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Biomedical subjects

M Moroni

Publications and source records attributed to M Moroni.

At least 91 records · Page 5Linked to original sources

Human T-lymphotropic virus type 2 (HTLV-2) provirus in circulating cells of the monocyte/macrophage lineage in patients dually infected with human immunodeficiency virus type 1 and HTLV-2 and having predominantly sensory polyneuropathy.

We investigated the presence of human T-lymphotropic virus type 2 (HTLV-2) DNA in the peripheral blood mononuclear cell subsets obtained from 18 patients coinfected with human immunodeficiency virus type 1 and HTLV-2, 6 of whom also had predominantly sensory polyneuropathy (PSP). HTLV-2 DNA and RNA were found in CD8- and CD19-positive cells, and, for patients with PSP, in CD14-positive cells as well. Furthermore, the patients with PSP had higher proviral loads than those without PSP.

AIDS-Related Opportunistic Infections↗

Occurrence of prostasome-like membrane vesicles in equine seminal plasma.

Equine seminal plasma was shown to contain membrane vesicles that are similar to the well characterized prostasomes in human seminal plasma. Determination of nucleoside and nucleotide concentrations of these particles have shown that ATP, ADP and adenosine are the main components of the nucleotidic pool. 5' nucleotidase, endopeptidase and dipeptidyl peptidase i.v. activities have been found on the surface of the particles. The interaction between these prostasome-like vesicles and spermatozoa was demonstrated by electron micrograph scans which revealed the steps of a fusion-like process leading to mixing of the membranes. In addition, endopeptidase activity, a marker enzyme of these seminal vesicles that is normally absent from equine spermatozoa, was shown to be acquired by these cells after interaction with the vesicles. The addition of these vesicles to equine spermatozoa resulted in the modification of adenylate catabolism. Therefore, a role in stabilizing the energy charge of the spermatozoa thus allowing longer viability is proposed for these organelles.

Adenosine↗

Endothelin-1 and 5-fluorouracil-induced cardiotoxicity.

Cardiotoxicity is an uncommon side-effect of 5-FU-based chemotherapy. Coronary artery vasospasms have been postulated to be involved in the pathogenesis of this rare but serious problem. We found high plasma levels of ET-1, a potent natural vasoconstrictor, in two patients who experienced two of the commonest clinical manifestations of 5-FU-induced cardiac toxicity--i.e., angina pectoris and chronic heart failure. We, therefore, propose ET-1 as the ultimate mediator of this toxicity, even though the mechanism of ET-1 increase in peripheral venous blood is still unknown. Finally, another important question still remains unresolved: is the release of ET-1 from normal coronary endothelial cells the prime cause or simply the consequence of 5-FU-related cardiotoxicity?

Aged↗

Platelet agonists and calcium homeostasis in endothelial cells: possible role in the interaction of endothelium with hemostatic system.

BACKGROUND AND OBJECTIVE: The endothelium is complex tissue that modulates a vast array of biological functions and Ca++ transients are critically important to these endothelium-dependant functions. We addressed the hypothesis that some platelet agonists and products of activation of the hemostatic system could determine Ca++ transients in a bovine pulmonary artery endothelial cell line (CPA-47). DESIGN AND METHODS: The effect of thrombin, collagen, ADP, PAF, PDGF, GRGDS, and the TxA2 mimetic U46619 on CPA-47-cytoplasmic Ca++ transients was evaluated using a Platelet ionized Calcium Aggregometer, after cells were loaded with the photoprotein aequorin. RESULTS: ADP, GRGDS, PAF, U46619 and collagen were able to induce rapid Ca++ transients in CPA-47 endothelial cells and the response was stable after repeated additions, while thrombin acted slightly differently, as cells became refractory to this agonist after the first response, but they remained sensitive to the other inducers. Only PDGF was completely ineffective. Furthermore, calcium-channel blockers verapamil and flunarizine (but not nifedipine) caused a reduction only of thrombin-induced cytoplasmic Ca++ transients, while the addition of depolarizing concentration of KCl suggests the presence also of voltage-operated channels on endothelial cell membrane. Finally, EGTA caused the complete suppression of Ca++ transients induced by all the tested agonists but collagen. INTERPRETATION AND CONCLUSIONS: Our study demonstrated that the different agents tested are able to induce Ca++ transients on bovine endothelial cultured cells, similarly to that observed in platelets and other non excitable cells, including tumor cells, and that calcium channel blockers had only a limited inhibitory effect on these changes; these results may help more thorough understanding of the biochemical basis of the interaction between endothelium and the hemostatic system.

Animals↗

Atrial septal aneurysm in a patient with pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a rare heritable disorder of the connective tissue characterized by marked clinical heterogeneity. Common cardiovascular complications of PXE include renovascular hypertension, premature coronary artery disease and calcification of peripheral arteries frequently leading to claudicatio intermittens; fibrous thickening of the endocardium and atrioventricular valves, leading to restrictive cardiomyopathy and/or mitral valve prolapse have been also described. We herein report on a PXE patient who developed an atrial septal aneurysm as a previously undescribed cardiologic manifestation of her disease.

Adult↗

Risk of Kaposi's sarcoma-associated herpes virus transmission from donor allografts among Italian posttransplant Kaposi's sarcoma patients.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a newly discovered herpes virus found in all forms of Kaposi's sarcoma (KS) including KS among immunosuppressed transplant patients. It is unknown whether this virus is transmitted by organ transplantation or is reactivated during immunosuppression among those patients infected before transplantation. To investigate the risk of KSHV transmission during organ transplantation, we conducted a case-control study of transplant recipients with and without KS matched to their respective donors. Sera were collected at time of transplantation and tested in a randomized and blinded fashion using four KSHV serologic assays testing for antibodies to both latent and lytic phase antigens. Ten (91%) of 11 organ recipients who developed KS were seropositive prior to transplantation by one or more of the assays compared with two (12%) of 17 control organ recipients (OR = 75, 95% CI = 4.7, 3500). KS cases were more likely to have been born in southern Italy where KS is endemic than the recipient controls or either donor group. Only four (36%) of 11 donors to case patients and three (18%) of 17 donors to control patients were seropositive (P = .38, two-tailed Fisher's exact test). KSHV transmission could not be ruled out for the single KS patient seronegative at transplantation and clear evidence for organ-related transmission was found for another KS patient outside of the case-control study. Antibodies to KSHV are detectable in the sera from most transplant recipients before initiation of immunosuppressive treatment suggesting that KS among immunosuppressed transplant patients is primarily due to virus reactivation. KSHV transmission, however, from an infected allograft can occur, and our study reports the first documented case of person-to-person transmission of KSHV.

Adult↗

High prevalence of false-negative anti-HTLV type I/II enzyme-linked immunosorbent assay results in HIV type 1-positive patients.

A high frequency of false-negative anti-HTLV-I/II ELISA results has been reported by several authors. To verify the possible underestimate of the prevalence of HTLV-II infection in subjects infected by HIV-1, we used the PCR to investigate the presence of HTLV DNA in peripheral blood mononuclear cells (PBMCs) collected from a group of 67 HIV-1-positive anti-HTLV-I/II ELISA-negative individuals; the study population included 31 patients with HIV-1-related peripheral neuropathy (PN), 15 with non-Hodgkin lymphoma (NHL), and 23 without PN or NHL. Two subjects had both PN and NHL. All of the patients who were positive at PCR were investigated for the presence of serum anti-HTLV-I/II antibodies by means of Western blot (WB). Eighteen (26.9%) of the 67 anti-HTLV-I/II ELISA-negative patients had HTLV DNA in their PBMCs and WB-detectable serum antibodies directed against one or more HTLV antigens. The individuals affected by predominantly sensory polyneuropathy (PSP) had a significantly higher prevalence of HTLV DNA than the others. All of the patients in whom HTLV-I/HTLV-II discrimination was successful had HTLV-II, with the exception of one patient who was infected by HTLV-I. The present study confirms the possibility of HTLV infection in the absence of ELISA-detectable serum anti-HTLV-I/II antibodies, especially in the particular setting of HIV-1-infected individuals. Moreover, the fact that the prevalence of HTLV DNA was significantly higher in the subjects affected by predominantly sensory polyneuropathy further supports the possibility of an association between HIV-1-related PSP and HTLV-II.

Adult↗

Predictors of cytomegalovirus disease, natural history and autopsy findings in a cohort of patients with AIDS.

OBJECTIVE: To identify the predictors of acquiring cytomegalovirus (CMV) disease, and to describe natural history, therapeutic management and autopsy findings in affected patients. DESIGN: Observational study of a consecutive cohort of AIDS patient diagnosed and followed in the same institution. METHODS: All of the patients with CMV were included. Statistical analyses were performed to establish the risk of acquiring the disease at or after AIDS presentation, survival, and the occurrence and time of relapses in relation to maintenance therapy. The presence of CMV infection at autopsy was also investigated. RESULTS: CMV disease was diagnosed in 304 (24.8%) out of 1,227 patients, its incidence increasing according to the year of AIDS diagnosis. Women, homosexual men, patients given zidovudine and Pneumocystis carinii pneumonia (PCP) prophylaxis before AIDS, and severely immunodepressed patients were at higher risk for the disease. CMV disease was an independent factor of worse survival (hazard ratio, 1.7 versus PCP; 95% confidence intervals, 1.28-2.13). Patients untreated during the acute phase had a 4.3 higher risk of dying than those treated. Relapses occurred less frequently and later in patients given continuous maintenance treatment (23 out of 113; 17 months) than in untreated patients (13 out of 16; 3 months) or those given discontinuous therapy (22 out of 40; 7 months), whereas survival was independent from treatment. CMV infection was found in 97 out of 134 patients at autopsy, but was unassociated with relapse. CONCLUSIONS: CMV is a severe disease whose frequency is higher in severely immunodepressed patients. Continuous treatment leads to a lower relapse rate even if it does not change survival or eradicate the infection.

AIDS-Related Opportunistic Infections↗

Comparable biological and molecular determinants in HIV type 1-infected long-term nonprogressors and recently infected individuals.

Human immunodeficiency virus type 1 (HIV-1) isolability, rate of replication, phenotype, plasma viremia, and specific intracellular transcripts were cross-sectionally analyzed in 61 HIV-1-seropositive individuals to evaluate the correlations between the virological and molecular correlates of protection and progression in different clinical subsets: recently infected subjects (RIs), long-term nonprogressors (LTNPs), late progressors (LPs), and typical progressors (TPs). Comparison of the major virological and molecular features of HIV-1 infection has defined distinct profiles for different subsets of patients. LTNPs or RIs, as well as LPs or TPs, exhibited similar titers of coculture p24 antigen; the differences between the former and the latter were statistically significant at all the time points tested (p = 0.0001; 0.0003 and 0.0001). Whereas LTNPs and RIs revealed comparable low levels of indexes of viral replication, LPs and TPs showed higher genome and mRNA copy numbers (p = 0.0004 and p = 0.0008, respectively). We demonstrated close biological and molecular similarities between RIs and LTNPs on the one hand, and LPs and TPs on the other. In LTNPs both viral biological properties and viral load are important determinants of the course of the disease.

CD4 Lymphocyte Count↗

Human seminal plasma soluble 5'-nucleotidase: regulatory aspects of the dephosphorylation of nucleoside 5'-monophosphates.

Human seminal plasma contains two enzyme activities both capable of dephosphorylating all nucleoside 5-monophosphates with different efficiency and specificity. Broad-spectrum soluble 5'-nucleotidase is the object of this paper which deals with the definition of the response of this enzyme to effectors, some physiological and others not naturally occurring. The enzyme did not show any product regulation as all the nucleosides tested caused a moderate effect on the hydrolysis of the substrates. Theophylline and other xanthine derivatives had no effect on enzyme activity, whereas glycerate 2,3-bisphosphate, like other soluble 5'-nucleotidases, caused a stimulation of the enzyme, especially toward CMP and UMP. 5-Deoxy-5-isobutylthiadenosine resulted in no inhibition of the hydrolysis of AMP and IMP. The enzyme was affected neither by monovanadate nor by decavanadate, whereas it was strongly inhibited by Ap5 A. Variations in adenylate energy charge did not cause any alteration of the enzyme activity toward AMP and only a slight decrease of the hydrolysis of IMP. These regulatory properties, distinct from those of other soluble 5'-nucleotidases, show that this form, newly isolated from human seminal plasma, is subject to an almost unique, tissue-specific regulation.

5'-Nucleotidase↗

Italian multicentre study of didanosine compassionate use in advanced HIV infection. Italian BMS-906 Study Group.

The aim of the present study, a multicentre trial of didanosine (ddI) compassionate use, was to identify factors associated with a better outcome in patients given ddI monotherapy. Enrolled were 1047 HIV-positive patients intolerant of and/or unresponsive to zidovudine (ZDV) therapy, with CD4+ cell counts of < 200/microliter or AIDS. Didanosine was given at a dose of 250 mg b.i.d. (patients > or = 60 kg) or 167 mg b.i.d. (patients < 60 kg). Clinical examinations and laboratory tests were performed every two months. Endpoints included death, the occurrence of a new AIDS-defining disease, or permanent discontinuation of ddI for a severe adverse event. At entry, the median CD41 cell count was 47/microliter and the median duration of prior ZDV treatment 19 months; 446 patients (43%) were classified as having AIDS. Severe toxicity occurred in 143 subjects (14%); the frequency of pancreatitis was very low (0.2%). The benefit in terms of CD4+ cell counts was greater for patients whose counts exceeded 100/microliter at entry and remained at this level until month 12 in those patients still receiving treatment. Death and/or new AIDS-defining events were observed in 374 cases (36%) over a median follow-up of eight months. AIDS dementia was observed in 11 patients (1%). Multivariate analysis of survival without disease progression showed that the factors associated with a worse outcome include the severity of immunodepression, a diagnosis of AIDS at entry, and a history of both intolerance of and clinical resistance to ZDV. Surprisingly, the patients who had received previous prolonged treatment with ZDV had a better outcome. In conclusion, severely immunodepressed patients previously administered long-term monotherapy may receive a short-term benefit from being switched to another antiretroviral drug.

AIDS Dementia Complex↗

A comparison of brain biopsy and CSF-PCR in the diagnosis of CNS lesions in AIDS patients.

Twenty patients with AIDS who had intracranial lesions underwent both brain biopsy and cerebrospinal fluid (CSF) examination to compare histological diagnosis with the polymerase chain reaction (CSF-PCR) for the identification of infectious agents. CSF-PCR was performed for herpes simplex virus, varicella zoster virus, cytomegalovirus (CMV), JC virus (JCV), Epstein-Barr virus (EBV), Toxoplasma gondii and Mycobacterium tuberculosis. A definitive diagnosis was obtained by brain biopsy in 14 patients (2 with astrocytoma, 12 with brain infection). CSF-PCR was positive for EBV DNA in 3 of 3 cases of primary cerebral lymphoma, positive for JCV DNA in 6 of 7 biopsy-proven (and one autopsy-proven) cases of progressive multifocal leukoencephalopathy (PML). CSF-PCR was positive for CMV DNA in one biopsy-proven and one autopsy-proven case of CMV encephalitis (the former also had PML) and positive for M. tuberculosis DNA in one case of tuberculous encephalitis. None of the five toxoplasmic encephalitis cases (one definite, four presumptive) were T. gondii DNA positive. There was close correlation between histology and CSF-PCR for CMV encephalitis, PML and PCL. Antitoxoplasma therapy affected the sensitivity of both histological and CSF-PCR methods.

AIDS Dementia Complex↗