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Biomedical subjects

Marco A Lima

Publications and source records attributed to Marco A Lima.

9 recordsLinked to original sources

Frequency and phenotype of JC virus-specific CD8+ T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy.

JC virus (JCV)-specific CD8+ cytotoxic T lymphocytes (CTL) are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy (PML) and cross-recognize the polyomavirus BK virus (BKV). We sought to determine the frequency and phenotype in fresh blood of CD8+ T cells specific for two A*0201-restricted JCV epitopes, VP1(p36) and VP1(p100), and assess their impact on JC and BK viremia and viruria in 15 healthy subjects, eight human immunodeficiency virus-positive (HIV+) individuals, and nine HIV+ patients with PML (HIV+ PML patients) classified as survivors. After magnetic pre-enrichment of CD8+ T cells, epitope-specific cells ranged from 0.001% to 0.022% [corrected] by tetramer staining, with no significant difference among the three study groups. By use of seven-color flow cytometry, there was no predominant differentiation phenotype subset among JCV-specific CD8+ T cells in healthy individuals, HIV+ subjects, or HIV+ PML patients. However, in one HIV+ PML patient studied in the acute phase, there was a majority of activated effector memory cells. BKV DNA was undetectable in all blood samples by quantitative PCR, while a low JC viral load was found in the blood of only one HIV+ and two HIV+ PML patients. JCV and BKV DNA were detected in 33.3% and 13.3% of all urine samples, respectively, independent of the presence of JCV-specific CTL. The detection of JCV DNA in the urine was associated with the presence of a JCV VP1(p100) CTL response. Immunotherapies aiming at increasing the cellular immune response against JCV may be valuable in the treatment of HIV+ individuals with PML.

Adult↗

JC virus induces a vigorous CD8+ cytotoxic T cell response in multiple sclerosis patients.

We sought to compare the ongoing CD8+ cytotoxic T lymphocytes (CTL) immune response of MS patients to self and viral antigens. Using 51Cr release and tetramer staining assays, we found that the CTL response against VP1, the major capsid protein of the polyomavirus JC (JCV), was significantly higher than the one against epitopes of MBP and PLP. The JCV-specific CTL response was also significantly stronger in MS patients than healthy control subjects. These findings may shed a new light on the recent events related to the development of progressive multifocal leukoencephalopathy in three natalizumab-treated patients.

Capsid Proteins↗

Seizures and their outcome in progressive multifocal leukoencephalopathy.

Seizures are not expected in progressive multifocal leukoencephalopathy (PML), a condition considered to be restricted to the white matter. Review of medical records of 89 patients with possible or proven PML showed an 18% prevalence of seizures. Seizures usually responded well to treatment and did not affect survival. The presence of PML lesions immediately adjacent to the hemispheric cortex was the only risk factor associated with seizures in this population.

Adolescent↗

Extensive hydromyelia.

Hydromyelia is frequently associated with dissociated sensory loss, scoliosis, and upper limb weakness. This report describes the case of a 9-year old male with an extensive hydromyelia associated with a spinal cord tumor and an oligosymptomatic clinical presentation.

Astrocytoma↗

New features of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy and natalizumab.

Over the past three decades, progressive multifocal leukoencephalopathy (PML) evolved from being a clinical rarity to become an important cause of neurological complications in acquired immunodeficiency syndrome (AIDS) patients. Recently this disease unexpectedly occurred in patients receiving the novel immunomodulatory medication natalizumab. These changes in the epidemiology of PML also brought new questions with regard to the pathogenesis of this disease. The authors review the current challenges in the diagnosis and management of patients with PML, based on the recent advances in the understanding of the JC virus biology and discuss potential methods to monitor disease evolution and predict outcome.

AIDS-Related Opportunistic Infections↗

Atypical radiological presentation of progressive multifocal leukoencephalopathy following liver transplantation.

Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain caused by JC virus (JCV), occurs following transplantation and other conditions associated with immunosuppression. On magnetic resonance imaging (MRI), PML lesions typically appear as hyperintense signal on T2-weighted and FLAIR images located in the subcortical white matter, which are devoid of contrast enhancement or mass effect. The prognosis is poor, but unusual inflammatory forms of PML characterized by contrast enhancement have been associated with a cellular immune response against JCV and a better prognosis. The authors report an atypical presentation of PML with contrast-enhancing lesions and mass effect on the MRI in a liver transplant recipient,who had a progressive course and fatal outcome.

Adult↗

End-to-end anastomosis in growing vessels using a novel suturing technique: VCS metallic staples.

For pediatric transplants, a suturing technique is needed that allows the vessel to grow along with better healing of the anastomosis, through eliminating exogenous and thrombogenic material in the intimal side, thus minimizing the risk of vascular stenosis. In this study, 12 55-day-old lambs were subjected to end-to-end anastomosis of the right carotid artery and external jugular vein using vascular closure staple (VCS) clips (the vessels from the left side served as controls). Animals were followed up with duplex ultrasound. After 6 months, angiography was performed and animals were euthanized for microscopic study of the vessels. Duplex ultrasonography and angiography showed all vessels to be patent, with no flow disturbances and no stenosis at the anastomotic site at 6 months. Stenotic segments caudal to the anastomosis site were seen in two veins. No significant changes were seen macroscopically in any of the veins, whereas one of the arteries developed a pseudoaneurysm at the anastomotic site. Histological structure was normal in all the studied veins. Arteries showed different degrees of modifications that did not affect patency or flow in any case. Measurements taken after 6 months confirm that this technique allows the vessel to grow. This technique may be useful in vascular pediatric surgery.

Anastomosis, Surgical↗

Ultrasonographic assessment of metallic clip carotid anastomosis in sheep.

The aim of this study was to use ultrasonography to assess an experimental carotid arteriotomy followed by end-to-end anastomosis in the lamb. Animals were subjected to an experimental surgical procedure consisting of a right carotid artery arteriotomy and subsequent end-to-end anastomosis with nonpenetrating metallic clips. Left side arteries were used as control. Duplex ultrasonography was performed postoperatively to assess the evolution of the experimental anastomosis. Measurements were made on the right carotid to assess blood flow, peak systolic velocity, and end diastolic velocity, as well as arterial diameter. Animals were periodically checked during the six-month postoperative period. Operated vessels appeared normal during follow up, with pulsatile movements and size similar to non operated carotid arteries. A hyperechoic band, perpendicular to the vessel main axis, was seen on the longitudinal image in operated arteries, but not in the control group. This band corresponded to the anastomosis area, where the clips were positioned. No image suggestive of thrombosis was observed in any operated artery, and blood flow was maintained through the experiment. Finally, a decrease of vessel lumen diameter was evidenced at the level of the anastomosis during the first 30 postoperative days, but it was not present after the 90th postsurgical day. Duplex ultrasonography is a useful imaging technique for the assessment of anatomical details, acoustical properties of the vascular lumen, and study of the intimal surface and vessel wall in growing arteries subjected to surgery. Metallic clips as suturing technique in arterial anastomosis allow for normal vascular growth, as shown by the evolution of flow velocity and vessel diameter.

Analysis of Variance↗