1,720,988 research outputs found
JC viremia and multiple sclerosis
No full textAbstract
Following the development of progressive multifocal leukoencephalopathy (PML) in two multiple sclerosis (MS) patients treated with natalizumab and interferon-beta (IFNbeta), a possible correlation between JC virus (JCV), the etiological agent of PML, and MS has received heightened interest. In particular, attention has focused on assessing whether IFNbeta treatment could affect the replication of JCV and thus its frequency in the peripheral blood of MS patients and whether the presence of JCV DNA in peripheral blood could be a predictive marker of the risk of developing PML. In order to answer to these questions, peripheral blood samples were collected from 59 INFbeta-treated, 39 untreated relapsing-remitting MS patients, and 98 healthy controls (HCs) and JCV DNA levels were determined and quantified by means of a real-time polymerase chain reaction (Q-PCR) assay. Overall, no differences were found in the presence or viral load of JCV DNA of MS patients and the HCs, but JCV DNA was significantly less frequent in the peripheral blood of IFNbeta-treated patients (13.6%) compared to the untreated MS patients (46.1%) and the healthy controls (28.6%). These results suggest that the presence of JCV in the blood of MS patients cannot be considered as a marker or a risk factor for PML development. In addition, they indicate that treatment with INFbeta can lead to the reduction of presence of the JCV genome in the peripheral blood of MS patients and, thus, that this drug probably does not increase the risk of PML in MS patients treated with IFNbeta
Conditioning response to granulocyte colony-stimulating factor via the dipeptidyl peptidase IV-adenosine deaminase complex
No full textAbstract
G-CSF is routinely used to mobilize hematopoietic stem cells (HSCs) from bone marrow (BM) into peripheral blood before aphaeresis, but HSC harvesting can be suboptimal. On the other hand, transplanted HSCs sometimes fail to engraft a recipient BM microenvironment when G-CSF is used after transplantation, as pushing-CSF will push HSCs away from marrow. So, G-CSF action needs to be potentiated by other drugs. Marrow stromal cells establish a local CXCL12 concentration gradient that is the primary homing signal for HSCs. Pharmacological interventions that modify this gradient, therefore, have potential to help HSC mobilization (by decreasing CXCL12) and engraftment (by increasing CXCL12). CXCL12 inactivation is primarily mediated by dipeptidyl peptidase-IV. We review here the currently available drugs affecting this enzyme that could be used in the clinic to achieve phase-specific help for G-CSF
Lithium and hematology: established and proposed uses
No full textLithium (as lithium carbonate) is an inexpensive drug, widely used in psychiatry for over 50 years in treatment of mood instability (bipolar disorder) and as an adjunct to antidepressants. Hematological effects of neutrophilia and increased circulating CD34+ cells of marrow origin have long been known. Lithium was at the center of hematological investigations in the 1980s, but no definitive use in hematology has yet emerged. We review evidence that lithium increases G-CSF and augments G-CSF effects. We suggest possible therapeutic uses of lithium in neutropenia. In bone marrow transplantation, preharvest lithium-assisted hematopoietic stem cell mobilization may be useful as well
,Hypothesis: Central nervous system delivery of cyclosporine A for therapy of progressive multifocal leukoencephalopathy
No full textPhenobarbital-associated bone marrow aplasia: a case report and review of the literature
No full textWe report on a 22-year-old female who developed aplastic anemia after administration of phenobarbital for 6 years. Being refractory to steroid and anti-lymphocyte serum, the patient received allogeneic stem cell transplantation, achieving complete remission. We discuss here the potential mechanisms by which phenobarbital and other anti-epileptic drugs can cause aplastic anemia and review the literature for previous case reports and epidemiological studies
Progressive multifocal leukoencephalopathy: what's new?
No full textProgressive multifocal leukoencephalopathy (PML), a severe demyelinating disease that is caused by human JC polyomavirus, was first described as a complication of immune suppression 50 years ago and emerged as a major complication of HIV infection in the 1980s. The prognosis has remained dismal since then, with discouraging results from clinical trials of various therapeutic approaches, including immunomodulation and/or inhibition of viral replication. PML is caused by reactivation of latent JC virus, and serotonergic 5-HT(2a) receptors have been identified as being critical for viral infection of glial cells. In recent years, immunosuppressive therapeutic antibodies have been associated with an increased incidence rate of PML. Here, the authors review findings on the pathogenesis of PML and the encouraging case reports of novel treatments
JC virus DNA in healthy brain tissue: a challenge for progressive multifocal leukoencephalopathy diagnosis
No full textBrains from 10 patients aged 68 to 96 years at time of death were studied for JC viral DNA and common papovaviral capsid protein. In situ hybridization of JC viral DNA was performed by affinity cytochemistry using a biotinylated fragment of JC viral DNA. Immunohistochemistry was performed on brain tissue by the avidin DH-biotinylated horseradish peroxidase technique using polyclonal antibody raised against the papovaviral capsid protein. Viral protein and DNA were detected in 4 of 10 patients. JC virus may be present in the brains of aged patients more frequently than previously suspected
Sialic acid moieties and 5-HT2a: two faces of the same receptor for JC virus?
No full textFor the human polyomaviruses JC virus (JCV) and BK virus (BKV), the first step to a successful infection involves binding to sialic acid moieties located on the surfaces of host cells. By stripping and then reconstituting specific sialic acid linkages on host cells, we show that JCV uses both alpha(2,3)-linked and alpha(2,6)-linked sialic acids on N-linked glycoproteins to infect cells. For both JCV and BKV, the sialic acid linkages required for cell surface binding directly correlate with the linkages required for infection. In addition to sialic acid linkage data, these data suggest that the third sugar from the carbohydrate chain terminus is important for virus binding and infection
Enhancement of hematopoietic stem cell engraftment by inhibition of CXCL12 proteolysis with sitagliptin, an oral dipeptidyl-peptidase IV inhibitor: a report in a case of delayed graft failure
No full text5-HT2a antagonists as a new treatment for JCV-associated progressive multifocal leukoencephalopathy
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