lesions with a spindle cell component were consistently negative. HHV-8 detection by polymerase chain reaction can represent a valuable method for diagnosing KS, particularly in small skin biopsy samples that might show histologic overlap with non-KS lesions. In early patch stage lesions, however, the diagnostic value of the method is hampered by the occurrence of cases in which HHV-8 sequences are still undetectable.

DNA, Viral↗
PubMed1997

Human herpesvirus-6 reactivation in a longitudinal study of two HIV-1 infected patients.

After primary infection, human herpesvirus-6 (HHV-6) persists in latent form and can be reactivated in immunocompromised subjects. A longitudinal study of HHV-6 infection was carried out in two HIV-1 seropositive patients to provide in vivo evidence of HHV-6 reactivation. Concomitant with a significant rise of anti-HHV-6 IgG detected by IFA, a transient increase of HHV-6 viral load was shown in PBLs by PCR. During HHV-6 reactivation it was also identified either cell-free HHV-6 by PCR in plasma or IgM antibody titers. HHV-6 reactivation was followed by a temporary decrease in CD4+ count and by a progressive dramatic loss of CD4+ during the following 18 months. HHV-6 strain characterization by PCR demonstrated that first patient (MM) initially showed the B variant, followed by reactivation and persistence of the A variant, while in the second (SG) only the A variant was detected. The evidence of HHV-6 reactivation suggests its involvement in immunologic damage underlying the disease.

AIDS-Related Opportunistic Infections↗
PubMed1996

Frequency and distribution of herpesvirus-like DNA sequences (KSHV) in different stages of classic Kaposi's sarcoma and in normal tissues from an Italian population.

The frequency and distribution of herpesvirus-like DNA sequences (KSHV) were investigated by PCR in the pathologic skin lesions of a series of 22 HIV-negative elderly patients with classic Kaposi's sarcoma (KS) from Italy, one of the few regions of the world where classic KS is prevalent. Viral sequences were clearly identifiable in 15 cases, in particular in 2 of 5 patch, in 3 of 6 plaque and in 10 of 11 nodular lesions. Our findings confirm the association of these herpesvirus-like DNA sequences with KS in unrelated populations, providing evidence of the putative KS-associated agent in all different histologic lesions of the disease, mainly in the nodular stage. The search for other herpesviruses by PCR showed that Epstein-Barr virus (EBV) sequences were present in 7 of 22 pathologic skin lesions. In 4 cases, both EBV and KSHV were present. On the contrary, all 22 classic KS specimens were negative for human herpesvirus-6 sequences. Two of 3 patch and the 1 nodular lesions from AIDS-related KS patients examined were positive for KSHV but negative for both EBV and HHV-6 sequences. Furthermore, we evaluated the prevalence of KSHV sequences in the normal population of the same geographical area. Thirteen peripheral blood mononuclear cell samples, 9 salivary gland tissues and 6 saliva samples from healthy subjects were invariably found negative for KSHV, using the same PCR technique. Of interest, 2 of 11 hyperplastic tonsils harboured these herpesvirus-like sequences, suggesting that, like other herpesviruses, the KS- associated agent may be harboured in a proportion of normal individuals and tonsils may represent at least one of the possible reservoirs of this putative lymphotropic gamma-herpesvirus in vivo.

Acquired Immunodeficiency Syndrome↗