Pathogenic mechanisms of meningitis/encephalitis caused by human herpesvirus-6 in immunocompetent adult patients.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
Pasquale Ferrante
Publications and source records attributed to Pasquale Ferrante.
Progressive gray matter damage in patients with relapsing-remitting multiple sclerosis: a longitudinal diffusion tensor magnetic resonance imaging study.
BACKGROUND: Diffusion tensor magnetic resonance imaging (DT MRI) has the potential to provide in vivo information about tissue microstructure. In multiple sclerosis (MS), DT MRI has disclosed the presence of occult structural damage in the normal-appearing brain tissues. OBJECTIVE: To investigate whether DT MRI is sensitive to longitudinal changes of brain damage that may occur beyond the resolution of T2-weighted images in patients with relapsing-remitting MS. DESIGN: Twenty-six untreated patients with relapsing-remitting MS were followed up for 18 months. Dual-echo, DT and postcontrast T1-weighted MRIs of the brain were obtained at baseline and then every 3 months. Mean diffusivity (D) histograms of normal-appearing gray (GM) and white matter were produced. Total T2-hyperintense and T1-hypointense lesion volumes; normalized whole brain tissue, GM, and white matter volumes; percentage brain volume change between the study entry and exit images; average lesion D; and fractional anisotropy were also calculated. RESULTS: During the study period, a significant decrease of normalized whole brain tissue, average lesion fractional anisotropy and normal-appearing GM D histogram peak height, and a significant increase of average normal-appearing GM D and T2-hyperintense lesion volumes were observed. Changes of normal-appearing GM diffusivity were independent of the concomitant changes of normalized whole brain tissue and GM volumes. CONCLUSIONS: The DT MRI findings show progressive microstructural changes in the normal-appearing GM of patients with untreated relapsing-remitting MS. Such changes do not reflect a concomitant development of brain atrophy and confirm the importance of GM pathology in MS.
Adult↗
Detection of herpesvirus-6A in a case of subacute cerebellitis and myoclonic dystonia.
This is a case study of a child who developed roseola infantum first, then varicella, and was later affected by acute cerebellar syndrome, severe truncal ataxia, and myoclonic dystonia. Human herpesvirus 6 (HHV-6) A and B were detected in the cerebrospinal fluid (CSF) and peripheral blood, respectively, upon ataxia onset. The intricacy of this case suggests multifaceted conclusions ranging from the need for a multidirectional approach to neurological diseases, to confirmation of a more pronounced neurotropism of HHV-6A and a possible role of viruses in myoclonic dystonia syndrome, although this last hypothesis should be confirmed by larger studies.
Cerebellar Diseases↗
Distribution, characterization and significance of polyomavirus genomic sequences in tumors of the brain and its covering.
The etiology of brain tumors and meningiomas is still unknown. Several factors have been considered, such as genetic predisposition and environmental risk factors, but the hypothesis that one or more infectious agents may play a role in tumor pathogenesis has also been investigated. Therefore, emphasis was placed on the neurooncogenic family Polyomaviridae and the presence of human polyomavirus DNA sequences and JCV mRNA were examined in malignant human brain biopsies. Italian patients affected with different types of neoplasias of the brain and its covering were enrolled. The patients underwent surgical tumor excision and the presence of the polyomavirus genome in biopsy and other body fluids was evaluated by PCR. In addition, the genomic organization of JCV was examined in depth, with the aim of providing information on genotype distribution and TCR rearrangements in the population affected with intracranial neoplasms. On the whole, polyomavirus DNA was found in 50% of the biopsy specimens studied, JC virus DNA and BK virus DNA were amplified in 40.6% mainly glioblastomas and 9.4% of the tissue specimens, respectively, while none of the biopsy specimens tested contained Simian virus 40 DNA. Genotype 1 and Mad 4 TCR organization were the most frequent in the population enrolled. Although a cause and effect was not demonstrated and the specific role of the viruses remains unknown, the findings appear to confirm the hypothesis that JCV and BKV could be important co-factors in tumor pathogenesis.
Adult↗
Programmed cell death of myelin basic protein-specific T lymphocytes is reduced in patients with acute multiple sclerosis.
We investigated the apoptosis of myelin basic protein (MBP)-specific T lymphocytes in multiple sclerosis (MS) patients with acute (AMS) or stable (SMS) MS by evaluating the expression of apoptosis markers on peripheral cells. Cells of healthy controls (HC) were evaluated as well. Results showed that mitogen-stimulated apoptosis was comparable among patients and controls, whereas MBP-stimulated CD4+ and CD8+ 7-AAD+ and 7-AAD+ Fas+ cell (apoptotic cells) were significantly reduced in AMS patients. A reduction of the apoptotic rate of myelin-specific CD4+ and CD8+ T lymphocytes could be involved in the immune-mediated destruction of the myelin sheath seen in AMS patients.
Acute Disease↗
A case of a progressive multifocal leukoencephalopathy patient with four different JC virus transcriptional control region rearrangements in cerebrospinal fluid, blood, serum, and urine.
JC virus (JCV) is the etiological agent of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system (CNS). During the acquired immunodeficiency syndrome (AIDS) epidemic, it was the cause of the death in up to 8% of AIDS patients. The genomic organization of JCV and, in particular, the hypervariability of the transcriptional control region (TCR), a regulatory noncoding region, are well known. Given that the TCR plays a central role in the viral replication of JCV, a crucial role in the determination of the neurotropism and in the pathogenic capabilities of the virus is also suspected. Here the authors describe a case of PML that did not respond to highly active antiretroviral therapy (HAART) therapy. There was a simultaneous presence of JCV strains with four different TCR structures in urine, peripheral blood cells, serum, and cerebrospinal fluid (CSF) samples. These data confirmed that the presence of the archetype TCt is restricted to urine, while also suggesting that the degree of the rearrangement varies and increases from the peripheral blood to CSF.
Adult↗
The manifestation of AIDS in Africa: an epidemiological overview.
The HIV epidemic in Africa has changed over the last decade and the incidence of AIDS, which was very low at the beginning of nineties, is now dramatically increasing. In this paper, we analyze the current situation of AIDS epidemiology on the continent, based on data generated by the antenatal care surveillance systems. As described here, the spread and prevalence of HIV differ in each African country, with South Africa now facing the worst situation. In addition, we have focused our attention on the modes and risks of viral transmission, highlighting the spread of HIV in particular subpopulations, which, for different reasons, prove to be more affected by the epidemic, such as sex workers and children. Genotype evolution and distribution in the various geographical areas are also considered. From this brief overview, it appears clear that poverty, the lack of technologies and inadequate resources, due mostly to social and economic instability, are widening the already existent gap between Africa and industrialized countries.
Acquired Immunodeficiency Syndrome↗
Correlation between disease severity and in vitro cytokine production mediated by MSRV (multiple sclerosis associated retroviral element) envelope protein in patients with multiple sclerosis.
MSRV is a retroviral element previously isolated in cell cultures from patients with multiple sclerosis. It is part of a new multi-copy endogenous retrovirus family named HERV-W and displays pro-inflammatory properties both in vitro in human PBMC cultures and in vivo in a humanized SCID mice model. In the present study, we have evaluated potential links between the pro-inflammatory properties of MSRV envelope protein and MS disease. Thus, cytokine productions mediated by the surface unit of MSRV envelope protein were evaluated in PBMC of MS patients and compared with healthy controls. Divergent reactivity to ENV-SU between MS and control PBMC was observed and was reflected by a significant increase of IFN-gamma, IL-6 and IL-12p40 production by the tested MS population. Interestingly, the overproduction of IL-6 and IL-12p40 was found to correlate with disease severity (EDSS) in most patients. Altogether our data suggest that MSRV envelope protein may induce an abnormal cytokine secretion, thus contributing to the inflammatory process in MS.
Adult↗
Human alpha defensin in HIV-exposed but uninfected individuals.
Human alpha defensins 1, 2, and 3 are produced by CD8 T cells of HIV-infected long-term nonprogressors and have an antiviral activity. alpha Defensins were examined in peripheral blood mononuclear cells (PBMCs), cervical-vaginal mononuclear cells (CVMCs), and cervical biopsies of 9 HIV-1-exposed but uninfected women (ESNs), 10 HIV-infected patients (HIV), and 13 low-risk healthy controls (HCs). Results showed that, whereas alpha defensin production and alpha defensin-expressing CD8 lymphocytes were comparable in ESNs and HIV patients, constitutive alpha defensin production by peripheral CD8 and CVMCs was augmented in ESNs compared with HCs (P = 0.001 and P = 0.058, respectively); alpha defensin mRNA was increased in PBMCs of ESNs; unstimulated, alpha defensin-expressing peripheral and mucosal CD8 lymphocytes were 10-fold higher in ESNs compared with HCs (P = 0.003 and P = 0.01, respectively); and alpha defensin mRNA and alpha defensin-expressing cells were augmented in cervical biopsies of ESN compared with HCs (mRNA:P = 0.03). The differences were reduced upon in vitro mitogen stimulation. A robust constitutive production of alpha defensin is seen in HIV-exposed uninfected individuals; these peptides could have a role in the potentially protective immune response that characterizes ESNs.
Biopsy↗
Peripheral blood dendritic cells increase in kidney-transplant patients without rejection.
Explore the source record for details and available documents.
Cell Movement↗
HLA-multiple sclerosis association in continental Italy and correlation with disease prevalence in Europe.
The association with HLA-DRB1 alleles was tested in 609 Continental Italian MS patients and 836 controls. The phenotype frequency of DRB1*15 in the patients was significantly higher (0.316 vs. 0.112; p(c)<10(-6); Odds Ratio (OR)=3.64) with no dose effect. DRB1*10 was also significantly increased (OR=2.19; p(c)=0.047) and DRB1*07 decreased (OR=0.60; p(c)=1.3 x 10(-3)) independently of DR15 and of each other. We did not detect an influence of the DR phenotype on disease course, age at onset/diagnosis, gender or familiarity. No association with Class I was detected in a random subset of patients and controls. A comparison of the HLA association data in Northern and Southern European populations shows a parallel between disease prevalence and DR15 frequency.
Adult↗
Growth hormone in T-lymphocyte thymic and postthymic development: a study in HIV-infected children.
OBJECTIVES: Growth hormone (GH) plays a role in thymic function, and recombinant GH may stimulate thymopoiesis in HIV-infected individuals. We performed immunologic analyses in 26 antiretroviral-treated children matched for age, pubertal status, clinical parameters, and antiretroviral exposure who did or did not show an impaired response to GH-release stimulation tests with arginine + GH-releasing hormone. RESULTS: The following abnormalities were found in GH-deficient compared with GH-nondeficient children after >4 years of therapy: CD4 count ( P = .02) and percentage ( P = .03), CD4 as percentage of normal cells for age ( P = .003), serum interleukin-7 concentration ( P = .02), and thymic volume ( P = .01). Naive CD4 (4+62+RA+ and 4+CCR7+RA+) and CD8 (8+CCR7+RA+) lymphocytes were lower in GH-deficient children ( P = .003; P = .007; and P = .02, respectively). Postthymic pathways were also impaired in GH-deficient children. Thus, central memory (4+CCR7+RA-) CD4+ cells were reduced ( P = .006), whereas effector memory (4+CCR7-RA-) CD4+ cells ( P = .002) and late effector CD8+ lymphocytes (8+CCR7-RA+ and 8+27-28-) ( P = .009 and P = .002, respectively) were increased in these children. CONCLUSIONS: Growth hormone plays a role in thymic and postthymic pathways, and defective GH production may be associated with incomplete immunoreconstitution. Immunomodulant agents (including GH) could be useful in patients with defective GH production.
Adolescent↗
Immunomodulation induced by tucaresol in HIV infection: results of a 16 week pilot Phase I/II trial.
OBJECTIVE: Immune reconstitution in highly active antiretroviral therapy (HAART)-treated individuals is incomplete and immunomodulatory compounds are needed to improve the outcome of HIV therapy. In a Phase I/II clinical trial performed on HIV-positive patients we analysed the safety and immunomodulating effects of tucaresol, a novel compound that has previously been described tn enhance cell-mediated immune responses. PATIENTS AND METHODS: Sixteen weeks pulse dose escalation protocol. Four groups of HIV-positive patients were enrolled: group A (n=6): HAART, CD4+ 300-500 cells/microl, HIV RNA <80 copies/ml; group B (n=6): HAART-naive, CD4+ <500 cells/microl, HIV RNA >10 000 copies/ml; group C (n=3): HAART-naive, CD4+ >500 cells/microl, HIV RNA <10000 copies/ml; and group D (n=6): HAART, CD4+ <200cells/microl, HIV RNA <80 copies/ml. Tucaresol was added to HAART in group A and D patients; group B patients started tucaresol with HAART, group C patients received tucaresol alone. Clinical and immunological analyses were performed at different time points. RESULTS: Tucaresol-related serious adverse events were observed in the first week of therapy in 2/21 patients who were viraemic when commencing treatment, but did not occur in patients on stable HAART. Tucaresol did not affect HIV viraemia whereas increases in CD4+ percentages, mainly supported by naive CD4+ cells, were observed. CD8+/28-/45RA+ cells and HIV-specific CD8+ IFNgamma- and perforin-producing cells improved whereas IL-10 mRNA diminished in tucaresol-treated patients. The effects were greater with 25 mg given every other day for 1 week. CONCLUSION: In HAART-receiving patients with proper virus suppression, tucaresol was not associated with serious adverse events and resulted in qualitative and quantitative stimulation of HIV-specific cytotoxic T lymphocyte activity and generation of naive T cells. These data may support further exploration of tucaresol use in reconstitution of immune system parameters in HIV patients with proper virus suppression while on HAART.
Adult↗
1-40 Beta-amyloid protein fragment modulates the expression of CD44 and CD71 on the astrocytoma cell line in the presence of IL1beta and TNFalpha.
The modulation of CD44, VCAM-1 and CD71 expression was analysed by flow cytometry in the 1321N1 astrocytoma cell line in the presence of interleukin-1beta (IL1beta), tumour necrosis factor-alpha (TNFalpha) and 1-40 or 25-35 beta-amyloid (Abeta) fragments. The percentage of 1321N1 astrocytoma cell line expressing these markers increased significantly after treatment with TNFalpha or IL1beta. The presence of Abeta 1-40 fragment, alone or in combination with IL1beta, induced an increase in the percentage of cells expressing CD44, but not VCAM-1. However, the concomitant presence of Abeta 1-40 fragment and of IL1beta or TNFalpha caused an increase in the percentage of CD71 positive cells. In contrast, the shorter Abeta 25-35 fragment was always inactive. These results indicates that Abeta 1-40 fragment, in association with cytokines, can activate this astrocyte-derived cell line and add further elements in favour of the hypothesis that beta-amyloid can act as immunological mediator.
Amyloid beta-Peptides↗
A whole genome screen for linkage disequilibrium in multiple sclerosis performed in a continental Italian population.
We have systematically screened the genome for evidence of linkage disequilibrium (LD) with multiple sclerosis (MS) by typing 6000 microsatellite markers in case-control and family based (AFBAC) cohorts from the Italian population. DNA pooling was used to reduce the genotyping effort involved. Four DNA pools were considered: cases (224 Italian MS patients), controls (231 healthy Italians), index (185 index cases from trio families) and parents (the 370 parents of the patient included in the Index pool), respectively. After refining analysis of the most promising 14 markers to emerge from this screening process, only marker D2S367 retained evidence for association.
Alleles↗
Significant association of HLA A2-DR11 with CD4 naive decrease in autistic children.
Nine autistic children and 37 ethnically homogenous controls were enrolled in the study to assess their human leukocyte antigen (HLA) pattern, and eight healthy children were studied to define their peripheral blood cell subsets. We observed a significant decrease in CD4+ naive and an increase in CD4+ memory T cells in autistic children. These differences were significantly more pronounced in the autistic children bearing the HLA A2 and DR11 alleles. These data support the hypothesis that autism could be due to an immune imbalance occurring in genetically predisposed children.
Autistic Disorder↗
Molecular characterisation of JC virus strains detected in human brain tumours.
AIMS: The aim of this study was to evaluate the presence and significance of JC virus (JCV) in human brain tumours. METHODS: Histology, immunohistochemistry (IHC) and molecular biology techniques were employed to examine specimens of tumour tissue, peripheral blood and cerebrospinal fluid taken from 22 patients with primary neuro-epithelial tumours. Furthermore, the coding viral protein (VP1) region and non-coding transcription control region (TCR) of JCV genome isolated from the tumours were submitted to sequence analysis in order to detect viral rearrangements or mutations. RESULTS: JCV genome was found in nine of the 22 tumour specimens (40.9%), including eight astrocyte-derived tumours (seven glioblastomas and one astrocytoma) and one oligodendroglioma, and in two of the 15 cerebrospinal fluid specimens (13.3%) with positive tumour tissue (one glioblastoma and one astrocytoma). Sequence analysis of JCV VP1, which was amplified in seven tissue samples and the two cerebrospinal fluid samples, revealed only genotype 1 (four 1a and three 1b), whereas TCR was amplified in six tissue samples and only one cerebrospinal fluid sample. TCR sequence analysis was possible in four cases and identified three Mad-4 and one type II sequences; the TCR genomic structures of JCV isolated from cerebrospinal fluid were the same as those sequenced from corresponding tumour tissue, thus indicating a possible cerebrospinal fluid dissemination of neoplastic cells carrying viral DNA. CONCLUSIONS: Our results suggest a possible role of JCV in the induction of brain tumours, especially in those originating from brain cells normally targeted by JCV infection.
Adult↗
Analysis of JC virus genotype distribution and transcriptional control region rearrangements in human immunodeficiency virus-positive progressive multifocal leukoencephalopathy patients with and without highly active antiretroviral treatment.
After the introduction of highly active antiretroviral therapy (HAART), the incidence of many acquired immunodeficiency syndrome (AIDS)-related opportunistic infections, but not of progressive multifocal leukoencephalopathy (PML), has been dramatically decreased. However, it has been shown that about 50% of the HAART-treated PML patients had a significantly prolonged (>6 months) survival time, in comparison to the short (<6 months) survival time of the classical form of PML. In order to verify if a particular genotype or genomic rearrangements of JC virus (JCV) could affect the clinical course of PML, the authors performed nucleotide sequencing of 25 virion protein (VP1) and 18 transcriptional control region (TCR) DNA amplified in the cerebrospinal fluid (CSF) of HAART-untreated PML patients, of 17 HAART-treated PML patients, and in the urine of 23 healthy individuals. In nontreated PML patients, 52% and 44% of amplified JCV were respectively type 1 and type 2, whereas in HAART-treated PML patients, 59% of the amplified JCV were type 1, 23% type 2, and 18% type 4, without differences between long and short survivors. In both groups, the amplified TCR had unique and extensive rearrangements, whereas archetype TCR without rearrangements was detected in all the healthy subjects and in the CSF of two long-survivor PML patients. The data obtained indicate that the introduction of HAART has induced changes in JCV genotype distribution and probably reduced the rate of rearrangements of TCR region among PML patients.
Acquired Immunodeficiency Syndrome↗