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Biomedical subjects

V Manzari

Publications and source records attributed to V Manzari.

7 recordsLinked to original sources

4-Hydroxynonenal, a product of cellular lipid peroxidation, which modulates c-myc and globin gene expression in K562 erythroleukemic cells.

Several studies point to the existence of an inverse correlation between cellular lipid peroxidation and both cell proliferation and neoplastic transformation. Here, we show that 4-hydroxynonenal (HNE) concentrations close to the level found in normal cells (in the range of 1 and 3 microM) can specifically induce changes in the expression of c-myc and gamma-globin mRNA in K562 cells, without inducing any toxic effects or affecting cell viability. Since we have determined that K562 cells have undetectable levels of endogenous lipid peroxidation, all these effects can be assigned to the exogenous HNE treatment. After a 1-h treatment with 1 microM HNE, c-myc mRNA levels decrease transiently during the first 4 h, rebounding later to higher levels, and normalizing to basal expression after 4 days. Run-on experiments show a transient transcriptional block 20 min after HNE treatment and subsequent posttranscriptional regulation. According to S1 mapping, mRNA changes are exerted on c-myc transcripts initiated from both the principal constitutive start sites (P1 and P2). gamma-Globin mRNA levels concomitantly increase 3- to 4-fold, but no significant changes of housekeeping gene expression are observed. On the basis of these results it appears that the restoration in human erythroleukemic K562 cells of HNE concentrations closer to the level in normal cells can modulate the expression of specific genes.

Aldehydes

Amplifications of multiple regions of the HTLV-I genome from DNA of an Italian spastic paraparesis patient but not from DNA of multiple sclerosis patients.

We searched for evidence of infection by the human T-cell lymphoma/leukemia virus type I (HTLV-I) in patients with multiple sclerosis (40 cases); brainstem encephalitis (1 case); Friedreich's ataxia (1 case); spastic paraparesis of unknown etiology (1 case). All patients were from the region of Abruzzo, Italy. Sera were all negative for anti-HTLV-I reactivity by the Western blotting (WB) analysis. DNAs from peripheral blood mononuclear cells were amplified using the polymerase chain reaction (PCR) technique with primers specific for the HTLV-I gag, pol, and env proviral regions. HTLV-I sequences were amplified only in the patient with spastic paraparesis of unknown etiology. In this case, HTLV-I infection might have been related to blood transfusions received 2 years prior to the onset of the neurologic symptoms. Members of the patient's family were negative for HTLV-I by PCR and WB. These data indicate that HTLV-I associated myelopathy is present also in Italy, but fail to substantiate an association of HTLV-I with multiple sclerosis.

Adolescent

High frequency of Epstein-Barr virus genome detection in Hodgkin's disease of HIV-positive patients.

Lymph nodes obtained from 7 HIV-positive and 20 HIV-negative patients with Hodgkin's disease were examined for the presence of Epstein-Barr virus antigens and genome. EBV antigens were observed in only 2 out of 20 HIV-negative patients, whereas lymph nodes of HIV-positive patients did not reveal evidence of EBV antigens. By in situ hybridization and Southern blot analysis, EBV genome was found in 5 out of 7 HIV-positive patients; the EBV genome was detected in the nucleus of Reed-Sternberg and Hodgkin's cells. EBV DNA was observed by in situ hybridization and Southern blot analysis in only 3 out of 20 HIV-negative patients with Hodgkin's disease. In both groups, Reed-Sternberg and Hodgkin's cells were negative for C3d EBV receptor. Our results show a statistically significant increased expression of EBV DNA in HIV-positive patients with Hodgkin's disease, as compared with HIV-negative patients with HD.

Adolescent

HTLV-I and HIV-1 infection in patients with lymphadenopathy syndrome detected during routine breast screening at a tumor prevention center.

Lymphadenopathy with no apparent cause had been reported in a group of women participating in a mammary tumor prevention program. A screening for retrovirus infection was organized to detect the virus as possible etiological agents. Data show a high percentage of positivity for HIV-1 among these lymphadenopathy patients, and surprisingly for HTLV-I, while no such positivity for either virus was found in matched controls or in patients where a different causal agent for lymphadenopathy was found. Of 26 seropositives, 23 deny any risk factor for HIV-1 and do not come from a HTLV-I known endemic area, but while it is impossible to exclude their knowledge of risk factors, it is worth noting that none of them presented a HTLV-I/HIV-1 double infection, which is very frequent in intravenous drug abusers, the major risk group in Italy. On the basis of these data spread of HTLV-I and HIV-1 appears to be more important in Italy than previously thought, and not confined to well-defined groups or, at least, among those who believe they do not belong to a risk group and therefore can represent a major vehicle for virus diffusion. Institution of screening for HTLV-I in blood donors should be taken immediately, and retrovirus infection risk criteria must be revised.

Adult

Globin mRNA sequences in polyadenylated and nonpolyadenylated nuclear precursor-messenger RNA from avian erythroblasts.

Nuclear RNA from immature duck erythrocytes was fractionated into polyadenylated and nonpolyadenylated fractions, and globin mRNA sequences were determined by hybridization to DNA complementary to globin mRNA. 80--90% of labeled nuclear RNA is found to be nonpolyadenylated, and 70--80% of the globin mRNA sequences present in the nucleus are found in nonpolyadenylated molecules. These data suggest that polyadenylation does not specifically select for globin mRNA sequences. The nonpolyadenylated globin mRNA sequences present in the nucleus are found mostly in molecules of small size, close to the size of polyribosomal globin mRNA, suggesting that polyadenylation is a later event in globin mRNA formation.

Animals

Simultaneous detection of reverse transcriptase and high molecular weight RNA in tissue of patients with Hodgkin's disease and patients with leukemia.

Complexes of high-molecular-weight RNA and reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) have been detected in 14(77.8%) of 18 spleen from patients with Hodgkin's disease and in all samples tested of peripheral leukocytes and spleens from leukemic patients. The enzyme and its template are localized in a particle having a density between 1.16 and 1.19 g/ml. These observations describe characteristic features of RNA tumor viruses.

Hodgkin Disease

Post-transfusional human retrovirus infection in 41 Italian beta-thalassemic patients.

BACKGROUND: Previous studies have demonstrated that HTLV-I is present in Italy both in endemic form in Southern Apulia and in epidemic form among the population of intravenous drug addicts. In the present paper we intend to evaluate the risk for transfusional HTLV-I transmission in our country, as well as the already known risk for HIV1. METHODS: A population of 41 polytransfused Italian beta-thalassemic patients was examined by serological methods and PCR (polymerase chain reaction) for human retrovirus infection. Genomic DNA from PBMCs was analyzed by PCR with primer pairs specific for the HTLV-I gag, pol and env regions, and the HTLV-II env region. RESULTS: Two patients were found to be weakly seroreactive to p19 and p24 HTLV-I/HTLV-II proteins by Western blot. The analysis of genomic DNA from PBMCs by PCR revealed sequence homology to HTLV-I only in these two patients. On the contrary, PCR with primer pairs specific for HTLV-II showed no beta-thalassemic patient was infected by this retrovirus. Surprisingly, Western blot analysis for detecting anti-HIV1 antibodies in these polytransfused subjects showed a seropositivity in two patients (not the same found to be infected with HTLV-I) in spite of a screening for HIV1 antibodies in the blood bank. CONCLUSIONS: These findings suggest that in Italy polytransfused people should still be considered at risk for HIV1 as well as HTLV-I infection, even if the incidence cannot be evaluated from such a small sample. The authors stress the importance of a through medical history of potential blood donors to eliminate possibly infected subjects.

Adolescent