Access and use of immunoglobulins in supportive cancer care: A thematic analysis of a systematic review data set.

Background: Secondary immunodeficiency (SID) disorders are known to occur in patients with haematological malignancies (HM) due to immunosuppressive treatments. Recurring infections causing subsequent morbidity and mortality commonly occur in this patient cohort. Immunoglobulin replacement therapy (IgRT) benefits patients with primary antibody deficiencies.

Access and use of immunoglobulins in secondary supportive cancer care: A systematic literature review.

Background: Immunoglobulin replacement therapy (IgRT) benefits patients with primary immuno deficiency (PID) originating from the innate or polygenic defects in the immune system. However, evidence supporting their therapeutic role is not as explicit in secondary immuno deficiency (SID) resulting from the treatment of haematological malignancies.

Objectives: This study aimed to (1) create a dataset of relevant research papers, which explore the use of IgRT in SID for analysis, (2) assess the risk of bias within this dataset and (3) study the characteristics of these papers.

Changes in cellular prion protein expression, processing and localisation during differentiation of the neuronal cell line CAD 5.

Background Information: Cellular prion protein (PrP ) is infamous for its role in prion diseases. The physiological function of PrP remains enigmatic, but several studies point to its involvement in cell differentiation processes. To test this possibility, we monitored PrP changes during the differentiation of prion-susceptible CAD 5 cells, and then we analysed the effect of PrP ablation on the differentiation process.

Are prions transported by plasma exosomes?

Blood has been shown to contain disease-associated misfolded prion protein (PrP(TSE)) in animals naturally and experimentally infected with various transmissible spongiform encephalopathy (TSE) agents, and in humans infected with variant Creutzfeldt-Jakob disease (vCJD). Recently, we have demonstrated PrP(TSE) in extracellular vesicle preparations (EVs) containing exosomes from plasma of mice infected with mouse-adapted vCJD by Protein Misfolding Cyclic Amplification (PMCA). Here we report the detection of PrP(TSE) by PMCA in EVs from plasma of mice infected with Fukuoka-1 (FU), an isolate from a Gerstmann-Sträussler-Scheinker disease patient.

Mechanisms of prion-induced neurodegeneration.

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders characterised by long incubation period, short clinical duration, and transmissibility to susceptible species. Neuronal loss, spongiform changes, gliosis and the accumulation in the brain of the misfolded version of a membrane-bound cellular prion protein (PrP(C)), termed PrP(TSE), are diagnostic markers of these diseases. Compelling evidence links protein misfolding and its accumulation with neurodegenerative changes.

Protein misfolding cyclic amplification (PMCA): Current status and future directions.

Transmissible spongiform encephalopathies (TSEs) most commonly known as prion diseases are invariably fatal neurological disorders that affect humans and animals. These disorders differ from other neurodegenerative conformational diseases caused by the accumulation in the brain of misfolded proteins, sometimes with amyloid properties, in their ability to infect susceptible species by various routes. While the infectious properties of amyloidogenic proteins, other than misfolded prion protein (PrP(TSE)), are currently under scrutiny, their potential to transmit from cell to cell, one of the intrinsic properties of the prion, has been recently shown in vitro and in vivo.

First demonstration of transmissible spongiform encephalopathy-associated prion protein (PrPTSE) in extracellular vesicles from plasma of mice infected with mouse-adapted variant Creutzfeldt-Jakob disease by in vitro amplification.

The development of variant Creutzfeldt-Jakob disease (vCJD) in three recipients of non-leukoreduced red blood cells from asymptomatic donors who subsequently developed the disease has confirmed existing concerns about the possible spread of transmissible spongiform encephalopathies (TSEs) via blood products. In addition, the presence of disease-associated misfolded prion protein (PrP(TSE)), generally associated with infectivity, has been demonstrated in the blood of vCJD patients. However, its origin and distribution in this biological fluid are still unknown.

Candidate cell substrates, vaccine production, and transmissible spongiform encephalopathies.

Transmissible spongiform encephalopathy (TSE) agents have contaminated human tissue-derived medical products, human blood components, and animal vaccines. The objective of this study was to determine the potential susceptibility to infection of 5 cell lines used or proposed for manufacture of biological products, as well as other lines. Cell lines were exposed to the infectious agents of sporadic and variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (BSE).

Fukuoka-1 strain of transmissible spongiform encephalopathy agent infects murine bone marrow-derived cells with features of mesenchymal stem cells.

Background: The possible risk of iatrogenic transmissible spongiform encephalopathies (TSEs, prion diseases) from transplantation of marrow-derived mesenchymal stem cells (MSCs) is uncertain. While most cell lines resist infection, a few propagate TSE agents.

Study Design And Methods: We generated MSC-like (MSC-L) cell cultures from bone marrow (BM) of mice inoculated with the human-derived Fukuoka-1 (Fu) strain of TSE agent.

Susceptibilities of nonhuman primates to chronic wasting disease.

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy, or prion disease, that affects deer, elk, and moose. Human susceptibility to CWD remains unproven despite likely exposure to CWD-infected cervids. We used 2 nonhuman primate species, cynomolgus macaques and squirrel monkeys, as human models for CWD susceptibility.

Murine bone marrow stromal cell culture with features of mesenchymal stem cells susceptible to mouse-adapted human TSE agent, Fukuoka-1.

Transmission of transmissible spongiform encephalopathies (TSEs)/prion diseases through transplantation of bone marrow (BM) has never been reported in humans. However, the use of fetal bovine serum in current protocols for generating mesenchymal stem cells (MSCs) carries the risk of iatrogenic spread. We developed a cell model from murine BM-derived MSCs and tested its susceptibility to Fukuoka-1 (Fu) strain of TSEs.

Persistent propagation of variant Creutzfeldt-Jakob disease agent in murine spleen stromal cell culture with features of mesenchymal stem cells.

The transmission of variant Creutzfeldt-Jakob disease (vCJD) through blood transfusions has created new concerns about the iatrogenic spread of transmissible spongiform encephalopathies (TSEs)/prion diseases through blood and plasma-derived products and has increased the need to develop efficient methods for detection of the agent in biologics. Here, we report the first successful generation of spleen-derived murine stromal cell cultures that persistently propagate two mouse-adapted isolates of human TSE agents, mouse-adapted vCJD, and Fukuoka 1. These new cell cultures can be used efficiently for studies of the pathogenesis of the disease, for development of diagnostics and therapeutics, and as a rapid ex vivo assay for TSE inactivation/removal procedures.

Detection of misfolded prion protein in blood with conformationally sensitive peptides.

Background: The long-standing goal of a preclinical diagnostic test for transmissible spongiform encephalopathy (TSE) has recently become urgent because of the discovery that humans with variant Creutzfeldt-Jakob disease can transmit disease via blood transfusions.

Study Design And Methods: The misfolded protein diagnostic (MPD) assay employs a pyrene-labeled palindromic sequence of prion peptides that undergoes a cascade of coil to beta-sheet conversion in the presence of the misfolded prion protein (PrP(TSE)). The ability of the assay to detect PrP(TSE) in brain, serum, and plasma was tested.

Gerstmann-Sträussler-Scheinker: a new phenotype with 'curly' PrP deposits.

Gerstmann-Sträussler-Scheinker (GSS) is a hereditary prion disease typically associated with prion protein (PrP)-containing plaques. The protease-resistant, scrapie PrP (PrPSc) is represented by internal fragments, whereas the C-terminal fragments associated with the other prion diseases are generally underrepresented. Different histopathologic and PrPSc features associated with at least 13 PrP gene (PRNP) mutations have been described in GSS.

Protease-resistant prion protein in lymphoreticular tumors of variant Creutzfeldt-Jakob disease mice.

We report protease-resistant prion protein (PrPres) in spontaneous lymphoreticular tumors of mice infected with the agent of variant Creutzfeldt-Jakob disease (vCJD). PrPres may accumulate in lymphoreticular system tumors of asymptomatic persons with vCJD. The statistical power of estimates of vCJD prevalence might be increased by expanding screening to include samples of lymphoreticular neoplasms.

The modern landscape of transfusion-related iatrogenic Creutzfeldt-Jakob disease and blood screening tests.

The idea that blood in naturally occurring transmissible spongiform encephalopathies is not infectious has imploded in the face of recent transmissions from the blood of naturally occurring scrapie in sheep and of variant Creutzfeldt-Jakob disease in humans. Although donor exclusion criteria ensure that the number of any further iatrogenic cases will be small, the risk of future blood-borne disease transmissions could be entirely eliminated by a diagnostic preclinical screening test. A variety of methodological approaches to blood testing are under development, with different levels of success, but no method has yet achieved the critical goal of discriminating transmissible spongiform encephalopathy-infected from healthy uninfected humans.

Effect of protease treatment on plasma infectivity in variant Creutzfeldt-Jakob disease mice.

Background: The emergence of variant Creutzfeldt-Jakob disease (vCJD) and of a probable transmission of the disease through blood transfusion from a presymptomatic case has underlined the need for a reliable, sensitive, and specific screening test. This study was initiated to explain why attempts to identify protease-resistant prion protein (PrPres) following treatment with proteinase K (PK) in blood or blood components have so far failed.

Study Design And Methods: RIII mice were inoculated intracerebrally (i.

Advances in screening test development for transmissible spongiform encephalopathies.

The blood of patients with transmissible spongiform encephalopathy or prion disease can no longer be considered free of infectivity. There have been two recent reports of highly probable transfusion-associated iatrogenic variant Creutzfeldt-Jakob disease infections, and there is supporting experimental evidence of scrapie transmission by the transfusion of blood from sheep with naturally occurring disease. In the absence of a preclinical diagnostic test for transmissible spongiform encephalopathy, the main precautionary measures undertaken by blood agencies employ donor exclusion criteria, ensuring that the number of any further iatrogenic cases will be small.

Similar levels of infectivity in the blood of mice infected with human-derived vCJD and GSS strains of transmissible spongiform encephalopathy.

Background: The possible transmission of variant CJD (vCJD) through blood transfusion or use of plasma-derived products prompted this study comparing infectivity in murine models of vCJD and Gerstmann-Sträussler-Scheinker (GSS) disease, a non-vCJD form of transmissible spongiform encephalopathy (TSE).

Study Design And Methods: RIII/Fa/Dk (RIII) or Swiss-Webster (Swiss) mice were inoculated intracerebrally (IC) with mouse-adapted strains of vCJD or GSS (Fukuoka-1) of similar infectivity. Groups of RIII mice were euthanized 17 weeks after inoculation (during the incubation period), and another 23 weeks after inoculation (when symptomatic).

Failure of immunocompetitive capillary electrophoresis assay to detect disease-specific prion protein in buffy coat from humans and chimpanzees with Creutzfeldt-Jakob disease.

The emergence of a new environmentally caused variant of Creutzfeldt-Jakob disease (vCJD), the result of food-born infection by the causative agent of bovine spongiform encephalopathy (BSE), has stimulated research on a practical diagnostic screening test. The immunocompetitive capillary electrophoresis (ICCE) assay has been reported to detect disease-specific, proteinase-resistant prion protein (PrPres) in the blood of scrapie-infected sheep. We have applied this method to blood from CJD-infected chimpanzees and humans.

Stability of the prion protein-encoding (PRNP) gene in HeLa cells.

To assess the risk of the de novo emergence of the agent of transmissible spongiform encephalopathies in cultured cells, we examined the stability of the prion protein-encoding (PRNP) gene in HeLa cells and in cultures contaminated with HeLa cells that have been passaged extensively for over 50 years. Various sub-lineages of HeLa cells showed that some contained a mixture of a truncated PRNP gene (R3-R4 deletion) and a full-length PRNP gene, while others were homozygous for the R3-R4 deletion. That finding suggests that the progenitor of several popular sub-lineages of HeLa must have lost part or all of chromosome 20 early in the history of HeLa cells.

Spontaneous mutations in the prion protein gene causing transmissible spongiform encephalopathy.

We analyzed the prion protein gene (PRNP) region in patients with transmissible spongiform encephalopathy associated with the PRNP D178N mutation. The results suggest that the D178N chromosomes had independent origins in each affected pedigree or apparently sporadic case. A de novo spontaneous PRNP mutation was observed.

Cytokine regulation of E-selectin in rat CNS microvascular endothelial cells: differential response of CNS and non-CNS vessels.

We have compared the induced expression of E-selectin in primary cultures of rat brain microvascular endothelial cells (EC), pericytes and in non-CNS microvascular endothelium stimulated with the cytokines, IL-1beta (20 ng/ml), and tumor necrosis factor (TNF)-alpha (75 ng/ml). Expression was studied at both the protein and mRNA levels. Fluorescence in-situ hybridization (FISH) was used to examine de novo synthesis of E-selectin mRNA.