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Biomedical subjects

D Fioriti

Publications and source records attributed to D Fioriti.

10 recordsLinked to original sources

The human polyomavirus BK: Potential role in cancer.

In human cancer, a role has been suggested for the human polyomavirus BK, primarily associated with tubulointerstitial nephritis and ureteric stenosis in renal transplant recipients, and with hemorrhagic cystitis in bone marrow transplant (BMT) recipients. After the initial infection, primarily unapparent and without clinical signs, the virus disseminates and establishes a persistent infection in the urinary tract and lymphocytes. There is correlative evidence regarding potential role of polyomavirus BK in cancer. In fact, the BK virus (BKV) DNA (complete genome and/or subgenomic fragments containing the early region) is able to transform embryonic fibroblasts and cells cultured from kidney and brain of hamster, mouse, rat, rabbit, and monkey. Nevertheless, transformation of human cells by BKV is inefficient and often abortive. Evidence supporting a possible role for BKV in human cancer has accumulated slowly in recent years, after the advent of polymerase chain reaction (PCR). BKV is known to commonly establish persistent infections in people and to be excreted in the urine by individuals who are asymptomatic, complicating the evaluation of its potential role in development of human cancer. Therefore, there is no certain proof that human polyomavirus BK directly causes the cancer in humans or acts as a cofactor in the pathogenesis of some types of human cancer.

Animals↗

Investigation on the role of cell transcriptional factor Sp1 and HIV-1 TAT protein in PML onset or development.

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), characterized by multiple areas of demyelination and attendant loss of brain function. PML is often associated with immunodepression and it is significantly frequent in AIDS patients. The viral genome is divided into early and late genes, between which lies a non-coding control region (NCCR) that regulates JCV replication and presents a great genetic variability. The NCCR of JCV archetype (CY strain) is divided into six regions: A-F containing binding sites for cell factors involved in viral transcription. Deletions and enhancements of these binding sites characterize JCV variants, which could promote viral gene expression and could be more suitable for the onset or development of PML. Therefore, we evaluated by means of polymerase chain reaction (PCR) the presence of JCV genome in cerebrospinal fluid (CSF) of HIV positive and negative subjects both with PML and after sequencing, we analyzed the viral variants found focusing on Sp1 binding sites (box B and D) and up-TAR sequence (box C). It is known that Sp1 activates JCV early promoter and can contribute in maintaining methylation-free CpG islands in active genes, while up-TAR sequence is important for HIV-1 Tat stimulation of JCV late promoter. Our results showed that in HIV-positive subjects all NCCR structures presented enhancements of up-TAR element, whereas in HIV-negative subjects both Sp1 binding sites were always retained. Therefore, we can support the synergism HIV-1/JCV in CNS and we can hypothesize that both Sp1 binding sites could be important to complete JCV replication cycle in absence of HIV-coinfection.

Adult↗

Rearrangement patterns of JC virus noncoding control region from different biological samples.

The JC virus (JCV) is generally considered the etiological agent of progressive multifocal leukoencephalopathy (PML), a demyelinating brain illness, often associated with immunosuppression and significantly frequent in acquired immunodeficiency syndrome (AIDS) patients. The primary infection by JCV is usually asymptomatic and the virus can remain in a latent status in the kidney. As a consequence of immunological alterations of the host, the virus can show a genetic variability in the noncoding control region (NCCR) due to deletions, duplications, and insertions as compared with the archetype. The NCCR of the archetype strain can be divided into six regions, named boxes A to F. In this study, the authors evaluated the presence of the JCV genome in different biological samples, such as urine, peripheral blood mononuclear cells (PBMCs) and cerebral spinal fluid (CSF) by means of polymerase chain reaction (PCR). After sequencing of the PCR fragments, the NCCR structure of isolated JCV strains was analyzed in order to verify the presence of different viral variants. An analysis of the homology and of the multiple alignment of the obtained sequences in comparison with the archetype strain has been carried out. The results indicated the presence of different rearrangements among the analyzed samples. Whereas in the urine, the NCCR structure always appeared very similar to that of the archetype, in the PBMCs and CSF, the NCCR sequences showed specific and characteristic rearrangements as compared to the archetype. These different rearrangements could be correlated with the emerging of an NCCR organization more suitable for the development of PML.

AIDS-Related Opportunistic Infections↗

Infectious agents in tissues from spontaneous abortions in the first trimester of pregnancy.

Some evidence suggests that intrauterine infection plays a major role in the pathogenesis of early pregnancy loss, but the implication and prevalence of microrganisms in the aetiology of spontaneous abortion during the first trimester of pregnancy has not yet been well established. In this study, we analysed the tissues relative to the product of conception from abortions during the first trimester (51 spontaneous abortions and 56 voluntary pregnancy interruptions) in women attending the Gynecological Sciences Perinatology and Puericulture Department of "Policlinico Umberto I". Specimens were investigated by cultural methods for the presence of yeasts, gram positive, gram negative bacteria, and genital mycoplasma. By molecular diagnostic procedures, DNA sequences of Chlamydia trachomatis, herpes simplex viruses, adenovirus, human papillomaviruses and human polyomaviruses BK and JC were searched. None of these agents could be found in voluntary pregnancy interruption samples, with the exception of 3.6% of specimens positive for adenovirus, whereas spontaneous abortion tissues were positive for at least one microrganism by 31.5%. Data analysis showed the occurrence of both monomicrobial and polymicrobial infections.

Abortion, Spontaneous↗

Detection and sequence analysis of human polyomaviruses DNA from autoptic samples of HIV-1 positive and negative subjects.

The distribution of DNA of BK and JC human polyomaviruses (BKV and JCV) was investigated in samples from autopsies of different organs in 2 groups of patients: Human Immunodeficiency Virus -1 (HIV) positive and negative. Samples from various organs were analysed by a nested polymerase chain reaction (PCR) for the non-coding control and for the VP1 regions of both viruses. The results obtained showed that BKV DNA was present in both males and females with a higher prevalence in HIV-positive subject samples (spleen: 33%; kidney: 44%; brain: 22%, uterine cervix:100%; prostatic urethra: 50%). In prostatic urethra samples of HIV-positive subjects, the JCV DNA was revealed in a low percentage (33%), while it was not found at all in uterine cervix samples of both groups. The varying presence of BK and JC viral DNA in the different organs seems to reflect the different pathogenetic attitude of these viruses. JCV was mainly present in the brain (55%), confirming its typical neurotropism and its etiological role in neurological disorders found in immunodeficient patients. BKV, on the other hand, was mainly present in the kidney (44%) and in genital organs (uterine cervix: 100%; prostatic urethra: 50%) with the latter finding favouring the hypothesis of a possible sexual transmission of BKV. Furthermore, our results confirm the crucial role of the immune system in the persistence of human polyomaviruses in the host.

Adult↗

Urothelial bladder carcinoma and viral infections: different association with human polyomaviruses and papillomaviruses.

Bladder cancer is the second most commonly occurring genitourinary cancer in adults. The interaction of different carcinogenic and cocarcinogenic agents are responsible for bladder urothelial carcinoma: alcohol and smoking habits, Schistosoma haematobium infection, exposition to chemicals, analgesic and antineoplastic drugs prolonged use. Recently also viral infections have been associated to this pathology. In this study the correlation between viral infections and bladder carcinoma has been evaluated. A group of 32 patients affected by primary bladder neoplasia has been analysed. A control group of 20 autoptic samples of healthy bladder was analysed. The DNA of the following viruses has been searched by polymerase chain reaction (PCR): Adenovirus, Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), Human Papillomaviruses (HPV), Polyomaviruses (BKV and JCV). In the examined population the association bladder carcinoma-HPV, found by others, has not been confirmed. The high percentage of human polyomaviruses present in the samples is a statistically significant data (p=0.0087) and allows to presume that BKV and JCV may play a role in the aetiology of bladder tumor. In particular the polyomavirus BK, which is found in significative percentage both in single infection (p=0.0036) and in co-infections with other viral species (p=0.035), may be an important co-factor in the pathogenesis of bladder carcinoma.

Adult↗

BKV infection and hemorrhagic cystitis after allogeneic bone marrow transplant.

Hemorrhagic cystitis (HC) is a well-known complication after allogeneic bone marrow transplant (BMT) and can be related to adenovirus or human polyomavirus BK (BKV) infections. In this study a group of 20 patients after allogeneic BMT has been examined. BMT urine samples were analysed for the presence of Adenovirus and BKV DNAby means of polymerase chain reaction (PCR). 5/20 BMT patients developed HC after BMT. The presence of BKV DNA in urine samples was evident in 3/15 patients without HC and in 5/5 patients with HC. In 2/5 HC-patients the BKV DNA was not found after therapy with Cidofovir and Ribavirin. The search for adenovirus DNA in all samples was negative. The analysis of BKV non-coding control region (NCCR) isolated from urine samples revealed a structure very similar to the archetype in all samples. The RFLP (Restriction Fragment Length Polymorphism assay) showed the presence of BKV subtypes I and IV, with the prevalence of subtype I (4/5). This study supports the hypothesis that HC is mainly related to BKV rather than to adenovirus infection in BMT patients. Moreover, since BKV subtype I was predominant, it is reasonable to hypothesize that a specific BKV subtype could be associated with the development of HC.

Adenoviridae↗

Interstitial cystitis and infectious agents.

Interstitial cystitis (IC) is a syndrome consisting of severe refractory bladder symptoms of unknown etiology. The disease tends to affect Caucasian women with a mean age of 40 years, with 25% of patients under the age of 30. Few population based epidemiological studies of IC have been performed. We analyzed a case of interstitial cystitis in a 42-year-old non-smoker woman. In two biopsy samples the presence of viral DNA of human polyomavirus BK (BKV), human herpes virus type 1 and type 2 (HHV- 1 and HHV-2), adenovirus, human papillomavirus (HPV) and bacterial DNA (Chlamydia trachomatis and Mycoplasma genitalium) were evaluated by means of polymerase chain reaction (PCR). Both samples resulted positive only for BKV and HPV DNA. HPV genotyping revealed the presence of HPV-66 that is associated with a high risk of cancer development. Thus the finding of a viral co-infection could support the hypothesis of the multi-factorial origin of this pathology.

Adenoviridae↗

Listeria monocytogenes in a young patient with non Hodgkins lymphoma: case report.

Listeria monocytogenes is an intracellular food-borne pathogen, widely distributed in the environment, which rarely causes clinical infection in healthy people, but may cause severe disease in immunocompromised patients. A case of listeriosis is certified in an immunocompromised patient, thus confirming this microorganism to be an opportunistic human pathogen.

Adolescent↗

Encrusted cystitis in an immunocompromised patient: possible coinfection by Corynebacterium urealyticum and E. coli.

Encrusted cystitis is a severe chronic inflammatory disease of the bladder characterized by excessively alkaline urine and calcifications within the bladder wall. A case of a 60 year-old man affected by systemic lupus erythematosus (SLE), which developed encrusted cystitis due to Corynebacterium urealyticum with E. coli co-infection, shows that the treatment of encrusted cystitis with a endoscopic debulking of the encrusted stones and an antimicrobial therapy specific for C. urealyticum often is not sufficient for the complete resolution of symptoms.

Corynebacterium↗